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Isothiourea‐Catalysed Regioselective Acylative Kinetic Resolution of Axially Chiral Biaryl Diols
Author(s) -
Qu Shen,
Greenhalgh Mark D.,
Smith Andrew D.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201805631
Subject(s) - regioselectivity , kinetic resolution , chemistry , axial symmetry , resolution (logic) , combinatorial chemistry , kinetic energy , catalysis , stereochemistry , organic chemistry , enantioselective synthesis , computer science , physics , quantum mechanics , artificial intelligence
Abstract An operationally simple isothiourea‐catalysed 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.