Table 1.

Optimization of the Friedel–Crafts spirocyclization reaction.^[a]

Entry	Acid	X equiv	Conditions	4 a: % Yield[a]
1	In(OTf)3	2.00	CH2Cl2, 0 °C–rt, 4 h	0
2	BF3⋅OEt2	1.10	CH2Cl2, 0 °C, 1.5 h	16
3	TFA	2.00	CH2Cl2, 0 °C, 1.5 h	7 (52)[b]
4	TfOH	2.00	CH2Cl2, 0 °C, 1.5 h	24
5	HPF6	1.05	CH2Cl2, 0 °C, 2 h	37
6	HBF4	1.05	CH2Cl2, 0 °C, 1 h	43
7	HBF4	0.50	CH2Cl2, 0 °C–rt, 6 h	20
8	HBF4	1.50	CH2Cl2, 0 °C, 1 h	41
9	HBF4	1.05	CHCl3, 0 °C, 1 h	64 (63) [c]
10	HBF4	0	CHCl3, 0 °C, 1 h	0 (85)[d]

All reactions were carried out using 2 a (0.10 mmol). [a] Yields were determined by ¹H NMR analysis using dibromomethane as an internal standard after protection of the amine intermediate with Boc₂O. [b] Yield of product from the intermolecular addition of trifluoroacetate to ABB. [c] 0.2 mmol scale. Isolated yield. [d] Returned 2 a.