Table 1.

Optimization studies for enantioselective alkynylation of C–P bond with terminal alkynes

Entry	Ligand	Additive	Solvent	Base	3a
					Yield (%)a	e.e. (%)b	dr
1	L1	CuI	2-Me-THF	Cs2CO3	65	51	>25:1
2	L2	CuI	2-Me-THF	Cs2CO3	18	54	>25:1
3	L3	CuI	2-Me-THF	Cs2CO3	93	8	>25:1
4	L4	CuI	2-Me-THF	Cs2CO3	>99	86	>25:1
5	L5	CuI	2-Me-THF	Cs2CO3	42	82	>25:1
6	L6	CuI	2-Me-THF	Cs2CO3	86	91	>25:1
7	L6	CuBr	2-Me-THF	Cs2CO3	90	91	>25:1
8	L6	CuCl	2-Me-THF	Cs2CO3	47	90	>25:1
9	L6	CuBr	TBME	Cs2CO3	19	95	>25:1
10	L6	CuBr	DME	Cs2CO3	55	91	>25:1
11	L6	CuBr	Toluene	Cs2CO3	16	89	>25:1
12	L6	CuBr	CH3CN	Cs2CO3	Trace	N.D.	N.D.
13	L6	CuBr	2-Me-THF	K2CO3	78	93	>25:1
14	L6	CuBr	2-Me-THF	K3PO4	76	93	>25:1
15	L6	CuBr	2-Me-THF	DBU	30	90	>25:1
16	L6	CuBr	2-Me-THF	Et3N	0	N.D.	N.D.
17c	L6	CuBr	2-Me-THF	Cs2CO3	98	92	>25:1
18c,d	L6	CuBr	2-Me-THF	Cs2CO3	>99 (83)	93	>25:1

The enantioselective alkynylation of C–P bond was performed by using 1a (0.2 mmol), 2a (0.4 mmol), [Pd(allyl)Cl]₂ (5 mol%), chiral phosphine (22 mol%), additive (0.75 equiv), and base (2.0 equiv) in solvent (2.0 mL) at 60 °C for 12 h.

N.D. not detected.

^aThe yield was determined by ¹H NMR using CH₂Br₂ as the internal standard. Isolated yields are reported in parentheses.

^bee values of the major isomers are shown and determined by chiral HPLC analysis. dr values were determined by ¹H NMR analysis of the crude reaction mixtures.

^c[Pd(allyl)Cl]₂ (2.5 mol%), L6 (11 mol%) and the reaction was performed at 45 °C for 36 h.

^dCuBr (1 equiv) was used.