Table 2.

Three-component direct Mannich reaction catalyzed by bifunctional catalysts 9 or 10^a

entry	X/ R1 / R2	1/3/4	time (h)	yield (%)b	ee (%)c
1	H/Ph/Ph	a/a/a	48	96	96
2	4-Me/Ph/Ph	b/a/b	40	95	96
3	4-MeO/Ph/Ph	c/a/c	48	88	96
4	4-F/Ph/Ph	d/a/d	36	96	95
5	4-Cl/Ph/Ph	e/a/e	24	95	94
6	4-Br/Ph/Ph	f/a/f	24	97	94
7	4-CN/Ph/Ph	g/a/g	40	97	97
8	4-NO2/Ph/Ph	h/a/h	24	93	93
9	2-Br/Ph/Ph	i/a/i	48	96	95
10	3-Br/Ph/Ph	j/a/j	24	96	95
11	H/4-BrC6H4/Ph	a/b/k	30	95	98
12	H/4-ClC6H4/Ph	a/c/l	35	95	96
13	H/4-MeOC6H4/Ph	a/d/m	72	75	96
14	H/Et/Ph	a/e/n	96	75	>99
15	H/PhCH2/Ph	a/f/o	24	95	96
16	H/Ph/OBoc	a/g/p	24	96d	>99
17	4-Br/Ph/OBoc	f/g/q	40	96e	>99
18f	H/4-MeOC6H4/OBoc	a/h/r	48	95g	>99

^aUnless otherwise indicated, all reactions were carried out at 0 °C with aldehyde 1 (0.20 mmol), p-toluenesulfonamide (2, 0.40 mmol), ketone 3 (0.40 mmol), catalyst 9 (0.020 mmol, 10 mol %), and 4 Å MS (50. 0 mg) in toluene (2.0 mL).

^bYield of the isolated product after column chromatography. Only a single diastereomer was detected by the ¹H NMR analysis of the crude reaction product in all cases (dr >99:1) except for entries 16–18.

^cDetermined by HPLC analysis.

^dThe dr of this reaction was 93:7.

^eThe dr of this reaction was 92:8.

^fCatalyst 10 (10 mol %) was used, and the opposite enantiomer was obtained as the major product.

^gThe dr of this reaction was 90:10.