Asymmetric Synthesis of Highly Substituted β-Lactones by Nucleophile-Catalyzed [2+2] Cycloadditions of Disubstituted Ketenes with Aldehydes


  • We thank Ivory D. Hills for X-ray crystallographic studies. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences: R01-GM57034; National Cancer Institute: training grant CA009112), Merck, and Novartis. Funding for the MIT Department of Chemistry Instrumentation Facility has been furnished in part by NSF CHE-9808061 and NSF DBI-9729592.


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α,α-Disubstituted β-lactones can be obtained by the cycloaddition of the corresponding ketenes with aldehydes (see scheme). For the first time, a chiral PPY derivative, 1, serves as an efficient catalyst for the asymmetric synthesis of β-lactones (PPY=4-pyrrolidin-1-ylpyridine). To date, this is the only catalyst that is effective for enantioselective cycloadditions of disubstituted ketenes with aldehydes.