Organocatalyzed Isomerization of α‐Substituted Alkynoates into Trisubstituted Allenoates by Dynamic Kinetic Resolution

Abstract

The left hand claps the right: Highly enantioselective isomerization of racemic α‐substituted alkynoates into nonracemic trisubstituted allenoates was achieved through the catalytic dynamic kinetic resolution mediated by bifunctional benzothiadiazine. This reaction proceeded with good conversion and high enantioselectivity to give the desired allenoates in good yields without recovering the significant amounts of starting materials.

Bifunctional Guanidines as Hydrogen-Bond-Donating Catalysts

“…When α-substituted 3-butynoates 15 [37] are similarly treated with the bifunctional catalysts, the corresponding trisubstituted allenoesters 16 would be obtained via 1,3-proton migration [9]. However, such an asymmetric reaction has not been reported yet.…”

“…Therefore, there have been so far many reports on the asymmetric synthesis of optically active allenes [27,28]. Among them, we focused on the base-catalyzed isomerization of alkynylesters into allenoesters from the atom-economical perspective [8,9,[29][30][31]. …”

“…In this chapter, the asymmetric reactions using bifunctional guanidine catalysts as well as the chemical structure and design concept of these catalysts are described [8][9][10][11][12].…”

Direct Synthesis of Chiral Allenoates from the Asymmetric CH Insertion of α‐Diazoesters into Terminal Alkynes

“…Previous reports [3b,c] showed that ligands could accelerate the reaction. [9] Herein, we report the first asymmetric C À H insertion between terminal alkynes and a-diazoesters in the presence of cost-efficient copper(I) salts and chiral guanidinium salts.V arious trisubstituted chiral allenoates were afforded directly in high yield and enantioselectivity under mild reaction conditions.Some experiments were carried out to probe into the reaction mechanism. Path Aw ould involve CÀHi nsertion to form ac hiral organocopper intermediate,w hich could be protonated enantioselectively to give the chiral allenoates.Alternatively,the reaction could proceed by cooperative catalysis.C opper salts could accelerate the formation of an alkynoate precursor (path B), followed by the guanidine catalyst serving as achiral base to facilitate the enantioselective isomerization to the final allenoates (path C).…”

“…[5] They are also found in many natural products [6] and as backbones of chiral ligands in asymmetric catalysis. [8] Nevertheless,t he catalytic asymmetric synthesis of axially chiral allenes,especially starting from prochiral substrates,is still in its infancy.T he asymmetric isomerization of the FG-CH 2 ÀCCm oiety by chiral base catalysts,s uch as guanidines, [9] were among the early examples.R ecently,s ome ingenious asymmetric protocols for the synthesis of chiral allenes,i ncluding the kinetic resolution of racemic allenoates, [10a] functionalization of 1-alkyl allene-1,3-dicarboxylates, [10b] b-hydride elimination of enoltriflates, [10c] carbonylation of propargylic carbonates, [10d] and addition to activated enynes, [10e] were reported by the groups of Gong, Maruoka, Frantz, Ma, and Zhang,respectively. [8] Nevertheless,t he catalytic asymmetric synthesis of axially chiral allenes,especially starting from prochiral substrates,is still in its infancy.T he asymmetric isomerization of the FG-CH 2 ÀCCm oiety by chiral base catalysts,s uch as guanidines, [9] were among the early examples.R ecently,s ome ingenious asymmetric protocols for the synthesis of chiral allenes,i ncluding the kinetic resolution of racemic allenoates, [10a] functionalization of 1-alkyl allene-1,3-dicarboxylates, [10b] b-hydride elimination of enoltriflates, [10c] carbonylation of propargylic carbonates, [10d] and addition to activated enynes, [10e] were reported by the groups of Gong, Maruoka, Frantz, Ma, and Zhang,respectively.…”