Synthesis and Screening of New Chiral Ligands for the Copper‐Catalysed Enantioselective Allylic Substitution

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_N2′/S_N2 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_N2′ product 13 (Scheme 8 and Table 3)).