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Synthesis of New Chiral Bidentate (Phosphinophenyl)benzoxazine P,N‐Ligands
Author(s) -
Kündig E. Peter,
Meier Peter
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19990908)82:9<1360::aid-hlca1360>3.0.co;2-v
Subject(s) - chemistry , racemization , diphenylphosphine , stereocenter , medicinal chemistry , denticity , enantiomer , oxazoline , ligand (biochemistry) , stereochemistry , asymmetric induction , benzonitrile , trifluoromethanesulfonate , enantioselective synthesis , organic chemistry , phosphine , crystal structure , catalysis , biochemistry , receptor
Two new chiral bidentate (phosphinophenyl)benzoxazine P,N‐ligands 2a and 2b were synthesized from highly enantiomer‐enriched 2‐(1‐aminoalkyl)phenols 4 . Ligand rac ‐ 2a was obtained on refluxing the t ‐Bu‐substituted (aminomethyl)phenol 4a with 2‐(diphenylphosphino)benzonitrile in chlorobenzene in the presence of anhydrous ZnCl 2 followed by decomplexation ( Scheme 2 ). This reaction, when carried out with (+)‐( S )‐ 4a , was accompanied by racemization at the stereogenic center of the alkyl side chain. The enantiomerically pure ligands (+)‐( R )‐ 2a and (−)‐( S )‐ 2a were obtained using a stepwise procedure via the amides (−)‐( R )‐ and (+)‐( S )‐ 5b , respectively, followed by cyclization to benzoxazines (+)‐( R )‐ and (−)‐( S )‐ 7b , respectively, with triflic anhydride and by F‐atom substitution by diphenylphosphide ( Schemes 3 and 5 ). In the case of the i‐Pr analogue 2b , this last step resulted in racemization ( Scheme 6 ). This was overcome by preparing the bromo derivative and introducing the diphenylphosphine group via Br/Li exchange and reaction with chlorodiphenylphosphine ( Scheme 7 ). The first application of (+)‐( R )‐ 2a in an asymmetric Heck reaction showed high enantioselectivity (91%) ( Scheme 8 ).