Table 1. Optimization Studies for the Formation of 6a^a,b.

entry	catalyst (mol %)	[O] (equiv)	additive (equiv)	solvent	T (°C)	product yield (%) 6a
1c	Pd(OAc)2 (10)	Cu(OAc)2 (3)	–	DMF	140	49
2c	Pd(TFA)2 (10)	Cu(OAc)2 (3)	–	DMF	140	51
3d	Pd(OAc)2 (10)	Cu(OAc)2 (3)	–	DMF	140	55
4e	Pd(OAc)2 (10)	Cu(OAc)2 (3)	–	DMF	140	62
5	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (4)	DMF	140	71
6	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (2)	DMF	140	67
7	Pd(OAc)2(10)	Cu(OAc)2(3)	PivOH (6)	DMF	140	78
8f	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (6)	DMF	140	76
9	Pd(OAc)2 (10)	CuBr2 (3)	PivOH (6)	DMF	140	trace
10	Pd(OAc)2 (10)	Cu(NO3)2 (3)	PivOH (6)	DMF	140	trace
11	Pd(OAc)2 (5)	Cu(OAc)2 (3)	PivOH (6)	DMF	140	67
12	Pd(OAc)2 (10)	Cu(OAc)2 (2)	PivOH (6)	DMF	140	73
13	Pd(OAc)2 (10)	Cu(OAc)2 (1)	PivOH (6)	DMF	140	58
14	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (6)	DMF	120	32
15	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (6)	DMF	160	75
16	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (6)	CH3CN	140	trace
17	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (6)	1,4-Dioxane	140	trace
18	Pd(OAc)2 (10)	Cu(OAc)2 (3)	PivOH (6)	DMAc	140	46
19	Pd(OAc)2 (10)	–	PivOH (6)	DMF	140	trace
20	–	Cu(OAc)2 (3)	PivOH (6)	DMF	140	ND

^aThe Ugi-reaction was carried out using 1a (1.0 mmol), 2a (1.0 mmol), 3a (1.05 mmol), and 4a (1.05 mmol) in MeOH (1 M) for 12 h at rt.

^bReaction conditions: 5a (0.3 mmol), Pd(OAc)₂ (10 mol %), [O] (0.9 mmol), PivOH (1.8 mmol), solvent (1 mL), 140 °C, N₂, isolated yields.

^cSolvent (6 mL).

^dSolvent (3 mL).

^eSolvent (1 mL).

^fReaction time: 16 h.