Directed ortho-metalation versus reductive amination in the preparation of polytopic, highly substituted, and sterically congested amine-S-arylthiocarbamates as thiophenol precursors

Abstract

The synthesis of polydentate amine-S-arythiocarbamates was tested by directed ortho-lithiation of 2,4-disubstituted thiophenols, or the corresponding O- and S-arylthiocarbamates by deprotonation or lithium–bromine exchange, followed by addition of the electrophiles N(CH2CH2X)3 (X=Br, I). In the case of the thiophenol, deprotonation resulted in a trithioether-amine upon addition of the electrophile. With the O- and S-thiocarbamates, the reactions resulted in the migration of the thiocarbamoyl group to the ortho-position (Fries rearrangement), or nucleophilic attack of the carbonyl group by butyllithium, respectively. An alternative route employed 2,4-disubstituted phenols to obtain the corresponding salicylaldehydes, and subsequently the O-arylthiocarbamates for Newman–Kwart thermal rearrangement (NKR). Finally, the formyl group on the S-arylthiocarbamates allowed reductive amination to assemble polytopic compounds with amine and S-thiocarbamate groups.