Subscribe to RSS
DOI: 10.1055/s-0028-1087318
Nickel-Catalyzed Asymmetric Negishi Cross-Couplings
Contributor(s):Mark Lautens, Praew ThansandoteMassachusetts Institute of Technology, Cambridge, USA
Nickel-Catalyzed Asymmetric Cross-Couplings of Racemic Propargylic Halides with Arylzinc Reagents
J. Am. Chem. Soc. 2008, 130: 12645-12647
Publication History
Publication Date:
20 November 2008 (online)
Key words
nickel - Negishi cross-coupling - propargylic halides - arylzinc
Significance
This report summarizes a stereoconvergent synthesis of substituted propargylic compounds by an asymmetric, nickel-catalyzed Negishi cross-coupling with arylethylzinc reagents. A variety of alkyl groups are tolerated and the yields and enantioselectivities are good for a broad scope. This methodology was successfully performed on a gram scale for the rapid synthesis of an intermediate to a potent dihydrofolate reductase inhibitor.
Comment
The methodology is noteworthy since neither arylzinc compounds nor propargylic halides have been shown as suitable coupling partners for Negishi cross-couplings. Since few diarylzinc compounds are commercially available, the authors generated the diarylzinc reagents by coupling diethylzinc with commercially available arylboronic acids.