Table 1.

Optimization of the cyanomethylation of 2,2,2-trifluoroacetophenone.^[a]

Entry	Base (mol%)	Solvent	Time (h)	Temp (°C)	Yield (%)[b]
1	DBU (50)	THF	42	25	49
2	Et3N (50)	THF	42	25	45
3	DIPEA (50)	THF	42	25	29
4	DABCO (50)	THF	42	25	13
5	TMEDA (50)	THF	42	25	23
6	DMAP (50)	THF	42	25	36
7	Barton’s base (50)	THF	42	25	42
8	K2CO3 (50)	THF	42	25	<5
9	Cs2CO3 (50)	THF	42	25	9
10	None	THF	42	25	nr
11	Et3N (50)	CH2Cl2	48	25	<5
12	Et3N (50)	1,4-dioxane	48	25	27
13	Et3N (50)	toluene	48	25	<5
14	Et3N (50)	CH3CN	48	25	8
15	Et3N (50)	CH3OH	48	25	<5
16	Et3N (50)	H2O	48	25	nr
17	Et3N (10)	neat, MW	0.75	100	89
18	Et3N (50)	THF	16	60	99
19	Et3N (20)	THF	21	60	98[d]
20[c]	Et3N (20)	THF	24	60	98[d]
21[c]	Et3N (10)	THF	36	60	91

^[a]Conditions: 0.3 mmol of 1a, 0.9 mmol of 2, 1 mL of solvent.

^[b]By NMR analysis.

^[c]Two equivalents of 2 were used. The reaction is slow and takes 3 days with 1.5 equivalents of 2.

^[d]Isolated yields.