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 SN2′/SN2 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 SN2′ product 13 (Scheme 8 and Table 3)).