Optimization of the dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones^a.

Entry	[Cu] cat.	Prolinamide	2a b (%)	drc	erd
1	Cu(OTf)2	P1	76	8 : 1	82 : 18
2	CuI	P1	44	>20 : 1	72 : 28
3	Cu(OAc)2	P1	40	7 : 1	70 : 30
4	Cu(MeCN)4PF6	P1	98	12 : 1	87 : 13
5	Cu(MeCN)4BF4	P1	76	11 : 1	78 : 22
6	Cu(acac)2	P1	93	10 : 1	80 : 20
7	Cu(MeCN)4PF6	P2	99	>20 : 1	82 : 18
8	Cu(MeCN)4PF6	P3	90	18 : 1	80 : 20
9	Cu(MeCN)4PF6	P4	99	>20 : 1	89.5 : 10:5
10	Cu(MeCN)4PF6	P5	90	18 : 1	89 : 11
Change from entry 9
11	Reaction run at 100 °C		—	nd	nd
12	Reaction concentration [0.04 M]		91	>20 : 1	90 : 10
13	Reaction concentration [0.02 M]		93	>20 : 1	91 : 9
14e	P6 used as organocatalyst		82	>20 : 1	92.5 : 7.5
15 e , f	TFA used instead of 4-BrPhCO 2 H		81	>20 : 1	96 : 4

^aGeneral conditions: 1a (0.2 mmol), [Cu] catalyst (0.02 mmol, 10 mol%), 4-bromobenzoic acid (0.1 mmol, 50 mol%), prolinamide catalyst (0.06 mmol, 30 mol%), in CPME (0.1 M, 2 mL) at 120 °C, under an argon atmosphere for 48 h.

^bIsolated yield.

^cdr calculated via¹H NMR analysis of the crude reaction mixture.

^der value was determined via chiral HPLC analysis of the pure product.

^eReaction concentration [0.02 M].

^fP6 (30 mol%) was used as prolinamide catalyst.