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Article

α-Carbonyl Rh-Carbenoid Initiated Cascade Assembly of Diazobarbiturates with Alkylidene Pyrazolones for Synthesis of Spirofuropyrimidines

by
Yue Zhang
,
Yu-Hang Mi
,
Kuo Wang
and
Hong-Wu Zhao
*
College of Life Science and Bio-Engineering, Beijing University of Technology, No. 100 Pingleyuan, Chaoyang District, Beijing 100124, China
*
Author to whom correspondence should be addressed.
Molecules 2024, 29(13), 3178; https://doi.org/10.3390/molecules29133178
Submission received: 14 June 2024 / Revised: 1 July 2024 / Accepted: 1 July 2024 / Published: 3 July 2024
(This article belongs to the Special Issue Recent Advances in Transition Metal Catalysis)
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Abstract

:
Catalyzed by Rh2(esp)2 (10 mol%) and (±)-BINAP (20 mol%) in DCE at 80 °C, the cascade assembly between diazobarbiturates and alkylidene pyrazolones proceeded readily and produced spiro-furopyrimidines in 38–96% chemical yields. The chemical structure of the prepared spirofuro-pyrimidines was firmly confirmed by X-ray diffraction analysis.

1. Introduction

Furopyrimidines constitute a family of privileged drug scaffolds and their analogs have a wide range of bioactivities such as antifungal, antitumor, antifolate, antimicrobial, antivirus, and antihuman cytomegalovirus properties [1,2,3]. Since the significant bioactivities with furopyrimidine skeletons, numerous efficient and facile synthetic protocols have been accomplished to approach highly functionalized furopyrimidine analogs [4,5,6,7,8,9,10,11,12]. Moreover, in this context, mechanistically diverse synthetic methodologies have been invented to deliver structurally unique and potentially bioactive spirofuropyrimidines [13,14,15,16,17,18]. Presently, the metal carbenoid-initiated cascade assembly of multiple molecules has barely been applied in the preparation of spirofuropyrimidines [19]. So, the development of metal carbenoid-based three-molecule cascades is highly desirable for preparing spirofuropyrimidines efficiently and facilely.
α-Diazocarbonyls represent a class of synthetically robust and versatile building blocks and by acting as typical metallocarbene precursors, they have found a broad spectrum of applications in preparing drug-like scaffolds and biologically active natural products [20,21,22,23,24,25,26,27]. Normally, treated with transition metal catalysts, α-diazocarbonyls can readily decompose into highly reactive metal carbenoids by removing N2 [28,29,30,31,32,33,34,35,36,37,38]. Regarding these highly reactive metal carbenoids generated in situ, they normally can behave as 1- or 3-atom synthons to perform numerous mechanistically different synthetic methodologies which often feature high chemo-, regio- and stereoselectivities Scheme 1 (1) [39,40,41,42,43,44,45,46,47,48,49,50,51]. Particularly, the in situ formed heterocycle-derived cyclic metal carbenoids are capable of functioning as 1- or 3-atom synthons to undergo the highly efficient and concise [n + 1] or [n + 3] cycloaddition with a wide range of structurally diverse and reactive organic synthons, thus delivering drug-like spiro or fused multiheterocyclic skeletons bearing structural complexities and diversities [52,53,54,55,56,57,58,59,60].
Diazobarbiturates belong to a type of structurally unique α-carbonyl diazoheterocycles and in the presence of Rh-catalysts, they can readily conduct insertion reaction, [2 + 1] cycloaddition, and [3 + 2] cycloaddition through the in situ formed α-carbonyl Rh-carbenoid synthons [61,62,63]. Nevertheless, the three-molecule assembly of barbiturate-derived Rh-carbenoids with heterocycle-based conjugated olefins has never been touched for the construction of spiro/fused furopyrimidine scaffolds. Therefore, the design and exploration of the mechanistically new three-molecule cascade assembly by employing diazobarbiturates and heterocycle-based olefins as reactants are highly urgent and needed for preparing potentially bioactive spiro/fused multiheterocyclic skeletons.
Herein, we designed and explored the transition metal-catalyzed cascade assembly of diazobarbiturates with alkylidene pyrazolones for the construction of spiro/fused multiheterocyles Scheme 1 (2). Typically, alkylidene pyrazolones exhibit plenty of chemical properties and have found a variety of applications in the preparation of structurally diverse and unique spiropyrazole analogs [64,65,66]. We found that the transition metal-catalyzed cascade assembly did not occur via the expected [3 + 3 + 2] pathway; on the contrary, it performed the unexpected [3 + 1 + 1] cascade and furnished potential bioactive spirofuropyrimidines in reasonable chemical yields. To the best of our knowledge, such a work has not been reported in the literature to date.

2. Results and Discussion

Initially, along with Rh2(OAc)4 (10 mol) and ligand (±)-L1 (20 mol%) in DCE at 80 °C, we checked the ratio effects of 1a/2a on the cascade assembly of diazobarbiturate 1a with alkylidene pyrazolone 2a (Table 1, entries 1–3). The variable ratios of 1a/2a largely influenced the chemical yield of the cascade assembly. The ratio of 0.1 mmol/0.15 mmol proved to be most suitable (entries 1–2 vs. 3). Together with ligand (±)-L1 (20 mol%) and 0.1 mmol/0.15 mmol ratio of 1a/2a in DCE at 80 °C, we examined numerous structurally varying transition metal catalysts for their effects on the cascade assembly cascade (Table 1, entries 4–14). Ph3PAuCl, (CH3CN)4·CuBF4, DPPE·NiCl2, DPPE·PdCl2, and Pd(DPPE)2 failed to facilitate the cascade assembly (entries 4–8). Both Pd2(dba)3 and (F3CSO2)NAg afforded product 3a in trace amounts (entries 9–10). Ru(OAc)3 provided 3a in lower chemical yield (entry 11). Regarding Rh(I) and Rh(III) complexes, they were unable to catalyze the cascade assembly (entries 12–13). Delightfully, we found that Rh2(esp)2 performed efficiently to give 3a in excellent chemical yield (entries 3–13 vs. 14). Moreover, we optimized the catalytic loading of Rh2(esp)2 and discovered that the 10 mol% loading of Rh2(esp)2 was most suitable for the cascade assembly (entries 14 vs. 15–18).
Next, in combination with Rh2(esp)2 in DCE at 80 °C, we explored several ligands for their effects on the cascade assembly of diazobarbiturate 1a with alkylidene pyrazolone 2a (Table 2, entries 1–7). The examined ligands significantly affected the chemical yield of the cascade assembly. Without a ligand, the cascade assembly produced product 3a in trace amounts (entry 1). Moreover, ligand (±)-L2 inhibited the cascade assembly (entry 2). In the case of ligands (±)-L3, (±)-L4, dppf, dppb, and (±)-L5, they provided product 3a in moderate to high chemical yields (entries 3–7). Pleasantly, ligand (±)-L1 behaved the most efficiently and delivered product 3a in the highest chemical yield (entry 8). In the presence of Rh2(esp)2 (10 mol%) and (±)-L1 (20 mol%) in DCE at 80 °C, we scrutinized several organic solvents for their effects on the cascade assembly and found that these organic solvents inhibited the cascade assembly from taking place (entries 9–12). Therefore, for the cascade assembly, we determined the optimal reaction conditions as below: 0.1 mmol/0.15 mmol ratio of 1a/2a, 10 mol% of Rh2(esp)2, and 20 mol% of (±)-L1 in 1,2-DCE at 80 °C. In addition, we checked several chiral ligands for their asymmetric inductions in the cascade between 1a and 2a, and found that in all the tested cases, product 3a was formed without enantioselectivity (entry 13–15, see details in Supplementary Materials).
Under the well-established reaction conditions, we extended the reaction scope of the cascade assembly by diversifying diazobarbiturate 1 and alkylidene pyrazolone 2 (Table 3). The screened substrates 1 and 2 differed substantially in their reactivities and efficiencies and influenced the chemical yield of the cascade assembly significantly. In the cascade assembly with diazobarbiturate 1a, the substrates 2a–2c behaved efficiently to provide product 3a in excellent chemical yields (entries 1–3). In contrast, the substrates 2d, 2e, and 2i performed poorly and yielded their products 3 in lower chemical yields (entries 4–5 and 9). Even badly, the substrates 2f, 2g, and 2h failed to react with the substrate 1a (entries 6–8). The substrate 2a performed the cascade assembly more efficiently than the substrates 2e–2i, presumably because it utilized a phenyl as an R3 group (entries 1 vs. 5–9). Moreover, the substrates 2a–2c containing a phenyl as the R3 group endured the structural variations in the R4 and R5 groups (entries 1–3). Lastly, the substrate 2d bearing a phenyl as the R5 group provided product 3a in the decreased chemical yield (entries 1 vs. 4).
Moreover, by utilizing structurally variable diazobarbiturates 1, we checked their cascade assemblies with alkylidene pyrazolone 2c (Table 3, entries 10–15). The substrates 1b (R1 = R2 = cyclohexyl), 1f (R1 = R2 = Butert), and 1g (R1 = R2 = MeC6H4) behaved poorly and failed to deliver their product 3 (entries 10, 14–15). The substrate 1e furnished product 3f in a lower chemical yield (entry 13). The substrates 1c and 1d increased the chemical yield of their product 3 significantly (entries 11–12 vs. 10, 13–15). The substrates 1c and 1d with sterically less hindered the R1 and R2 groups performed more efficiently than the substrates 1b and 1e–1g with sterically more crowded R1 and R2 groups in their cascade assemblies (entry 11–12 vs. 10, 13–15). So, in the cascade assembly with alkylidene pyrazolone 2c, the substrates 1a and 1d using Me or Et as the R1 and R2 groups often performed efficiently to provide products 3a and 3e in excellent chemical yields (entries 3 and 12).
Meanwhile, to enrich the structural variation in product 3, we accomplished the cascade assemblies of the substrates 1a and 1d with the substrates 2j–2r (Table 3, 16–32). All the tested cascade assemblies exhibited desirable reactivities, thus producing their product 3 in moderate to excellent chemical yields (entries 16–32). In the cascade assemblies with the substrates 1a and 1d, the substrate 2 allowed the wide variation in the R3 group from electron-poor to electron-rich aryls. Significantly, we observed that the substitution pattern and electronic property of R3 affected the chemical yield of the crossed cascade assemblies (e.g., entries 16 vs. 24; 26 vs. 29). In addition, we explored the cascade assemblies of the substrate 1h (R1 = Me, R2 = Bn) with the substrates 2a and 2c and these cascade assemblies were unable to take place (entries 33–34). Moreover, we determined the chemical structure of 3a by single crystal X-ray analysis and assigned that of all the other obtained spirobarbiturates by analogy as shown in Figure 1 (CCDC 2309187) [67].
To shed light on the formation of product 3a, on the basis of the works in the literature [68,69,70] and the LC-HRMS analysis carried out by us (see details in Supplementary Materials), we proposed the reaction mechanism for the cascade assembly of diazobarbiturate 1a with alkylidene pyrazolone 2b as illustrated in Scheme 2. Treated with the Rh(II)/(L1)n complex formed in situ, diazobarbiturate 1a transforms into its Rh-carbenoid Int-1. Then, the intermediate Int-1 performs the [2 + 2] cycloaddition with alkylidene pyrazolone 2b to yield intermediate Int-2. Finally, via the transition state TS, Rh-carbenoid Int-1 undergoes the [3 + 2] cycloaddition with Int-2 to afford 3a along with liberating Rh-carbenoid 4 which further transforms into 5.

3. Materials and Methods

Proton (1H), carbon (13C), and fluorine (19F) NMR spectra were recorded on the Bruker (Billerica, MD, USA) Avance HD III spectrometer (400 MHz for 1H NMR, 100 MHz for 13C NMR and 376 MHz for 19F NMR) and calibrated using tetramethylsilane (TMS) as the internal reference. High-resolution mass spectra (HRMS) were obtained on an Agilent Technologies (Santa Clara, CA, USA) LC/MSD TOF spectrometer under electrospray ionization (ESI) conditions. The melting point of the compounds was determined by a melting point instrument. Flash column chromatography was performed on silica gel (0.035–0.070 mm) using compressed air. X-ray single crystals were obtained on the Rigaku (Wilmington, MA, USA) 002 Saturn 944 spectrometer. Thin layer chromatography (TLC) was carried out on 0.25 mm SDS silica gel-coated glass plates (60F254). Eluted plates were visualized using a 254 nm UV lamp. Unless otherwise indicated, all the reagents were commercially available and used without further purification. All the solvents were distilled from the appropriate drying agents immediately before use. Diazobarbiturates 1a–1g were synthesized according to the reported procedures [61,62,71,72,73], and alkylidene pyrazolones 2a–2r were prepared according to the literature procedures [74,75,76,77,78,79,80,81,82].

3.1. General Procedure for Cascade Assembly Reaction

A mixture of diazobarbiturate 1 (1.0 equiv, 0.1 mmol), alkylidene pyrazolone 2 (1.5 equiv, 0.15 mmol), Rh2(esp)2 (10.0 mmol%), and (±)-L1 (20.0 mmol%) in DCE (1.5 mL) was stirred at 80 °C. After the reaction was completed as indicated by the TLC plate, the solvent was removed under reduced pressure. The resulting crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate = 1:1~5:1) to afford product 3 (38–96% yields).

3.2. Gram-Scale Synthesis of Compound 3a

Molecules 29 03178 i005
A mixture of diazobarbiturate 1a (1.0 equiv, 6.0 mmol, 1.0920 g), alkylidene pyrazolone 2a (1.5 equiv, 9.0 mmol, 2.3670 g), Rh2(esp)2 (10.0 mmol%, 0.4550 g), and (±)-L1 (20.0 mmol%, 0.7440 g) in DCE (15 mL) was stirred at 80 °C. After the reaction was completed as indicated by the TLC plate, the solvent was concentrated under reduced pressure. The resulting crude product was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate = 1:1) to afford product 3a as a white solid (1.0800 g, 90% yield).

3.3. Characterization of Product 3

1,1′,3,3′-tetramethyl-5-phenyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3a) [13]: white solid (yield: 18.6 mg, 93%). M.P. = 240.0–240.3 °C; 1H NMR (400 MHz, CDCl3): δ 7.32 (dd, J = 5.12, 1.72 Hz, 3H), 7.05 (dd, J = 5.20, 3.64 Hz, 2H), 4.91 (s, 1H), 3.50 (s, 3H), 3.40 (s, 3H), 3.28 (s, 3H), and 2.53 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 163.0, 162.7, 158.6, 151.2, 149.6, 132.8, 129.5, 128.9, 128.2, 90.3, 85.5, 59.2, 30.0, 29.5, 28.4, and 28.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H19N4O6 399.12976; found 399.12991.
1,1′,3,3′,5-pentamethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3b): white solid (yield: 6.4 mg, 38%). M.P. = 202.5–202.8 °C; 1H NMR (400 MHz, CDCl3): δ 3.81 (q, J = 6.92 Hz, 1H), 3.44 (s, 3H), 3.38 (s, 3H), 3.37 (s, 3H), 3.30 (s, 3H), and 1.33 (d, J = 6.88 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.8, 163.4, 161.2, 159.2, 151.1, 149.9, 88.9, 87.9, 47.8, 29.8, 29.5, 29.0, 28.0, and 15.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C14H17N4O6 337.11435; found 337.11426.
5-(2,3-dihydrobenzofuran-5-yl)-1,1′,3,3′-tetramethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3c): white solid (yield: 12.3 mg, 56%). M.P. = 265.1–265.3 °C; 1H NMR (400 MHz, CDCl3): δ 6.86 (s, 1H), 6.77 (d, J = 8.20 Hz, 1H), 6.67 (d, J = 8.20 Hz, 1H), 4.84 (s, 1H), 4.52 (t, J = 8.84 Hz, 2H), 3.48 (s, 3H), 3.37 (s, 3H), 3.26 (s, 3H), 3.13 (t, J = 8.64 Hz, 2H), and 2.63 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.6, 163.2, 162.5, 161.1, 158.7, 151.2, 149.7, 128.3, 128.0, 124.7, 124.6, 109.5, 90.5, 85.9, 71.6,59.1, 29.9, 29.4, 29.4, 28.6, and 28.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H21N4O7 441.14014; found 441.14048.
1,1′,3,3′-tetrabenzyl-5-phenyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3d): white solid (yield: 24.1 mg, 72%). M.P. = 112.2–112.5 °C; 1H NMR (400 MHz, CDCl3): δ 7.63–7.20 (m, 25H), 5.24–4.99 (m, 6H), 4.74 (s, 1H), and 4.09(q, J = 14.16 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 158.4, 150.8, 149.2, 136.9, 135.4, 134.9, 134.8, 132.2, 129.8, 129.5, 129.2, 129.1, 129.0, 128.9, 128.8, 128.6, 128.4, 128.2, 127.7, 90.4, 85.7, 59.2, 47.3,45.8, 45.7, and 44.7 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C43H35N4O6 703.25720; found 703.25511.
1,1′,3,3′-tetraethyl-5-phenyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3e) [13]: white solid (yield: 20.7 mg, 91%). M.P. = 164.9–165.1 °C; 1H NMR (400 MHz, CDCl3): δ 7.35–7.31 (m, 3H), 7.10 (d, J = 1.88 Hz, 1H), 7.09 (d, J = 4.08 Hz, 1H), 4.89 (s, 1H), 4.14–3.94 (m, 6H), 3.34 (q, J = 7.08 Hz, 1H), 3.08 (q, J = 7.12 Hz, 1H), 1.44 (t, J = 7.12 Hz, 3H), 1.36 (t, J = 7.08 Hz, 3H), 1.20 (t, J = 7.04 Hz, 3H), and 0.68 (t, J = 7.12 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 162.7, 162.4, 158.4, 150.4, 148.9, 132.9, 129.4, 128.9, 128.6, 89.6, 86.0, 59.1, 39.1, 38.2,37.9, 36.7, 13.8, 13.3, 13.1, and 12.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H27N4O6 455.19257; found 455.19251.
1,1′,3,3′-tetraisopropyl-5-phenyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3f): white solid (yield: 12.0 mg, 47%). M.P. = 170.1–170.4 °C; 1H NMR (400 MHz, CDCl3): δ 7.31 (t, J = 2.12 Hz, 3H), 7.11–7.10 (m, 2H), 5.16–5.01 (m, 3H), 4.72 (s, 1H), 4.46–4.41 (m, 1H), 1.60 (dd, J = 7.88,4.68 Hz, 6H), 1.53 (t, J = 4.28 Hz, 6H), 1.41 (dd, J = 10.36, 4.60 Hz, 6H), and 0.83 (d, J = 4.36 Hz, 5H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.9, 162.5, 158.9, 150.4, 148.8, 133.4, 129.3, 129.0, 128.8, 90.0, 87.1, 57.9, 48.5, 48.5, 48.0, 20.4, 20.4, 20.3, 19.4, 19.4, 19.1, 18.8, and 18.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H35N4O6 511.25552; found 511.25511.
1,1′,3,3′-tetramethyl-5-(p-tolyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3g) [13]: white solid (yield: 14.0 mg, 68%). M.P. = 141.1–141.3 °C; 1H NMR (400 MHz, CDCl3): δ 7.14 (d, J = 7.84 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 4.90 (s, 1H), 3.53 (s, 3H), 3.43 (s, 3H), 3.30 (s, 3H), 2.60 (s, 3H), and 2.32 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.6, 163.1, 162.6, 158.7, 151.2, 149.6, 139.4, 129.7, 129.6, 128.1, 90.3, 85.7, 59.0, 30.0, 29.5, 28.4, 28.2, and 21.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H21N4O6413.14566; found 413.14556.
5-(4-bromophenyl)-1,1′,3,3′-tetramethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3h): white solid (yield: 15.7 mg, 66%). M.P. = 262.0–262.4 °C; 1H NMR (400 MHz, CDCl3): δ 7.47(d, J = 8.48 Hz, 2H), 6.95 (d, J = 8.4 Hz, 2H), 4.88 (s, 1H), 3.51 (s, 3H), 3.42 (s, 3H), 3.29 (s, 3H), and 2.65 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.3, 162.8, 162.8, 158.6, 151.1, 149.5, 132.1, 132.0, 130.0, 123.7, 89.8, 85.3, 58.3, 30.0, 29.6, 28.5, and 28.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H18BrN4O6 477.04028; found 477.04042.
5-(3-chlorophenyl)-1,1′,3,3′-tetramethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3i) [13]: white solid (yield: 15.6 mg, 72%). M.P. = 146.3–146.5 °C; 1H NMR (400 MHz, CDCl3): δ 7.35–7.33 (m, 1H), 7.29–7.26 (m, 1H), 7.06 (t, J = 1.76 Hz, 1H), 6.97 (d, J =7.56 Hz, 1H), 4.88 (s, 1H), 3.52 (s, 3H), 3.42 (s, 3H), 3.30 (s, 3H), and 2.67 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.2, 163.0, 162.7, 158.5, 151.1, 149.4, 135.1, 135.0, 130.1, 129.6, 128.4, 126.5, 89.9, 85.2, 58.3, 30.0, 29.6, 28.5, and 28.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H18ClN4O6 433.09106; found 433.09094.
1,1′,3,3′-tetramethyl-5-(4-(naphthalen-2-yl)phenyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3j): white solid (yield: 17.5 mg, 78%). M.P. = 149.8–150.1 °C; 1H NMR (400 MHz, CDCl3): δ 7.82–7.78 (m, 3H), 7.57 (d, J = 0.68 Hz, 1H), 7.51–7.49 (m, 2H), 7.14 (q, 1H), 5.11 (s, 1H), 3.56 (s, 3H), 3.46 (s, 3H), 3.33 (s, 3H), and 2.35 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 163.0, 162.7, 158.7, 151.3, 149.6, 133.5, 133.0, 130.2, 128.8, 128.1, 128.0, 127.7, 127.0, 126.8, 125.1, 90.3, 85.7, 59.3, 30.0, 29.6, 28.4, and 28.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21N4O6 449.14536; found 449.14556.
1,1′,3,3′-tetramethyl-5-(4-(trifluoromethyl)phenyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3k): white solid (yield: 18.6 mg, 80%). M.P. = 249.6–249.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.61(d, J = 5.36 Hz, 2H), 7.23 (d, J = 5.36 Hz, 2H), 4.98 (s, 1H), 3.54 (s, 3H), 3.45 (s, 3H), 3.31 (s, 3H), and 2.59 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.1, 162.9, 162.6, 158.6, 151.1, 149.4, 137.0, 131.8, 131.6, 128.9, 125.9, 125.9, 124.5, 122.7, 89.7, 85.1, 58.4, 30.0, 29.6, 28.4, and 28.2 ppm; 19F NMR (376 MHz, CDCl3): δ −62.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H18F3N4O6 467.11768; found 467.11730.
5-(4-methoxyphenyl)-1,1′,3,3′-tetramethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3l) [13]: white solid (yield: 10.3 mg, 48%). M.P. = 137.3–137.6 °C; 1H NMR (400 MHz, CDCl3): δ 6.96 (d, J = 5.64 Hz, 2H), 6.82 (d, J = 5.76 Hz, 2H), 4.87 (s, 1H), 3.76 (s, 3H), 3.49 (s, 3H), 3.39 (s, 3H), 3.27 (s, 3H), and 2.61 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.6, 163.1, 162.6, 160.4, 158.7, 151.2, 149.7, 129.4, 124.6, 114.3, 90.3, 85.7, 58.8, 55.4, 29.9, 29.5, 28.5, and 28.2, ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H21N4O7 429.14038; found 429.14048.
1,1′,3,3′-tetramethyl-5-(4-nitrophenyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3m) [13]: white solid (yield: 13.7 mg, 62%). M.P. = 299.5–299.7 °C; 1H NMR (400 MHz, DMSO): δ 8.16 (d, J = 5.36 Hz, 2H), 7.52 (d, J = 5.44 Hz, 2H), 5.36 (s, 1H), 3.42 (s, 3H), 3.23 (s, 3H), 3.13 (s, 3H), and 2.51 (s, 3H) ppm; 13C NMR (100 MHz, DMSO): δ 165.6, 163.3, 163.2, 158.6, 151.3, 150.4, 148.0, 142.9, 130.8, 123.5, 90.0, 85.8, 55.0, 30.3, 29.6, 28.3, and 28.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H18N5O8 444.11469; found 444.11499.
5-(2-bromophenyl)-1,1′,3,3′-tetramethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3n): white solid (yield: 15.7 mg, 66%). M.P. = 254.4–254.8 °C; 1H NMR (400 MHz, CDCl3): δ 7.57 (d, J = 5.32 HZ, 1H), 7.33 (t, J = 5.04 HZ,1H), 7.22–7.16 (m, 2H), 5.58 (s, 1H), 3.52 (s, 3H), 3.40 (s, 3H), 3.32 (s, 3H), and 2.71 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.1, 163.1, 162.7, 158.4, 151.2, 149.5, 132.9, 132.4, 131.0, 130.8, 128.0, 124.4, 88.8, 86.1, 56.8, 30.0, 29.5, 28.5, and 28.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H18BrN4O6 477.04086; found 477.04042.
1,1′,3,3′-tetramethyl-5-(m-tolyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3o): white solid (yield: 18.5 mg, 90%). M.P. = 135.7–135.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.25–7.15 (m, 2H), 6.86 (d, J = 6.32 Hz, 2H), 4.89 (s, 1H), 3.54 (s, 3H), 3.44 (s, 3H), 3.32 (s, 3H), 2.58 (s, 3H), and 2.32 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 163.0, 162.6, 158.6, 151.2, 149.6, 138.8, 132.7, 130.2, 128.8, 128.8, 125.3, 90.4, 85.6, 59.3, 30.0, 29.7, 29.5, 28.4, 28.2, and 21.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H21N4O6 413.14529; found 413.14556.
1,1′,3,3′-tetraethyl-5-(p-tolyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3p) [13]: white solid (yield: 19.2 mg, 82%). M.P. = 134.9–135.2 °C; 1H NMR (400 MHz, CDCl3): δ 7.12 (d, J = 5.08 Hz, 2H), 6.97 (d, J = 5.08 Hz, 2H), 4.85 (s, 1H), 4.12–3.94 (m, 6H), 3.36 (q, J = 4.40 Hz, 1H), 3.10 (q, J = 4.40 Hz, 1H), 2.31 (s, 3H), 1.43 (t, J = 4.72 Hz, 3H), 1.34 (t, J = 4.72 Hz, 3H), 1.20 (t, J = 4.64 Hz, 3H), and 0.69 (t, J = 4.72 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 162.8, 162.3, 158.4, 150.4, 148.9, 139.4, 129.8, 129.6, 128.4, 89.7, 86.1, 58.9, 39.0, 38.2, 37.9, 36.7, 29.7, 21.1, 13.8, 13.3, 13.1, and 12.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H29N4O6 469.20752; found 469.20816.
5-(4-bromophenyl)-1,1′,3,3′-tetraethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3q): white solid (yield: 25.3 mg, 95%). M.P. = 150.1–150.2 °C; 1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 8.48 Hz, 2H), 6.97 (d, J = 8.40 Hz, 2H), 4.82 (s, 1H), 4.12–3.91 (m, 6H), 3.42 (q, J = 7.08 Hz, 1H), 3.16 (q, J = 7.12 Hz, 1H), 1.42 (t, J = 7.12 Hz, 3H), 1.33 (t, J = 7.04 Hz, 3H), 1.19 (t, J = 7.04 Hz, 3H), and 0.73 (t, J = 7.12 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.2, 162.5, 158.3, 150.3, 148.8, 132.1, 132.0, 130.2, 123.7, 89.2, 85.7, 58.3, 39.1, 38.3, 38.0, 36.8, 13.8, 13.3, 13.0, and 12.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H26BrN4O6 533.10266; found 533.10302.
5-(3-chlorophenyl)-1,1′,3,3′-tetraethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3r): white solid (yield: 22.7 mg, 93%). M.P. = 179.6–179.8 °C; 1H NMR (400 MHz, CDCl3): δ 7.34–7.25 (m, 2H), 7.08 (t, J = 1.72 Hz, 1H), 7.00 (d, J = 7.52 Hz, 1H), 4.84 (s, 1H), 4.14–3.94 (m, 6H), 3.44 (q, J = 7.08 Hz, 1H), 3.20 (q, J = 7.12 Hz, 1H), 1.44 (t, J = 7.12 Hz, 3H), 1.35 (t, J = 7.04 Hz, 3H), 1.21 (t, J = 7.04 Hz, 3H), and 0.73 (t, J = 7.12 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.2, 162.6, 162.4, 158.3, 150.3, 148.8, 135.1, 135.0, 130.2, 129.6, 128.8, 126.8, 89.3, 85.6, 58.4, 39.1, 38.3, 38.0, 36.8, 13.8, 13.3, 13.0, and 12.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H26ClN4O6 489.15314; found 489.15354.
1,1′,3,3′-tetraethyl-5-(4-(naphthalen-2-yl)phenyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3s): white solid (yield: 20.2 mg, 80%). M.P. = 189.5–189.7 °C; 1H NMR (400 MHz, CDCl3): δ 7.82–7.77 (m, 3H), 7.58 (s, 1H), 7.52–7.47 (m, 2H), 7.18 (dd, J = 8.44, 1.60 Hz, 1H), 5.08 (s, 1H), 4.18–3.95 (m, 6H), 3.15 (q, J = 7.08 Hz, 1H), 2.91 (q, J = 7.04 Hz, 1H), 1.47 (t, J = 7.08 Hz, 3H), 1.40 (t, J = 7.08 Hz, 3H), 1.22 (t, J = 7.04 Hz, 3H), and 0.40 (t, J = 7.04 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 162.8, 162.5, 158.5, 150.5, 148.9, 133.6, 133.1, 130.3, 128.8, 128.3, 128.0, 127.6, 126.8, 126.7, 125.4, 89.7, 86.1, 59.3, 39.1, 38.3, 37.8, 36.8, 13.8, 13.3, 13.1, and 12.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H29N4O6 505.20953; found 505.20816.
1,1′,3,3′-tetraethyl-5-(4-methoxyphenyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3t): white solid (yield: 15.7 mg, 65%). M.P. = 119.2–119.6 °C; 1H NMR (400 MHz, (CD3)2CO): δ 7.11 (d, J = 5.68 Hz, 2H), 6.87 (d, J = 5.84 Hz, 2H), 4.94 (s, 1H), 4.06–3.86 (m, 6H), 3.79 (s, 3H), 3.39 (q, J = 4.28 Hz, 1H), 3.09 (q, J = 4.24 Hz, 1H), 1.38 (t, J = 4.72 Hz, 3H), 1.31 (t, J = 1.76 Hz, 3H), 1.12 (t, J = 4.68 Hz, 3H), and 0.71 (t, J = 4.72 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 162.9, 162.2, 160.4, 158.4, 150.4, 148.9, 129.7, 124.7, 114.3, 89.8, 86.2, 58.6, 55.3, 39.0, 38.2, 37.9, 36.7, 13.8, 13.3, 13.1, and 12.5 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H29N4O7 485.20370; found 485.20308.
1,1′,3,3′-tetraethyl-5-(4-nitrophenyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3u) [13]: yellow solid (yield: 22.5 mg, 90%). M.P. = 207.7–207.8 °C; 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 8.64Hz, 2H), 7.30 (d, J = 8.56 Hz, 2H), 4.94 (s, 1H), 4.12–3.91 (m, 6H), 3.40 (q, J = 6.32 Hz, 1H), 3.13 (q, J = 6.32 Hz, 1H), 1.43 (t, J = 7.12 Hz, 3H), 1.35 (t, J = 7.04 Hz, 3H), 1.19 (t, J = 6.96 Hz, 3H), and 0.68 (t, J = 7.04 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 164.9, 162.8, 162.2, 158.3, 150.2, 148.5, 148.4, 140.3, 129.9, 123.9, 88.8, 85.5, 57.8, 39.2, 38.5, 38.0, 36.8, 13.8, 13.3, 13.0, and 12.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H26N5O8 500.17752; found 500.17759.
5-(2-bromophenyl)-1,1′,3,3′-tetraethyl-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3v): white solid (yield: 14.9 mg, 56%). M.P. = 164.8–164.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 7.64 Hz, 1H), 7.34–7.28 (m, 1H), 7.18 (d, J = 6.92 Hz, 2H), 5.52 (s, 1H), 4.08–3.93 (m, 6H), 3.58 (q, J = 6.32 Hz, 1H), 3.26 (q, J = 6.32 Hz, 1H), 1.42 (t, J =7.00 Hz, 3H), 1.33 (t, J = 7.16 Hz, 3H), 1.21 (t, J = 7.00 Hz, 3H), and 0.73 (t, J = 7.08 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.2, 162.6, 162.4, 158.2, 150.4, 148.9, 132.8, 132.8, 131.5, 130.6, 127.9, 124.8, 88.1, 86.8, 56.3, 39.1, 38.6, 37.9, 36.8, 13.8, 13.1, and 12.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H26BrN4O6 533.10181; found 533.10302.
1,1′,3,3′-tetraethyl-5-(m-tolyl)-1,5-dihydro-2H,2′H-spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]-2,2′,4,4′,6′(1′H,3H,3′H)-pentaone (3w): white solid (yield: 17.1 mg, 73%). M.P. = 169.3–169.6 °C; 1H NMR (400 MHz, CDCl3): δ 7.22–7.12 (m, 2H), 6.88 (d, J = 6.80 Hz, 2H), 4.84 (s, 1H), 4.11–3.93 (m, 6H), 3.34 (q, J = 6.44 Hz, 1H), 3.09 (q, J = 6.40 Hz, 1H), 2.30 (s, 3H), 1.43 (t, J = 7.08 Hz, 3H), 1.35 (t, J = 7.00 Hz, 3H), 1.20 (t, J = 6.96 Hz, 3H), and 0.68 (t, J = 7.04 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.5, 162.8, 162.4, 158.4, 150.4, 148.9, 138.6, 132.7, 130.2, 129.2, 128.8, 125.6, 89.8, 86.0, 59.1, 39.1, 38.2, 37.9, 36.7, 21.3, 13.8, 13.3, 13.1, and 12.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H29N4O6 469.20792; found 469.20816.

4. Conclusions

Conclusively, under the catalysis of Rh2(esp)2 and (±)-BINAP in DCE at 80 °C, the cascade assembly between diazobarbiturates and alkylidene pyrazolones proceeds readily and delivers the spirofuropyrimidines in reasonable chemical yields. Moreover, the design and exploration of the other cascade assemblies of α-diazocarbonyl metal carbenoids are ongoing in our organic lab and will be reported in due course.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules29133178/s1, NMR spectral copies of products 3. X-ray crystal data of product 3a.

Author Contributions

Funding acquisition, project administration, supervision, and writing—original draft preparation, H.-W.Z.; investigation, methodology, formal analysis, data curation, and writing—review and editing, Y.Z.; investigation and methodology, Y.-H.M. and K.W. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Beijing Municipal Commission of Education (No. JC015001200902), Beijing Municipal Natural Science Foundation (No. 7102010, No. 2122008, No. 2172003, No. 2222002), Basic Research Foundation of Beijing University of Technology (X4015001201101), Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality (No. PHR201008025), and Doctoral Scientific Research Start-up Foundation of Beijing University of Technology (No. 52015001200701) for financial supports.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study are included in the article.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 29 03178 sch001
Scheme 1. Representative synthetic methodologies of α-carbonyl metal carbenoids.
Scheme 1. Representative synthetic methodologies of α-carbonyl metal carbenoids.
Molecules 29 03178 sch001
Molecules 29 03178 g001
Figure 1. X-ray single crystal structure of 3a (with thermal ellipsoids shown at the 50% probability level).
Figure 1. X-ray single crystal structure of 3a (with thermal ellipsoids shown at the 50% probability level).
Molecules 29 03178 g001
Molecules 29 03178 sch002
Scheme 2. Proposed mechanism for the formation of product 3a.
Scheme 2. Proposed mechanism for the formation of product 3a.
Molecules 29 03178 sch002
Table 1. Screening of 1a/2a ratios and transition metal catalysts [a].
Table 1. Screening of 1a/2a ratios and transition metal catalysts [a].
Molecules 29 03178 i001
Entry[M] [f]Time (h)Yield [b] (%)
1 [c]Rh2(OAc)4640
2 [d]Rh2(OAc)4665
3Rh2(OAc)4675
4Ph3PAuCl6NR [e]
5(CH3CN)4·CuBF46NR [e]
6DPPE·NiCl28NR [e]
7DPPE·PdCl28NR [e]
8Pd(DPPE)28NR [e]
9Pd2(dba)36trace
10(F3CSO2)NAg6trace
11Ru(OAc)3621
12[Rh(COD)2]BF46NR [e]
13[Rh3O(OAc)6(H2O)3]OAc6NR [e]
14Rh2(esp)2693
15 [g]Rh2(esp)2625
16 [h]Rh2(esp)2616
17 [i]Rh2(esp)26trace
18 [j]Rh2(esp)26NR [e]
[a] reactions were carried out with 1a (0.1 mmol), 2a (0.15 mmol), catalyst (10 mol%, 0.01 mmol), and (±)-L1 (20 mol%, 0.02 mmol) in 1,2-DCE (1.5 mL) at 80 °C. [b] isolated yield. [c] 1a/2a = 0.15 mmol/0.1 mmol. [d] 1a/2a = 0.1 mmol/0.1 mmol. [e] no reaction. [f] Rh2(OAc)4: Bis[rhodium(α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid); Ph3PAuCl: Chloro(triphenylphosphine)gold; (CH3CN)4·CuBF4: Tetrakis(acetonitrile)copper(I) tetrafluoroborate; DPPE·NiCl2: 1,2-Bis(diphenylphosphino)ethane nickel(II) chloride; DPPE·PdCl2: [1,2-Bis(diphenylphosphino)ethane]dichloropalladium(II); Pd(DPPE)2: Bis[1,2-bis(diphenylphosphino)ethane]palladium(0); Pd2(dba)3: Tris(dibenzylideneacetone)dipalladium; (F3CSO2)NAg: Sliver bis(trifluoromethane sulfonimide); Ru(OAc)3: Ruthenium acetate; [Rh(COD)2]BF4: Bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; [Rh3O(OAc)6(H2O)3]OAc: Rhodium acetate; Rh2(esp)2: Bis[rhodium(α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid). [g] 20 mol% Rh2(esp)2 and 40 mol% (±)-L1. [h] 5 mol% Rh2(esp)2 and 10 mol% (±)-L1. [i] 2.5 mol% Rh2(esp)2 and 5 mol% (±)-L1. [j] 1.25 mol% Rh2(esp)2 and 2.5 mol% (±)-L1.
Table 2. Screening of ligands and solvents [a].
Table 2. Screening of ligands and solvents [a].
Molecules 29 03178 i002
EntryLigandSolventTime (h)Yield [b] (%)ee [d] (%)
1-1,2-DCE6trace-
2(±)-L21,2-DCE6NR [c]-
3(±)-L31,2-DCE645-
4(±)-L41,2-DCE667-
5dppf1,2-DCE668-
6dppb1,2-DCE677-
7(±)-L51,2-DCE882-
8(±)-L11,2-DCE693-
9(±)-L1PhCF36NR [c]-
10(±)-L1HFIP6NR [c]-
11(±)-L1C6F66NR [c]-
12(±)-L1CHCl36NR [c]-
13(S)-L21,2-DCE6450
14(R, R)-L31,2-DCE6670
15(R)-L51,2-DCE6930
[a] reactions were carried out with 1a (0.1 mmol), 2a (0.15 mmol), Rh2(esp)2 (10 mol%, 0.01 mmol), and ligand (20 mol%, 0.02 mmol) in solvent (1.5 mL) at 80 °C. [b] isolated yield. [c] no reaction. [d] Determined by chiral HPLC analysis.
Table 3. Substrate scope [a].
Table 3. Substrate scope [a].
Molecules 29 03178 i003
Entry1 (R1, R2)2 (R3, R4, R5)3Time (h)Yield [b] (%)
11a (Me, Me)2a (Ph, Ph, Me)3a693
21a (Me, Me)2b (Ph, Me, Me)3a686
31a (Me, Me)2c (Ph, Me, H)3a696
41a (Me, Me)2d (Ph, Ph, Ph)3a657
51a (Me, Me)2e (Me, Ph, Me)3b638
61a (Me, Me)2f (Priso, Ph, Me)-6NR [c]
71a (Me, Me)2g Molecules 29 03178 i004-6NR [c]
81a (Me, Me)2h (2-thiophenyl, Ph, Me)-6NR [c]
91a (Me, Me)2i (5-benzofuranyl, Ph, Me)3c656
101b (cyclohexyl, cyclohexyl)2c (Ph, Me, H)-6NR [c]
111c (Bn, Bn)2c (Ph, Me, H)3d688
121d (Et, Et)2c (Ph, Me, H)3e691
131e (Priso, Priso)2c (Ph, Me, H)3f647
141f (Butert, Butert)2c (Ph, Me, H)-6NR [c]
151g (4-MeC6H4, 4-MeC6H4)2c (Ph, Me, H)-6NR [c]
161a (Me, Me)2j (4-MeC6H4, Ph, Me)3g368
171a (Me, Me)2k (4-BrC6H4, Ph, Me)3h366
181a (Me, Me)2l (3-ClC6H4, Ph, Me)3i372
191a (Me, Me)2m (2-naphthyl, Ph, Me)3j678
201a (Me, Me)2n (4- F3CC6H4, Ph, Me)3k680
211a (Me, Me)2o (4-MeOC6H4, Ph, Me)3l348
221a (Me, Me)2p (4-O2NC6H4, Ph, Me)3m662
231a (Me, Me)2q (2-BrC6H4, Ph, Me)3n666
241a (Me, Me)2r (3-MeC6H4, Ph, Me)3o690
251d (Et, Et)2j (4-MeC6H4, Ph, Me)3p682
261d (Et, Et)2k (4-BrC6H4, Ph, Me)3q695
271d (Et, Et)2l (3-ClC6H4, Ph, Me)3r693
281d (Et, Et)2m (2-naphthyl, Ph, Me)3s680
291d (Et, Et)2o (4-MeOC6H4, Ph, Me)3t665
301d (Et, Et)2p (4-O2NC6H4, Ph, Me)3u690
311d (Et, Et)2q (2-BrC6H4, Ph, Me)3v663
321d (Et, Et)2r (3-MeC6H4, Ph, Me)3w673
331h (Me,Bn)2a (Ph, Ph, Me)-6NR [c]
341h (Me, Bn)2c (Ph, Me, H)-6NR [c]
[a] reactions were carried out with 1a (0.1 mmol), 2a (0.15 mmol), Rh2(esp)2 (10 mol%,0.01 mmol), and (±)-L1(20 mol%, 0.02 mmol) in 1,2-DCE (1.5 mL) at 80 °C. [b] isolated chemical yield. [c] no reaction.
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Zhang, Y.; Mi, Y.-H.; Wang, K.; Zhao, H.-W. α-Carbonyl Rh-Carbenoid Initiated Cascade Assembly of Diazobarbiturates with Alkylidene Pyrazolones for Synthesis of Spirofuropyrimidines. Molecules 2024, 29, 3178. https://doi.org/10.3390/molecules29133178

AMA Style

Zhang Y, Mi Y-H, Wang K, Zhao H-W. α-Carbonyl Rh-Carbenoid Initiated Cascade Assembly of Diazobarbiturates with Alkylidene Pyrazolones for Synthesis of Spirofuropyrimidines. Molecules. 2024; 29(13):3178. https://doi.org/10.3390/molecules29133178

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Zhang, Yue, Yu-Hang Mi, Kuo Wang, and Hong-Wu Zhao. 2024. "α-Carbonyl Rh-Carbenoid Initiated Cascade Assembly of Diazobarbiturates with Alkylidene Pyrazolones for Synthesis of Spirofuropyrimidines" Molecules 29, no. 13: 3178. https://doi.org/10.3390/molecules29133178

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