Trimethylsilyl ethylsulfonyl SES Derivatives

Since its introduction in 1986 the 2-(trunethytsilyl)ethyIsulfonyl group has been widely adopted in alkaloid, carbohydrate and amino add chemistry. It is every bit as stable as the arylsulfonyl groups discussed above it is impervious to the ravages of trifluoroacetic add, hot 6 M HCl, trifluoroborane etherate. or 40% HF in ethanol. Nevertheless, under very specific non reductive conditions, it can be cleaved. The link with 2-(trimethylsilyl)ethyl esters, 2-(trimethylsilyl)ethoxycarbon-yl derivatives, and 2-(trimethylsilyl)ethoxymethyl ethers hardly needs comment. 

A synthesis of Agelastatin A by Weinreb and co-workers featured the use of a 13 bis[2-(trimethylsilyl)ethylsuifonyl] sulfodiimide 137 2 as an enophile in a two-step allylic amination reaction [ heme 8.137]. The initial ene reaction produced a dipolar intermediate 1373 that underwent a [2,3] Sigmatropic shift to afford the SES-protected allylic amine derivative 137,4. Reductive cleavage of the N-S bond followed by cleavage of the Boc group with trifluoroacetic acid gave the sulfonamide 1373 in 50-60% overall yield. Final deprotection of the SES group with TBAF returned the desired amine 137,6 in 90% yield. 

1 was converted into the N-tritylsulfenyl (TrS) protected uridine derivative 

Introduction of the o-nitrophenylsulfenyl group is simple using commercially available 2-nitrobenzenesulfenyl chloride (mp 74-76 C) and aqueous base 

All of the foregoing N-protecting groups (except sulfenamides) render the nitrogen atom essentially non-basic. In cases where a synthetic endeavour simply requires the suppression of N-acylation or proton abstraction from a primary or secondary amine, it may be useful to protect the nitrogen as a tertiary amine. 

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