Table 2.

Optimization of C–H arylation of N‐Boc‐pyrrolidinecarboxamide 5.

Entry	Round	Varied conditions	Yield 6a [%][a]	RSM 5 [%][a]
1	1	AgOAc, Pd(OAc)2, toluene (0.3 m)	18[b]	82[b]
2	1	AgOAc, Pd(TFA)2, toluene (0.3 m)	0	100
3	1	AgOAc, Pd(OAc)2, tert‐amyl‐OH (0.3 m)	10	90
4	1	AgOAc, Pd(OAc)2, no solvent	21	79
5[c]	2	Ag2CO3, Pd(OAc)2, toluene (0.3 m)	24	76
6[c], [d]	2	Ag2CO3, PivOH, Pd(OAc)2, toluene (0.3 m)	40[e]	60[e]
7[d]	2	K2CO3, PivOH, Pd(OAc)2, toluene (0.3 m)	3	97
8	2	CsOAc, Pd(OAc)2, toluene (0.3 m)	12	88
9[c], [d]	3	Ag2CO3, PivOH, Pd(OAc)2, toluene (0.2 m)	33	67
10[c], [d]	3	Ag2CO3, PivOH, Pd(OAc)2, toluene (0.5 m)	33	67
11[c], [d]	3	Ag2CO3, PivOH, Pd(OAc)2, toluene (1.0 m)	36	64
12[c], [d]	3	Ag2CO3, PivOH, Pd(OAc)2, no solvent	34	66

^[a]Yield of product 6a or recovered starting material 5 determined by ¹H NMR spectroscopy with respect to an internal standard (1,3,5‐trimethoxybenzene).

^[b]Average yield of 3 reactions.

^[c]1 equiv. Ag₂CO₃.

^[d]30 mol‐% PivOH.

^[e]Average yield of 2 reactions.