Efficient synthesis of 1,2,4-dithiazolidine-3,5-diones [dithiasuccinoyl-amines] from bis(chlorocarbonyl)disulfane plus bis(trimethylsilyl)amines.
The 1,2,4-dithiazolidine-3,5-dione heterocycle, also referred to as a dithiasuccinoyl (Dts)-amine, serves as a readily removable amino protecting group for building blocks used in syntheses of peptides, glycopeptides, and PNA; it is also useful as a masked isocyanate and (inversely) as a sulfurization reagent for trivalent phosphorus. Bis(chlorocarbonyl)disulfane, the two-sulfur analogue of succinyl chloride, has been envisioned as a reagent for facile single-step elaboration of the heterocycle. However, reactions of bis(chlorocarbonyl)disulfane directly with primary amines fail to yield Dts-amines for reasons that are discussed. Inspired by several precedents from the organosilicon chemistry literature that a trimethylsilyl group may serve as a "large proton," a successful, high-yield preparation of Dts-amines through reactions of bis(chlorocarbonyl)disulfane with bis(trimethylsilyl)amines has been developed. Studies aimed at elucidating mechanistic reasons for these observations are also presented.
Barany
Michael J
MJ
University of Minnesota, Department of Chemistry, 207 Pleasant Street S.E., Minneapolis, Minnesota 55455, USA. barany@umn.edu
Hammer
Robert P
RP
Merrifield
R B
RB
Barany
George
G
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry*; D013457:Sulfur Compounds / Q000737:chemistry*; D045162:Thiazolidinediones / Q000138:chemical synthesis*; D014297:Trimethylsilyl Compounds / Q000737:chemistry*
C099736:1,2,4-dithiazolidine-3,5-dione; D000588:Amines; D013457:Sulfur Compounds; D045162:Thiazolidinediones; D014297:Trimethylsilyl Compounds