Facile, Asymmetric Addition of Acetylene to Aldehydes:In Situ Generation of Reactive Zinc Acetylide

Abstract

This study documents a process in which acetylene is employed directly in nucleophilic additions to aldehydes to give adducts in high levels of enantiomeric induction, up to 98% ee. To the best of our knowledge, this represents the first time in which acetylene itself has been utilized in such ligand-controlled enantioselective additions.

The Enantioselective Addition of Alkyne Nucleophiles to Carbonyl Groups

“…xlviii,xlix,l Excellent yields and enantioselectivities were observed for aliphatic aldehydes with broad tolerance of alkyne substitution including acetylene gas ( 57b ). li Aromatic and unsaturated aldehydes ( 57c and 57d ) were alkynylated in lower yield due to a competitive Cannizzaro disproportionation reaction. The robust reaction was shown to perform well without purfication of reagents and in reagent-grade toluene containing up to 300 ppm water.…”

Addition of Terminal Acetylides to CO and CN Electrophiles

“…Also noteworthy are the addition reactions involving functionalized alkynes that not only furnish products that can be employed as versatile building blocks, but also illustrate the mildness of the metalation reaction, which is compatible with functionality (Equation 3.26). In subsequent work, ethyne itself has been shown to participate in the addition reactions, giving products with high enantioselectivity, but at the current level of development the process can be slow (Equation 3.27) [55]. As an alternative to ethyne, 2-methyl-3-butyn-2-ol (42) can be employed (Equation 3.28); the acetone protecting group on the acetylene can subsequently be conveniently removed (Equation 3.29) [56].…”

Density functional computations of alkynylation of ethanimine catalyzed by chiral zinc(II)‐complexes

“…The enantioselective formation of the CC bonds has attracted much attention of the scientists 1–19. The enantioselective addition of terminal alkynes to aldehydes 7–18, ketones 19, or imines 2, 10 directly affords to optically active propargyl alcohols or amines that are useful and versatile building blocks that enjoy wide application in chemical synthesis. The chiral zinc(II) complexes are the active catalysts used to induce high stereoselectivity for these reactions 7–19.…”