Phosphine-Catalyzed Dual Umpolung Domino Michael Reaction: Facile Synthesis of Hydroindole- and Hydrobenzofuran-2-Carboxylates

Abstract

A highly atom-economical, chemoselective, and stereoselective Lewis base (LB)-catalyzed dual umpolung domino Michael reaction between cyclohexadienones and alkynyl esters has been developed. PPh3, as a LB catalyst, afforded either the hydroindole-2-carboxylates or hydrobenzofuran-2-carboxylates 3 as a single diastereomer in high yields (up to 89%). An obtained product could be easily transformed to a (S*,S*,R*)-octahydroindole-2-carboxylic acid ((S*,S*,R*)-Oic) analogue.

Metal‐Free Dearomatization: Direct Access to Spiroindol(en)ines in Batch and Continuous‐Flow

“…In an attempt to further enhance the yield we screened different phosphines. With tris(4‐methoxyphenyl)phosphine ( p ‐MeOPh) 3 P under our optimized reaction conditions, the yield increased to 87 % (entry 6) . On the contrary, electron‐rich PBu 3 and PMe 2 Ph afforded very low yields (entries 7–9).…”

“…With tris(4-methoxyphenyl)phosphine (p-MeOPh) 3 Pu nder our optimized reactionc onditions, the yield increased to 87 %( entry 6). [20] On the contrary, electron-rich PBu 3 and PMe 2 Ph afforded very low yields (entries 7-9). More electron deficientP ( p-FC 6 H 4 ) 3 gave only 50 % yield of the desired product 2a (entry 10), whereas (CF 3 Ph) 3 P, P(OPh) 3 and P(p-Tol) 3 totally met with failure (entry [11][12][13].…”

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

“…α-Substituted α,β-unsaturated carbonyl compounds can be readily accessed by the Rauhut-Currier (RC) reaction, also called the vinylogous MBH reaction, through the coupling of two different α,β-unsaturated enones wherein one acts as a latent enolate. 85) As part of our research into the development of enantioselective domino reactions, [41][42][43][44][45][46][47][48][49][50][51][52][86][87][88][89][90] we became interested in designing sequences to address optically active α-methylidene-γ-lactams. We envisioned that the amidation of 28 with 27, followed by the BA-LB-catalyzed carbon-carbon bond-forming reaction of intermediary 29, would result in the generation of α-methylidene-γ-lactams 30 in high yield with high enantiocontrols (Chart 13).…”

“…Based on the pioneering efforts of Cristau 99) (stoichiometric process), Trost 100) (catalytic process for alkynes), Lu 101 (for allenes) and Zhang 102) (enantioselective version), there has been increasing interest in γ-umpolung additions of various nucleophiles to electrondeficient allenes and alkynes. 103) As part of our research into chiral LB catalysis, [41][42][43][44][45][46][47][48][49][50][51][52] we became interested in designing new sequences to approach important structures via nucleophilic attack to the γ-position of allenoates. Before the elimination of the LB catalyst, if the zwitterionic intermediate C would react with electrophiles, the result may be a formal dual umpolung coupling (Chart 18).…”

“…This review article describes our recent research on the development of organocatalyzed domino reactions initiated by enantioselective MBH-type processes. [41][42][43][44][45][46][47][48][49][50][51][52] 41,42) Isoindoline skeletons are standard structures in a variety of natural products and pharmaceuticals, such as nuevamine 53) and pagoclone, 54) as well as their functionalized derivatives. 55) As such, these materials show a range of biological potencies involving anti-leukemic, anxiolytic, anti-tumoral, and potent endothelin A receptor antagonist activities.…”