Table 1.

Optimization of the oxa-Pictet-Spengler reaction.^a

entry	Lewis acids	solvent	temp (ºC)	conversion (%)b	dr (6aα/6aβ)c
1	BF3·OEt2	CH2Cl2	0-rt	80(75)	66:34
2	Yb(OTf)3	CH2Cl2	0-rt	10	80:20
3	Y(OTf)3	CH2Cl2	0-rt	23	67:33
4d	TiCl4	CH2Cl2	−78-rt	70	70:30
5	SnCl4	CH2Cl2	0-rt	100	60:40
6	FeCl3	CH2Cl2	0-rt	100	52:48
7	Cu(OTf)2	CH2Cl2	0-rt	85	89:11
8e	Cu(OTf)2	CH2Cl2	0-rt	95(90)	91:9
9	Cu(OTf)2	DCE	0-rt	(64)	90:10
10	Cu(OTf)2	CHCl3	0-rt	(43)	94:6
11f	Cu(OTf)2	CH2Cl2	0-rt	(32)	93:7
12g	Cu(OTf)2	CH2Cl2	0-rt	(48)	91:9
13	FeCl3	THF	0-rt	(50)	34:66

^aReaction was performed with 0.2 mmol 5, 0.4 mmol aldehyde, and 50 mol % Lewis acid at 0 ºC. The temperature was allowed to subseqeuntly raise to rt over 4 h with 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.

^d2 h reaction time.

^eOvernight.

^fUsing 1,1-dimethoxybutane instead of butaldehyde.

^gUsing 20 mol % Lewis acid.