Next Article in Journal
Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis
Previous Article in Journal
Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 22
Issue 21
10.3390/ijms222111856
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Intermolecular Diels-Alder Cycloadditions of Furfural-Based Chemicals from Renewable Resources: A Focus on the Regio- and Diastereoselectivity in the Reaction with Alkenes

by
Konstantin I. Galkin
1,2 and
Valentine P. Ananikov
1,*
1
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, 119991 Moscow, Russia
2
Laboratory of Functional Composite Materials, Bauman Moscow State Technical University, 2nd Baumanskaya Street 5/1, 105005 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(21), 11856; https://doi.org/10.3390/ijms222111856
Submission received: 14 October 2021 / Revised: 29 October 2021 / Accepted: 29 October 2021 / Published: 1 November 2021
(This article belongs to the Section Macromolecules)
Browse Figures
Versions Notes

Abstract

:
A recent strong trend toward green and sustainable chemistry has promoted the intensive use of renewable carbon sources for the production of polymers, biofuels, chemicals, monomers and other valuable products. The Diels-Alder reaction is of great importance in the chemistry of renewable resources and provides an atom-economic pathway for fine chemical synthesis and for the production of materials. The biobased furans furfural and 5-(hydroxymethyl)furfural, which can be easily obtained from the carbohydrate part of plant biomass, were recognized as “platform chemicals” that will help to replace the existing oil-based refining to biorefining. Diels-Alder cycloaddition of furanic dienes with various dienophiles represents the ideal example of a “green” process characterized by a 100% atom economy and a reasonable E-factor. In this review, we first summarize the literature data on the regio- and diastereoselectivity of intermolecular Diels-Alder reactions of furfural derivatives with alkenes with the aim of establishing the current progress in the efficient production of practically important low-molecular-weight products. The information provided here will be useful and relevant to scientists in many fields, including medical and pharmaceutical research, polymer development and materials science.

1. Introduction

To date, the development of efficient technologies for catalytic or biocatalytic conversion of renewable plant biomass into viable targeted products remains one of the most important and challenging tasks for modern chemical science [1,2,3,4,5]. The primary advantage of biorefining based on renewable carbon sources over traditional refining using exhaustible resources is the realization of a carbon-neutral cycle, leading to zero total carbon emissions into the environment during chemical production and consumption. Biobased furans—furfural (FF) and 5-(hydroxymethyl)furfural (HMF)—can be obtained by acid-catalyzed dehydration of carbohydrates and are recognized as “platform chemicals”. As expected, the key role of biobased technologies is to replace the key existing products of oil-based refinement with renewables [4,6,7]. The tremendous synthetic potential explains the unprecedented scale of research in the fields of synthesis and application of furanic platform chemicals for the production of biofuels, chemicals, polymers and other industrially important products, which was evidenced by the increasing number of relevant publications (partially since 2010, Figure 1) and was highlighted in many recent reviews [7,8,9,10,11,12,13,14,15,16,17,18,19,20].
One of the focused reactions of furan chemistry is the [4+2]-cycloaddition, well known as the Diels-Alder (DA) reaction, in the classic mechanism based on the interaction of the highest occupied molecular orbital of furanic diene (HOMOdiene) and the lowest unoccupied molecular orbital of dienophile (LUMOdienophile). The DA reaction may proceed with high efficiency under solvent-free and/or noncatalytic conditions, representing the ideal example of a “green” process characterized by a 100% atom economy and a low to moderate E-factor [21,22]. Intermolecular furan/alkene DA reactions have a high potential for application in fine organic synthesis, biomedical areas, materials sciences, polymers and bio-organic chemistry (Figure 2) [23,24,25,26,27,28,29,30].
The direct Diels-Alder reaction of FF or HMF with common alkenes is thermodynamically unfavorable [31,32,33], but this type of cycloaddition can be performed after decreasing the HOMO–LUMO gap through reduction of the aldehyde group into more donor functionality. Another approach is redox-neutral chemical activation through modification of aldehyde into acetal or hydrazone with the possibility of aldehyde deprotection. In general, the nature of the substituent at the C2 position in the furan ring strongly affects reactivity in DA cycloadditions; furans with electron-donating groups are well-suited as substrates, while electron-poor furans display low reactivity [34,35].
In the case of highly active dienophiles, DA adducts may be formed under noncatalytic conditions; for other substrates, catalysis by Lewis acids is usually needed. Reactions of furans with alkene dienophiles are often characterized by facile retro-DA (rDA) reactions due to the low reactivity of furan as a diene that leads to low diastereo- and regioselectivity of the cycloaddition (Scheme 1). The orbital HOMOdiene and LUMOdienophile energy difference seems to control the diastereomer distribution [32,36]. Charge interactions between diene and dienophile favor orthoselectivity, while steric hindrance promotes metaselectivity but without strong kinetic or thermodynamic preference for a single regioisomer [32,37].
Information about the selectivity of DA reactions is helpful to scientists in many fields, including medical and pharmaceutical research, polymer development and materials science. The regio- and diastereoselectivity of DA cycloaddition are important parameters for the high-yielding synthesis of chemically pure products, especially in the development of drugs, because diastereomers may exhibit different biological activities [38]. The endo- and exo-DA adducts have different steric properties and convert to furan and alkene components at different temperatures, which may be important in the development of various dynamic systems [39,40]. Moreover, the stereo structure of cyclic alkenes may influence the reactivity in ring-opening metathesis polymerization used for the synthesis of stereoregular polymers [41]. This difference for furan-derived oxanorbornanes was clearly demonstrated by Kilbinger and coworkers. They showed in several examples that furan/maleimide DA adducts react quickly and selectively with the G3 catalyst, resulting in the formation of monomolecular carbene complexes that display low reactivity with the second molecule of oxanorbornane (both endo or exo) due to unfavorable steric factors (Scheme 2a). In contrast, exo-oxanorbornane counterparts undergo efficient homopolymerization under the same reaction conditions (Scheme 2b) [41].
Several approaches may be used to increase the regio- and diastereoselectivity of DA reactions: fine-tuning of steric and electronic properties of dienes or dienophiles; variation of reaction conditions such as temperature, time, type of solvent and pressure; and catalysis by Lewis acids. Generally, for furan/alkene cycloadditions, exo isomers are more stable and form under thermodynamic control of the reaction (at high temperature), while endo isomers are kinetically preferred [36,42,43,44].
In this review, we summarized the recent literature about the regio-, stereo- and diastereoselectivity of intermolecular Diels-Alder (IMDA) cycloadditions of simple furfural derivatives with alkenes used for the synthesis of cyclic aliphatic or aromatic products. Some aspects, such as the influence of a catalyst or solvent, the type of diene and dienophile and, in some cases, comparison with other furanic substrates, were highlighted. Several reviews have covered the synthetic potential of biobased furans for the production of biofuels, chemicals and materials [10,11,15,18,30,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59], as well as the mechanisms and selectivity of DA cycloadditions [60,61,62,63,64]. These discussions will not be repeated here. Instead, a dedicated survey of the literature focused on the selectivity of IMDA cycloadditions of FF derivatives with alkenes (which has not been previously reported) will be provided here.

2. Selectivity of Diels-Alder Cycloaddition with Furfural Derivatives as Substrates

2.1. 2-Methylfuran

2-Methylfuran (2-MF) is the simplest 2-substituted furan produced by the reduction of the aldehyde group in FF. The selectivity of IMDA reactions of 2-MF with common cyclic and acyclic alkenes is presented in Table 1 and Table 2. Noncatalytic reactions of 2-MF with maleic or citraconic anhydride led to cycloadducts with exo configurations even at room temperature (Table 1, entries 1–3). The current literature provides scarce information about the selectivity of reactions of 2-MF with maleimides under kinetic conditions. In the case of maleimides reacting with 2-MF at room temperature, the formation of >20% endo isomer was observed (entry 4), while at temperatures more than 60 °C, exclusive formation of the exo isomer was found for most maleimides (Table 1). However, in a water medium for some N-substituted maleimides, the content of endo isomers was higher even under high temperature (entries 8, 10). For N-carboxyethyl maleimide reacting with furan, 2-MF or 2,5-dimethylfuran, the best exoselectivity was obtained in the case of furan, while 2,5-dimethylfuran showed the best endoselectivity under kinetic conditions (entries 16–19) [65]. The cycloadduct of 2-MF with N-phenyl maleimide was isolated in a pure, optically active form with 90% ee using dynamic enantioselective crystallization by continuous suspension in heptane or hexane solution with glass beads at 80 °C in the presence of trifluoroacetic acid (TFA) to accelerate the deracemization (entry 13) [44].
An important possible application of 2-MF is the protection of double bonds in functionalized alkenes against nucleophiles using the DA reaction. For example, modification of the 2-MF/maleimide DA adduct by alkylation or a Mitsunobu reaction, followed by thermal deprotection, was used for the synthesis of N-alkylated maleimides (Scheme 3) [69,70].
Representative reactions of 2-MF with acyclic alkenes containing one or two electron-withdrawing groups (EWGs) are covered in Table 2. High endoselectivity was obtained for the HfCl4-catalyzed reaction of 2-MF with dimethyl maleate at low temperatures (Table 2, entries 1, 2). However, under the same conditions, benzyl acrylate showed exoselectivity for cycloaddition (entries 7, 8). An adduct of 2-MF and trans-4,4,4-trifluorocrotonic acid formed with high regio- and diastereoselectivity (entry 3). An enantioselective version of DA reactions with some fluorinated alkene dienophiles was implemented using chiral oxazaborolidine organocatalysts, which affords corresponding chiral oxabicyclic products with high yields and selectivity (entries 4–6). In the case of acrylonitrile reacting with 2-MF, regio- and diastereoselectivity was poor even in the presence of Lewis acid catalysts (entries 9, 10). Orthoadducts of 2-MF with 1-cyanovinyl acetate or 2-chloroacrylonitrile that are favored over meta-isomers due to electronic reasons were obtained under kinetic conditions with high regioselectivity (entries 11–15). A shift towards endo-products was found for reactions of 2-MF with allenic esters in the presence of Eu(fod) as the catalyst (entries 16–19).
Table
Table 2. IMDA cycloadditions of 2-MF with acyclic alkenes.
Table 2. IMDA cycloadditions of 2-MF with acyclic alkenes.
Ijms 22 11856 i041
№DienophileConditionsSelectivityYield of Adducts (%), [Ref.]
1Dimethyl maleateHfCl4, CH2Cl2, −30 °CEndo/exo 84:1694, [76]
2Dimethyl maleateHfCl4, CH2Cl2, −50 °CEndo/exo > 98:282, [76]
3 Ijms 22 11856 i00422 °C Ijms 22 11856 i00590, [77]
4 Ijms 22 11856 i006 Ijms 22 11856 i007
Ar = 1-naphthyl (cat.),
CH2Cl2, −78 °C		 Ijms 22 11856 i008
99 de, 99 ee		99, [78]
5 Ijms 22 11856 i009 Ijms 22 11856 i010
Ar = 1-naphthyl (cat.),
CH2Cl2, −78 °C		 Ijms 22 11856 i011
99 de, 99 ee		74, [78]
6 Ijms 22 11856 i012 Ijms 22 11856 i013
(cat.), CH2Cl2, −78 °C		Ortho (endo/exo 94:6), 98 ee (for endo isomer)74, [79]
7Benzyl acrylateHfCl4, CH2Cl2, −30 °CEndo/exo 28:72 (mixture of regio isomers)84, [76]
8Benzyl acrylateHfCl4, CH2Cl2, −50 °CEndo/exo (31:69) (mixture of regio isomers)85, [76]
9AcrylonitrileZnI2, neat, 50 °CN.d.69, [80]
10AcrylonitrileNeat, 60 °COrtho 66 (endo/exo 61:39), meta 34 (endo/exo 56:44)69, [31,32]
111-Cyanovinyl acetateZnI2, neat, 0 °C, 8 daysOrtho (endo/exo 1:1) 252, [81]
121-Cyanovinyl acetateZnI2, neat, 20 °C, 26 hOrtho endo217, [81]
131-Cyanovinyl acetateZnI2, neat, RT, 24 hOrtho (endo/exo 3:1) 230, [82]
141-Cyanovinyl acetateMgI2, neat, RT, 24 hOrtho (endo/exo 4:1) 257, [82]
152-ChloroacrylonitrileZnI2, neat, 0 °COrtho/meta 10:1 (mixture of endo/exo)91 1, [83]
16 Ijms 22 11856 i014Benzene, reflux Ijms 22 11856 i015
Endo/exo 1,1:1		70, [84]
17 Ijms 22 11856 i016Eu(fod), RT Ijms 22 11856 i017
Endo/exo 2,1:1		80, [84]
18 Ijms 22 11856 i018Eu(fod), RT Ijms 22 11856 i019
Endo/exo ~2,8:1		80, [84]
19 Ijms 22 11856 i020Benzene, reflux Ijms 22 11856 i021
Endo/exo ~1:1		73, [84]
20Itaconic anhydride
Ijms 22 11856 i022		Neat, 23 °COrtho (endo:exo)/meta (endo:exo) 3:1/11:8 313 4, [85]
1 Yield of DA adduct after hydrogenation. 2 Endo- and exoconformation with regard to the position of the OAc group. 3 Structure of regio- and diastereomers in DA cycloaddition of C-2-substituted furans with itaconic anhydride are provided in Scheme 5. 4 Was detected by NMR. N.d.—not determined.

2.2. Furanic Acetals

With rare exceptions, furfural does not react with dienophiles, but the introduction of aldehyde groups by DA reaction may be performed using an acetalization strategy that reduces the electron-withdrawing character of the carbonyl group. Table 3 highlights the results of reactions of furanic acetals with cyclic and linear alkenes. Literature data about the stereoselectivity of reactions of furanic acetals with cyclic alkenes are scarce. Predominant formation of endoadducts under kinetic conditions was detected by NMR when N-methyl maleimide was used as a dienophile (entry 1). For reactions of furfural acetals with mono-substituted acyclic alkenes, regioselectivity significantly depended on the type of substrates and reaction conditions. For dioxolane acetal reacting with methyl vinyl ketone, methyl acrylate or acrolein at 60 °C, a mixture of regio- and stereoisomers was obtained with predominant meta- and endoselectivity. In the case of acrylonitrile reacting with furanic acetals, the selectivity of cycloadditions was poor even in the presence of Lewis acid catalysts (entries 5–9). For the ZnCl2-catalyzed reaction of ethylthioacetal with acrylonitrile at 30 °C, 91% orthoselectivity and moderate endoselectivity were observed (entry 10). According to DFT calculations, the regioselectivity of reactions of furanic acetals with alkenes is a result of two opposite factors: charge interactions between the furan and alkene favor orthoselectivity, while steric factors promote metaselectivity [32].

2.3. Functionalized Furfural Derivatives

Mild reduction of the aldehyde group in FF is a path to important furanic building blocks furfuryl alcohol (FA) and furfuryl amine (FAM), which are widely used for the development of functional or dynamic molecular and biomolecular systems. Examples of possible areas of applications include but are not limited to the synthesis of biologically active compounds [87,88,89,90], oxanorbornane-based amphiphiles [91,92,93,94], supramolecular systems [95], self-assemblies [96], self-healing polymers and other dynamic systems [28].
The diastereoselectivity of DA reactions of FA, FAM and some common derivatives with cyclic and acyclic alkenes is shown in Table 4, Table 5 and Table 6. Preferable formation of exoadducts was observed for reactions of maleic and citraconic anhydrides with selected furanic substrates even at low temperatures (Table 5 and Table 6), except for the vinylated derivative of FA, which showed preferable endoselectivity (Table 5, entries 5–10).
The adduct of FA with maleic anhydride (1-exo) is unstable and undergoes irreversible intramolecular cyclization during storage or warming, yielding the corresponding thermodynamically stable lactone 2-exo (Scheme 4) [102].
The diastereoselectivity of the reactions with N-alkyl- and N-benzyl-substituted maleimides was in accordance with typical kinetic profiles demonstrating a shift towards endo- and exo-products under kinetic or thermodynamic conditions, respectively (Table 4, Table 5 and Table 6). However, this relationship was disrupted for some N-aryl maleimides reacting with various furanic substrates under both kinetic and thermodynamic conditions. For example, the diastereoselectivity of the cycloaddition of vinyl-substituted FA and N-Ph-maleimide shifted from a 1:2.8 endo/exo ratio under kinetic conditions to Et2O to a 4:1 endo/exo ratio in toluene at 80 °C (Table 5, entries 11, 12).
Table
Table 5. IMDA cycloadditions of FA derivatives with cyclic alkenes.
Table 5. IMDA cycloadditions of FA derivatives with cyclic alkenes.
Ijms 22 11856 i044
№RDienophileConditionsSelectivityYield of Adducts
(%), [Ref.]
1AllylN-Me-maleimideToluene, 50 °C, 24 hN.d.65 (endo), [103]
2AllylN-Ph-maleimideToluene, 50 °C, 24 hN.d.26 (exo), [103]
3BnMaleic anhydrideToluene, RT, 3 daysExo43, [91]
4BnCitraconic anhydride
Ijms 22 11856 i036		15 kbar, CH2Cl2, 60 hExo (ortho/meta 5:7)31 1, [68]
5VinylMaleic anhydrideEt2O, 22‒24 °C, 48 hEndo72, [104]
6VinylMaleic anhydrideEt2O, 35 °C, 48 hEndo/exo 8:166, [104]
7VinylMaleic anhydrideTHF, 22‒24 °C, 90 hEndo/exo 8:166, [104]
8VinylMaleic anhydrideMeCN, 22‒24 °C, 48 hEndo/exo 4:168, [104]
9VinylMaleic anhydrideToluene, 22‒24 °CEndo/exo 12:164, [104]
10VinylMaleic anhydrideToluene, 80 °CEndo/exo 4:166, [104]
11VinylN-Ph-maleimideEt2O, 22‒24 °CEndo/exo 1:2.847, [104]
12VinylN-Ph-maleimideToluene, 80 °CEndo/exo 4:166, [104]
13AcMaleic anhydrideEt2O, 25 °C, 7 daysExo34, [105]
14AcMaleic anhydrideToluene, RT, 97 hExo74, [88]
15AcCitraconic anhydride
Ijms 22 11856 i037		15 kbar, CH2Cl2, 60 hExo (ortho/meta
6:5)		59 1, [68]
16AcN-Me-maleimideCH2Cl2, 23 °CEndo/exo 77:23N.d., [86]
17AcN-DodecylmaleimideTHF, 23 °CEndo/exo 64:36N.d., [86]
18AcN-Ph-maleimideCH2Cl2, 23 °CEndo/exo 65:35N.d., [86]
19AcN-(p-Nitrophenyl)maleimideCH2Cl2, 23 °CEndo/exo 55:45N.d., [86]
20AcN-(p-Methoxyphenyl)maleimideCH2Cl2, 23 °CEndo/exo 67:33N.d., [86]
21AcN-(Methoxy-2-propyl)maleimideCH2Cl2, 23 °CEndo/exo 76:24N.d., [86]
22AcN-(2-Methoxyethyl)maleimideCH2Cl2, 23 °CEndo/exo 75:25N.d., [86]
23BzMaleic anhydrideToluene, 80 °C, 456 hExo46, [88]
24 2BzMaleic anhydrideEt2O, 24 °C, 24 hEndo84, [106]
25BzN-Me-maleimideCH2Cl2, 23 °CEndo/exo 70:30N.d., [86]
26BzN-DodecylmaleimideTHF, 23 °CEndo/exo 63:37N.d., [86]
27COiBuN-Pr-maleimideCHCl3, 55 °CEndo/exo 60:40N.d., [107]
28COiBuN-iBu-maleimideCHCl3, 55 °CEndo/exo 45:55N.d., [107]
29COiBuN-tBu-maleimideCHCl3, 55 °CEndo/exo 51:49N.d., [107]
30COiBuN-Bn-maleimideCHCl3, 55 °CEndo/exo 44:56N.d., [107]
31COiBu Ijms 22 11856 i038CHCl3, 55 °CEndo/exo 26:74N.d., [107]
32COiBuN-(2-Methylphenyl)-maleimideCHCl3, 55 °CEndo/exo 67:33N.d., [107]
33COiBuBMICHCl3, 55 °CEndo/exo 19:81N.d., [107]
34COtBuN-Me-maleimideCH2Cl2, 23 °CEndo/exo 71:29N.d., [86]
35COtBuN-DodecylmaleimideTHF, 23 °CEndo/exo 62:38N.d., [86]
1 Yield of DA adduct after hydrogenation. 2 BHMF dibenzoate as a substrate. N.d.—not determined.
Information about the regio- and diastereoselectivity of functional FF derivatives with acyclic alkenes is scarce. A mixture of regio- and diastereoisomers with approximately equal distribution was detected after the noncatalytic reaction of FA with acrylonitrile (Table 4, entry 14). A mixture of regio- and diastereomers with ortho (endo:exo)/meta (endo:exo) 2:1/8:6 ratio was formed from itaconic anhydride reacting with FA acetate (Scheme 5) [85]. However, unfavorable thermodynamic parameters of cycloaddition with this dienophile were overcome using FA as a substrate, where proximal (ortho) DA adducts undergo further intramolecular cyclization, shifting the reaction equilibrium towards metastable lactone 5, which was isolated in 94% yield (Scheme 5) [85].
Overall, the diastereoselectivity of DA reactions of alkenes with FF derivatives containing donor substituents at the C2 position is not always predictable, because it strongly depends on the structure of both the diene and dienophile. More predictable diastereoselective construction of functionalized oxabicyclic structures may be performed using HMF-derived 2,5-disubstituted furans that predominantly react with cyclic alkenes with high endoselectivity (Table 4, entries 1–2; Table 5, entry 24) [33,43,106,108].
Table
Table 6. IMDA cycloadditions of FAM derivatives with cyclic alkenes.
Table 6. IMDA cycloadditions of FAM derivatives with cyclic alkenes.
Ijms 22 11856 i045
№RDienophileConditionsSelectivityYield of Adducts (%),
[Ref.]
1AcMaleic anhydrideEt20, 23 °CExo100, [109]
2AcMaleimideH3BO3/PEG-400, 90 °CExo84, [110]
3AcN-Ph-maleimideH3BO3/PEG-400, 90 °CExo78, [110]
4AcN-(4-Chlorobenzyl)maleimideH3BO3/PEG-400, 90 °CExo92, [110]
5Boc 1Maleic anhydrideToluene, 50 °CExo94, [111]
6Boc 1Thiomaleic anhydrideBenzene, RTExo68, [112]
7Boc 1 Ijms 22 11856 i039EtOAc, refluxEndo/exo (1:3.4)85, [113]
1 tert-Butyloxycarbonyl.
Examples of DA reactions of furfural derivatives containing acceptor-type substituents with alkenes are rare. After the reaction of 2-furoic acid with β-alanine-substituted maleimide, only a small amount of one isomer was detected at 40 °C after 128 h [26]. Interestingly, a very low equilibrium constant for this reaction was observed in DMF media, while the equilibrium constant in water was at least two orders of magnitude greater. This difference was explained by the statement that water has a significant effect on the entropy of the reaction. The model reaction of methyl furoate with 1,6-bis(N-maleimido)hexane was investigated by NMR. Only approximately 20% conversion was detected after 4 days at 70 °C in a DMSO-d6 medium [35]. However, despite the low reactivity of furans with acceptor substituents, dynamic materials containing furanic ester-[35] or oxime-[114] functionalized polymers and maleimide functionalities showed moderate self-healing efficiency based on the DA reaction.
Bruijnincx and coworkers reported a new strategy for the direct introduction of furans containing aldehyde groups into DA cycloaddition [34]. Reactions of furanic aldehydes with water-soluble maleimides at 60 °C in a water medium led to the formation of DA adducts with good selectivity (Table 7). In the case of furfural, good exoselectivity of cycloaddition was achieved, while for some HMF derivatives, endoselectivity was preferable. In-water formation of the DA adduct was also detected for 2-acetylfuran, which reacts with N-methylmaleimide with the formation of only the exoadduct (entry 9). DFT calculations showed that the formation of furan/maleimide DA adducts through hydration of the aldehyde group is thermodynamically possible if hydration occurs both prior to (which increases the rate of the forward DA reaction) or after the cyclization step (which decreases the rate of the retro-DA reaction) [34].

3. Regioselectivity in the Synthesis of Aromatics Using the IMDA Reaction of Furfural Derivatives with Alkenes

The dehydration of furan/alkene adducts is an important sustainable approach to accessing renewable aromatic chemicals (Scheme 6) [7,30,37,115,116,117]. Utilization of HMF-derived C6 renewable furans (especially 2,5-dimethylfuran or 2,5-furandicarboxylic acid) provides access to para-substituted aromatics (as a route towards “green” polymers) and various polysubstituted aromatic products (Scheme 6) [116]. The presence of only one substituent in furfural increases the diversity of possible aromatic products to ortho- and meta-xylylene derivatives as well as various 1,2,3-trisubstituted compounds (Scheme 6).
Several approaches were used for the construction of aromatic rings using furan/alkene DA reactions starting from furanic, oxanorbornene or oxanorbornane furfural-derived compounds. For some furanic and alkene substrates, dehydration occurs spontaneously following the DA reaction stage. The tandem Diels-Alder cycloaddition/dehydration reaction of 2-MF with ethylene is an important approach to renewable toluene (Table 8). This type of DA cycloaddition is thermodynamically difficult and therefore requires the use of a catalyst, high temperature and pressure. Heterogeneous Brønsted-acidic catalysts, mainly zeolites or MOFs, are beneficial for these reactions [118]. Significant problems include side reactions such as the formation of furanic dimers (benzofurans), larger oligomers, products of furan hydrolysis and other reactions [115,118,119,120]. The introduction of acrylic acid instead of ethylene in reactions with 2-MF over zeolites or using ionic liquid catalysts showed good efficiency in the formation of aromatics [121]. Fast pyrolysis of a mixture of 2-MF and propylene using various zeolites under continuous flow conditions gives a mixture of monocyclic and polycyclic aromatic hydrocarbons with low selectivity [122].
Furfural dimethyl hydrazone reacts with active dienophiles such as maleic anhydride or maleimides, yielding corresponding arene derivatives through noncatalytic in situ DA cycloaddition followed by spontaneous dehydration (Table 9) [126,127,128]. One-pot synthesis of arenes starting from furfural using a hydrazine strategy was carried out with good yields in water (entries 7–11) [129].
Acid-catalyzed dehydration of furan-derived oxanorbornenes to aromatic products requires strong reaction conditions and therefore may be used only for a narrow range of substrates. Renewable 3-methylphthalic anhydride (MPA) was obtained using acid-catalyzed dehydration of the corresponding 2-MF-derived DA adduct 8 with only 48% maximum yield (Scheme 7) [130]. An important problem in this synthetic approach is the facile retro-DA reaction, which is forced to carry out these transformations at industrially non-practical temperatures (−30 °C and lower) [124,125]. A novel approach to MPA synthesis that overcomes the problem of the rDA reaction is the introduction of oxanorbornane 9 (which is unable to recycle) instead of 8 into the aromatization stage (Scheme 7) [67,131,132]. Aromatization of 9 by solid acid catalysts led to MPA with 67% maximum yield. Some important byproducts, such as 2-methyl benzoic acid and 3-methyl benzoic acid, were also formed during this reaction, and their ratio depended on the catalyst used [67,131]. Higher selectivity of aromatization was achieved by oxidative dehydrogenation of 9 into phthalate 10 using a silicomolybdic acid catalyst in diethyl carbonate (Scheme 7) [132].
The deprotonation of DA adducts formed from 2-(furan-2-yl)-1,3-dioxolane and acrylonitrile by CH3ONa/DMSO superbase affords aromatic products at 30 °C with high total yield and a good ortho/meta ratio (Table 10, entries 1, 2) [31]. The study of kinetic features of the aromatization stage showed that the meta-adduct is more reactive than the ortho-isomer, which made it possible to isolate pure meta-adducts from the reaction mixture at 50% conversion, with subsequent regeneration of the ortho-isomer. Aromatization of DA adducts by tBuONa/DMSO superbase was also efficient for 2-MF and methyl group-protected FA but showed a low yield of aromatics in the case of unprotected FA (Table 10, entries 3–5) [31].
Recently, a new dynamic kinetic trapping strategy was developed for the construction of “drop-in” phthalide systems using tandem IMDA/lactonization and then aromatization reactions (Scheme 8) [37]. The first stage of this process is the reversible formation of unstable adducts (mixture of regio- and stereoisomers) of FA (11a–c) or BAMF (14) with acrylates substituted by EWGs (HFIP, TFE or 4NP) at an oxygen atom. The role of EWG in the dienophile was the activation of both double bonds for the IMDA reaction and the carbonyl group towards diastereoselective intramolecular cyclization and into a more thermodynamically stable exo-lactone (the next step). The last aromatization stage was performed using an Ac2O/strong acid mixture yielding phthalides 13 or 16 with maximum 98% and 60% yields, respectively.

4. Conclusions

The IMDA reactions of biobased furans with alkene dienophiles are an important strategy for accessing practically important products, such as fundamental building blocks, fine chemicals, biologically active compounds or various organic and hybrid dynamic systems. Based on the literature highlighted in this review, we can assume that the problem of low regio- and stereoselectivity, which significantly reduces the synthetic potential of furan/alkene DA cycloaddition in fine organic synthesis and materials development, is still not solved for many functional furfural derivatives and alkene substrates. The reactivity of furfural-derived acceptor furans towards common alkenes, as well as the synthesis and aromatization of DA adducts of functional furfural derivatives with acyclic alkenes, are very poorly represented in the current literature. However, these types of reactions are important sustainable approaches towards functional aliphatic or aromatic products and therefore require further scientific investigations.
Rapid progress in this area can be anticipated, taking into account emerging trends in sustainable development towards the incorporation of bioderived chemicals and materials into the chemical industry. The focus of this review clearly shows that selectivity issues are far from solved and do not match current requirements. More studies are needed to develop practical and easy-to-use procedures to achieve high selectivity in reactions involving simple bioderived furanic starting materials.

Author Contributions

K.I.G., literature search, review and original draft writing; V.P.A., revision and supervision. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Russian Science Foundation, grant number 17-13-01176-p.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data sharing is not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

2-MF2-methylfuran
Acacetate
BAMF2,5-bis(acetoxymethyl)furan
BHMF2,5-bis(hydroxymethyl)furan
BMI4,4’-bis(maleimido)diphenylmethane
BOCtert-butyloxycarbonyl
Bnbenzyl
Bzbenzoyl
DADiels–Alder
DFTdensity functional theory
DMFdimethylformamide
DMSOdimethyl sulfoxide
Emim1-ethyl-3-methylimidazolium
EWGelectron-withdrawing group
FAMfurfuryl amine
FFfurfural
HMF5-(hydroxymethyl)furfural
HOMOhighest occupied molecular orbital
IMDAintermolecular Diels–Alder
LUMOlowest unoccupied molecular orbital
MOFmetal organic framework
MPA3-methylphthalic anhydride
N.d.not determined
NMRnuclear magnetic resonance
PEGpolyethylene glycol
rDAretro-Diels–Alder
RTroom temperature
Tftriflate
TFAtrifluoroacetic acid
THFtetrahydrofuran

References

  1. Gérardy, R.; Debecker, D.P.; Estager, J.; Luis, P.; Monbaliu, J.-C.M. Continuous flow upgrading of selected C2–C6 Platform chemicals derived from biomass. Chem. Rev. 2020, 120, 7219–7347. [Google Scholar] [CrossRef] [PubMed]
  2. Wu, X.; Luo, N.; Xie, S.; Zhang, H.; Zhang, Q.; Wang, F.; Wang, Y. Photocatalytic transformations of lignocellulosic biomass into chemicals. Chem. Soc. Rev. 2020, 49, 6198–6223. [Google Scholar] [CrossRef]
  3. Khokhlova, E.A.; Kachala, V.V.; Ananikov, V.P. The first molecular level monitoring of carbohydrate conversion to 5-hydroxymethylfurfural in ionic liquids. B2O3-An efficient dual-function metal-free promoter for environmentally benign applications. ChemSusChem 2012, 5, 783–789. [Google Scholar] [CrossRef]
  4. Mika, L.T.; Cséfalvay, E.; Nemeth, A. Catalytic conversion of carbohydrates to initial platform chemicals: Chemistry and sustainability. Chem. Rev. 2017, 118, 505–613. [Google Scholar] [CrossRef]
  5. Sudarsanam, P.; Zhong, R.; Bosch, S.V.D.; Coman, S.M.; Parvulescu, V.I.; Sels, B.F. Functionalised heterogeneous catalysts for sustainable biomass valorisation. Chem. Soc. Rev. 2018, 47, 8349–8402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Bozell, J.J.; Petersen, G.R. Technology development for the production of biobased products from biorefinery carbohydrates—the US Department of Energy’s “Top 10” revisited. Green Chem. 2010, 12, 539. [Google Scholar] [CrossRef]
  7. Galkin, K.I.; Ananikov, V.P. When Will 5-Hydroxymethylfurfural, the “Sleeping Giant” of sustainable chemistry, awaken? ChemSusChem 2019, 12, 2976–2982. [Google Scholar] [CrossRef] [PubMed]
  8. Mariscal, R.; Maireles-Torres, P.; Ojeda, M.; Sádaba, I.; Granados, M.L. Furfural: A renewable and versatile platform molecule for the synthesis of chemicals and fuels. Energy Environ. Sci. 2016, 9, 1144–1189. [Google Scholar] [CrossRef]
  9. Li, X.; Jia, P.; Wang, T. Furfural: A promising platform compound for sustainable production of C4 and C5 chemicals. ACS Catal. 2016, 6, 7621–7640. [Google Scholar] [CrossRef]
  10. Van Putten, R.J.; van der Waal, J.C.; de Jong, E.; Rasrendra, C.B.; Heeres, H.J.; de Vries, J.G. Hydroxymethylfurfural, a versatile platform chemical made from renewable resources. Chem. Rev. 2013, 113, 1499–1597. [Google Scholar] [CrossRef]
  11. Kucherov, F.A.; Romashov, L.V.; Galkin, K.I.; Ananikov, V.P. Chemical transformations of biomass-derived C6-furanic platform chemicals for sustainable energy research, materials science, and synthetic building blocks. ACS Sustain. Chem. Eng. 2018, 6, 8064–8092. [Google Scholar] [CrossRef]
  12. Galkin, K.I.; Ananikov, V.P. The increasing value of biomass: Moving from C6 carbohydrates to multifunctionalized building blocks via 5-(hydroxymethyl)furfural. ChemistryOpen 2020, 9, 1135–1148. [Google Scholar] [CrossRef]
  13. Khemthong, P.; Yimsukanan, C.; Narkkun, T.; Srifa, A.; Witoon, T.; Pongchaiphol, S.; Kiatphuengporn, S.; Faungnawakij, K. Advances in catalytic production of value-added biochemicals and biofuels via furfural platform derived lignocellulosic biomass. Biomass Bioenergy 2021, 148, 106033. [Google Scholar] [CrossRef]
  14. Shen, G.; Andrioletti, B.; Queneau, Y. Furfural and 5-(hydroxymethyl)furfural: Two pivotal intermediates for bio-based chemistry. Curr. Opin. Green Sustain. Chem. 2020, 26, 100384. [Google Scholar] [CrossRef]
  15. Xu, C.; Paone, E.; Rodríguez-Padrón, D.; Luque, R.; Mauriello, F. Recent catalytic routes for the preparation and the upgrading of biomass derived furfural and 5-hydroxymethylfurfural. Chem. Soc. Rev. 2020, 49, 4273–4306. [Google Scholar] [CrossRef] [PubMed]
  16. Zhao, Y.; Lu, K.; Xu, H.; Zhu, L.; Wang, S. A critical review of recent advances in the production of furfural and 5-hydroxymethylfurfural from lignocellulosic biomass through homogeneous catalytic hydrothermal conversion. Renew. Sustain. Energy Rev. 2021, 139, 110706. [Google Scholar] [CrossRef]
  17. Fang, W.; Riisager, A. Recent advances in heterogeneous catalytic transfer hydrogenation/hydrogenolysis for valorization of biomass-derived furanic compounds. Green Chem. 2021, 23, 670–688. [Google Scholar] [CrossRef]
  18. Gupta, K.; Rai, R.K.; Singh, S.K. Metal catalysts for the efficient transformation of biomass-derived HMF and furfural to value added chemicals. ChemCatChem 2018, 10, 2326–2349. [Google Scholar] [CrossRef]
  19. Chen, S.; Wojcieszak, R.; Dumeignil, F.; Marceau, E.; Royer, S. How catalysts and experimental conditions determine the selective hydroconversion of furfural and 5-Hydroxymethylfurfural. Chem. Rev. 2018, 118, 11023–11117. [Google Scholar] [CrossRef] [Green Version]
  20. Drault, F.; Snoussi, Y.; Paul, S.; Itabaiana, I.; Wojcieszak, R. Recent advances in carboxylation of furoic acid into 2,5-furandicarboxylic acid: Pathways towards bio-based polymers. ChemSusChem 2020, 13, 5164–5172. [Google Scholar] [CrossRef] [PubMed]
  21. Dakshinamoorthy, D.; Weinstock, A.K.; Damodaran, K.; Iwig, D.F.; Mathers, R.T. Diglycerol-based polyesters: Melt polymerization with hydrophobic anhydrides. ChemSusChem 2014, 7, 2923–2929. [Google Scholar] [CrossRef] [PubMed]
  22. Dakshinamoorthy, D.; Lewis, S.P.; Cavazza, M.P.; Hoover, A.M.; Iwig, D.F.; Damodaran, K.; Mathers, R.T. Streamlining the conversion of biomass to polyesters: Bicyclic monomers with continuous flow. Green Chem. 2014, 16, 1774–1783. [Google Scholar] [CrossRef]
  23. Liu, X.; Du, P.; Liu, L.; Zheng, Z.; Wang, X.; Joncheray, T.; Zhang, Y. Kinetic study of Diels-Alder reaction involving in maleimide–furan compounds and linear polyurethane. Polym. Bull. 2013, 70, 2319–2335. [Google Scholar] [CrossRef]
  24. Liu, Y.-L.; Chuo, T.-W. Self-healing polymers based on thermally reversible Diels-Alder chemistry. Polym. Chem. 2013, 4, 2194–2205. [Google Scholar] [CrossRef]
  25. Tasdelen, M.A. Diels-Alder “click” reactions: Recent applications in polymer and material science. Polym. Chem. 2011, 2, 2133–2145. [Google Scholar] [CrossRef]
  26. Koehler, K.C.; Durackova, A.; Kloxin, C.J.; Bowman, C.N. Kinetic and thermodynamic measurements for the facile property prediction of diels-alder-conjugated material behavior. AIChE J. 2012, 58, 3545–3552. [Google Scholar] [CrossRef]
  27. Briou, B.; Améduri, B.; Boutevin, B. Trends in the Diels-Alder reaction in polymer chemistry. Chem. Soc. Rev. 2021, 50, 11055–11097. [Google Scholar] [CrossRef]
  28. Gandini, A. The furan/maleimide Diels-Alder reaction: A versatile click–unclick tool in macromolecular synthesis. Prog. Polym. Sci. 2013, 38, 1–29. [Google Scholar] [CrossRef]
  29. Gevrek, T.N.; Sanyal, A. Furan-containing polymeric materials: Harnessing the Diels-Alder chemistry for biomedical applications. Eur. Polym. J. 2021, 153, 110514. [Google Scholar] [CrossRef]
  30. Settle, A.E.; Berstis, L.; Rorrer, N.A.; Roman-Leshkóv, Y.; Beckham, G.T.; Richards, R.M.; Vardon, D.R. Heterogeneous Diels-Alder catalysis for biomass-derived aromatic compounds. Green Chem. 2017, 19, 3468–3492. [Google Scholar] [CrossRef]
  31. Scodeller, I.; Mansouri, S.; Morvan, D.; Muller, E.; de Oliveira Vigier, K.; Wischert, R.; Jerome, F. Synthesis of renewable meta-xylylenediamine from biomass-derived furfural. Angew. Chem. Int. Ed. 2018, 57, 10510–10514. [Google Scholar] [CrossRef]
  32. Scodeller, I.; Vigier, K.D.O.; Muller, E.; Ma, C.; Guégan, F.; Wischert, R.; Jérôme, F. A combined experimental–theoretical study on Diels-Alder reaction with bio-based furfural: Towards renewable aromatics. ChemSusChem 2021, 14, 313–323. [Google Scholar] [CrossRef] [PubMed]
  33. Kucherov, F.A.; Galkin, K.I.; Gordeev, E.G.; Ananikov, V.P. Efficient route for the construction of polycyclic systems from bioderived HMF. Green Chem. 2017, 19, 4858–4864. [Google Scholar] [CrossRef] [Green Version]
  34. Cioc, R.C.; Lutz, M.; Pidko, E.A.; Crockatt, M.; Van Der Waal, J.K.; Bruijnincx, P.C.A. Direct Diels-Alder reactions of furfural derivatives with maleimides. Green Chem. 2021, 23, 367–373. [Google Scholar] [CrossRef]
  35. Ax, J.; Wenz, G. Thermoreversible networks by Diels-Alder reaction of cellulose furoates with bismaleimides. Macromol. Chem. Phys. 2012, 213, 182–186. [Google Scholar] [CrossRef]
  36. Boutelle, R.C.; Northrop, B.H. Substituent effects on the reversibility of furan–maleimide cycloadditions. J. Org. Chem. 2011, 76, 7994–8002. [Google Scholar] [CrossRef]
  37. Lancefield, C.S.; Folker, B.; Cioc, R.C.; Stanciakova, K.; Bulo, R.E.; Lutz, M.; Crockatt, M.; Bruijnincx, P.C.A. Dynamic trapping as a selective route to renewable phthalide from biomass-derived furfuryl alcohol. Angew. Chem. Int. Ed. 2020, 59, 23480–23484. [Google Scholar] [CrossRef]
  38. Salvati, M.E.; Balog, A.; Wei, D.D.; Pickering, D.; Attar, R.M.; Geng, J.; Rizzo, C.A.; Hunt, J.; Gottardis, M.M.; Weinmann, R.; et al. Identification of a novel class of androgen receptor antagonists based on the bicyclic-1H-isoindole-1,3(2H)-dione nucleus. Bioorganic Med. Chem. Lett. 2005, 15, 389–393. [Google Scholar] [CrossRef]
  39. Bakhtiari, A.B.; Hsiao, D.; Jin, G.; Gates, B.D.; Branda, N.R. An efficient method based on the photothermal effect for the release of molecules from metal nanoparticle surfaces. Angew. Chem. Int. Ed. 2009, 48, 4166–4169. [Google Scholar] [CrossRef]
  40. Park, J.; Heo, J.-M.; Seong, S.; Noh, J.; Kim, J.-M. Self-assembly using a retro Diels-Alder reaction. Nat. Commun. 2021, 12, 1–10. [Google Scholar] [CrossRef]
  41. Pal, S.; Alizadeh, M.; Kong, P.; Kilbinger, A.F.M. Oxanorbornenes: Promising new single addition monomers for the metathesis polymerization. Chem. Sci. 2021, 12, 6705–6711. [Google Scholar] [CrossRef]
  42. Nicolaou, K.C.; Snyder, S.A.; Montagnon, T.; Vassilikogiannakis, G. The Diels-Alder reaction in total synthesis. Angew. Chem. Int. Ed. 2002, 41, 1668–1698. [Google Scholar] [CrossRef]
  43. Chang, H.; Huber, G.W.; Dumesic, J.A. Chemical-switching strategy for synthesis and controlled release of norcantharimides from a biomass-derived chemical. ChemSusChem 2020, 13, 5213–5219. [Google Scholar] [CrossRef] [PubMed]
  44. Uemura, N.; Toyoda, S.; Ishikawa, H.; Yoshida, Y.; Mino, T.; Kasashima, Y.; Sakamoto, M. Asymmetric Diels-Alder reaction involving dynamic enantioselective crystallization. J. Org. Chem. 2018, 83, 9300–9304. [Google Scholar] [CrossRef]
  45. Lewkowski, J. Synthesis, chemistry and applications of 5-hydroxymethyl-furfural and its derivatives. Arkivoc 2005, 2001, 17. [Google Scholar] [CrossRef] [Green Version]
  46. Wozniak, B.; Tin, S.; de Vries, J.G. Bio-based building blocks from 5-hydroxymethylfurfural via 1-hydroxyhexane-2,5-dione as intermediate. Chem. Sci. 2019, 10, 6024–6034. [Google Scholar] [CrossRef] [Green Version]
  47. Rosatella, A.A.; Simeonov, S.P.; Frade, R.F.M.; Afonso, C.A.M. 5-Hydroxymethylfurfural (HMF) as a building block platform: Biological properties, synthesis and synthetic applications. Green Chem. 2011, 13, 754. [Google Scholar] [CrossRef]
  48. Kong, X.; Zhu, Y.; Fang, Z.; Kozinski, J.A.; Butler, I.S.; Xu, L.; Song, H.; Wei, X. Catalytic conversion of 5-hydroxymethylfurfural to some value-added derivatives. Green Chem. 2018, 20, 3657–3682. [Google Scholar] [CrossRef]
  49. Hu, L.; Lin, L.; Wu, Z.; Zhou, S.; Liu, S. Recent advances in catalytic transformation of biomass-derived 5-hydroxymethylfurfural into the innovative fuels and chemicals. Renew. Sustain. Energy Rev. 2017, 74, 230–257. [Google Scholar] [CrossRef]
  50. Fan, W.; Verrier, C.; Queneau, Y.; Popowycz, F. 5-Hydroxymethylfurfural (HMF) in Organic Synthesis: A review of its recent applications towards fine chemicals. Curr. Org. Synth. 2019, 16, 583–614. [Google Scholar] [CrossRef]
  51. Hu, L.; Xu, J.; Zhou, S.; He, A.; Tang, X.; Lin, L.; Xu, J.; Zhao, Y. Catalytic advances in the production and application of biomass-derived 2,5-Dihydroxymethylfuran. ACS Catal. 2018, 8, 2959–2980. [Google Scholar] [CrossRef]
  52. Xia, H.; Xu, S.; Hu, H.; An, J.; Li, C. Efficient conversion of 5-hydroxymethylfurfural to high-value chemicals by chemo- and bio-catalysis. RSC Adv. 2018, 8, 30875–30886. [Google Scholar] [CrossRef] [Green Version]
  53. Zang, H.; Wang, K.; Zhang, M.; Xie, R.; Wang, L.; Chen, E.Y.-X. Catalytic coupling of biomass-derived aldehydes into intermediates for biofuels and materials. Catal. Sci. Technol. 2018, 8, 1777–1798. [Google Scholar] [CrossRef]
  54. Liu, B.; Zhang, Z. One-pot conversion of carbohydrates into furan derivatives via furfural and 5-Hydroxylmethylfurfural as intermediates. ChemSusChem 2016, 9, 2015–2036. [Google Scholar] [CrossRef]
  55. Pal, P.; Saravanamurugan, S. Recent advances in the development of 5-Hydroxymethylfurfural oxidation with base (Nonprecious)-metal-containing catalysts. ChemSusChem 2019, 12, 145–163. [Google Scholar] [CrossRef]
  56. Singh, S.K. Heterogeneous bimetallic catalysts for upgrading biomass-derived furans. Asian J. Org. Chem. 2018, 7, 1901–1923. [Google Scholar] [CrossRef]
  57. Chernyshev, V.M.; Kravchenko, O.A.; Ananikov, V.P. Conversion of plant biomass to furan derivatives and sustainable access to the new generation of polymers, functional materials and fuels. Russ. Chem. Rev. 2017, 86, 357–387. [Google Scholar] [CrossRef]
  58. Mascal, M. 5-(Chloromethyl)furfural (CMF): A platform for transforming cellulose into commercial products. ACS Sustain. Chem. Eng. 2019, 7, 5588–5601. [Google Scholar] [CrossRef]
  59. Kong, Q.-S.; Li, X.-L.; Xu, H.-J.; Fu, Y. Conversion of 5-hydroxymethylfurfural to chemicals: A review of catalytic routes and product applications. Fuel Process. Technol. 2020, 209, 106528. [Google Scholar] [CrossRef]
  60. Sauer, J. Diels-Alder reactions II: The reaction mechanism. Angew. Chem. Int. Ed. 1967, 6, 16–33. [Google Scholar] [CrossRef]
  61. Sauer, J.; Sustmann, R. Mechanistic Aspects of Diels-Alder Reactions: A Critical Survey. Angew. Chem. Int. Ed. 1980, 19, 779–807. [Google Scholar] [CrossRef]
  62. Craig, D. Stereochemical aspects of the intramolecular Diels-Alder reaction. Chem. Soc. Rev. 1987, 16, 187–238. [Google Scholar] [CrossRef]
  63. Coxon, J.M.; Froese, R.D.J.; Ganguly, B.; Marchand, A.P.; Morokuma, K. On the origins of diastereofacial selectivity in diels-alder cycloadditions. Synlett 1999, 1999, 1681–1703. [Google Scholar] [CrossRef]
  64. Fernandez, I.; Bickelhaupt, F.M. Deeper insight into the Diels-Alder Reaction through the activation strain model. Chem. Asian J. 2016, 11, 3297–3304. [Google Scholar] [CrossRef]
  65. Sánchez, A.; Pedroso, E.; Grandas, A. Maleimide-dimethylfuran exo adducts: Effective maleimide protection in the synthesis of oligonucleotide conjugates. Org. Lett. 2011, 13, 4364–4367. [Google Scholar] [CrossRef] [PubMed]
  66. Zhang, H.; Jiang, M.; Wu, Y.; Li, L.; Wang, Z.; Wang, R.; Zhou, G. Development of high-molecular-weight fully renewable biopolyesters based on oxabicyclic diacid and 2,5-Furandicarboxylic acid: Promising as packaging and medical materials. ACS Sustain. Chem. Eng. 2021, 9, 6799–6809. [Google Scholar] [CrossRef]
  67. Thiyagarajan, S.; Genuino, H.C.; Sliwa, M.; van der Waal, J.C.; de Jong, E.; van Haveren, J.; Weckhuysen, B.M.; Bruijnincx, P.C.; van Es, D.S. Substituted phthalic anhydrides from biobased furanics: A new approach to renewable aromatics. ChemSusChem 2015, 8, 3052–3056. [Google Scholar] [CrossRef]
  68. Beusker, P.H.; Aben, R.W.M.; Seerden, J.-P.G.; Smits, J.M.M.; Scheeren, H.W. Exploration of high-pressure cycloadducts of furans and citraconic anhydride as precursors for CD-ring fragments of paclitaxel and its analogues. Eur. J. Org. Chem. 1998, 1998, 2483–2492. [Google Scholar] [CrossRef]
  69. Lu, Z.; Weber, R.; Twieg, R.J. Improved synthesis of DCDHF fluorophores with maleimide functional groups. Tetrahedron Lett. 2006, 47, 7213–7217. [Google Scholar] [CrossRef] [Green Version]
  70. Daeffler, C.S.; Miyake, G.M.; Li, J.; Grubbs, R.H. Partial kinetic resolution of oxanorbornenes by ring-opening metathesis polymerization with a chiral ruthenium initiator. ACS Macro Lett. 2014, 3, 102–104. [Google Scholar] [CrossRef] [Green Version]
  71. Liu, P.; Yasir, M.; Kilbinger, A.F.M. Catalytic living ring opening metathesis polymerisation: The importance of ring strain in chain transfer agents. Angew. Chem. Int. Ed. 2019, 58, 15278–15282. [Google Scholar] [CrossRef] [Green Version]
  72. Yasir, M.; Liu, P.; Markwart, J.C.; Suraeva, O.; Wurm, F.R.; Smart, J.; Lattuada, M.; Kilbinger, A.F.M. One-step ring opening metathesis block-like copolymers and their compositional analysis by a novel retardation technique. Angew. Chem. Int. Ed. 2020, 59, 13597–13601. [Google Scholar] [CrossRef]
  73. Román, E.; Gil, M.; Luque-Agudo, V.; Serrano, J. Expeditious ‘On-Water’ Cycloaddition between N-substituted maleimides and furans. Synlett 2014, 25, 2179–2183. [Google Scholar] [CrossRef]
  74. Jarosz, S.; Mach, M.; Szewczyk, K.; Skóra, S.; Ciunik, Z. Synthesis of Sugar-Derived 2′- and 3′-Substituted furans and their application in diels−alder reactions. Eur. J. Org. Chem. 2001, 2001, 2955. [Google Scholar] [CrossRef]
  75. Jeong, H.; John, J.M.; Schrock, R.R. Formation of Alternating trans-A-alt-B copolymers through ring-opening metathesis polymerization initiated by molybdenum imido alkylidene complexes. Organometallics 2015, 34, 5136–5145. [Google Scholar] [CrossRef]
  76. Hayashi, Y.; Nakamura, M.; Nakao, S.; Inoue, T.; Shoji, M. The HfCl4-Mediated Diels-Alder reaction of furan. Angew. Chem. Int. Ed. 2002, 41, 4079–4082. [Google Scholar] [CrossRef]
  77. Troelsen, N.S.; Shanina, E.; Gonzalez-Romero, D.; Dankova, D.; Jensen, I.S.A.; Sniady, K.J.; Nami, F.; Zhang, H.; Rademacher, C.; Cuenda, A.; et al. The 3F Library: Fluorinated Fsp(3) -Rich fragments for expeditious (19) F NMR based screening. Angew. Chem. Int. Ed. 2020, 59, 2204–2210. [Google Scholar] [CrossRef] [PubMed]
  78. Shibatomi, K.; Kobayashi, F.; Narayama, A.; Fujisawa, I.; Iwasa, S. A Diels-Alder approach to the enantioselective construction of fluoromethylated stereogenic carbon centers. Chem. Commun. 2012, 48, 413–415. [Google Scholar] [CrossRef] [PubMed]
  79. Ryu, D.H.; Kim, K.H.; Sim, J.Y.; Corey, E.J. Catalytic enantioselective Diels-Alder reactions of furans and 1,1,1-trifluoroethyl acrylate. Tetrahedron Lett. 2007, 48, 5735–5737. [Google Scholar] [CrossRef]
  80. Morton, C.J.; Gilmour, R.; Smith, D.M.; Lightfoot, P.; Slawin, A.M.; MacLean, E.J. Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 1: The search for alkenyl-DPPs. Unsaturated nitriles in standard DPP syntheses: A novel cyclopenta[c]pyrrolone chromophore. Tetrahedron 2002, 58, 5547–5565. [Google Scholar] [CrossRef]
  81. Kernen, P.; Vogel, P. The homoconjugated electron-releasing carbonyl group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one. Helvetica Chim. Acta 1993, 76, 2338–2343. [Google Scholar] [CrossRef]
  82. Harrity, J.P.A.; Stevenson, N.G.; De Savi, C. Furan Diels-Alder cycloaddition approach to the highly oxygenated core of scyphostatin. Synlett 2006, 2006, 2272–2274. [Google Scholar] [CrossRef]
  83. Chen, J.-C.; Zheng, G.-J.; Zhang, C.; Fang, L.-J.; Li, Y.-L. Enhancive synthesis of -lβ, 11-Diol-4-en-eudesmol. Chin. J. Chem. 2010, 21, 904–906. [Google Scholar] [CrossRef]
  84. Ishar, M.P.S.; Wali, A.; Gandhi, R.P. Regio- and stereo-selectivity in uncatalysed and catalysed Diels-Alder reactions of allenic esters with furan and 2-methylfuran. J. Chem. Soc. Perkin Trans. 1 1990, 1, 2185–2192. [Google Scholar] [CrossRef]
  85. Pehere, A.D.; Xu, S.; Thompson, S.K.; Hillmyer, M.A.; Hoye, T.R. Diels-Alder reactions of furans with itaconic anhydride: Overcoming unfavorable thermodynamics. Org. Lett. 2016, 18, 2584–2587. [Google Scholar] [CrossRef] [Green Version]
  86. Froidevaux, V.; Borne, M.; Laborbe, E.; Auvergne, R.; Gandini, A.; Boutevin, B. Study of the Diels-Alder and retro-Diels-Alder reaction between furan derivatives and maleimide for the creation of new materials. RSC Adv. 2015, 5, 37742–37754. [Google Scholar] [CrossRef]
  87. Lee, H.-Y.; Lee, S.-S.; Kim, H.S.; Lee, K.M. A formal total synthesis of Dysiherbaine and Neodysiherbaine A. Eur. J. Org. Chem. 2012, 2012, 4192–4199. [Google Scholar] [CrossRef]
  88. Baba, Y.; Hirukawa, N.; Tanohira, A.N.; Sodeoka, M. Structure-based design of a highly selective catalytic site-directed inhibitor of ser/thr protein phosphatase 2B (Calcineurin). J. Am. Chem. Soc. 2003, 125, 9740–9749. [Google Scholar] [CrossRef]
  89. Zhang, J.; Lawrance, G.A.; Chau, N.; Robinson, P.J.; McCluskey, A. From Spanish fly to room-temperature ionic liquids (RTILs): Synthesis, thermal stability and inhibition of dynamin 1 GTPase by a novel class of RTILs. New J. Chem. 2008, 32, 28–36. [Google Scholar] [CrossRef]
  90. McCluskey, A.; Ackland, S.P.; Bowyer, M.C.; Baldwin, M.L.; Garner, J.; Walkom, C.C.; Sakoff, J.A. Cantharidin analogues: Synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines. Bioorganic Chem. 2003, 31, 68–79. [Google Scholar] [CrossRef]
  91. Ganesan, M.; Muraleedharan, K.M. Oxanorbornane-based amphiphilic systems: Design, synthesis and material properties. RSC Adv. 2012, 2, 4048–4051. [Google Scholar] [CrossRef]
  92. Ramesh, N.; Ganesan, M.; Sarangi, N.K.; Muraleedharan, K.M.; Patnaik, A. Tailoring strained oxanorbornane headgroups to dimensionally controlled nanostructures through hydrogen bonding. RSC Adv. 2014, 4, 9762–9770. [Google Scholar] [CrossRef]
  93. Li, F.; Li, X.; Zhang, X. Dynamic Diels-Alder reactions of maleimide–furan amphiphiles and their fluorescence ON/OFF behaviours. Org. Biomol. Chem. 2018, 16, 7871–7877. [Google Scholar] [CrossRef]
  94. Ochi, R.; Nishida, T.; Ikeda, M.; Hamachi, I. Design of peptide-based bolaamphiphiles exhibiting heat-set hydrogelation via retro-Diels-Alder reaction. J. Mater. Chem. B 2014, 2, 1464–1469. [Google Scholar] [CrossRef] [PubMed]
  95. Ikeda, M.; Ochi, R.; Kurita, Y.-S.; Pochan, D.J.; Hamachi, I. Heat-induced morphological transformation of supramolecular nanostructures by retro-Diels-Alder reaction. Chem. A Eur. J. 2012, 18, 13091–13096. [Google Scholar] [CrossRef]
  96. Fan, B.; Trant, J.F.; Hemery, G.; Sandre, O.; Gillies, E.R. Thermo-responsive self-immolative nanoassemblies: Direct and indirect triggering. Chem. Commun. 2017, 53, 12068–12071. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  97. Djidi, D.; Mignard, N.; Taha, M. Thermosensitive polylactic-acid-based networks. Ind. Crop. Prod. 2015, 72, 220–230. [Google Scholar] [CrossRef]
  98. Heath, W.H.; Palmieri, F.; Adams, J.R.; Long, B.K.; Chute, J.; Holcombe, T.W.; Zieren, S.; Truitt, M.J.; White, J.L.; Willson, C.G. Degradable cross-linkers and strippable imaging materials for step-and-flash imprint lithography. Macromolecules 2008, 41, 719–726. [Google Scholar] [CrossRef]
  99. Budd, M.; Stephens, R.; Afsar, A.; Salimi, S.; Hayes, W. Exploiting thermally-reversible covalent bonds for the controlled release of microencapsulated isocyanate crosslinkers. React. Funct. Polym. 2019, 135, 23–31. [Google Scholar] [CrossRef]
  100. Taimoory, S.M.; Sadraei, S.I.; Fayoumi, R.A.; Nasri, S.; Revington, M.; Trant, J.F. Preparation and characterization of a small library of thermally-labile end-caps for variable-temperature triggering of self-immolative polymers. J. Org. Chem. 2018, 83, 4427–4440. [Google Scholar] [CrossRef]
  101. Czifrak, K.; Lakatos, C.; Karger-Kocsis, J.; Daroczi, L.; Zsuga, M.; Keki, S. One-pot synthesis and characterization of novel shape-memory poly(epsilon-caprolactone) based polyurethane-epoxy co-networks with Diels(-)Alder couplings. Polymers 2018, 10, 504. [Google Scholar] [CrossRef] [Green Version]
  102. Pelter, A.; Singaram, B. The reactions of furfuryl alcohols with maleic anhydride. J. Chem. Soc. Perkin Trans. 1983, 1, 1383–1386. [Google Scholar] [CrossRef]
  103. Clavier, H.; Broggi, J.; Nolan, S.P. Ring-rearrangement metathesis (RRM) mediated by ruthenium-indenylidene complexes. Eur. J. Org. Chem. 2010, 2010, 937–943. [Google Scholar] [CrossRef]
  104. Oparina, L.A.; Vysotskaya, O.V.; Stepanov, A.V.; Ushakov, I.A.; Apartsin, K.A.; Gusarova, N.; Trofimov, B.A. Furfuryl vinyl ethers in [4+2]-cycloaddition reactions. Russ. J. Org. Chem. 2017, 53, 203–209. [Google Scholar] [CrossRef]
  105. Buser, S.; Vasella, A. 7-Oxanorbornane and norbornane mimics of a Distortedβ-D-Mannopyranoside: Synthesis and evaluation asβ-mannosidase inhibitors. Helvetica Chim. Acta 2005, 88, 3151–3173. [Google Scholar] [CrossRef]
  106. Galkin, K.I.; Kucherov, F.; Markov, O.N.; Egorova, K.S.; Posvyatenko, A.V.; Ananikov, V.P. Facile chemical access to biologically active norcantharidin derivatives from biomass. Molecules 2017, 22, 2210. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  107. Canadell, J.; Fischer, H.; De With, G.; van Benthem, R.A.T.M. Stereoisomeric effects in thermo-remendable polymer networks based on Diels-Alder crosslink reactions. J. Polym. Sci. Part A Polym. Chem. 2010, 48, 3456–3467. [Google Scholar] [CrossRef]
  108. Truong, T.T.; Nguyen, H.T.; Phan, M.N.; Nguyen, L.-T.T. Study of Diels-Alder reactions between furan and maleimide model compounds and the preparation of a healable thermo-reversible polyurethane. J. Polym. Sci. Part A Polym. Chem. 2018, 56, 1806–1814. [Google Scholar] [CrossRef]
  109. Hart, M.E.; Chamberlin, A.R.; Walkom, C.; Sakoff, J.A.; McCluskey, A. Modified norcantharidins; synthesis, protein phosphatases 1 and 2A inhibition, and anticancer activity. Bioorg. Med. Chem. Lett. 2004, 14, 1969–1973. [Google Scholar] [CrossRef]
  110. Galvis, C.E.P.; Kouznetsov, V.V. An unexpected formation of the novel 7-oxa-2-azabicyclo[2.2.1]hept-5-ene skeleton during the reaction of furfurylamine with maleimides and their bioprospection using a zebrafish embryo model. Org. Biomol. Chem. 2013, 11, 407–411. [Google Scholar] [CrossRef]
  111. Saroj, S.; Janni, D.S.; Ummadi, C.R.; Manheri, M.K. Functionalizable oxanorbornane-based head-group in the design of new Non-ionic amphiphiles and their drug delivery properties. Mater. Sci. Eng. C 2020, 112, 110857. [Google Scholar] [CrossRef] [PubMed]
  112. Crich, D.; Sasaki, K.; Rahaman, M.Y.; Bowers, A.A. One-pot syntheses of dissymmetric diamides based on the chemistry of cyclic monothioanhydrides. Scope and limitations and application to the synthesis of glycodipeptides. J. Org. Chem. 2009, 74, 3886–3893. [Google Scholar] [CrossRef]
  113. Kuang, X.; Liu, G.; Dong, X.; Liu, X.; Xu, J.; Wang, D. Facile fabrication of fast recyclable and multiple self-healing epoxy materials through diels-alder adduct cross-linker. J. Polym. Sci. Part A Polym. Chem. 2015, 53, 2094–2103. [Google Scholar] [CrossRef]
  114. Mukherjee, S.; Brooks, W.L.A.; Dai, Y.; Sumerlin, B.S. Doubly-dynamic-covalent polymers composed of oxime and oxanorbornene links. Polym. Chem. 2016, 7, 1971–1978. [Google Scholar] [CrossRef]
  115. Green, S.K.; Patet, R.E.; Nikbin, N.; Williams, C.L.; Chang, C.-C.; Yu, J.; Gorte, R.J.; Caratzoulas, S.; Fan, W.; Vlachos, D.; et al. Diels-Alder cycloaddition of 2-methylfuran and ethylene for renewable toluene. Appl. Catal. B Environ. 2016, 180, 487–496. [Google Scholar] [CrossRef] [Green Version]
  116. Kucherov, F.A.; Romashov, L.V.; Averochkin, G.M.; Ananikov, V.P. Biobased C6-furans in organic synthesis and industry: Cycloaddition chemistry as a key approach to aromatic building blocks. ACS Sustain. Chem. Eng. 2021, 9, 3011–3042. [Google Scholar] [CrossRef]
  117. Ravasco, J.; Gomes, R.F.A. Recent advances on Diels-Alder-driven preparation of bio-based aromatics. ChemSusChem 2021, 14, 3047–3053. [Google Scholar] [CrossRef]
  118. Patet, R.E.; Koehle, M.; Lobo, R.F.; Caratzoulas, S.; Vlachos, D.G. General acid-type catalysis in the dehydrative aromatization of furans to aromatics in H-[Al]-BEA, H-[Fe]-BEA, H-[Ga]-BEA, and H-[B]-BEA Zeolites. J. Phys. Chem. C 2017, 121, 13666–13679. [Google Scholar] [CrossRef]
  119. Chang, C.-C.; Green, S.K.; Williams, C.L.; Dauenhauer, P.J.; Fan, W. Ultra-selective cycloaddition of dimethylfuran for renewable p-xylene with H-BEA. Green Chem. 2014, 16, 585–588. [Google Scholar] [CrossRef]
  120. Wang, D.; Osmundsen, C.M.; Taarning, E.; Dumesic, J.A. Selective production of aromatics from alkylfurans over solid acid catalysts. ChemCatChem 2013, 5, 2044–2050. [Google Scholar] [CrossRef]
  121. Yeh, J.Y.; Chen, S.S.; Li, S.C.; Chen, C.H.; Shishido, T.; Tsang, D.C.W.; Yamauchi, Y.; Li, Y.P.; Wu, K.C. Diels-Alder conversion of acrylic acid and 2,5-Dimethylfuran to para-Xylene over Heterogeneous Bi-BTC metal-organic framework catalysts under mild conditions. Angew. Chem. Int. Ed. 2021, 60, 624–629. [Google Scholar] [CrossRef] [PubMed]
  122. Cheng, Y.T.; Wang, Z.; Gilbert, C.J.; Fan, W.; Huber, G.W. Production of p-xylene from biomass by catalytic fast pyrolysis using ZSM-5 catalysts with reduced pore openings. Angew. Chem. Int. Ed. 2012, 51, 11097–11100. [Google Scholar] [CrossRef]
  123. Zhao, R.; Zhao, Z.; Li, S.; Parvulescu, A.-N.; Müller, U.; Zhang, W. Excellent performances of dealuminated H-Beta Zeolites from organotemplate-free synthesis in conversion of biomass-derived 2,5-Dimethylfuran to renewable p -Xylene. ChemSusChem 2018, 11, 3803–3811. [Google Scholar] [CrossRef]
  124. Ni, L.; Xin, J.; Dong, H.; Lu, X.; Liu, X.; Zhang, S. A simple and mild approach for the synthesis of p -Xylene from Bio-Based 2,5-Dimethyfuran by using metal triflates. ChemSusChem 2017, 10, 2394–2401. [Google Scholar] [CrossRef]
  125. Ni, L.; Xin, J.; Jiang, K.; Chen, L.; Yan, D.; Lu, X.; Zhang, S. One-step conversion of biomass-derived furanics into aromatics by brønsted acid ionic liquids at room temperature. ACS Sustain. Chem. Eng. 2018, 6, 2541–2551. [Google Scholar] [CrossRef]
  126. Potts, K.T.; Walsh, E.B. Furfural dimethylhydrazone: A versatile diene for arene cycloaromatization. J. Org. Chem. 2002, 49, 4099–4101. [Google Scholar] [CrossRef]
  127. Jacques, V.; Czarnik, A.W.; Judge, T.M.; Van der Ploeg, L.H.T.; DeWitt, S.H. Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs. Proc. Natl. Acad. Sci. USA 2015, 112, E1471–E1479. [Google Scholar] [CrossRef] [Green Version]
  128. Karaluka, V.; Murata, K.; Masuda, S.; Shiramatsu, Y.; Kawamoto, T.; Hailes, H.C.; Sheppard, T.D.; Kamimura, A. Development of a microwave-assisted sustainable conversion of furfural hydrazones to functionalised phthalimides in ionic liquids. RSC Adv. 2018, 8, 22617–22624. [Google Scholar] [CrossRef] [Green Version]
  129. Higson, S.; Subrizi, F.; Sheppard, T.D.; Hailes, H.C. Chemical cascades in water for the synthesis of functionalized aromatics from furfurals. Green Chem. 2016, 18, 1855–1858. [Google Scholar] [CrossRef] [Green Version]
  130. Mahmoud, E.; Watson, D.A.; Lobo, R.F. Renewable production of phthalic anhydride from biomass-derived furan and maleic anhydride. Green Chem. 2014, 16, 167–175. [Google Scholar] [CrossRef] [Green Version]
  131. Thiyagarajan, S.; Genuino, H.C.; van der Waal, J.C.; de Jong, E.; Weckhuysen, B.M.; van Haveren, J.; Bruijnincx, P.C.; van Es, D.S. A facile solid-phase route to renewable aromatic chemicals from biobased furanics. Angew. Chem. Int. Ed. 2016, 55, 1368–1371. [Google Scholar] [CrossRef] [PubMed]
  132. Liu, D.-H.; He, H.-L.; Zhang, Y.-B.; Li, Z. Oxidative aromatization of biobased chemicals to benzene derivatives through tandem catalysis. ACS Sustain. Chem. Eng. 2020, 8, 14322–14329. [Google Scholar] [CrossRef]
Ijms 22 11856 g001 550
Figure 1. Number of publications mentioning biobased furans per year. Source: Scopus. Keyword: “furfural”.
Figure 1. Number of publications mentioning biobased furans per year. Source: Scopus. Keyword: “furfural”.
Ijms 22 11856 g001
Ijms 22 11856 g002 550
Figure 2. Diels-Alder cycloaddition with biobased furans as an approach towards practically important products. Summarizing and analyzing scientific data about the regio- and diastereoselectivity of intermolecular Diels-Alder cycloadditions between furfural derivatives and alkenes was a general aim of this review.
Figure 2. Diels-Alder cycloaddition with biobased furans as an approach towards practically important products. Summarizing and analyzing scientific data about the regio- and diastereoselectivity of intermolecular Diels-Alder cycloadditions between furfural derivatives and alkenes was a general aim of this review.
Ijms 22 11856 g002
Ijms 22 11856 sch001 550
Scheme 1. Possible regio- and diastereomers in Diels-Alder cycloaddition of C-2-substituted furans with mono-substituted alkenes.
Scheme 1. Possible regio- and diastereomers in Diels-Alder cycloaddition of C-2-substituted furans with mono-substituted alkenes.
Ijms 22 11856 sch001
Ijms 22 11856 sch002 550
Scheme 2. Different reactivities of endo (a) and exo (b) furan-derived oxanorbornanes in Ru-catalyzed ring-opening metathesis polymerization. R = H, Me, n-propyl or n-pentyl. G3 = third generation Grubbs catalyst.
Scheme 2. Different reactivities of endo (a) and exo (b) furan-derived oxanorbornanes in Ru-catalyzed ring-opening metathesis polymerization. R = H, Me, n-propyl or n-pentyl. G3 = third generation Grubbs catalyst.
Ijms 22 11856 sch002
Ijms 22 11856 sch003 550
Scheme 3. Synthesis of N-substituted maleimides from 2-MF and maleimide using the DA approach.
Scheme 3. Synthesis of N-substituted maleimides from 2-MF and maleimide using the DA approach.
Ijms 22 11856 sch003
Ijms 22 11856 sch004 550
Scheme 4. Formation of lactone 2-exo after DA reaction of FA with maleic anhydride.
Scheme 4. Formation of lactone 2-exo after DA reaction of FA with maleic anhydride.
Ijms 22 11856 sch004
Ijms 22 11856 sch005 550
Scheme 5. Diels—Alder reactions of FA and FA acetate with itaconic anhydride.
Scheme 5. Diels—Alder reactions of FA and FA acetate with itaconic anhydride.
Ijms 22 11856 sch005
Ijms 22 11856 sch006 550
Scheme 6. Aromatization of furan/alkene DA adducts as a route towards biobased aromatics.
Scheme 6. Aromatization of furan/alkene DA adducts as a route towards biobased aromatics.
Ijms 22 11856 sch006
Ijms 22 11856 sch007 550
Scheme 7. Synthesis of arenes by aromatization of 2-MF-derived tricycles.
Scheme 7. Synthesis of arenes by aromatization of 2-MF-derived tricycles.
Ijms 22 11856 sch007
Ijms 22 11856 sch008 550
Scheme 8. Synthesis of phthalides from furanic alcohols using a dynamic kinetic trapping strategy. HFIP = 1,1,1,3,3,3-hexafluoroisopropyl. TFE = 2,2,2-trifluoroethyl. 4NP = 4-nitrophenyl.
Scheme 8. Synthesis of phthalides from furanic alcohols using a dynamic kinetic trapping strategy. HFIP = 1,1,1,3,3,3-hexafluoroisopropyl. TFE = 2,2,2-trifluoroethyl. 4NP = 4-nitrophenyl.
Ijms 22 11856 sch008
Table
Table 1. IMDA cycloadditions of 2-MF with cyclic alkenes.
Table 1. IMDA cycloadditions of 2-MF with cyclic alkenes.
Ijms 22 11856 i040
№Dienophile
Ijms 22 11856 i001		ConditionsSelectivityYield of DA
Adducts (%),
[Ref.]
1X = ONeat, RT, N2, 24 hExo91, [66]
2X = ONeat, RT, 10–15 °C, 2–3 hExo96 (crude), [67]
3Citraconic
anhydride
Ijms 22 11856 i002		CH2Cl2, RT, 15 kbarExo (ortho/meta 1:1)65 1, [68]
4X = NHEt2O, RT, 3 daysEndo/exo 221 (for endo), [69]
5X = NHTHF, reflux, 4 hExo94, [70]
6X = NMeToluene, 90 °CExo92, [71]
7X = NMeEt2O, 90 °CExo66, [72]
8X = NEtH2O, 65 °CEndo/exo 1.4:1100, [73]
9X = N(tBu)H2O, 65 °CExo100, [73]
10X = NPhH2O, 65 °CEndo/exo 1.6:1100, [73]
11X = NPh4:1 Toluene/benzene, RT, 1.1 GPaEndo/exo 1.66:185, [74]
12X = NPhCDCl3, 60 °CExo with traces of endo90, [44]
13X = NPhHexane or heptane, TFA, glass beads, 80 °C, 5–8 days 3(-)-Exo, 86–90 ee80, [44]
14X = NPhF5Neat, refluxExo50, [75]
15 Ijms 22 11856 i003THF, 65 °CExo64, [70]
16X = NCH2CH2COOHCHCl3, 38 °C, 5 daysEndo/exo 28:72100, [65]
17 4X = NCH2CH2COOHCHCl3, 38 °C, 5 daysExo100, [65]
18 5X = NCH2CH2COOHCH2Cl2, RT, overnightEndo/exo 78:22100, [65]
19 5X = NCH2CH2COOHCH3CN, 60 °C, 6 hEndo/exo 22:78100, [65]
1 Yield of DA adduct after hydrogenation. 2 Ratio of diastereomers was not provided. 3 The reaction was conducted under dynamic enantiomeric crystallization conditions. 4 Furan as a substrate. 5 2,5-Dimethylfuran as a substrate.
Table
Table 3. IMDA cycloadditions of furfural acetals with alkenes.
Table 3. IMDA cycloadditions of furfural acetals with alkenes.
Ijms 22 11856 i042
№Furfural
Acetal		DienophileConditionsSelectivityYield of Adducts (%), [Ref.]
1 Ijms 22 11856 i023N-MethylmaleimideCH2Cl2, 23 °CEndo/exo 87:13N.d., [86]
2 Ijms 22 11856 i024Methyl vinyl ketoneNeat, 60 °COrtho 13 (endo/exo 74:26),
meta 87 (endo/exo 65:35)		36, [32]
3 Ijms 22 11856 i025Methyl acrylateNeat, 60 °COrtho 33 (endo/exo 87:13),
meta 67 (endo/exo 77:23)		40, [32]
4 Ijms 22 11856 i026AcroleinNeat, 60 °COrtho 38 (endo/exo 71:29),
meta 62 (endo/exo 43:57)		28, [32]
5 Ijms 22 11856 i027AcrylonitrileNeat, 60 °C, 120 hOrtho 48 (endo/exo 72:28),
meta 52 (endo/exo 42:58)		76, [32]
6 Ijms 22 11856 i028AcrylonitrileZnCl2, neat, 60 °COrtho 50 (endo/exo 70:30),
meta 50 (endo/exo 56:44)		75, [32]
7 Ijms 22 11856 i029AcrylonitrileZnI2, neat, 60 °COrtho 53 (endo/exo 70:30),
meta 67 (endo/exo 60:40)		75, [31]
8 Ijms 22 11856 i030AcrylonitrileZnCl2, neat, 60 °COrtho 43 (endo/exo 85:15),
meta 57 (endo/exo 56:44)		68, [32]
9 Ijms 22 11856 i031AcrylonitrileZnCl2, neat, 60 °COrtho 39 (endo/exo 67:33), meta 61 (endo/exo 54:46)67, [32]
10 Ijms 22 11856 i032AcrylonitrileZnCl2, neat, 30 °COrtho 91 (endo/exo 66:33),
meta 9 (endo/exo 53:47)		73, [32]
11 Ijms 22 11856 i033AcrylonitrileZnCl2, neat, 60 °COrtho 53 (endo/exo 60:40), meta 47 (endo/exo 54:46)81, [32]
12 Ijms 22 11856 i034AcrylonitrileZnCl2, neat, 60 °COrtho 52 (endo/exo 62:38),
meta 48 (endo/exo 56:44)		85, [32]
N.d.—not determined.
Table
Table 4. IMDA cycloadditions of FA with alkenes.
Table 4. IMDA cycloadditions of FA with alkenes.
Ijms 22 11856 i043
№DienophileConditionsSelectivityYield of Adducts (%), [Ref.]
1 1MaleimideEthyl acetate, 24 °CEndo/exo 96:487, [33]
2 2MaleimideEthyl acetate, 24 °CEndo/exo 97:342, [33]
3N-Me-maleimideEt2O, 90 °CEndo/exo 21:7943, [72]
4N-Bn-maleimideCH3CN, 35 °CEndo/exo 70:3075, [96]
5N-PropargylmaleimideCH3CN, 35 °CEndo/exo 80:2072, [96]
6N-(2-Hydroxymethyl)maleimideEthyl acetate, 80 °CExo76, [97]
7N-(2-Hydroxyethyl)maleimideBenzene, refluxExo86, [98]
8N-(3-Hydroxypropyl)maleimideToluene, 80 °CEndo/exo 30:70 377, [99]
9N-(4-Hydroxyphenyl)maleimideAcetone, 55 °CExo71, [40]
10N-(4-Hydroxyphenyl)maleimideAcetonitrile, 35 °CEndo/exo 80:20N.d., [40]
11N-(p-Methoxyphenyl)maleimideCH3CN, 40 °C, 18 hMostly exo89, [100]
12N-(p-Nitrophenyl)maleimideCH3CN, 60 °CEndo/exo 70:2352, [100]
13BMI 4Toluene, 75–80 °C, 2 daysMostly exo92, [101]
14AcrylonitrileNeat, 60 °COrtho 56 (endo/exo 69:31), meta 44 (endo/exo 56:44)81, [32]
15 Ijms 22 11856 i035Neat, RT, 96 hN.d.66, [37]
1 2,5-bis(Hydroxymethyl)furan (BHMF) as a substrate. 2 2,5-bis(Acetoxymethyl)furan (BAMF) as a substrate. 3 Slowly transformed to the exo isomer over a period of several months. 4 4,4′-bis(Maleimido)diphenylmethane. N.d.—not determined.
Table
Table 7. Direct DA reaction of furanic aldehydes with maleimides in water medium.
Table 7. Direct DA reaction of furanic aldehydes with maleimides in water medium.
Ijms 22 11856 i046
№Furanic SubstrateR1Products, Selectivity 1
1R = HMe6a (endo/exo 18:40), 7a (endo/exo 1:3)
2R = HH6b (endo/exo 8:30), 7b (endo/exo 0:0)
3R = HEt6c (endo/exo 8:28, 7c (endo/exo 1:6)
4R = HnPr6d (endo/exo 1:7), 7d (endo/exo 1:11)
5R = HPh6e (endo/exo 0:1), 7e (endo/exo 1:5)
6R = MeMe6f (endo/exo 3:8), 7f (endo/exo 0:3)
7R = CH2OHMe6g (endo/exo 37:13), 7g (endo/exo 0:0)
8R = CH2OMeMe6h (endo/exo 7:5), 7h (endo/exo 3:3)
92-AcetylfuranMe7i (endo/exo traces:32)
Reaction conditions: H2O, 60 °C, 16 h. 1 Determined by 1H NMR (data were obtained from reference [34]).
Table
Table 8. Synthesis of toluene by DA reaction of 2-MF with alkenes.
Table 8. Synthesis of toluene by DA reaction of 2-MF with alkenes.
Ijms 22 11856 i047
№RConditionsProducts Yield (%), [Ref.]
1HH-BEA zeolite, heptane, 62 bar, 250 °CToluene (46%), [119]
2HH-Beta-22 zeolite, 300 °C, 20 hToluene (50%), [123]
3COOHBi-BTC, 160 °C, 24 hToluene (65%), 2-methyl benzoic acid (23%), [121]
4COOH[Emim]NTf2, Sc(OTf)3, 15 °C, 0.5 hToluene (12%), 2-methyl benzoic acid (2%), 3-methyl benzoic acid (9%), [124]
5COOH[BSO3HMIm]HSO4, 100 °C, 2hToluene (12%), 2-methyl benzoic acid (30%), 3-methyl benzoic acid (3%), [125]
Table
Table 9. Preparation of phthalimides from furfural using a hydrazine strategy.
Table 9. Preparation of phthalimides from furfural using a hydrazine strategy.
Ijms 22 11856 i048
№SubstratesConditionsYield of Aromatic Product, [Ref.]
52-Furaldehyde dimethylhydrazone,
maleic anhydride		CHCl3, RT94, [126]
62-Furaldehyde dimethylhydrazone,
N-Et-maleimide		CHCl3, RT90, [126]
72-Furaldehyde, N,N-dimethylhydrazine, N-Et-maleimideH2O, 50 °C97, [129]
82-Furaldehyde, N,N-dimethylhydrazine, maleimideH2O, 50 °C86, [129]
92-Furaldehyde, N,N-dimethylhydrazine, N-cyclopropylmaleimideH2O, 50 °C80, [129]
102-Furaldehyde, N,N-dimethylhydrazine, N-Ph-maleimideH2O, 50 °C73, [129]
112-Furaldehyde, N,N-dimethylhydrazine, N-(4-Methylbenzyl)maleimideH2O, 50 °C68, [129]
Table
Table 10. Preparation of aromatics by base-catalyzed dehydration of acrylonitrile-derived oxanorbornenes.
Table 10. Preparation of aromatics by base-catalyzed dehydration of acrylonitrile-derived oxanorbornenes.
Ijms 22 11856 i049
№OxanorborneneYield of DA Adducts 1Yield of Aromatic Products 1
1R = dioxolane acetal76 (ortho/meta ~1:1) 284 (ortho/meta ~1:1.5)
2R = dioxolane acetal76 (ortho/meta ~1:1)86 (ortho/meta ~1:1.8) 3
3R = Me53 (ortho), 13 (meta)97 (ortho), 62 (meta) 4
4R = CH2OEt36 (ortho), 18 (meta)94 (ortho), 100 (meta) 4
5R = CH2OH47 (ortho), 26 (meta)21 (ortho), 42 (meta) 4
1 Data were obtained from reference [31]. 2 After 120 h of the reaction. 3 CH3ONa as a base. 4 Relative to the corresponding ortho- or meta-DA cycloadduct.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Galkin, K.I.; Ananikov, V.P. Intermolecular Diels-Alder Cycloadditions of Furfural-Based Chemicals from Renewable Resources: A Focus on the Regio- and Diastereoselectivity in the Reaction with Alkenes. Int. J. Mol. Sci. 2021, 22, 11856. https://doi.org/10.3390/ijms222111856

AMA Style

Galkin KI, Ananikov VP. Intermolecular Diels-Alder Cycloadditions of Furfural-Based Chemicals from Renewable Resources: A Focus on the Regio- and Diastereoselectivity in the Reaction with Alkenes. International Journal of Molecular Sciences. 2021; 22(21):11856. https://doi.org/10.3390/ijms222111856

Chicago/Turabian Style

Galkin, Konstantin I., and Valentine P. Ananikov. 2021. "Intermolecular Diels-Alder Cycloadditions of Furfural-Based Chemicals from Renewable Resources: A Focus on the Regio- and Diastereoselectivity in the Reaction with Alkenes" International Journal of Molecular Sciences 22, no. 21: 11856. https://doi.org/10.3390/ijms222111856

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop