Optimization of the reaction conditions for the cross-coupling of unsymmetrical internal alkynes^a.

Entry	Ligand	Additive	Yield of 5bab (%)	ee of 5bac (%)	rrd
1e	(S)-L1	—	<5	—	—
2	(S)-L1	A1	64	92	20/1
3	(S)-L1	A2	29	92	20/1
4	(S)-L1	A3	31	92	20/1
5	(S)-L1	A4	58	92	20/1
6	(S)-L1	NEt3	0	—	—
7	(S)-L1	PPh3	0	—	—
8	(S)-L1	P(OEt)3	0	—	—
9	(S)-L2	A1	62	88	20/1
10	(S)-BINAP	A1	0	—	—
11	L6	A1	24	35	20/1
12f	(S)-L1	A1	No reaction	—	—
13g	(S)-L1	A1	Complex mixture of products	—	—

^aReactions were carried out with 1b (0.2 mmol), 4a (0.1 mmol), Ni(OAc)₂·4H₂O (10 mol%), ligand (20 mol%), Zn⁰ (0.3 mmol) and additive (0.1 mmol) in 1 mL TFE (0.1 M) at 80 °C, unless noted otherwise.

^bYields are of isolated products.

^cDetermined by HPLC analysis on a chiral stationary phase.

^d 5ab/5ab′.

^eUsing TFE/HFIP (4/1) or TFE as solvent.

^f 4b was used instead of 4a.

^g 4c was used instead of 4a.