The high steric repulsion between substituents on the carbon center makes the generation of quarternary centers challenging. Varinder Aggarwal and co-workers, University of Bristol, UK, have shown that tertiary boronic esters can be used to create quaternary stereogenic centers enantioselectively. They used Matteson homologation conditions, with bromomethyl lithium replacing LiCH₂Cl, to convert the teriary boronic ester into a quaternary center bearing an α-primary alcohol.

A range of substrates could be prepared this way, all with a good enantiomeric ratio. The inclusion of a vinyl group could be performed by a Zweifel-type olefination of the boronic esters with vinylmagnesium bromide. This methodology was applied to the synthesis of the natural product (+)-sporochnol and the serotonin antagonist (S)-1,2-diphenyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-2-methyl-1-butanone.

Images: (c) Wiley-VCH

• Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications
  R. P. Sonawane, V. Jheengut, C. Rabalakos, R. Larouche-Gauthier, H. K. Scott, V. K. Aggarwal,
  Angew. Chem. Int. Ed. 2011.
  DOI: 10.1002/anie.201008067