Functionalized Chiral Vinyl Aminosulfoxonium Salts: Asymmetric Synthesis and Application to the Synthesis of Enantiopure Unsaturated Prolines, β,γ-Dehydro Amino Acids, and Cyclopentanoid Keto Aminosulfoxonium Ylides

Abstract

Methylation of the enantiopure functionalized vinyl sulfoximines 5a − e and 14a − d followed by a F^- ion or DBU-mediated isomerization of the vinyl aminosulfoxonium salts 7a − e and 15a − d, respectively, gave the allyl aminosulfoxonium salts 10a − e and 17a − d, respectively. A concomitant intramolecular substitution of the aminosulfoxonium group of 10a − e and 17a − d by the amino group afforded the unsaturated prolines 8a − e and 18a − d, respectively. The starting vinyl sulfoximines are accessible through a highly selective and stereo-complementary aminoalkylation of the corresponding sulfonimidoyl-substituted mono- and bis(allyl)titanium complexes with the imino ester 4. The vinyl aminosulfoxonium salts 34, 7a − d, and E-15c experienced upon treatment with the Cl^- ion a migratory substitution with formation of the δ-chloro-β,γ-dehydro amino acids 36, E/Z-37a − d, and 38, respectively. A migratory substitution of the hydroxy-substituted vinyl aminosulfoxonium salts 46a and 46b furnished the δ-chloro allyl alcohols E/Z-48a and E-48b, respectively. A facile one-pot conversion of the vinyl sulfoximines 31b, 5c and 45a to the allyl chlorides 36, E/Z-37c and E/Z-48a, respectively, was achieved upon treatment with a chloroformiate. A tandem cyclization of the vinyl aminosulfoxonium salts 7b, Al-7b and 57 with LiN(H)tBu yielded the cyclopentanoid keto aminosulfoxonium ylides 54, Al-54, 59, 60 and 61, respectively. The structure of the tricyclic keto aminosulfoxonium ylide Al-54 has been determined by X-ray crystal structure analysis. Ab initio calculations and a NBO analysis of the tricyclic keto aminosulfoxonium ylide XXIII show a polar structure stabilized by electrostatic interactions between the ylidic C atom and both the carbonyl C atom and the S atom.