Benzyltriethylammonium Tetrathiomolybdate : applications in organic synthesis

Abstract

Benzyltriethylammonium Tetrathiomolybdate: Applications in Organic Synthesis This thesis deals with the chemistry of benzyltriethylammonium tetrathiomolybdate, [PhCH?NEt?]?MoS?, and its utility as a reagent in organic synthesis.

Chapter 1 A general methodology for the facile conversion of amides and lactams to the corresponding thioamides and thiolactams is described. A number of amides and lactams were converted to their thiocarbonyl derivatives in excellent yields via formation of Vilsmeier intermediates, followed by treatment with tetrathiomolybdate. Amides derived from amino acids were also converted to the corresponding thioamides. A few examples are shown in Scheme I.

Chapter 2 New methodology for the deprotection of propargyl esters and ethers, and propargyloxy carbonyl (Poc) protecting groups mediated by tetrathiomolybdate, is presented. This chapter is divided into three parts: Part A — Selective deprotection of propargyl esters Propargyl esters are selectively cleaved in the presence of methyl, t-butyl, allyl and benzyl esters. No racemization was observed in amino?acid derived esters, making the method highly suitable for peptide synthesis. Part B — Deprotection of propargyl ethers The same reaction conditions deprotect propargyl ethers of alcohols and phenols. Nitro, carbonyl, allyl and other sensitive groups remain unaffected, making this reagent superior to Ti? or Pd²?, which are normally used. Part C — Development of the Poc protecting group A new protecting group for amines, the propargyloxycarbonyl (Poc) group, has been developed. It is easily removed using tetrathiomolybdate. Importantly, Poc works well for sulfur?containing amino acids, unlike benzyloxycarbonyl (Z) or allyloxycarbonyl (Alloc), which fail due to catalyst poisoning.

Chapter 3 This chapter describes the induced internal redox reaction of tetrathiomolybdate in the reduction of N?oxides, nitrones, sulfoxides and peroxides. Benzyltriethylammonium tetrathiomolybdate is highly selective:

No over?reduction occurs in nitrones. Nitro and halogen substituents remain unaffected.

Representative examples are shown in Scheme III.

Chapter 4 This chapter, divided into three parts, concerns the synthesis of disulfides. Part A — Sulfur transfer in water Water is used as the solvent for sulfur?transfer reactions mediated by tetrathiomolybdate. This is useful for synthesizing sugar disulfides and carboxyl?containing disulfides. Part B — Vinylic disulfides A facile conversion of vinylic halides to vinylic disulfides using tetrathiomolybdate is presented. Vinyl halides with ??carbonyl groups are especially reactive. The vinylic disulfides are then transformed into monothio?1,3?diketones, which are difficult to prepare by other methods. Part C — One?pot conversion of alcohols to disulfides Primary alcohols can be converted to disulfides by:

Converting alcohols to isourea derivatives or phosphonium salts, then Treating with tetrathiomolybdate.

This method works best for primary alcohols. Representative results are shown in Scheme IV.