Efficient Stereoselective Alkenylation through a Homolytic Domino Reaction Involving a 1,5 Sulfur-to-Carbon Translocation

An effective method for cis-stereoselective attachment of functionalized alkenyl appendages to sp³ carbon is reported. This method is based on a free-radical process, involving a sequence of addition?elimination steps, resulting in alkenyl group transposition from divalent sulfur to a prochiral carbon radical. Absolute stereoselectivity is secured since the new carbon?carbon bond is formed in a ring-closure reaction leading to a bridged bicyclic carbon-centered radical intermediate. The latter undergoes β-scission of the C?S bond, leaving the alkenyl side chain in its predetermined position while releasing a thiyl radical. This thiyl radical is trapped by tri-n-butylstyryltin, affording a (styrylsulfanyl)methyl side chain and a tri-n-butyltin radical that continues the chain. When 2-(alkenylsulfanyl)methyl-4-bromo(or iodo)pyrrolidines were used as starting materials 2,4-cis-disubstituted 4-alkenyl-2-(styrylsulfanyl)methylpyrrolidines were obtained as products (70?90% yield). Tri-n-butylstyryltin was used rather then the more common n-Bu₃SnH as tin radicals sources because the latter led predominantly to bridged bicyclic 3-thia-6-azabicyclo[3.2.1]octanes (up to 77% yield). An additional advantage of using tri-n-butylstyryltin derives from the discovery that the resulting styrylsulfide functionality is an excellent synthetic equivalent to the formyl group. Thus, using a Pummerer-type oxidative desulfurization, 4-cis-alkenyl-proline aldehydes were obtained.