Table 1. Optimization for direct C(sp ³)–H bond activation.

entry	ligand	additive 1	additive 2	recovery of 1a (%)	yield of 3a (%)
1	none	Ag2CO3	(n-BuO)2PO2H	86	8
2	PPh3	Ag2CO3	(n-BuO)2PO2H	80	10
3	dppf	Ag2CO3	(n-BuO)2PO2H	93	Trace
4	Pyridine	Ag2CO3	(n-BuO)2PO2H	96	0
5	1,10-phen	Ag2CO3	(n-BuO)2PO2H	94	Trace
6	Ac-Leu-OH	Ag2CO3	None	24	65
7	Ac-Val-OH	Ag2CO3	None	18	70
8	Ac-isoLeu-OH	Ag2CO3	None	40	54
9	Ac-Gly-OH	Ag2CO3	None	5	86
10	Boc-Gly-OH	Ag2CO3	None	89	5
11	Cbz-Gly-OH	Ag2CO3	None	92	4
12	Ac-Gly-OH	Ag2CO3	(n-BuO)2PO2H	48	40
13	Ac-Gly-OH	Ag2CO3	1-AdCO2H	65	26
14	Ac-Gly-OH	Cu(OAc)2	None	88	5
15	Ac-Gly-OH	BQ	None	90	Trace
16	Ac-Gly-OH	Cu(OAc)2/O2	None	92	Trace

Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), Pd(OAc)₂ (5 mol%), additive 1 (0.1 mmol), K₂CO₃ (0.05 mmol), ligand (0.03 mmol), additive 2 (0.02 mmol), HFIP (1 ml), 100 °C, 24 h. Yields were based on LC-MS analysis using acetyl benzene as an internal standard.