Asymmetric Allylic Alkylation with Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung Strategy

Abstract

An atom‐economic and highly efficient vinylogous umpolung strategy is developed for deconjugated carbonyl compounds, which generate electron‐deficient π‐allylpalladium complexes with Pd(OAc)2 under ligand‐free conditions. In cooperation with a chiral‐phosphonium‐based phase‐transfer catalyst, the asymmetric direct oxidative allylic alkylations of 3‐substituted oxindoles are furnished under O2 atmosphere. The γ‐ or even remote ϵ‐regioselective alkylation products, with substantial substituents, are delivered with excellent enantioselectivity, and can be further used to access diverse chiral spirocyclic architectures effectively. The Mukaiyama dienol silyl ether can be utilized similarly, indicating that the current active π‐allylpalladium species results from tautomerization of the PdII‐dienolate intermediate.

B(C6F5)3/Chiral Phosphoric Acid Catalyzed Ketimine–Ene Reaction of 2‐Aryl‐3H‐indol‐3‐ones and α‐Methylstyrenes

“…However, methods for the catalytic asymmetric construction of chiral 2‐allyl‐substituted indolin‐3‐one derivatives are still underdeveloped. Current strategies include chiral phase‐transfer‐catalyzed alkylation, Pd‐mediated alkylation, and electrophilic vinylogous reactions . The reported cases suffered from low enantioselectivity, narrow substrate scope, and harsh reaction conditions.…”

Lewis acid-catalyzed asymmetric reactions of β,γ-unsaturated 2-acyl imidazoles

“…T he exploration of reaction diversity from β,γ-unsaturated carbonyl compounds is interesting and of great synthetic value. These compounds and their analogs bearing one potential enolization have been demonstrated as highly active nucleophiles in a number of catalytic asymmetric reactions for the synthesis of natural products and bioactive compounds [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] . Especially, γ-addition as dienolate pronucleophiles with either metal catalysis [17][18][19][20][21][22][23][24][25][26][27][28] or organocatalysis [29][30][31][32][33][34][35][36] has been widely documented during the past several years, and the maintained πconjugation of γ-addition process leading to thermodynamically stable conjugated products (Fig.…”

“…1 = H, R = Ph, 12 h, 95% yield, >19:1 dr, 91% ee 4b, R 1 = 5-Cl, R = Ph, 5 h, 87% yield, >19:1 dr, 90% ee 4c, R 1 = 5-I, R = Ph, 6 h, 90% yield, >19:1 dr, 90% ee 4d, R 1 = 5-Me, R = Ph, 12 h, 75% yield, >19:1 dr, 90% ee 4e, R 1 = 6-Cl, R = Ph,16 h, 88% yield, >19:1 dr, 90% ee 4f, R 1 = 6-F, R = Ph, 24 h, 98% yield, 19:1 dr, 88% ee 4g, R 1 = 7-Br, R = Ph, 16 h, 95% yield, 19:1 dr, 88% ee 4h, R 1 = H, R = 2-naphthyl, 36 h, 99% yield, 19:1 dr, Pi t Bu, 3 Å M.S., CH 2 ClCHCl 2 , 0 °C 4i, R = Ph, 8 h, 94% yield, >19:1 dr, 99% ee 4j, R = 4-BrC 6 H 4 , 12 h, 98% yield, 14:1 dr, 98% ee 4k, R = 3-MeC 6 H 4 , 10 h, 99% yield, 16:1 dr, 96% ee 4l, R = 3-MeOC 6 H 4 , 8 h, 97% yield, >19:1 dr, 98% ee 4m, R = 2-MeC 6 H 4 , 10 h, 98% yield, >19:1 dr, 98% ee 4n, R = 3-thienyl, 8 h, 99% yield, >19:1 dr, 98% ee 4o[a] , R = Bn, 10 h, 96% yield, 13:1 dr, 85% ee 4p[a] , R = propyl, 4 h, 97% yield, 10:1 dr, 52% ee L = L 3 -RaPr 2 , CHCl 3 , 0 °C = Ph, R 2 = Ph, 10 h, 73% yield, >19:1 dr, 98% ee 4s, R = Ph, R 2 = 4-ClC 6 H 4 , h, 77% yield, >19:1 dr, 97% ee 4t , R = Ph, R 2 = 3-MeC 6 H 4 , 10 h, 70% yield, >19:1 dr, 98% ee 4u, R = Ph, R 2 = 3-BrC 6 H 4 , 8 h, 57% yield, >19:1 dr, 95% ee 4v, R = Ph, R 2 = 2-MeC6H4, 8 h, 55% yield, >19:1 dr, 97% ee 4w, R = 2-MeC 6 H 4 , R 2 = Ph, 8 h, 67% yield, >19:1 dr, 96% ee 4x, R = 3-MeOC 6 H 4 , R 2 = Ph, 8 h, 62% yield, >19:1 dr, 98% ee 4y, R = 4-BrC 6 H 4 , R 2 = Ph, 8 h, 72% yield, >19:1 dr, 97% ee L = L3-RaPr2, CH 2 ClCHCl 2 , 4 Å M.S.,35 °C …”

Asymmetric Allylic Alkylation with Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung Strategy

“…Outstanding enantiocontrol was attained for other 3-aryl-substituted oxindoles (entries [7][8][9]. Notably,a n oxindole bearing a1 -pyrrolyl group could be successfully applied (entry 10), and outstanding ee values were generally afforded by introducing various benzyl (entries [11][12][13] or [b] ee [%] [c] 1 [d] -K OAc Toluene 8--2 [d] TBAB KOAc Toluene 87 9-3 [d,e] TBAB KOAc Toluene 81 [b] ee [%] [c] 1H [e] The absolutec onfiguration of chiral 3n was determined by X-ray analysis of its derivative 12' ' (see the SupportingInformation). [11] The other products were assigned by analogy.…”

“…As pirocyclico xindole 11 bearing ap iperidine unit was produced smoothly from the product 3n through BF 3 ·Et 2 Omediated aza-Michael addition. Interestingly,t he spiro-pyrrolidine-quinoline skeleton 12 (the N-Boc deprotected derivative 12' ' was confirmed by X-ray analysis) [11] was constructed in am odest yield with retained enantioselectivity by transamidation/aza-Michael addition using tBuOK. [12] To elucidate the catalytic mechanism, more reactions were conducted.…”