Convergent and stereospecific synthesis of complex skipped polyenes and polyunsaturated fatty acids.
Skipped polyenes (that is, 1,4-dienes and higher homologues) are stereodefined components of a vast array of biologically important natural products, including polyunsaturated fatty acids. Although widespread in nature, these architectures are generally considered to represent significant barriers to efficient chemical synthesis. Partial reduction of skipped poly-ynes provides a pathway to a subset of such structures, but general chemical methods for the preparation of skipped polyenes that contain varied stereochemistries and substitution patterns are lacking. Here, we describe a metal-promoted reductive cross-coupling reaction between vinylcyclopropanes and alkynes (or vinylsilanes) that provides stereoselective access to a diverse array of skipped polyenes through a process that establishes one C-C bond, generates up to three stereodefined alkenes, and can be used to introduce stereogenic centres at the central positions of the skipped polyene motif. We also demonstrate the significance of the present bond construction by preparing substituted and stereodefined polyunsaturated synthetic fatty acids.
Macklin
Todd K
TK
Department of Chemistry, The Scripps Research Institute, Scripps-Florida, 130 Scripps Way #3A2, Jupiter, Florida 33458, USA.
Micalizio
Glenn C
GC
D000475:Alkenes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D003521:Cyclopropanes / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D010084:Oxidation-Reduction; D011090:Polyenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry
D000475:Alkenes; D000480:Alkynes; D003521:Cyclopropanes; D005231:Fatty Acids, Unsaturated; D008670:Metals; D011090:Polyenes; D014753:Vinyl Compounds