Previous Article in Journal
Generalized Linear Driving Force Formulas for Diffusion and Reaction in Porous Catalysts
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Reactions
Volume 5
Issue 2
10.3390/reactions5020016
reactions-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

Ir-Catalyzed ortho-C-H Borylation of Aromatic C(sp2)-H Bonds of Carbocyclic Compounds Assisted by N-Bearing Directing Groups

by
Hamad H. Al Mamari
Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 36, Al-Khod, Muscat 123, Oman
Reactions 2024, 5(2), 318-337; https://doi.org/10.3390/reactions5020016
Submission received: 29 February 2024 / Revised: 4 April 2024 / Accepted: 25 April 2024 / Published: 1 May 2024
Browse Figures
Versions Notes

Abstract

:
C-H borylation is a powerful strategy for the construction of C-B bonds due to the synthetic versatility of C-B bonds. Various transition metals affect the powerful functionalization of C-H bonds, of which Ir is the most common. Substrate-directed methods have enabled directed Ir-catalyzed C-H borylation at the ortho position. Amongst the powerful directing groups in Ir-catalyzed C-H borylation are N-containing carbocyclic systems. This review covers substrate-directed Ir-catalyzed ortho-C-H borylation of aromatic C(sp2)-H bonds in N-containing carbocyclic compounds, such as anilines, amides, benzyl amines, hydrazones, and triazines.

1. Introduction

Functionalization of inert C-H bonds has emerged as a powerful strategy for making functional and versatile bonds [1,2,3,4,5,6,7]. Transformation of inert non-functional C-H bonds into reactive functional bonds is an attractive chemically powerful strategy. Thus, the functionalization of C-H bonds should provide rapid access to functionalized molecules from simple starting materials. In this process, step and reaction economies can be achieved by shortening the number of steps in multi-step synthesis, simplifying reaction conditions, or minimizing the need for pre-functionalized reagents. C-H Bond functionalization is typically catalyzed by transition metals. Functionalization of C-H bonds by second-row transition metals, such as Pd [8,9,10,11], Rh [12,13,14,15,16], and Ru [17,18,19,20,21], has received widespread attention from the scientific community. Earth-abundant first-row transition metals, ref. [22] such as Ni [23,24,25], Mn [26,27], Fe [28,29], and Co [30,31,32,33,34], have also been used in the field. Given the ubiquitous nature of C-H bonds in molecules, controlling what C-H bonds are functionalized is a challenge. The issue of regioselectivity or site-selectivity in C-H bond functionalization is a constant target. One approach to solve the issue is the use of directing groups, which include two general types, monodentate and bidentate [35]. The classification depends on the number of Lewis basic atoms that can participate in the functionalization reaction through chelation assistance. Lewis basic atoms coordinate the Lewis acidic metal used in the reaction, hence directing it in proximity to a C-H bond to be cleaved and subsequently functionalized. The formation of cyclometallated complexes or chelates is controlled by ring size, of which five-membered chelates are thermodynamically more stable and thus favored over other ring sizes [36]. Thus, the atom distance between the Lewis basic atom in the directing group and the C-H bond to be functionalized is critical. For the formation of the more common five-membered chelates, the atom distance should be two carbons. Monodentate directing groups possess one Lewis basic atom that allows the formation of a single (typically five-membered) chelate, while bidentate directing groups possess two Lewis basic atoms that facilitate the formation of double or bis-five-membered chelates. In bidentate directing groups, the atom distance between the first Lewis basic atom and the C-H bond to be functionalized is critical, as noted in monodentate directing groups. In addition, the atom distance between the two Lewis basic atoms constituting the bidentate directing group is important as well [37]. Many monodentate and bidentate directing groups have been established in the field of C-H bond functionalization [10,11,12]. A wide range of functionalization reactions of C-H bonds by “direction” or chelation assistance are possible based on the catalysis of various transition metals.
Conversion of C-H bonds into C-B bonds is a unique type of C-H bond functionalization [38,39,40,41,42,43,44]. This is based on the synthetic versatility and utility of alkyl and aryl boronates in organic synthesis. C-B bonds can be transformed into various bonds with a wide range of functional groups, such as amines, alcohols/phenols, aryl halides, and biaryls [45]. The synthetic versatility of C-B bonds allows C-H borylation to be used as a unique and powerful C-H functionalization strategy. As noted for C-H bond functionalization as a whole, controlling the pressing issue of regioselectivity or site-selectivity is a constant target.
C-H bond borylation is a unique type of C-H bond functionalization reaction that converts inert C-H bonds into C-B bonds. Metal-catalyzed C-H borylation is made possible by the catalysis of various transition metals, such as Ir [38,39,40,41,42,43,44], Co [46,47,48], Ni [49], and Fe [50].
As noted in C-H bond functionalization, controlling the pressing issue of regioselectivity or site-selectivity is a constant goal. Generally, the Ir-catalyzed C-H borylation reaction of carbocyclic compounds is sterically driven [38,39,40,41,42,43,44]. Electronic effects can also play a role in the site-selectivity of C-H borylation of heterocycles.
The regioselectivity or site-selectivity of C-H borylation can be controlled using directing groups via chelation assistance (Scheme 1) [51,52]. Directing groups containing Lewis basic atoms (vide supra) in substrate, 1 can direct C-H borylation to take place selectively at the ortho position to give ortho-borylated product 2 (Scheme 1).
Substrate-directed C-H borylation is possible with various functional groups, such as ketones [53], ethers [54], sulfides [55], and phenols [56,57,58].
Several Ir precatalysts can be used in Ir-catalyzed C-H borylation. The following Ir catalysts are used: [Ir(OMe)(COD)]2, [Ir(OH)(COD)]2, [Ir(OPh)(COD)]2, [Ir(OAc)(COD)]2, [Ir(Cl)(COD)]2, [Ir(COD)2]BF4, [Ir(COE)2Cl]2, Cp*Ir(PMe3)(H)(Bpin), (Ind)Ir(COD), (η6-mesitylene)Ir(Bpin)3, and Ir(acac)(cod). The structures of a few of these catalysts are shown below (Figure 1) [42,59].
Various differences are noted between these precatalysts, including their electronic and steric characteristics; their stability, ease of handling and manipulation; and their ability to form active Ir complexes with ligands. In turn, the ligands used can play a pivotal role in forming Ir complexes capable of catalyzing C-H bond borylation. Examples of bipyridine ligands are shown below (Figure 2) [42]. Ligands L1-L9 represent common bipyridine ligands used or can be used.
By far, [Ir(OMe)(COD)]2 is the most commonly used catalyst due to its air stability, ease of handling, and most efficient capability of forming Ir trisboryl complexes [Ir(Bpin)3(L2)-alkene] where L is dtbpy or tmphen (Figure 3). COE: cyclooctene, Bpin: 4,4,5,5-tetramethyl-1,3,2-dioxaboro-lanyl [60].
The mechanism of Ir-catalyzed C-H borylation has been studied [60,61]. Based on these findings, an Ir trisporyl complex A is formed upon treatment of an Ir precatalyst, such as the most commonly used [Ir(OMe)(COD)]2, with a ligand typically dtbpy (Scheme 2) [60,61,62]. Subsequent treatment of the Ir trisboryl complex with a carbocyclic compound or hydrocarbon gives intermediate B. A borylated carbocyclic compound is then released with concomitant formation of intermediate C. The addition of B2pin2 or H-BPin forms intermediate D, which subsequently regenerates the starting Ir tisboryl complex A in the catalytic cycle (Scheme 2).
Typically, C-H borylation is sterically driven [38,39,40,41,42,43,44]. Directing the reaction to regioselectively occur at an ortho position concerning a functional group is not straightforward [51,52]. ortho-Directing groups, including monodentate and bidentate directing groups typically used in directed C-H bond functionalization catalyzed by other transition metals may not simply be used to direct Ir-catalyzed C-H borylation reactions. A key challenge in ortho-C-H borylation is directing the reaction to occur regioselectively at the ortho-position. Coordination between the Lewis acidic Ir center and the Lewis basic directing group utilizing a vacant site in the metal center can be problematic. When a directing group coordinates with the Ir center in the 16-electron [Ir] trisboryl species 3, an Ir complex 4 is formed that does not advance the reaction forward to the desired ortho-C-H borylation (Scheme 3) [60,61].
Another problem may arise when ligands coordinate with the Ir trisboryl complex rendering the resultant Ir species inactive towards directed ortho-selective C-H borylation. This event could be notable when the ligand is strongly coordinating.
To overcome these problems, a chelate-directed C-H borylation strategy could be used [51,52]. The strategy relies on coordination between the Lewis acidic Ir center and the Lewis basic directing group as well as a judicious choice of the ligand. The latter is critical for the formation of vacant sites in the Ir center [60,61].
Another strategy to circumvent problems of Ir-catalyzed ortho-C-H borylation is to use monodentate or hemi-labile ligands to form a transient vacant coordination site on the Ir center. This strategy specifically circumvents the complications that arise when Lewis basic directing groups coordinate with Ir. The hemi-lability of ligands creates vacant coordination sites on the Ir center setting the stage for subsequent C-H bond cleavage [51].
Another solution for successfully directed C-H borylation is the use of a solid/silica-supported compact monophosphine–Ir system, such as Silica-SMAP–Ir developed by Sawmaura et al. The strategy has been employed to affect ortho-Ir-catalyzed C-H borylation of various functional groups [63,64,65,66,67,68].
The most common [Ir] precatalyst is the commercially available (1,5-cyclooctadiene)(methoxy)iridium(I) dimer [Ir(OMe)((COD)]2, which upon treatment with ligands and bis(pinacolato)diboron, B2pin2, can give rise to a 14-electron [Ir] species 5 (Scheme 4). Directing groups (represented by 6) can coordinate with the 14-electron [Ir] species 5 through vacant sites on the metal center. Upon Lewis base–Lewis acid interactions between the directing group and the Lewis acidic metal center, the 16-electron [Ir] species 7 should form. The Lewis base–Lewis acid coordination brings the Ir center in proximity to an ortho C-H in the directing group, thus facilitating C-H bond cleavage and forming the intermediate [Ir] species 8. Subsequently, the ortho position in the directing group is borylated with the Bpin moiety from the Ir center to give rise to ortho-borylated product 9 (Scheme 4) [59,60,61,62].
This review focuses on Ir-catalyzed ortho-C-H borylation of aromatic C(sp2)-H bond assisted by N-bearing directing groups. The review covers research findings on the topic from 2012 to 2023.

2. Discussion

2.1. Anilines

In 2012, the NHBoc group was reported to function as a directing group in Ir-catalyzed ortho-C-H borylation of N-Boc-protected anilines (10, Scheme 5) [69]. The directed C-H borylation employed [Ir(OMe)(COD)]2 as a precatalyst and B2pin2 as a boron source and proceeded with ortho selectivity. The reaction proceeded with good functional group tolerance and good yields (Scheme 5). For example, ether and halogens are tolerated as demonstrated by ortho-borylated NH-Boc anilines 11a and 11b, which were obtained with yields of 96% and 79%, respectively. The use of the cyano group as an electron-withdrawing group was tolerated as noted in borylated product 11c, which was obtained with a modest 40% yield. The free hydroxyl group was also tolerated as exemplified by borylated hydroxyl NH-Boc protected aniline 11d, which was obtained with a 78% yield. In addition, carbamates were also tolerated as demonstrated by borylated materials 11e and 11f, which were obtained with 44% and 62% yields, respectively (Scheme 3). The reaction reveals good functional group tolerance.
In 2013, Bpin was reported to function as a traceless directing group in Ir-catalyzed ortho-C-H borylation of anilines (12, Scheme 6) [70]. The methodology employed HBpin as a boron source, [Ir(OMe)(COD)]2 as a precatalyst, and 3,4,7,8-tetramethyl-1,10-phenanthroline (tmphen) as a ligand (Scheme 6).
The C-H borylation reaction was found to be more effective when using tmphen as a ligand and HBpin as a boron source. Various electronically different and differently monosubstituted anilines were borylated at the ortho position. For instance, electron-rich 4-methoxyaniline gave the corresponding ortho-borylated product 13c in 63% yield. Electron-deficient anilines such as 4-trifluoromethyl and 4-cyanoanilines afforded the corresponding borylation products 13b and 13d in decent yields of 87%, and 60%, respectively (Scheme 6).
3,4-Disubstituted anilines also participated in the Ir-catalyzed ortho-C-H borylation. For example, electron-rich 3-chloro-4-hydroxyaniline and 3-chloro-4-methoxyanilines gave the corresponding ortho-borylated anilines 13f and 13i with yields of 63% and 74%, respectively. Other disubstituted anilines such as dihalogenated 3-chloro-4-bromoaniline and the electron-poor 3-chloro-4-cyanoanilines gave the corresponding ortho-borylated anilines 13e and 13h in 92% and 90%, yields respectively (Scheme 6).
The regioselectivity of the borylation reaction was rationalized by hydrogen bonding between H in N-Bpin aniline and O in the Ir complex 14B in the postulated transition state shown (Figure 4). Principally, this is similar with previous mechanistic findings of the Ir-catalyzed ortho C-H borylation reported earlier (Scheme 5) where hydrogen bonding associates Bpin and NH Boc moieties to produce transition state 14A (Figure 4). It is noteworthy that unsubstituted anilines were not effective under the reaction conditions. Detailed mechanisms of Ir-catalyzed C-H borylation and directed Ir-catalyzed C-H borylation are given and discussed in Scheme 2 and Scheme 4 (vide supra).
The reaction mechanism was investigated and thus formulated (Scheme 7). Aniline 10 undergoes N borylation to give N-Bpin aniline 10A. The N-borylated intermediate then undergoes Ir-catalyzed ortho C-H borylation to give bis-borylated aniline 10B. Work up affords the ortho-borylated aniline 11 (Scheme 7).
It was observed that the ortho-selectivity of the reaction was greatly reduced when B2Pin2 was used instead of HBpin as a borylating agent. When B2Pin2 is used, aniline is not borylated at N. As a result, this suggests that NHBpin is a better directing group than NH2 in the Ir-catalyzed C-H borylation. Interestingly, when secondary anilines are used instead of anilines, the ortho selectivity is not observed. For example, when N-methyl-3-chloroaniline (15, Scheme 8) is subjected to the reaction conditions, ortho-borylated aniline is not produced. Instead, meta-related product 16 is formed in 86% yield (Scheme 8).

2.2. Amides

In 2019, the Ir-catalyzed ortho-C-H borylation of secondary aromatic amides was reported (17, Scheme 9) [71]. The borylation occurs with high ortho-selectivity and is governed by hydrogen-bonding interactions. The directed Ir-catalyzed C-H borylation employed [Ir(OMe)(COD)]2 as a precatalyst and B2pin2 as a boron source, and a bipyridine-based ligand that has an indole amide (BAIPy) was used (Scheme 7). Investigations of the borylation reaction were performed on various secondary amides using BAIPy ligand and 2,2′-bipyridine (Bpy) itself in control experiments. Exceptionally high ortho-selectivity was obtained using the BAIP ligand, whereas no such selectivity was observed using the Bpy ligand. For example, N-methylbenzamide gave the corresponding ortho-borylated product 18a in 94% yield. Electron-rich 3-methyl N-methyl benzamide gave the corresponding ortho-borylated product 18b in a 94% yield. para-Substituted N-methyl benzamides were successfully borylated to produce the corresponding ortho-borylated products with exceptionally high yields. For instance, electron-rich 4-Me (18c), 4-OMe (18d), and 4-t-Bu (16f) ortho-borylated products were obtained in 97%, 92%, and 76% yields, respectively. Electron-deficient 4-CF3 (18e), 4-Ph (18f), and 4-Cl (18h) ortho-borylated products were obtained in 99%, 90%, and 91% yields, respectively (Scheme 9).
ortho-Borylated products of 4-substituted N-benzylbenzamides were also obtained in high yields. For example, electron-rich 4-Me (18j), 4-OMe (18l), and 4-t-Bu (18m) ortho-borylated products were obtained in 95%, 89%, and >91% yields, respectively. Electron-deficient 4-CF3 (18k) and 4-Cl (18n) ortho-borylated products were obtained in >91% and 98% yields, respectively (Scheme 9). Electron-donating and electron-withdrawing groups are equally tolerated and delivered ortho-borylated products with excellent yields.
ortho-Borylated products of 3-substituted N-benzylbenzamides were also obtained with remarkably high yields. For example, electron-rich 3-Me (18o), 3-OMe (18q), and 3-OBn (18p) ortho-borylated products were obtained in 92%, 97%, and >91% yields, respectively. Halogenated products, such as 3-Br (18r), and 3-Cl (18s) ortho-borylated products were obtained in >91% and 98% yields, respectively (Scheme 9). This is a demonstration of halogen tolerance in the reaction.
It was postulated that the benzamide substrate reorganizes itself to interact with the indole and the amide moieties in the BAIPy ligand by hydrogen bonding to form a hydrogen-bonding-based transition state 19 (Figure 5). This prerequisite hydrogen bonding brings the Ir-metal center in proximity to the ortho-C-H bond, setting the stage for C-H bond cleavage followed by subsequent borylation with Bpin.
In 2021, tertiary benzamides have been reported to undergo Ir-catalyzed ortho-C-H borylation that employs [Ir(OMe)(COD)]2 as a precatalyst and B2pin2 as a boron source [72]. The borylation reaction features a unique 3-thiophenylpyridine ligand (20, Scheme 10). Bipyridine ligands did not take part in the ortho-selective C-H borylation. However, 2-phenylpyridines were found to be effective in the reaction, which led to the development of the 3-thiophenylpyridine ligand. It was postulated that the reactivity of this ligand was attributed to the higher acidity of the thiophenyl group at C2. Consequently, upon reaction with [Ir(OMe)(COD)]2, the ligand forms a cyclometalated complex with Ir, which sets the stage for C-H borylation.
To investigate the active catalyst system, ligand 20 was treated with two Ir precatalysts: (Ir(Cl)(COD)]2 and [Ir(OMe)(Cod)]2 (Scheme 10).
When the 3-thiophenylpyridine ligand was treated with the former, a cyclometallated dimeric iridium(III) complex 21 was formed. This complex was presumably formed by metal-mediated hydride transfer. When the ligand was treated with the latter, the Ir(I)-cyclometallated complex 22 was formed (Scheme 10). Both cyclometallated complexes were characterized and confirmed by X-ray [72].
After establishing the active catalytic species in the reaction, the scope of the Ir-catalyzed ortho-C-H borylation of tertiary benzamides (23, Scheme 11) was carried out under developed reaction conditions. The effects of substituents on N were studied under the reported optimum conditions (Scheme 11). Thus, various alkyl groups were compatible with the reaction conditions and were able to promote Ir-catalyzed ortho-selective C-H borylation of their benzamides. For example, ortho-borylated N,N-dicyclohexylbenzamide (24a) was obtained in 94% yield. The N,N-dimethyl counterpart (24b) was obtained in 82% yield, and N,N-diethyl (24c) and N,N-dihexyl (24d) benzamides were obtained in 92% yields. Other ortho-borylated benzamides of pyrrolidinyl (24i) and morphine (24j) groups were obtained in yields of 88% and 86%, respectively (Scheme 11).
The scope of the arene unit was explored using its N,N-diisopropylbenzamides (25, Scheme 12). Here, 2-substituted N,N-diisopropylbenzamides were successfully borylated at the ortho position to give the corresponding electron-rich 2-methyl (26a) and 2-phenyl (26b) benzamides in 82% and 73% yields, respectively. Various 3-substituted N,N-diisopropyl benzamides were tested under optimum reaction conditions. For example, ortho-borylated electron-rich 3-OMe (26c), 3-On-Bu (26h), 3-Me (26e), and 3-Ph (26f) benzamides were obtained in 92%, 93%, 95%, and 93% yields, respectively. A bromo substituent was tolerated to give the corresponding ortho-borylated product (26d) in 86% yield. Electron-withdrawing groups such as CF3 were also tolerated, giving rise to the corresponding ortho-borylated product (26g) in 90% yield (Scheme 12) [72].
In addition, the scope of para-substitution was explored using N,N-diisopropylbenzamides (Scheme 12). For example, ortho-borylated electron-rich 3-Me (26i), 3-OMe (26j), 3-On-Bu (26n), and 3-Ph (26l) benzamides were obtained in 98%, 92%, 96%, and 98% yields, respectively. A bromo substituent was tolerated to give the corresponding ortho-borylated product (26k) in a 94% yield. Electron-withdrawing groups such as CF3 were also tolerated, giving rise to the corresponding ortho-borylated product (26m) in 86% yield (Scheme 12). The reaction tolerates differently substituted and electronically different benzamides.
The versatility of the developed Ir-catalyzed ortho-C-H borylation with the thiophenylpyridine ligand was demonstrated by tolerance of various functional groups (27, Scheme 13) [72]. Thus, a functional group scope was explored under optimum reaction conditions (Scheme 12). For example, ketone, esters, and carbamates tolerated the reaction conditions to give the corresponding ortho-borylated arene products (28a), (28b), (28d), (25e), and (28f) in 91%, 69%, 80%, 71%, and 91% yields, respectively. Other N-based directing groups such as an imine, aniline, and benzylamine were also tolerated to give the corresponding ortho-borylated arene products (28c), (28g), and (28j) in 86%, 73%, and 93% yields, respectively. Methylthio and OMOM directing groups were tolerated as well, giving rise to the corresponding ortho-borylated arene products (28h) and (28i) in 82% and 68% yields, respectively (Scheme 13) [72].
In 2023, another ortho-selective borylation method for tertiary amides (29, Scheme 14) was reported [73]. The borylation was Ir catalyzed employing [Ir(OMe)(COD)]2 as a precatalyst and B2pin2 as a boron source, and 5-CF3 substituted bipyridine ligand CF3-Bpy was used (Scheme 14). The Ir-catalyzed C-H borylation delivered ortho-borylated benzamides in good yields. Tertiary benzamides with different N-substituents were successfully borylated at the ortho position to give the corresponding N,N-dimethyl, N,N-dicyclohexyl, N,N-diphenyl, and N-methyl-N-methoxy ortho-borylated arene products (30a), (30b), (30c), and (30d) in 83%, 98%, 85%, and 83% yields, respectively. Secondary benzamides were also tolerated under optimum reaction conditions to give the corresponding N-methyl, N-Ph, and N-C6F5 ortho-borylated arene products (30e), (30f), and (30g) in 87%, 83%, and 41% yields, respectively. Ester and ketone functional groups delivered the corresponding ortho-borylated arene products (30h) and (30i) in yields of 64% and 81%, respectively. Other functional groups that are based on indole, sulfoxide, and ester-functionalized amide gave the corresponding ortho-borylated arene products (30j), (30k), and (30l) in 73%, 99%, and 57% yields, respectively (Scheme 14).

2.3. Benzyl Amines

In 2012, Ir-catalyzed ortho-selective C-H borylation of benzylic amines (31, Scheme 15) was developed [74]. The reaction employs [Ir(OMe)(COD)]2 as a precatalyst, B2pin2 as a boron source, and features picolyl amine as a ligand.
Differently substituted N,N-dimethylbenzylamines were successfully borylated at the ortho position using the developed borylation methodology (Scheme 15). For example unsubstituted N,N-dimethylbenzylamine, electron-rich 2-methyl-N,N-dimethylbenzylamine and electron-poor 2-fluoro-N,N-dimethylbenzylamine were borylated at ortho positions to give the corresponding ortho-borylated products (32a), (32b), and (32c) in 63%, 73%, and 74% yields, respectively. meta-Substituted N,N-dimethylbenzylamines such as electron-rich 3-Me, 3-OMe, and 3-Cl gave the corresponding ortho-borylated products (32d), (32e), and (32f) in 55%, 82%, and 54% yields, respectively. para-Substituted N,N-dimethylbenzylamines such as 4-Me, 4-CO2Et, and 4-Br gave the corresponding ortho-borylated products (32g), (32h), and (32i) in 81%, 49%, and 37% yields, respectively (Scheme 15) [74].
A key structural feature of picolyamine is that it possesses an N-H bond that could form an H-bond with a benzylamine substrate. Thus, a transition Ir-complex was proposed, where picolyamine binds to the Ir precatalyst, forms hydrogen bonding with the benzylamine substrate, and makes a vacant coordination site on the Ir center available (34, Figure 6). Consequently, ortho-C-H cleavage followed by borylation of the benzylamine subsequently occur. Detailed mechanisms of Ir-catalyzed C-H borylation and directed Ir-catalyzed C-H borylation are given and discussed in Scheme 2 and Scheme 4 (vide supra).
A scope of amine directing effect was explored under optimum reaction conditions of the picolylamine-promoted Ir-catalyzed ortho-C-H borylation (Scheme 16). For example, N,N-dimethyl-2-phenylethylamine was borylated at the arene ortho position to give the corresponding ortho-borylated product 35a in a moderate 51% yield. A more sterically hindered benzylamine such as N,N-dimethyl-1-phenylethylamine gave corresponding ortho-borylated product 35b in 86% yield. Imidazolidine-based benzylamine was successfully borylated at the arene ortho position to give the corresponding ortho-borylated product 35c in a moderate 71% yield (Scheme 16) [74].
In 2019, an asymmetric enantioselective Ir-catalyzed aromatic ortho-C-H borylation of diaryl N,N-dimethyamines was reported [75]. The reaction employs [Ir(Cl)(COD)]2 as a precatalyst and B2pin2 as a boron source. The key feature of the regioselective asymmetric reaction is the use of chiral (S,S)-DPEN-derived bidentate boryl ligands, and the reaction features picolyl amine as a ligand.
The enantioselectivity in the asymmetric Ir-catalyzed C-H borylation relied on the use of chiral boryl silyl ligand (36, Scheme 17) that is based on commercially available (S,S)-DPEN. It was proposed that upon treatment of such chiral ligands with [Ir]-B2pin2, a vacant coordination site on the Ir center gives the proposed active catalytic Ir species 37 (Scheme 17).
The chiral ligand where the aryl group is 3,5-dimethylphenyl was found to be the optimum ligand. A wide range of diphenyl N,N-dimethyl amines (38, Scheme 18) was successfully borylated in a regioselective and enantioselective manner (Scheme 18). For example, chiral borylated product 39a was obtained in 88% yield and an excellent enantioselectivity of 94% ee. Other substituted amines on the aryl groups such as electron-rich 4-Me and 4-OMe and electron-poor 4-CF3 and 4-OCF3 were borylated at the ortho position with good yields and enantioselectivities to give ortho borylated products 39b, 39c, 39d, and 39e in 70%, 76%, 65%, and 86% yields and enantioselectivities of 88% ee, 85% ee, 95% ee, and 82% ee, respectively. Differently substituted ortho-borylated products such as 39f, 39g, 39h, and 39i were also obtained in 65%, 70%, 61%, and 89% yields and enantioselectivities of 92% ee, 87% ee, 82% ee, and 91% ee, respectively (Scheme 18) [75].

2.4. Hydrazones

In 2012, Ir-catalyzed ortho, ortho’-C-H diborylation of aromatic N,N-dimethylhydrazones (40, Scheme 19) was reported [76]. The reaction employs [Ir(OMe)(COD)]2 as a precatalyst, and B2pin2 as a boron source with a catalytic amount of HBpin. The developed diborylation reaction features the use of hemilabile pyridine-hydrazone N,N-ligand (L, Scheme 19).
The reaction tolerated a good range of substituted aryl hydrazones (Scheme 18). While unsubstituted substrate delivered the diborylation product 41a in 76% yield, the 3-Cl and electron-rich 3-OMe counterparts gave the corresponding o,o’-diborylated hydrazones 41b and 41c in 72% and 58% yields, respectively. In addition, other substituted aryl hydrazones such as 4F, 3,4-dichloro, and 3,5-dimethoxy were successfully diborylated to give the corresponding o,o’-diborylated hydrazones 41d, 41e, and 41f in 79%, 51%, and 60% yields, respectively (Scheme 19) [76].
The obtained o,o’-diborylated hydrazones were then further functionalized using the Suzuki–Miyaura cross-coupling reaction to provide access to the desired coupled products. The developed Ir-catalyzed selective o,o’-diborylation methodology provided access to densely functionalized benzaldehyde derivatives.

2.5. Triazines

In 2022, aryl triazines (42, Scheme 20) were reported to undergo ligand-free Ir-catalyzed C-H ortho-ortho’-diborylation [77]. The C-H borylation was directed by the triazine and employed [Ir(OMe)(COD)]2 as a precatalyst and B2pin2 as a boron source. The triazine functioned as both substrate and ligand; thus, no external ligand was necessary.
N,N-Diisopropyl aryl triazine was found to be the most effective under optimum reaction conditions (Scheme 20). Thus, unsubstituted N,N-diisopropyl aryl triazine was diborylated at both ortho positions to give bisborylated product 43a in a remarkable 99% yield. para-Substituted aryl N,N-diisopropyltriazines were successfully diborylated as well. Other ortho-ortho’-diborylated electron-rich 4-Me (43b) and electron-poor 4-OMe (43c), 4-CF3 (43d), and 4-Ph (43e) borylated products were obtained in 93%, 93%, 97%, and 95% yields, respectively. ortho-Substituted aryl N,N-diisopropyltriazines such as 2-Cl and 2-OMe were also borylated at the ortho-position to give the corresponding ortho-borylated products 2-Cl (43b) and 2-OMe (43c) in 92% and 90% yields. Other differently substituted aryl triazines as evidenced by 43h and 43i which were obtained in 90% and 91% yields. meta-Substituted aryl N,N-diisopropyltriazines such as 3-Me and 3-Br were also successfully borylated at the respective ortho position to give the corresponding ortho-borylated products 36j and 36k in 93% yields (Scheme 19). The reaction scope performed showed good functional group tolerance (Scheme 20) [77].

3. Conclusions

Directed Ir-catalyzed C-H borylation is a significant type of C-H bond functionalization. The directed borylation provides borylated products in a regioselective manner. Specifically, ortho-regioselective Ir-catalyzed C-H borylation of arenes directed by N-containing directing groups is of unique importance. Various N-bearing directing groups have been proven to be effective in steering Ir-catalyzed C-H borylation to occur at ortho positions in a regioselective manner. The directed C-H borylation was demonstrated by various N-bearing directing groups, including anilines, amides, benzyl amines, hydrazones, and triazines. The directing ability of such directing groups lies in their coordination power with vacant sites on intermediate Ir-catalytic species, thus setting the stage for interactions between the Ir center and an ortho C-H bond and facilitating C-H borylation through C-H bond cleavage.

Funding

This research received no external funding.

Conflicts of Interest

The author declares no conflict of interest.

References

  1. Shilov, A.E.; Shul’pin, G.B. Activation of C–H Bonds by Metal Complexes. Chem. Rev. 1997, 97, 2879–2932. [Google Scholar] [CrossRef]
  2. Kakiuchi, F.; Chatani, N. Catalytic Methods for C–H Bond Functionalization: Application in Organic Synthesis. Adv. Synth. Catal. 2003, 345, 1077–1101. [Google Scholar] [CrossRef]
  3. Engle, K.M.; Mei, T.-S.; Wasa, M.; Yu, J.Q. Weak Coordination as a Powerful Means for Developing Broadly Useful C–H Functionalization Reactions. Acc. Chem. Res. 2012, 45, 788–802. [Google Scholar] [CrossRef]
  4. Rej, S.; Das, A.; Chatani, N. Strategic Evolution in Transition Metal-Catalyzed Directed C–H Bond Activation and Future Directions. Coord. Chem. Rev. 2021, 431, 213683–213719. [Google Scholar] [CrossRef]
  5. Al Mamari, H.H.; Štefane, B.; Žugelj, H.B. Metal-Catalyzed C–H Bond Functionalization of Phenol Derivatives. Tetrahedron 2020, 76, 130925–130936. [Google Scholar] [CrossRef]
  6. Docherty, J.H.; Lister, T.M.; Mcarthur, G.; Findlay, M.T.; Domingo-Legarda, P.; Jacob Kenyon, J.; Choudhary, S.; Igor Larrosa, I. Transition-Metal-Catalyzed C–H Bond Activation for the Formation of C–C Bonds in Complex Molecules. Chem. Rev. 2023, 123, 7692–7760. [Google Scholar] [CrossRef]
  7. Dalton, T.; Faber, T.; Glorius, F. C–H Activation: Toward Sustainability and Applications. ACS Cent. Sci. 2021, 2, 245–261. [Google Scholar] [CrossRef]
  8. He, J.; Wasa, M.; Chan, K.S.L.; Shao, Q.; Yu, J.-Q. Palladium-Catalyzed Transformations of Alkyl C–H Bonds. Chem. Rev. 2017, 117, 8754–8786. [Google Scholar] [CrossRef]
  9. Chen, X.; Engle, K.M.; Wang, D.-H.; Yu, J.-Q. Palladium(II)-Catalyzed C–H Activation/C-C Cross-Coupling Reactions: Versatility and Practicality. Angew. Chem. Int. Ed. 2009, 48, 5094–5115. [Google Scholar] [CrossRef]
  10. Neufeldt, S.R.; Sanford, M.S. Controlling Site Selectivity in Palladium-Catalyzed C–H Bond Functionalization. Acc. Chem. Res. 2012, 45, 936–946. [Google Scholar] [CrossRef]
  11. Bay, K.L.; Yang, Y.-F.; Houk, K.N. Multiple Roles of Silver Salts in Palladium-Catalyzed C–H Activations. J. Organomet. Chem. 2018, 864, 19–25. [Google Scholar] [CrossRef]
  12. Colby, D.A.; Tsai, A.S.; Bergman, R.G.; Ellman, J.A. Rhodium Catalyzed Chelation-Assisted C–H Bond Functionalization Reactions. Acc. Chem. Res. 2012, 45, 814–825. [Google Scholar] [CrossRef]
  13. Rej, S.; Chatani, N. Rhodium-Catalyzed C(sp2)- or C(sp3)–H Bond Functionalization Assisted by Removable Directing Groups. Angew. Chem. Int. Ed. 2019, 58, 8304–8329. [Google Scholar] [CrossRef]
  14. Lewis, J.C.; Bergman, R.G.; Ellman, J.A. Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C–H Bond Activation. Acc. Chem. Res. 2008, 41, 1013–1025. [Google Scholar] [CrossRef]
  15. Vasquez-Cespedes, S.; Wang, X.; Glorius, F. Plausible Rh(V) Intermediates in Catalytic C–H Activation Reactions. ACS Catal. 2018, 8, 242–257. [Google Scholar] [CrossRef]
  16. Song, G.; Li, X. Substrate Activation Strategies in Rhodium(III)-Catalyzed Selective Functionalization of Arenes. Acc. Chem. Res. 2015, 48, 1007–1020. [Google Scholar] [CrossRef]
  17. Singh, K.S. Recent Advances in C–H Bond Functionalization with Ruthenium-Based Catalysts. Catalysts 2019, 9, 173/1–173/51. [Google Scholar] [CrossRef]
  18. Dana, S.; Yadav, M.R.; Sahon, A.K. Ruthenium-Catalyzed C-N and C–O Bond-Forming Processes from C–H Bond Functionalization. Top. Organomet. Chem. 2016, 55, 189–215. [Google Scholar]
  19. Ruiz, S.; Villuendas, P.; Urriolabeitia, E.P. Ru-catalyzed C-H functionalizations as a tool for selective organic synthesis. Tetrahedron Lett. 2016, 57, 3413–3432. [Google Scholar] [CrossRef]
  20. Li, B.; Dixneuf, P.H. Ruthenium(II)-Catalyzed sp2 C–H Bond Functionalization by C–C Bond Formation. Top. Organomet. Chem. 2015, 48, 119–193. [Google Scholar]
  21. Ackermann, L.; Vicente, R. Ruthenium-Catalyzed Direct Arylations through C–H Bond Cleavages. Top. Curr. Chem. 2010, 292, 211–229. [Google Scholar]
  22. Gandeepan, P.; Müller, T.; Zell, D.; Warratz, S.; Ackermann, L. 3d Transition Metals for C–H Activation. Chem. Rev. 2019, 119, 2192–2452. [Google Scholar] [CrossRef]
  23. Khake, S.M.; Chatani, N. Chelation-Assisted Nickel-Catalyzed C–H Functionalizations. Trends Chem. 2019, 1, 524–539. [Google Scholar] [CrossRef]
  24. Khake, S.M.; Chatani, N. Nickel-Catalyzed C–H Functionalization Using A Non-directed Strategy. Chem 2020, 6, 1056–1081. [Google Scholar] [CrossRef]
  25. Liu, Y.-H.; Xia, Y.-N.; Shi, B.-F. Ni-Catalyzed Chelation-Assisted Direct Functionalization of Inert C-H Bonds. Chin. J. Chem. 2020, 38, 635–662. [Google Scholar] [CrossRef]
  26. Cano, R.; Mackey, K.; McGlacken, G.P. Recent Advances in Manganese-Catalyzed C-H Activation: Scope and Mechanism. Catal. Sci. Technol. 2018, 8, 1251–1266. [Google Scholar] [CrossRef]
  27. Liu, W.; Ackermann, L. Manganese-Catalyzed C–H Activation. ACS Catal. 2016, 6, 3743–3752. [Google Scholar] [CrossRef]
  28. Lanzi, M.; Cera, G. Iron-Catalyzed C-H Functionalizations under Triazole-Assistance. Molecules 2020, 25, 1806. [Google Scholar] [CrossRef] [PubMed]
  29. Shang, R.; Ilies, L.; Nakamura, E. Iron-Catalyzed C–H Bond Activation. Chem. Rev. 2017, 117, 9086–9139. [Google Scholar] [CrossRef] [PubMed]
  30. Prakash, S.; Kuppusamy, R.; Cheng, C.H. Cobalt-Catalyzed Annulation Reactions via C–H Bond Activation. ChemCatChem 2018, 10, 683–705. [Google Scholar] [CrossRef]
  31. Wang, S.; Chen, S.-Y.; Yu, X.-Q. C–H Functionalization by High-Valent Cp*Co(III) Catalysis. Chem. Commun. 2017, 53, 3165–3180. [Google Scholar] [CrossRef] [PubMed]
  32. Yoshino, T.; Matsunaga, S. High-Valent Cobalt-Catalyzed C–H Bond Functionalization. Adv. Organomet. Chem. 2019, 68, 197–247. [Google Scholar] [CrossRef]
  33. Baccalini, A.; Vergura, S.; Dolui, P.; Zanoni, G.; Maiti, D. Recent Advances in Cobalt-Catalyzed C-H Functionalizations. Org. Biomol. Chem. 2019, 17, 10119–10141. [Google Scholar] [CrossRef] [PubMed]
  34. Moselage, M.; Lie, J.; Ackermann, L. Cobalt-Catalyzed C–H Activation. ACS Catal. 2016, 6, 498–525. [Google Scholar] [CrossRef]
  35. Sambiagio, C.; Schönbauer, D.; Blieck, R.; Dao-Huy, T.; Pototschnio, G.; Schaaf, P.; Wiesinger, T.; Zia, M.F.; Wencel-Delord, J.; Besset, T.; et al. A Comprehensive Overview of Directing Groups Applied in Metal-Catalyzed C–H Functionalization Chemistry. Chem. Soc. Rev. 2018, 47, 6603–6743. [Google Scholar] [CrossRef] [PubMed]
  36. Omae, I. Intramolecular five-membered ring compounds and their applications. Coord. Chem. Rev. 2004, 248, 995–1023. [Google Scholar] [CrossRef]
  37. Rouquet, G.; Chatani, N.N. Catalytic Functionalization of C(sp2)–H and C(sp3)–H Bonds by Using Bidentate Directing Groups. Angew. Chem. Int. Ed. 2013, 52, 11726–11743. [Google Scholar] [CrossRef] [PubMed]
  38. Hartwig, J.F. Borylation and Silylation of C–H Bonds: A Platform for Diverse C–H Bond Functionalizations. Acc. Chem. Res. 2012, 45, 864–873. [Google Scholar] [CrossRef] [PubMed]
  39. Mkhalid, I.A.I.; Barnard, J.H.; Marder, T.B.; Murphy, J.M.; Hartwig, J.F. C–H Activation for the Construction of C–B Bonds. Chem. Rev. 2010, 110, 890–931. [Google Scholar] [CrossRef]
  40. Neeve, E.C.; Geier, S.J.; Mkhalid, I.A.I.; Westcott, S.; Marder, T.B. Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse. Chem. Rev. 2016, 110, 9091–9161. [Google Scholar] [CrossRef]
  41. Ishiyama, T.; Miyaura, N. Transition metal-catalyzed borylation of alkanes and arenes via C-H activation. J. Organometal. Chem. 2003, 680, 3–11. [Google Scholar] [CrossRef]
  42. Ishiyama, T.; Takagi, J.; Hartwig, J.F.; Miyaura, N. A Stoichiometric Aromatic C-H Borylation Catalyzed by Iridium(I)/2,2′-Bipyridine Complexes at Room Temperature. Angew. Chem. Int. Ed. 2002, 41, 3056–3058. [Google Scholar] [CrossRef]
  43. Kuroda, Y.; Nakao, Y. Catalyst-enabled Site-selectivity in the Iridium-catalyzed C–H Borylation of Arenes. Chem. Lett. 2019, 48, 1092–1100. [Google Scholar] [CrossRef]
  44. Li, Y.; Wu, X.-F. Direct C–H Bond Borylation of (Hetero)Arenes: Evolution from Noble Metal to Metal Free. Angew. Chem. Int. Ed. 2020, 59, 1770–1774. [Google Scholar] [CrossRef] [PubMed]
  45. Hall, D.G. Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine; Wiley-VCH: Weinheim, Germany, 2005. [Google Scholar]
  46. Obligacion, J.V.; Semproni, S.P.; Chirik, P.J. Cobalt-Catalyzed C(sp2)-H Borylation. J. Am. Chem. Soc. 2014, 136, 4133–4136. [Google Scholar] [CrossRef] [PubMed]
  47. Palmer, W.N.; Obligacion, J.V.; Pappas, I.; Chirik, P.J. Cobalt-Catalyzed Benzylic Borylation: Enabling Polyborylation and Functionalization of Remote, Unactivated C(sp3)–H Bonds. J. Am. Chem. Soc. 2016, 138, 766–769. [Google Scholar] [CrossRef] [PubMed]
  48. Schaefer, B.A.; Margulieux, G.W.; Small, B.L.; Chirik, P.J.J. Evaluation of Cobalt Complexes Bearing Tridentate Pincer Ligands for Catalytic C–H Borylation. Organometallics 2015, 34, 1307–1320. [Google Scholar] [CrossRef]
  49. Furukawa, T.; Tobisu, M.; Chatani, N. Nickel-Catalyzed Borylation of Arenes and Indoles via C–H Bond Cleavage. Chem. Commun. 2015, 51, 6508–6511. [Google Scholar] [CrossRef] [PubMed]
  50. Dombray, T.; Werncke, C.G.; Jiang, S.; Grellier, M.; Vendier, L.; Bontemps, S.; Sortais, J.-B.; Sabo-Etienne, S.; Darcel, C. Iron-Catalyzed C-H Borylation of Arenes. J. Am. Chem. Soc. 2015, 137, 4062–4065. [Google Scholar] [CrossRef]
  51. Ros, A.; Fernández, R.; Lassaleta, J.M. Functional Group Directed C-H Borylation. Chem. Soc. Rev. 2014, 43, 3229–3243. [Google Scholar] [CrossRef]
  52. Bisht, R.; Halder, C.; Hassan, M.M.M.; Hoque, M.E.; Chaturvedi, J.; Chattopadhya, B. Metal-Catalyzed C-H Bond Activation and Borylation. Chem. Soc. Rev. 2022, 51, 5042–5100. [Google Scholar] [CrossRef] [PubMed]
  53. Itoh, H.; Kikuchi, T.; Ishiyama, T.; Miyaura, N. Iridium-catalyzed ortho-C–H Borylation of Aryl Ketones with Bis(pinacolato)diboron. Chem. Lett. 2011, 40, 1007–1008. [Google Scholar] [CrossRef]
  54. Xue, C.; Luo, Y.; Teng, H.; Ma, Y.; Nishiura, M.; Hou, Z. Ortho-Selective C–H Borylation of Aromatic Ethers with Pinacol-borane by Organo Rare-Earth Catalysts. ACS Catal. 2018, 8, 5017–5022. [Google Scholar] [CrossRef]
  55. Li, H.L.; Kuninobu, Y.; Kanai, M. Lewis Acid–Base Interaction-Controlled ortho-Selective C–H Borylation of Aryl Sulfides. Angew. Chem. Int. Ed. 2017, 56, 1495–1499. [Google Scholar] [CrossRef] [PubMed]
  56. Li, H.-L.; Kanai, M.; Kuninobu, Y. Iridium/Bipyridine- Catalyzed ortho-Selective C–H Borylation of Phenol and Aniline Derivatives. Org. Lett. 2017, 19, 5944–5947. [Google Scholar] [CrossRef]
  57. Chattopadhyay, B.; Dannatt, J.E.; Andujar-De Sanctis, I.L.; Gore, K.A.; Maleczka, R.E.; Singleton, D.A.; Smith, M.R. Ir-Catalyzed ortho-Borylation of Phenols Directed by Substrate–Ligand Electrostatic Interactions: A Combined Experimental/in Silico Strategy for Optimizing Weak Interactions. J. Am. Chem. Soc. 2017, 139, 7864–7871. [Google Scholar] [CrossRef] [PubMed]
  58. Yamazaki, K.; Kawamorita, S.; Ohmiya, H.; Sawamura, M. Directed Ortho Borylation of Phenol Derivatives Catalyzed by a Silica-Supported Iridium Complex. Org. Lett. 2010, 12, 3978–3981. [Google Scholar] [CrossRef] [PubMed]
  59. Sean, M.; Preshlock, S.M.; Ghaffari, B.; Peter, E.; Maligres, P.E.; Shane, W.; Krska, S.W.; Robert, E.; Maleczka, R.E., Jr.; Milton, R.; et al. High-Throughput Optimization of Ir-Catalyzed C–H Borylation: A Tutorial for Practical Applications. J. Am. Chem. Soc. 2013, 135, 7572–7582. [Google Scholar] [CrossRef] [PubMed]
  60. Raphael, J.; Oeschger, R.J.; Larsen, M.A.; Bismuto, A.; Hartwig, J.F. Origin of the Difference in Reactivity between Ir Catalysts for the Borylation of C–H Bonds. J. Am. Chem. Soc. 2019, 141, 16479–16485. [Google Scholar] [CrossRef]
  61. Boller, T.M.; Murphy, J.M.; Marko Hapke, M.; Tatsuo Ishiyama, T.; Miyaura, N.; Hartwig, J.F. Mechanism of the Mild Functionalization of Arenes by Diboron Reagents Catalyzed by Iridium Complexes. Intermediacy and Chemistry of Bipyridine-Ligated Iridium Trisboryl Complexes. J. Am. Chem. Soc. 2005, 127, 14263–14278. [Google Scholar] [CrossRef]
  62. Ishiyama, T.; Jun Takagi, J.; Kousaku Ishida, K.; Norio Miyaura, N.; Anastasi, N.R.; Hartwig, J.E. Mild Iridium-Catalyzed Borylation of Arenes. High Turnover Numbers, Room Temperature Reactions, and Isolation of a Potential Intermediate. J. Am. Chem. Soc. 2002, 124, 390–391. [Google Scholar] [CrossRef] [PubMed]
  63. Ochida, A.; Hara, K.; Ito, H.; Sawamura, M. Nonvolatile Me3P-like P-Donor Ligand:  Synthesis and Properties of 4-Phenyl-1-phospha-4-silabicyclo[2.2.2]octane. Org. Lett. 2003, 5, 2671–2674. [Google Scholar] [CrossRef] [PubMed]
  64. Ochida, A.; Ito, S.; Miyahara, T.; Ito, H.; Sawamura, M. Electronically Tunable Compact Trialkylphosphines: SMAPs-bridged Bicyclic Phosphines. Chem. Lett. 2006, 35, 294–295. [Google Scholar] [CrossRef]
  65. Kawamorita, S.; Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura, M. Directed Ortho Borylation of Functionalized Arenes Catalyzed by a Silica-Supported Compact Phosphine–Iridium System. J. Am. Chem. Soc. 2009, 131, 5058–5059. [Google Scholar] [CrossRef] [PubMed]
  66. Kawamorita, S.; Ohmiya, H.; Sawamura, M. Ester-Directed Regioselective Borylation of Heteroarenes Catalyzed by a Silica-Supported Iridium Complex. J. Org. Chem. 2010, 75, 3855–3858. [Google Scholar] [CrossRef] [PubMed]
  67. Kawamorita, S.; Murakami, R.; Iwai, T.; Sawamura, M. Synthesis of Primary and Secondary Alkylboronates through Site-Selective C(sp3)–H Activation with Silica-Supported Monophosphine–Ir Catalysts. J. Am. Chem. Soc. 2013, 135, 2947–2950. [Google Scholar] [CrossRef] [PubMed]
  68. Konishi, S.; Kawamorita, S.; Iwai, T.; Steel, P.G.; Marder, T.B.; Sawamura, M. Site-Selective C–H Borylation of Quinolines at the C8 Position Catalyzed by a Silica-Supported Phosphane–Iridium System. Chem. Asian. J. 2014, 9, 434–438. [Google Scholar] [CrossRef]
  69. Roosen, P.C.; Kallepalli, V.A.; Chattopadhyay, B.; Singleton, D.A.; Maleczka, R.E., Jr.; Smith, M.R., III. Outer-Sphere Direction in Iridium C–H Borylation. J. Am. Chem. Soc. 2012, 134, 11350–11353. [Google Scholar] [CrossRef] [PubMed]
  70. Preshlock, S.M.; Plattner, D.L.; Maligres, P.E.; Krska, S.W.; Maleczka, R.E., Jr.; Smith, M.R., III. A Traceless Directing Group for C-H Borylation. Angew. Chem. Int. Ed. 2013, 52, 12915–12919. [Google Scholar] [CrossRef]
  71. Bai, S.-T.; Bheeter, C.B.; Reek, J.N.H. Hydrogen Bond Directed ortho-Selective C-H Borylation of Secondary Aromatic Amides. Angew. Chem. Int. Ed. 2019, 58, 13039–13043. [Google Scholar] [CrossRef]
  72. Hoque, M.M.; Hassan, M.M.M.; Chattopadhyay, B. Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates. J. Am. Chem. Soc. 2021, 143, 5022–5037. [Google Scholar] [CrossRef] [PubMed]
  73. Marcos-Atanes, D.; Vidal, C.; Navo, C.D.; Peccati, F.; Jiménez-Osés, G.; Mascareñas, J.L. Iridium-Catalyzed ortho-Selective Borylation of Aromatic Amides Enabled by 5-Trifluoromethylated Bipyridine Ligands. Angew. Chem. Int. Ed. 2023, 62, e202214510. [Google Scholar] [CrossRef]
  74. Roering, A.J.; Hale, L.V.A.; Squier, P.A.; Ringgold, M.A.; Wiederspan, E.R.; Clark, T.B. Iridium-Catalyzed, Substrate-Directed C-H Borylation Reactions of Benzylic Amines. Org. Lett. 2012, 14, 3558–3561. [Google Scholar] [CrossRef] [PubMed]
  75. Zou, X.; Zhao, H.; Li, Y.; Gao, Q.; Ke, Z.; Senmiao Xu, S. Chiral Bidentate Boryl Ligand Enabled Iridium-Catalyzed Asymmetric C(sp2)–H Borylation of Diarylmethylamines. J. Am. Chem. Soc. 2019, 141, 5334–5342. [Google Scholar] [CrossRef] [PubMed]
  76. Ros, A.; López-Rodríguez, R.; Estepa, B.; Álvarez, E.; Fernández, R.; Lassaletta, J.M. Hydrazone as the Directing Group for Ir-Catalyzed Arene Diborylations and Sequential Functionalizations. J. Am. Chem. Soc. 2012, 134, 4573–4576. [Google Scholar] [CrossRef]
  77. Mao, S.; Yuan, B.; Wang, X.; Zhao, Y.; Wang, L.; Yang, X.-Y.; Chen, Y.-M.; Zhang, S.-Q.; Li, P. Triazene as the Directing Group Achieving Highly Ortho-Selective Diborylation and Sequential Functionalization. Org. Lett. 2022, 24, 3594–3598. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content.
Reactions 05 00016 sch001
Scheme 1. General representation of directed C-H borylation.
Scheme 1. General representation of directed C-H borylation.
Reactions 05 00016 sch001
Reactions 05 00016 g001
Figure 1. Common Ir precatalysts in Ir-catalyzed C-H borylation.
Figure 1. Common Ir precatalysts in Ir-catalyzed C-H borylation.
Reactions 05 00016 g001
Reactions 05 00016 g002
Figure 2. Bipyridine ligands.
Figure 2. Bipyridine ligands.
Reactions 05 00016 g002
Reactions 05 00016 g003
Figure 3. Ability of [Ir(OMe)(COD)]2 to form Ir trisboryl complexes.
Figure 3. Ability of [Ir(OMe)(COD)]2 to form Ir trisboryl complexes.
Reactions 05 00016 g003
Reactions 05 00016 sch002
Scheme 2. A plausible general mechanism of Ir-catalyzed C-H borylation.
Scheme 2. A plausible general mechanism of Ir-catalyzed C-H borylation.
Reactions 05 00016 sch002
Reactions 05 00016 sch003
Scheme 3. Possible coordination between the Ir trisboryl complex and directing groups.
Scheme 3. Possible coordination between the Ir trisboryl complex and directing groups.
Reactions 05 00016 sch003
Reactions 05 00016 sch004
Scheme 4. Envisaged directing role in the substrate-directed Ir-catalyzed C-H ortho-borylation of carbocycles.
Scheme 4. Envisaged directing role in the substrate-directed Ir-catalyzed C-H ortho-borylation of carbocycles.
Reactions 05 00016 sch004
Reactions 05 00016 sch005
Scheme 5. NH-Boc directed Ir-Catalyzed C-H ortho-borylation of protected anilines.
Scheme 5. NH-Boc directed Ir-Catalyzed C-H ortho-borylation of protected anilines.
Reactions 05 00016 sch005
Reactions 05 00016 sch006
Scheme 6. Ir-catalyzed C-H ortho-borylation of anilines.
Scheme 6. Ir-catalyzed C-H ortho-borylation of anilines.
Reactions 05 00016 sch006
Reactions 05 00016 g004
Figure 4. Hydrogen bonding between N-Bpin-aniline and O in the Bpin moiety.
Figure 4. Hydrogen bonding between N-Bpin-aniline and O in the Bpin moiety.
Reactions 05 00016 g004
Reactions 05 00016 sch007
Scheme 7. Mechanism for Ir-catalyzed C-H borylation of anilines.
Scheme 7. Mechanism for Ir-catalyzed C-H borylation of anilines.
Reactions 05 00016 sch007
Reactions 05 00016 sch008
Scheme 8. Ir-catalyzed C-H borylation of N-methyl aniline.
Scheme 8. Ir-catalyzed C-H borylation of N-methyl aniline.
Reactions 05 00016 sch008
Reactions 05 00016 sch009
Scheme 9. Ir-BAIPy-based directed C-H borylation of secondary amides.
Scheme 9. Ir-BAIPy-based directed C-H borylation of secondary amides.
Reactions 05 00016 sch009
Reactions 05 00016 g005
Figure 5. Hydrogen-bonding transition state for the directed C-HJ borylation.
Figure 5. Hydrogen-bonding transition state for the directed C-HJ borylation.
Reactions 05 00016 g005
Reactions 05 00016 sch010
Scheme 10. Formation of cyclometallated.
Scheme 10. Formation of cyclometallated.
Reactions 05 00016 sch010
Reactions 05 00016 sch011
Scheme 11. Effects of N-substituents of Ir-catalyzed C-H borylation of tertiary benzamides.
Scheme 11. Effects of N-substituents of Ir-catalyzed C-H borylation of tertiary benzamides.
Reactions 05 00016 sch011
Reactions 05 00016 sch012
Scheme 12. Arene scope of Ir-catalyzed C-H borylation of tertiary benzamides.
Scheme 12. Arene scope of Ir-catalyzed C-H borylation of tertiary benzamides.
Reactions 05 00016 sch012
Reactions 05 00016 sch013
Scheme 13. Functional group scope of Ir-catalyzed C-H borylation using thiophenylpyridine as a ligand.
Scheme 13. Functional group scope of Ir-catalyzed C-H borylation using thiophenylpyridine as a ligand.
Reactions 05 00016 sch013
Reactions 05 00016 sch014
Scheme 14. Ir-catalyzed C-H borylation using 5-CF3-bipyridine ligand.
Scheme 14. Ir-catalyzed C-H borylation using 5-CF3-bipyridine ligand.
Reactions 05 00016 sch014
Reactions 05 00016 sch015
Scheme 15. Ir-catalyzed C-H borylation of benzylamines.
Scheme 15. Ir-catalyzed C-H borylation of benzylamines.
Reactions 05 00016 sch015
Reactions 05 00016 g006
Figure 6. Proposed transition state for the Ir-catalyzed C-H borylation of benzylamines.
Figure 6. Proposed transition state for the Ir-catalyzed C-H borylation of benzylamines.
Reactions 05 00016 g006
Reactions 05 00016 sch016
Scheme 16. Amine directing effect scope of Ir-catalyzed C-H borylation of benzylamines.
Scheme 16. Amine directing effect scope of Ir-catalyzed C-H borylation of benzylamines.
Reactions 05 00016 sch016
Reactions 05 00016 sch017
Scheme 17. Use of chiral DPEN-derived boryl ligand and the proposed active Ir catalyst.
Scheme 17. Use of chiral DPEN-derived boryl ligand and the proposed active Ir catalyst.
Reactions 05 00016 sch017
Reactions 05 00016 sch018
Scheme 18. Ir-catalyzed regioselective asymmetric C-H borylation.
Scheme 18. Ir-catalyzed regioselective asymmetric C-H borylation.
Reactions 05 00016 sch018
Reactions 05 00016 sch019
Scheme 19. Ir-catalyzed C-H borylation of aryl hydrazones based on pyridine-hydrazone ligand.
Scheme 19. Ir-catalyzed C-H borylation of aryl hydrazones based on pyridine-hydrazone ligand.
Reactions 05 00016 sch019
Reactions 05 00016 sch020
Scheme 20. Ligand-free Ir-catalyzed C-H borylation of aryl triazines.
Scheme 20. Ligand-free Ir-catalyzed C-H borylation of aryl triazines.
Reactions 05 00016 sch020
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Al Mamari, H.H. Ir-Catalyzed ortho-C-H Borylation of Aromatic C(sp2)-H Bonds of Carbocyclic Compounds Assisted by N-Bearing Directing Groups. Reactions 2024, 5, 318-337. https://doi.org/10.3390/reactions5020016

AMA Style

Al Mamari HH. Ir-Catalyzed ortho-C-H Borylation of Aromatic C(sp2)-H Bonds of Carbocyclic Compounds Assisted by N-Bearing Directing Groups. Reactions. 2024; 5(2):318-337. https://doi.org/10.3390/reactions5020016

Chicago/Turabian Style

Al Mamari, Hamad H. 2024. "Ir-Catalyzed ortho-C-H Borylation of Aromatic C(sp2)-H Bonds of Carbocyclic Compounds Assisted by N-Bearing Directing Groups" Reactions 5, no. 2: 318-337. https://doi.org/10.3390/reactions5020016

Article Metrics

Back to TopTop