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Synthesis and Screening of New Chiral Ligands for the Copper‐Catalysed Enantioselective Allylic Substitution
Author(s) -
Ongeri Sandrine,
Piarulli Umberto,
Roux Maryline,
Monti Chiara,
Gennari Cesare
Publication year - 2002
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 - 10.1002/1522-2675(200210)85:10<3388::aid-hlca3388>3.0.co;2-i
Subject(s) - chemistry , allylic rearrangement , sn2 reaction , ligand (biochemistry) , nucleophilic substitution , enantioselective synthesis , substitution reaction , benzaldehyde , stereochemistry , benzoic acid , medicinal chemistry , diethylzinc , combinatorial chemistry , organic chemistry , catalysis , receptor , biochemistry
The synthesis of the new chiral ligands 6ae, 8ae, 9ae , and 11ae starting from the chiral β ‐[(Boc)amino]sulfonamide 3ae is reported. The β ‐amino group of 3ae was deprotected and condensed with 3,5‐dichlorosalicylaldehyde ( 4 ) to yield the known Schiff base 5ae , which was then reduced to the amino compound 6ae ( Scheme 3 ). Alternatively, condensation of the free amino compound with 2‐(diphenylphosphanyl)benzaldehyde ( 7 ) afforded the imino ligand 8ae which upon reduction yielded the amino ligand 9ae ( Scheme 4 ). The free amino compound derived from 3ae was also coupled with 2‐(diphenylphosphanyl)benzoic acid ( 10 ) to give ligand 11ae ( Scheme 5 ). These ligands were tested in the copper‐catalysed allylic substitution reaction of cinnamyl (=3‐phenylprop‐2‐enyl) phosphate 12 with diethylzinc as a nucleophile. Ligands 5ae, 6ae, 8ae , and 11ae gave excellent ratios (100 : 0) of the S N 2′/ S N 2 products ( Scheme 6 and Table 1 ). Ligand 11ce , identified from the screening of a small library of ligands of general formula 11 , promoted the allylic substitution reaction with moderate enantioselectivity (40% for the S N 2′ product 13 ( Scheme 8 and Table 3 )).