S-Allyl Thiocarbamates from Allylic Alcohols by in situ [3,3]-Sigmatropic Rearrangement of a Thiocarbonyldiimidazole Adduct

Abstract

Treatment of allylic alcohols with thiocarbonyldiimidazole generates an unstable O-allyl imidazolyl thione ester, which rearranges spontaneously and in high yield to the corresponding Sallyl imidazolyl thiol ester. Displacement of the imidazole by N-alkylanilines in the presence of a nucleophilic catalyst (HOBt or ECHIA) gives S-allyl N-aryl thiocarbamates in excellent yields (up to 97%) over two steps.Thiocarbamates are valuable as precursors of important sulfur-containing compounds 1 and strategic intermediates in the synthesis of natural products. 2 They also display biological activities as analgesics 3 and anaesthetics, 1,4 fungicides 1,3-5 and bactericides 3,4,6 or antiviral 1,4 and dermatological agents. 5,7 They have been reported to have hypnotic 3 and tuberculostatic activity 3 and can be employed in flavour and fragrance chemistry. 8 S-Alkyl thiocarbamates are most known for their use as commercial herbicides. 1,4,9 Allylic thiocarbamates have been used as terminators in radical-based cyclisation reactions. 10 Hoppe made extensive use of S-alkyl-, S-benzyl-, and Sallylthiocarbamates in his seminal work on lithiation and his studies of the configurational stability of the resulting sulfur-stabilised organolithium compounds. 11 The most straightforward methods for the preparation of thiocarbamates are nucleophilic substitutions of carbamoyl chlorides with thiols or thiolates, 12,13 alkyl chlorothioformates with amines, 13 or sequential attack on trichloroacetyl chloride by a thiol and an amine. 4 Less practical methods employ carbon monoxide and elemental sulfur, 4,14 reactions of unstable N,N-dialkylcarbamoyl lithiums with sulfur compounds, 9a or the condensation of gaseous carbonyl sulfide and an amine followed by treatment with a base and alkyl halide. 12 Condensation of a thiol with an isocyanate 6 or hydration of an organic thiocyanate 1,15 also affords a thiocarbamate. S-Allyl thiocarbamates 2 are readily prepared by rearrangement of their O-allyl counterparts 1 (Scheme 1), 4 driven by the thermodynamically favoured formation of a C=O bond from a C=S bond. 16 The rearrangement can be promoted thermally 17 or photochemically, 18 and metalcatalysed processes 17c,19 have also been reported. The thermal reaction seems to be a standard [3,3]-sigmatropic rearrangement, with a broad range of substituents tolerated 16,17 although the rate of the reaction strongly depends on the allylic substitution pattern. 16,17,20 Scheme 1 [3,3]-Sigmatropic rearrangement of O-allyl thiocarbamatesStarting from enantioenriched O-allyl thiocarbamates 1, the [3,3]-sigmatropic rearrangement proceeds with excellent transfer of chirality (up to 97% ee conservation). 11c,e Enantioselectivity can furthermore be achieved in the rearrangement of achiral or racemic O-allyl thiocarbamates. 19 Using a chiral bisphosphine ligand, Gais prepared cyclic and acyclic symmetrical S-allylic thiocarbamates with ee values ranging from 85% to ≥99% via a palladium-catalysed reaction. 19a,b Overman obtained good to excellent ee values (76-88%)...