Synthetic and mechanistic investigations of organometallic reactions : oxidative cyclization of diester dienolates and mechanistic studies of dithiane reactions in the presence of hexamethylphosphoramide

Typescript (photocopy).The oxidative cyclization of diester dienolates was investigated as a new synthetic method for cyclizing diesters. The proposed cyclization would use a transition metal salt to first complex with the terminal enolates to bring them together to facilitate cyclization and then act as an oxidant to couple the two enolates to produce a ring one carbon smaller than the Dieckmann cyclization and two carbons smaller than the acyloin cyclization. The new method was successful in cyclizing dimethyl glutarate and dimethyl suberate to dimethyl cyclopropyl- and dimethyl cyclohexyldicarboxylates, respectively, in yields ranging from 88% to 94%. Both copper(II) bromide and copper(II) chloride could be used. A variety of reaction conditions were investigated in order to optimize the conditions and to study their effect on the cis/trans isomer ratio of the cyclized products. Other diesters which were attempted failed to oxidatively cyclize. It was also discovered that dimethyl adipate and dimethyl pimelate could be cyclized to their respective Dieckmann products in quantitative yields using lithium di-isopropyl amide as the base. The mechanism of the reaction of dithianes with alkyl halides, ketones and enones in the presence of hexamethylphosphoramide (HMPA) was investigated using radical probes to determine if HMPA induces electron-transfer from the dithiane to the electrophile. The primary objective of these investigations was to determine if electron-transfer was the mechanism of HMPA-induced C-3 addition to enones. In preliminary studies, the reactions of alkyl halides and ketones with dithianes in the presence of HMPA were investigated using radical cyclization and radical ring-opening probes, respectively, but no evidence of radical intermediates in these reactions was obtained. However, in the enone investigations, the radical isomerization probe cis-2,2,6,6-tetramethyl-4-hepten-3-one was completely isomerized to the trans-enone in the presence of HMPA, providing good evidence of radical intermediates. Also, the radical scavenger p-dinitrobenzene prevented isomerization of the cis-enone when it was present, providing additional evidence for a radical pathway