Table 1.

Optimization of the stereodivergent asymmetric Mannich reaction.

Entry	Cu(I) source	Ligand	2	Conditions	Yield (%)	dra (anti/syn)	eeb (%)
1	Cu(PhMe)0.5OTf	L1	2a	DIPEAc, 25 °C	91	1.7:1	41
2	Cu(PhMe)0.5OTf	L1	2b	DIPEAc, 25 °C	85	5.2:1	80
3	Cu(PhMe)0.5OTf	L2	2b	DIPEAc, 25 °C	74	4.6:1	75
4	Cu(PhMe)0.5OTf	L1	2b	BTMG, 25 °C	98	5.8:1	83
5	Cu(MeCN)4PF6	L1	2b	BTMG, 25 °C	98	6.7:1	83
6	Cu(MeCN)4PF6	L1	2b	DBU, 25 °C	99	6.6:1	73
7	Cu(MeCN)4PF6	L1	2b	MTBD, 25 °C	99	5.8:1	83
8	Cu(MeCN)4PF6	L3	2b	BTMG, 25 °C	99	2.0:1	26
9	Cu(MeCN)4PF6	L4	2b	BTMG, 25 °C	99	4.0:1	79
10	Cu(MeCN)4PF6	L5	2b	BTMG, 25 °C	99	1.5:1	50
11	Cu(MeCN)4PF6	L6	2b	BTMG, 25 °C	99	1.5:1	31
12	Cu(MeCN)4PF6	L7	2b	BTMG, 25 °C	99	1.3:1	40
13	Cu(MeCN)4PF6	L8	2b	BTMG, 25 °C	99	1.1:1	47
14	Cu(MeCN)4PF6	L1	2b	BTMG, −35 °C	95	12.3:1	90
15d	Cu(MeCN)4PF6	L9	2b	BTMG, 25 °C	97	1:1.6	3
16d	Cu(MeCN)4PF6	L9	2a	BTMG, 25 °C	99	1:5.7	31
17d	Cu(MeCN)4PF6	L10	2a	BTMG, −35 °C	75	1:2.5	4
18d	Cu(MeCN)4PF6	L11	2a	BTMG, −35 °C	99	1:7.3	19
19d	Cu(MeCN)4PF6	L12	2a	BTMG, −35 °C	99	1:5.6	60
20d	Cu(MeCN)4PF6	L13	2a	BTMG, −35 °C	99	1:13.4	70
21d	Cu(MeCN)4PF6	L13	2c	BTMG, −35 °C	98	1:8.7	75
22d	Cu(MeCN)4PF6	L14	2a	BTMG, −35 °C	94	1:5.7	80
23d	Cu(MeCN)4PF6	L14	2c	BTMG, −35 °C	94	1:3.0	98

Reaction condition: 1a (0.055 mmol), 2 (0.050 mmol), Cu(I) source (0.005 mmol), ligand (0.006 mmol) and base in 0.3 mL toluene.

^aDetermined by ¹⁹F NMR analysis.

^bDetermined by chiral HPLC analysis.

^cThe base loading was 80 mol%.

^dThe Cu complex and base loading were 5 mol%.