Diastereoselective Reaction of Sulfoxonium Ylides, Aldehydes and Ketenes: An Approach to trans-γ-Lactones

Abstract

In this paper, a novel approach to γ-lactones from the reaction of sulfoxonium ylides, aldehydes, and ketenes is described. The new ylide-based method provides access to γ-lactones from disubstituted ketenes, in good yields, and with good diastereoselectivity favoring the trans-diastereomer (11 examples with dr ≥ 82:18, dr up to 92:8).

Recent Developments in Vinylsulfonium and Vinylsulfoxonium Salt Chemistry

“…Kerrigan’s group investigated γ -lactone synthesis by studying the reaction of lithium enediolates 156 with α , β -unsaturated sulfoxonium salts 154 [ 63 ]. This approach complemented their previously reported one-pot methodology for the preparation of γ -lactones from sulfoxonium ylides and disubstituted ketenes, in that it mainly provided access to γ -lactones 155 bearing α - and β -tertiary stereogenic centers [ 63 , 64 ]. The sulfoxonium salt 154 was prepared by procedures previously described by Johnson and co-workers [ 19 , 20 , 21 ].…”

“…Invariably, high diastereoselectivity (dr ≥ 88:12), favoring formation of the trans -diastereomer as the major isomer, was observed. Significantly, the reactions of lithium enediolates derived from α , α -disubstituted acetic acids were found to proceed smoothly to provide access to the desired α -quaternary center substituted γ -lactones, albeit with lower diastereoselectivity (dr 80:20) [ 63 , 64 ].…”

“…In the first mechanism, Pathway 1 ( Scheme 51 ), the lithium enediolate 156 adds to the sulfur of the vinylsulfoxonium salt 154 to give enolate intermediate 159 in stereoselective fashion as the E -isomer. Subsequent [ 3 , 3 ]-sigmatropic rearrangement, ylide protonation (by acid/lactone/intramolecular proton transfer), and 5-exo-tet cyclization would lead to the formation of lactone 155 as the trans -diastereomer [ 64 , 65 ]. This mechanism is consistent with the one that Kerrigan and co-workers have proposed for the formation of γ -lactones from sulfoxonium ylide, aldehydes, and ketenes in that both involve enolate 159 as a key intermediate [ 64 , 66 ].…”

Diastereoselective Synthesis of γ-Lactones through Reaction of Enediolates with α,β-Unsaturated Sulfoxonium Salts

“…1 Recently, we developed a diastereoselective method for γ-lactone synthesis from the reaction of an aminosulfoxonium ylide with aldehydes and ketenes (Scheme 1). 2,3 We originally proposed that a [3,3]-sigmatropic rearrangement of a sulfurane oxide intermediate was responsible for the good diastereoselectivity observed in that reaction. 2,4 To explore the mechanism further, we reasoned that the putative sulfurane oxide intermediate might be accessed through an independent route involving reaction of a lithium enediolate with a vinylsulfoxonium salt.…”

“…2 The lower diastereoselectivity may be attributed to the inability of 3n,o to undergo equilibration (through reversible deprotonation−protonation) or because of the closer similarity of the methyl and phenyl substituents' size (compared to hydrogen and phenyl substituents) and the lack of steric bias therein.…”