Stereoselective Conjugate Addition Reactions Using In Situ Metallated Terminal Alkynes and the Development of Novel Chiral P,N-Ligands

• Published in: Bulletin of the Chemical Society of Japan Vol. 80; no. 9; pp. 1635 - 1657
• Main Authors: Fujimori, Shinji, Knöpfel, Thomas F, Zarotti, Pablo, Ichikawa, Takashi, Boyall, Dean, Carreira, Erick M
• Format: Journal Article
• Language: English
• Published: Tokyo The Chemical Society of Japan 15.09.2007; Chemical Society of Japan
• ISSN: 0009-2673; 1348-0634
• DOI: 10.1246/bcsj.80.1635

In this account, new methods for the catalytic and stereoselective conjugate addition of terminal alkynes are described. Our laboratories have disclosed asymmetric addition reactions to aldehydes and imines using a combination of a zinc or copper salt and a terminal alkyne. Under these conditions, terminal alkyne is transformed in situ into an alkynyl metal species. Recently, it was found that these in situ generated alkynyl metal species can undergo conjugate additions to alkylidene malonate-type acceptors. In the zinc(II) triflate-catalyzed system, a highly diastereoselective conjugate addition has been realized using a chiral oxazepene acceptor. Subsequently, alternative conjugate addition protocols have been developed which employ a terminal alkyne, substoichiometric amounts of copper and a highly eletrophilic Meldrum’s acid derived acceptor. This reaction can be made enantioselective using a novel atropisomeric P,N-ligand (PINAP). With this ligand, excellent enantioselectivities can be achieved for the conjugate addition of aromatic alkynes to various Meldrum’s acid derived acceptors.