Table 1.

Development of the catalytic system for direct asymmetric conjugate addition of EtMgBr to carboxylic acid 1a^a

Entry	L/Cu(I)	LA	Solvent	T [°C]	Conv. [%]b	ee [%]c
1	L1/Cu(I)	–	CH2Cl2	−78	0	–
2	L1/Cu(I)	–	CH2Cl2	0	79d	Rac
3	L1/Cu(I)	Me3SiOTf	CH2Cl2	−78	74	47
4	L2/Cu(I)	Me3SiOTf	CH2Cl2	−78	70	9
5	L3/Cu(I)	Me3SiOTf	CH2Cl2	−78	72	47
6	L4/Cu(I)	Me3SiOTf	CH2Cl2	−78	87	56
7	L5/Cu(I)	Me3SiOTf	CH2Cl2	−78	75	47
8	L4/Cu(I)	Me3SiOTf	THF	−78	100	Rac
9	L4/Cu(I)	Me3SiOTf	Toluene	−78	62	80
10	L4/Cu(I)	Me3SiOTf	Ether	−78	91	88
11	L4/Cu(I)	Me3SiOTf	tBuOMe	−78	95	92
12e	L4/Cu(I)	tBuMe2SiOTf	tBuOMe	–78	95	95
13	L4/Cu(I)	BF3·Et2O	tBuOMe	−78	19	92
14f	L4/Cu(I)	BF3·Et2O	tBuOMe	−78	77	97
15f	L4/Cu(I)	Me3SiOTf	tBuOMe	−78	99	97
16g	L4/Cu(I)	Me3SiOTf	tBuOMe	−78	100	95
17	L4/Cu(I)	Me3SiOTf	tBuOMe	0	95	88
18	L4/Cu(I)	Me3SiOTf	tBuOMe	−20	97	97

^aReaction conditions: 0.1 M of 1a, 5 mol% of CuBr·SMe₂, 6 mol% of L, and 2–3 equiv. of LA followed by the addition of 2–3 equiv. of EtMgBr

^bConversion was determined by NMR of reaction crude

^cEnantiomeric excess was determined by chiral HPLC after transforming 2a to the corresponding N,N-dimethyl amide derivative

^dLess than 20% of 2a formed with many other byroducts

^eThe product was obtained as a mixture of silyl ester and free carboxylic acid in the ratio of 62:38, respectively

^fThe reaction was performed by first forming Li-carboxylate with nBuLi followed by addition of corresponding LA and EtMgBr

^gThe reaction was performed by first forming Na-carboxylate with NaH followed by the additions of Me₃SiOTf and EtMgBr