Sequential Phosphine-Catalyzed [4 + 2] Annulation of β′-Acetoxy Allenoates: Enantioselective Synthesis of 3-Ethynyl-Substituted Tetrahydroquinolines

Abstract

The first enantioselective sequential phosphine-catalyzed (SPC as abbreviation) mode for the formation of tetrahydroquinolines with an ethynyl-substituted all-carbon quaternary stereogenic center is reported. In this SPC process, a novel [4 + 2] annulation process was devised employing α-substituted allenoates as C2 synthons (α–β′, 1,2-dipole) for the first time. 3-Ethynyl-substituted tetrahydroquinolines were readily prepared in good yields and high enantioselectivities.

Construction of CF3-Containing Tetrahydropyrano[3,2-b]indoles through DMAP-Catalyzed [4+1]/[3+3] Domino Sequential Annulation

“…There has been no report on the addition of nucleophiles to the γ position of intermediate B , for there is no empty orbital in the ammonium ion of intermediate B to stabilize the carbon anion in the subsequently generated ammonium ylide (Scheme b) . To overcome the limitations, and on the basis of our group’s previous work in the exploration of novel reaction modes of β′-acetoxy allenoate and sequential annulations in organocatalysis to construct the polycycles, we envisioned that the DMAP (4-dimethylaminopyridine) would provide a π-system and make it a more stable corresponding ylide intermediate through a p-π conjugation between the carbon anion and the aromatic ring of DMAP. Herein, we sought to use o -aminotrifluoroacetophenone derivatives as electron donor–acceptor compounds to realize a DMAP-catalyzed [4+1]/[3+3] domino annulation for the efficient formation of a CF 3 -containing tetrahydropyrano­[3,2- b ]­indole system (Scheme c).…”

Asymmetric Reactions Catalyzed by Chiral Tertiary Phosphines

“…Very recently, Huang's group reported an enantioselective formal [4+2] cycloaddition via sequential phosphine‐catalyzed (SPC) mode for the formation of tetrahydroquinolines. [ 86 ] A range of 3‐ethynyl‐substituted tetrahydroquinolines 263 were readily prepared in good yields and high enantioselectivities in the catalysis of chiral phosphine 89 (Scheme 69). In this SPC process, a formal…”

Theoretical investigation on the mechanism and enantioselectivity of organocatalytic asymmetric Povarov reactions of anilines and aldehydes

“…Zhu has obtained functionalized THQ derivatives containing an ethynyl‐substituted all‐carbon quaternary center using phosphine sequentially catalyzed domino 1,6‐addition/annulation process with 97% yield and 20:1 dr. value [15]. Zhang has realized the first enantioselective mode of phosphine‐catalyzed [4 + 2] annulation with β′‐acetoxy allenoates [16]. Wang has reported the diastereoselective construction of cyclopropane‐fused THQ via sequential [4 + 2]/[2 + 1] annulation of α‐aryl vinylsulfoniums [17].…”

“…catalyzed [4 + 2] annulation with β 0 -acetoxy allenoates [16]. Wang has reported the diastereoselective construction of cyclopropane-fused THQ via sequential [4 + 2]/ [2 + 1] annulation of α-aryl vinylsulfoniums [17].…”