Asymmetric synthesis of densely functionalized medium-ring carbocycles and lactones through modular assembly and ring-closing metathesis of sulfoximine-substituted trienes and dienynes.

An asymmetric synthesis of densely functionalized 7-11-membered carbocycles and 9-11-membered lactones has been developed. Its key steps are a modular assembly of sulfoximine-substituted C- and O-tethered trienes and C-tethered dienynes and their Ru-catalyzed ring-closing diene and enyne metathesis (RCDEM and RCEYM). The synthesis of the C-tethered trienes and dienynes includes the following steps: 1) hydroxyalkylation of enantiomerically pure titanated allylic sulfoximines with unsaturated aldehydes, 2) α-lithiation of alkenylsulfoximines, 3) alkylation, hydroxy-alkylation, formylation, and acylation of α-lithioalkenylsulfoximines, and 4) addition of Grignard reagents to α-formyl(acyl)alkenylsulfoximines.

Asymmetric synthesis of spiroketal, spiroether, and oxabicycle building blocks via stereoselective spiro- and bicycloannulation of 2-hydroxy dihydropyrans.

A modular asymmetric synthesis of spiroketal, spiroether, and oxabicycle building blocks is described based on the spiro- and bicycloannulation of alpha-hydroxy dihydropyrans, which were obtained from sulfoximine-substituted homoallylic alcohols. Key steps of the syntheses are stereoselective Ferrier-type O- and C-glycosidation, ring-closing metathesis, and stereoselective Prins cyclization.

Asymmetric modular synthesis of highly functionalized medium-sized carbocycles and lactones via ring-closing metathesis of sulfoximine-substituted trienes.

A modular asymmetric synthesis of medium-sized carbocycles and lactones has been developed that affords highly substituted 7-, 9-, and 11-membered rings. The key steps are (1) the highly diastereoselective synthesis of sulfoximine-substituted homoallylic alcohols from allylic sulfoximines and unsaturated as well as saturated aldehydes, (2) an E-stereoselective alkylation and hydroxyalkylation of sulfoximine-substituted alkenyllithium derivatives, (3) the esterification of sulfoximine-substituted homoallylic alcohols, and (4) the ring-closing metathesis reaction of sulfoximine-substituted trienes with the ruthenium catalyst 8. Two examples for the further synthetic elaboration of the sulfoximine-substituted carbocycles are provided.