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 beta-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.
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Edward E
EE
Korshin
Yaroslav V
YV
Bilokin
Hailin
H
Zheng
Mario D
MD
Bachi