Conjugate Alkynylation of Electrophilic Double Bonds. From Regioselectivity to Enantioselectivity

Abstract

This review surveys the historical efforts addressed toward the development of the conjugate alkynylation reaction. The regio- and enantioselective conjugate alkynylation of electron-deficient double bonds, most commonly unsaturated carbonyl compounds, has been an elusive reaction for a long time. Intensive research during the last decades has resulted in the identification of a number of effective reagents and catalysts to perform this reaction. Non-stereoselective conjugate alkynylation of unsaturated carbonyl compounds was first achieved by using preformed alkynyl organometallics and later with terminal alkynes under catalytic conditions. These methods paved the way for the development of enantioselective procedures. After initial methods requiring stoichiometric amounts of chiral material, the findings by Corey on Ni-catalyzed addition of alkynylalanes and, particularly, by Carreira on Cu-catalyzed addition of terminal alkynes boosted the research on the development other asymmetric procedures catalyzed by Cu, Zn, Rh, Co, Ru and Pd complexes. The alkynylation of electrophilic alkenes conjugated with groups other than carbonyl and the alkynylation of extended conjugated systems are also discussed in the last part of this review.1 Introduction2 Non-Stereoselective Conjugate Alkynylation of α,β-Unsaturated Carbonyl Compounds3 Enantioselective Conjugate Alkynylation of α,β-Unsaturated Carbonyl Compounds4 Non-Stereoselective and Enantioselective Alkynylation of Other Electrophilic Alkenes5 γ-Alkynylation of α,β-Unsaturated Amides and δ-Alkynylation of Electrophilic Dienes6 Alternative Enantioselective Procedures7 Conclusion and Outlook

Coordination Assistance: A Powerful Strategy for Metal-Catalyzed Regio- and Enantioselective Hydroalkynylation of Internal Alkenes

“…Previous developments for asymmetric alkynylation with terminal alkyne were mainly focused on polar substrates such as carbonyls, imines, and α,β-unsaturated carbonyls ( 16 , 19 , and 21 ) (Figure ). , In these methods, the terminal alkyne usually undergoes deprotonation to form a metal alkynylide as the key intermediate . Metal-catalyzed enantioselective hydroalkynylation of conjugated diene ( 24 ) and strained alkene ( 27 ) were also developed .…”

Switchable Enantioselectivity in Conjugate Alkyne Addition of β,γ-Unsaturated α-Keto Esters by Asymmetric Binary Acid Catalysis

“…Conjugated addition of alkynes to α,β-unsaturated carbonyls is of significant synthetic interest . A pioneering work by the group of Carreira has achieved Cu­(II)-catalyzed asymmetric conjugate alkyne addition via an in situ metalation .…”

Iridium-Catalyzed Regioselective Hydroalkynylation of Internal Alkenes Directed by an Oxime

“…Transition-metal-catalyzed hydrofunctionalization of alkenes is a straightforward and atom-economical method to synthesize valuable compounds from simple, cheap, and abundant starting materials . In particular, catalytic hydroalkynylation of alkenes is especially suited for the construction of C­(sp 3 )–C­(sp) bonds from alkenes and alkynes. , The synthetic utility of the hydroalkynylation process is manifested by the diverse transformations of the resulting alkynyl group, enabling access to an array of functionalized molecules . Carreira, Hayashi, and others have explored the catalytic conjugate addition of terminal alkynes to α,β-unsaturated compounds .…”