Unsymmetrical Organotrisulfide Formation via Low-Temperature Disulfanyl Anion Transfer to an Organothiosulfonate.

New methodology is presented for the formation of unsymmetrical organotrisulfides in a high yield and purity, relatively free of polysulfide byproducts. The highlight of the method is the low-temperature (-78 °C) deprotection of a disulfanyl acetate with sodium methoxide in THF to form a disulfanyl anion, which reacts rapidly in situ with an organothiosulfonate ( S-aryl or S-alkyl) within 30 seconds followed by quenching. The discovery of these new reaction conditions together with the relative greenness of the chemistry overall makes for an efficient protocol, from which a range of organotrisulfides covering aliphatic, aromatic, as well as cysteine and sugar groups can be accessed in a high yield and purity.

Chemoselective room temperature E1cB N-N cleavage of oxazolidinone hydrazides from enantioselective aldehyde α-hydrazination: synthesis of (+)-1,4-dideoxyallonojirimycin.

Room temperature E1cB N-N cleavage of oxazolidinone hydrazides via N-alkylation with diethyl bromomalonate and potassium or caesium carbonate as base in acetonitrile is presented. The new method has a much improved chemoselectivity, which is illustrated by a concise total synthesis of the piperidine iminosugar (+)-1,4-dideoxyallonojirimycin.

Vinylogous Mukaiyama aldol reactions with 4-oxy-2-trimethylsilyloxypyrroles: relevance to castanospermine synthesis.

BACKGROUND: The diastereoselectivity of a vinylogous Mukaiyama aldol reaction of a series of N-substituted 4-oxy-2-trimethylsilyloxypyrroles with a tartrate-based aldehyde has been explored as a model reaction for castanospermine synthesis. RESULTS: The study has revealed that the reaction is sensitive to the nature of the combination of N- and 4-oxy substituents. With a N-PMB or N-Bn and 4-methoxy combination, the reaction generates an aldol adduct with the correct absolute configurations for C-8 and C-8a of the indolizidine alkaloid castanospermine. The adduct was transformed to an indolizidine, whose ketal could not be transformed appropriately for the target alkaloid. CONCLUSION: The first successful diastereoselective Mukaiyama aldol strategy for the C-8 and C-8a stereogenic centres of castanospermine is presented using silyloxypyrrole chemistry. The results suggest that a full enantioselective synthesis can be realized provided that C-1 functionalisation is accomplished early in the synthesis, post-coupling.