Optimization studies for copper-catalysed regio- and enantioselective hydroamination of (E)-1a with 2a for asymmetric synthesis of α-amino acid 3aa ^a.

Entry	Cu/ligand	Yield of 3aa (%), syn/antib	e.r.c
			syn	anti
1	Cu(OAc)2·H2O/(R)-DTBM-BINAP	0, —	—	—
2	Cu(OAc)2·H2O/(R)-DTBM-SEGPHOS	60, 44 : 56	99 : 1	99 : 1
3	Cu(OAc)2·H2O/(R)-DTBM-MeO-BIPHEP	0, —	—	—
4	Cu(OAc)2·H2O/(R)-DM-SEGPHOS	42, 44 : 56	98 : 2	98 : 2
5	Cu(OAc)2·H2O/(R)-SEGPHOS	18,d 44 : 56	n.d.	n.d.
6	Cu(OAc)2·H2O/(R)-Xyl-BINAP	81, 43 : 57 (31, 41)e	97 : 3	97 : 3
7	Cu(OAc)2·H2O/(R)-BINAP	23, 44 : 56	94 : 6	94 : 6
8	Cu(OAc)2·H2O/(R)-DTBM-SEGPHOS	73, 42 : 58	96 : 4	96 : 4
9f	CuCl/(R)-Xyl-BINAP	65, 43 : 57	97 : 3	97 : 3

^aConditions: Cu (0.015 mmol), ligand (0.015 mmol), (E)-1a (0.30 mmol), 2a (0.15 mmol), (EtO)₃Si–H (0.45 mmol), CsOPiv (0.45 mmol), 1,4-dioxane (0.60 mL), RT, 18 h, N₂.

^bIsolated yields are shown. The syn/anti ratio is determined in the crude mixture.

^cThe enantiomeric ratios (e.r.) were determined by HPLC analysis on a chiral stationary phase.

^d1H NMR yield.

^eThe isolated yields of syn-3aa and anti-3aa after the separation.

^f4 h. n.d. = not determined.