Chemistry of tetrathiomolybdate : Application in organic synthesis

Abstract

Chemistry of Tetrathiomolybdate: Applications in Organic Synthesis K. R. Prabhu, Department of Organic Chemistry, IISc, Bangalore This thesis deals with the chemistry of benzyltriethylammonium tetrathiomolybdate, [PhCH?NEt?]?MoS? (1) and its usefulness in organic synthesis.

Chapter 1: Conversion of Organic Thiocyanates to Disulfides A general methodology for the conversion of organic thiocyanates to corresponding disulfides is described. A number of organic thiocyanates on treatment with tetrathiomolybdate (1) were converted to the corresponding disulfides. This methodology was extended to the synthesis of a 13-membered disulfide system in excellent yield. Unlike the reaction of organic halides and tosylates, there is no sulfur transfer from tetrathiomolybdate (1) to the substrates; instead, it turns out to be a reductive dimerization of organic thiocyanates to form the corresponding disulfides mediated by tetrathiomolybdate (1).

Chapter 2: Chemoselective Synthesis of Functionalized Diselenides Organic selenocyanates generated in situ from the corresponding halides react with tetrathiomolybdate (1) to produce excellent yields of the corresponding functionalized diselenides. A striking feature of the methodology is that a number of reducible functional groups in the substrate are tolerated by the reagent under the reaction conditions.

Chapter 3: Mild Synthesis of Cyclic Imines from ?-Azido Ketones A mild methodology for the synthesis of 5-, 6-, and 7-membered cyclic imines from ?-azido ketones is disclosed. ?-Azido ketones on treatment with tetrathiomolybdate (1) (CH?CN, 25 °C) afford the cyclic imines under very mild reaction conditions in excellent yield. Application of this mild and neutral methodology is demonstrated in the synthesis of pyrrolobenzodiazepines (PBDs), which are potential antitumor antibiotics.

Chapter 4: Induced Internal Redox Reaction and Michael Addition The application of induced internal redox reaction of tetrathiomolybdate in the cleavage of disulfides and synthesis of unsymmetrical disulfides is demonstrated. Addition of disulfides to ?,?-unsaturated carbonyl compounds in a Michael fashion to form ?-keto sulfides in the presence of tetrathiomolybdate (1) is presented. A one-pot reaction of alkyl halides with ?,?-unsaturated carbonyl compounds in the presence of two equivalents of tetrathiomolybdate to form the corresponding ?-keto sulfides is also described. This methodology was extended to the synthesis of cyclic ?-keto sulfides including a bicyclo[3.3.1]nonane system. Finally, a preliminary investigation on the cleavage of disulfide bonds in proteins mediated by tetrathiomolybdate (1) is presented.