Versatile C(sp(2) )-C(sp(3) ) Ligand Couplings of Sulfoxides for the Enantioselective Synthesis of Diarylalkanes

William M Dean; Mindaugas Šiaučiulis; Thomas E Storr; William Lewis; Robert A Stockman

doi:10.1002/anie.201602264

Versatile C(sp(2) )-C(sp(3) ) Ligand Couplings of Sulfoxides for the Enantioselective Synthesis of Diarylalkanes

Angew Chem Int Ed Engl. 2016 Aug 16;55(34):10013-6. doi: 10.1002/anie.201602264. Epub 2016 Jul 20.

Authors

William M Dean¹, Mindaugas Šiaučiulis¹, Thomas E Storr¹, William Lewis¹, Robert A Stockman²

Affiliations

¹ School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
² School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. robert.stockman@nottingham.ac.uk.

PMID: 27435802
DOI: 10.1002/anie.201602264

Abstract

The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98 % yield and greater than 99.5 % enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron-deficient heteroaromatic compounds, which are traditionally synthesized by transition metal catalyzed cross-couplings, and circumvents common issues associated with proto-demetalation and β-hydride elimination.

Keywords: arenes; cross-coupling; magnesium; reaction mechanisms; sulfur.

Publication types

Research Support, Non-U.S. Gov't