Table 3.

Ring contraction reaction optimization.^a

entry	base	additive	solvent	T (°C)	yieldb(%)
1	LiOt-Bu	—	t-BuOH	40	71
2	LiOt-Bu	—	THF	40	60
3	NaOt-Bu	—	THF	40	81
4e	KOt-Bu	—	THF	40	85
5	NaOH	—	THF	60	89
6	KOH	—	THF	60	87
7	LiOH	—	THF	60	19d
8	LiOH	t-BuOH	THF	60	78
9	LiOH	HFIPc	THF	60	87
10	LiOH	TFEc	THF	60	96
11	LiOCH2CF3	—	THF	60	90e
12	CsOH·H2O	—	THF	60	48
13	Cs2CO3	—	THF	60	61f
14	Cs2CO3	TFEc	THF	60	86
15	Cs2CO3	TFEc	CH3CN	60	100

^aConditions: β-hydroxyketone 10a (1.0 equiv), additive (1.5 equiv), base (1.5 equiv), solvent (0.1 M) at indicated temperature for 9–24 h.

^bGC yield using an internal standard at ≥ 98% conversion unless otherwise stated.

^cHFIP = 1,1,1,3,3,3-hexafluoro-2-propanol; TFE = 2,2,2-trifluoroethanol.

^dSeveral reaction intermediates observed by TLC and GC analysis; proceeded to 78% conversion.

^eIsolated yield.

^fReaction did not reach completion at 24 h; proceeded to 67% conversion.