Scientific Publications

Gold(I)-catalyzed coupling reactions for the synthesis of diverse small molecules using the build/couple/pair strategy.

Publication TypeJournal Article
AuthorsLuo, T., and Schreiber SL
AbstractThe build/couple/pair strategy has yielded small molecules with stereochemical and skeletal diversity by using short reaction sequences. Subsequent screening has shown that these compounds can achieve biological tasks considered challenging if not impossible ('undruggable') for small molecules. We have developed gold(I)-catalyzed cascade reactions of easily prepared propargyl propiolates as a means to achieve effective intermolecular coupling reactions for this strategy. Sequential alkyne activation of propargyl propiolates by a cationic gold(I) catalyst yields an oxocarbenium ion that we previously showed is trapped by C-based nucleophiles at an extrannular site to yield alpha-pyrones. Here, we report O-based nucleophiles react by ring opening to afford a novel polyfunctional product. In addition, by coupling suitable building blocks, we subsequently performed intramolecular pairing reactions that yield diverse and complex skeletons. These pairing reactions include one based on a novel aza-Wittig-6pi-electrocyclization sequence and others based on ring-closing metathesis reactions.
Year of Publication2009
JournalJournal of the American Chemical Society
Volume131
Issue15
Pages5667-74
Date Published (YYYY/MM/DD)2009/04/22
ISSN Number0002-7863
DOI10.1021/ja900414s
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/19331418?dopt=Abstract