Table 2.

Optimization of the oxa-Pictet-Spengler reaction with trimethyl orthoformate.^a

entry	Lewis acids	solvent	temp (ºC)	time (h)	conversion (%)b
1	FeCl3	CH2Cl2	0	1	40(31)
2	BF3·OEt2	CH2Cl2	0	1	20
3	Fe(OTf)3	CH2Cl2	0	2	23
4	AlCl3	CH2Cl2	0	1	<10
5	SnCl4	CH2Cl2	0	1	45(33)
6	EtAlCl2	CH2Cl2	0	1	60(51)
7	Et2AlCl	CH2Cl2	0	2	<10d
8	EtAlCl2	CH2Cl2	−40	16	45(36)
9	EtAlCl2	CH2Cl2	−20	16	80(70)
10	EtAlCl2	DCE	−20	16	74(62)
11e	EtAlCl2	CH2Cl2	−20	16	78(65)

^aReaction was performed with 0.2 mmol 5, 0.24 mmol trimethyl orthoformate, and 100 mol % Lewis acid at 0 ºC with 1 h stirring.

^bConversion was determined by HPLC analysis. The data in the parentheses are the isolated yields after column chromatography.

^cdr ratio was determined by the proton NMR of crude products.

^dformation of the side product 11 in 60% yield.

^e2 mmol 5 was loaded.