Straightforward Synthesis of Strained α,β-Epoxysulfones via Epoxidation of Vinylsulfones Using N-Methylmorpholine N-Oxide as Epoxidizing Reagent

Abstract

An efficient, stereoselective route to the a,b-epoxysulfones using N-methylmorpholine N-oxide (NMO) as epoxidizing reagent is described.The oxa-and azanorbornenic vinylsulfones 1 (Figure 1) are useful intermediates for the synthesis of substituted cyclohexane and cyclohexene derivatives via regio-and stereocontrolled ring-opening reactions. 1 Figure 1In particular, the nucleophilic (Michael) addition of organometallic reagents followed by b-elimination of the resulting arylsulfonyl-stabilized carbanion occurs with concomitant bridge opening 2 (Scheme 1) due to the strained character of the bicyclic system. Scheme 1This methodology has become a key step for the synthesis of compounds such as 7-deoxypancratistatin, 3 several carbasugars, 4 analogues of a ring of vitamin D 3 , 5 polypropionate (stereotetrads) fragments 6 and analogues of conduramines. 7On the other hand, although epoxysulfones are versatile synthons, particularly in the presence of nucleophilic reagents, 8 the chemistry of strained a,b-epoxysulfones such as 2 and 3 ( Figure 2) remains almost unexplored 9 despite the rich functionality present in these compounds.Usually these epoxysulfones have been synthesized by the nucleophilic epoxidation of a,b-unsaturated sulfones with t-BuOOLi, among other epoxidizing reagents. 10 Figure 2In the search for an alternative method, we speculate that if the Michael addition described in Scheme 1 could be carried out using a nucleophilic oxygen atom attached to a good leaving group, the elimination step may occur on this leaving group, thereby leaving the bicyclic skeleton intact and allowing for the synthesis of epoxysulfones such as 2 and 3 (Scheme 2). Scheme 2Assuming the exo attack of the nucleophilic reagent on the bicyclic system, 11 the exo stereochemistry of the oxirane functionality (endo-sulfone) remains secure. In this context an amine oxide constitutes an excellent candidate for testing this assumption. 12 In this way, vinylsulfones 4-8 ( Figure 3) were prepared 13 and treated with N-methyl-NR R 2 ArO 2 S X 1 ArO 2 S X R 1 ArO 2 S R 1 XM R 1 M (Michael) β-elimination R 2 R 2 R 2 X O SO 2 Ar 2a X = O 2b NR 2c CH 2 X O SO 2 Ar 3a X = O 3b NR X ArO 2 S X ArO 2 S O LG X O SO 2 Ar LG-O 2, 3