Copper-catalysed synthesis of alkylidene 2-pyrrolinone derivatives from the combination of α-keto amides and alkynes

Abstract

A Cu(I)-catalysed addition and cyclisation sequence has been developed for the synthesis of (E)-alkylidene pyrrolinone derivatives. The reactions incorporate simple α-keto amides and alkynes as substrates, and employ a commercially available Cu(I) catalyst. The process tolerates good variation of both starting materials, and delivers the desired pyrrolinones in good yields, with high levels of stereocontrol.Scheme 1 Selected examples of natural products and pharmaceutical compounds containing 2-pyrrolinone derivatives. † Electronic supplementary information (ESI) available. See

Fluorine-Assisted Rearrangement of Geminal Azidofluorides to Imidoyl Fluorides

“…Data for 23s : 19 F NMR (376 MHz, CDCl 3 ): δ 14.9; HRMS (EI) m / z calcd for C 11 H 11 NO 2 [M + OH – F] + , 189.0790; found, 189.0791. Data for 4s : 1 H NMR (400 MHz, CDCl 3 ): δ 8.35–8.33 (m, 2H), 7.64–7.59 (m, 1H), 7.49–7.45 (m, 2H), 7.13 (br s, 1H), 2.89–2.84 (m, 1H), 0.92–0.87 (m, 2H), 0.67–0.64 (m, 2H). Data for 24s : 1 H NMR (400 MHz, CDCl 3 ) 8.15–8.13 (m, 2H), 7.62–7.59 (m, 1H), 7.51–7.47 (m, 2H), 5.15 (tt, J = 8.2, 5.2, 1H), 0.79–0.75 (m, 2H), 0.63–0.58 (m, 2H); 13 C­{ 1 H} NMR (100 MHz, CDCl 3 ): 192.2, 133.8, 133.7, 130.3, 128.8, 86.8, 17.1, 1.9; HRMS (ESI) m / z calcd for C 11 H 12 NO 2 [M + H] + , 190.0868; found, 190.0885.…”

An overview on the copper‐promoted synthesis of five‐membered heterocyclic systems

“…In the case of N-sulfonyl of the α-keto amides, both electron-donating and electronwithdrawing groups at the para position were suitable, and electron-donating groups showed better yields of products (Scheme 14). [70] The synthesis of poly-heterocyclic compounds (53 and 55) was from 2-aminobenzoic acid (54) and/or 2-aminobenzamide (51) and 4-pentynoic acid (52) using copper as a catalyst in ionic liquid media. The optimized reaction conditions include Cu (OAc) 2 ÁH 2 O (5 mol%) as…”

“…[75] A copper(I)-catalyzed domino transformation for the synthesis of γ-butyrolactone derivatives (71) was presented by Zhu. Using alkenes (69), alkylnitriles (70) and water as the starting substrates, a variety of γbutyrolactone derivatives (71) was successfully and selectively generated in the presence of Cu (BF 4 ) 2 Á6H 2 O as catalyst, Bipy as ligand, DBU as base, Ca (OTf) 2 as Lewis acid and DTBP under a nitrogen atmosphere in acetonitrile at 140 C for 3.5 hr, and afterward 1.0 N hydrochloric acid at 80 C for 45 min. In the first attempt, α-methyl styrene substrates bearing both electron-rich and electron-deficient groups including Me, OMe and Cl were used to yield desired γ-butyrolactone derivatives.…”

“…N ‐substituents of the α ‐keto amides including N ‐sulfonyl, N ‐alkyl, 3‐ and 6‐membered N ‐carbocycles, N ‐methylthienyl, N ‐allylic and N ‐aryl were active starting materials in this reaction. In the case of N ‐sulfonyl of the α ‐keto amides, both electron‐donating and electron‐withdrawing groups at the para position were suitable, and electron‐donating groups showed better yields of products (Scheme ) …”

Ring Opening of Triflates Derived from Benzophospholan-3-one Oxides by Aryl Grignard Reagents as a Route to 2-Ethynylphenyl(diaryl)phosphine Oxides

“…Compounds possessing an ethynyl fragment became an attractive pattern in modern organic chemistry . The growing importance of the chemistry of carbon–carbon triple bonds is due to their unique and diverse chemical reactivity and remarkable synthetic potential as they can be used as precursors for many classes of compounds including alkanes, alkenes, aldehydes, and carboxylic acids on both laboratory and industrial scales. , Recently, ethynyl compounds have been intensively explored in catalytic reactions mediated by different metals (gold, copper, palladium, rhodium, and others), providing various cyclic products. Moreover, ethynyl compounds have a wide range of applications in the synthesis of biologically active compounds and have been broadly exploited in drug discovery and development .…”