Isothiourea-catalysed regioselective acylative kinetic resolution of axially chiral biaryl diols

Shen Qu, Mark D. Greenhalgh, Andrew D. Smith

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
1 Downloads (Pure)

Abstract

An operationally‐simple isothiourea‐catalyzed acylative kinetic resolution of unprotected 1,1′‐biaryl‐2,2′‐diol derivatives has been developed to allow access to axially chiral compounds in highly enantioenriched form (s values up to 190). Investigation of the reaction scope and limitations provided three key observations: i) the diol motif of the substrate was essential for good conversion and high s values; ii) the use of an α,α‐disubstituted mixed anhydride (2,2‐diphenylacetic pivalic anhydride) was critical to minimize diacylation and give high selectivity; iii) the presence of substituents in the 3,3′‐positions of the diol hindered effective acylation. This final observation was exploited for the highly regioselective acylative kinetic resolution of unsymmetrical biaryl diol substrates bearing a single 3‐substituent. Based on the key observations identified, acylation transition state models have been proposed to explain the atropselectivity of this kinetic resolution.
Original languageEnglish
JournalChemistry - A European Journal
VolumeEarly View
Early online date28 Jan 2019
DOIs
Publication statusE-pub ahead of print - 28 Jan 2019

Keywords

  • Biaryl
  • Kinetic resolution
  • Enantioselectivity
  • Regioselectivity
  • Axial chirality

Fingerprint

Dive into the research topics of 'Isothiourea-catalysed regioselective acylative kinetic resolution of axially chiral biaryl diols'. Together they form a unique fingerprint.

Cite this