Ben W. Glasspoole

Cross Coupling Reactions of Chiral Secondary Organoboronic Esters With Retention of Configuration

We report the first example of a coupling reaction of chiral secondary boronic esters generated by the hydroboration of vinyl arenes. In order for the reaction to take place in high yields, the use of silver oxide as a base and the presence of at least 8 equiv of triphenyl phosphine per Pd are required. The reaction proceeds with >90% retention of configuration in all cases except one. Remarkably, the linear boronate ester does not react under these conditions.

Synthesis of Enantiomerically Enriched Triarylmethanes by Enantiospecific Suzuki–Miyaura Cross-Coupling Reactions

The Suzuki-Miyaura cross-coupling of chiral, enantiomerically enriched dibenzylic boronic esters is described. The reaction proceeds with almost complete retention of stereochemistry, providing access to triarylmethanes, compounds that have high biological activity and are difficult to prepare in enantiomerically pure form using other methods.

Successive C–C Coupling of Dienes to Vicinally Dioxygenated Hydrocarbons: Ruthenium Catalyzed [4 + 2] Cycloaddition across the Diol, Hydroxycarbonyl, or Dione Oxidation Levels

The ruthenium(0) catalyst generated from Ru3(CO)12 and tricyclohexylphosphine or BIPHEP promotes successive C-C coupling of dienes to vicinally dioxygenated hydrocarbons across the diol, hydroxyketone, and dione oxidation levels to form products of [4 + 2] cycloaddition. A mechanism involving diene-carbonyl oxidative coupling followed by intramolecular carbonyl addition from the resulting allylruthenium intermediate is postulated.

Cross-coupling: The final frontier

Cross-coupling between a racemic secondary alkyl halide and an alkyl borane to produce an enantioenriched alkyl–alkyl product is one of the final substrate combinations to succumb to the synthetically powerful Suzuki–Miyaura methodology.

CHAPTER 11:Stereospecific and Stereoselective Suzuki–Miyaura Cross-Coupling Reactions

Recent advances in stereospecific and stereoselective Suzuki–Miyaura cross-coupling reactions generating chiral, enantiomerically enriched products are described. In terms of enantioenriched nucleophiles, at the present time, substrates which are effectively coupled in a stereospecific manner are limited to those with C–B bonds that are π-activated (i.e. benzylic, allylic or propargylic), in close proximity to carbonyl compounds, or have a geminal boron substituent. Prior to the work described in this highlight, the Suzuki–Miyaura cross-coupling of chiral organoboron species was limited to cyclopropyl systems. Stereoselective cross-couplings employing enantiopure secondary electrophiles are also rapidly advancing and the use of chiral, racemic electrophiles in conjunction with chiral ligands is an emerging powerful route for the creation of stereochemistry via Suzuki–Miyaura cross coupling. Advances in this area are presented in the second half of this chapter.