Table 1.

Initial Screen with Amines and VANOL, VAPOL and BINOL ligands.^a

entry	ligand	amine	phenol/alcoholb	catalyst#	time (h)	% yield 3c	erd
1	L-4	A-1	P-11	LAP 4-1-11	18	nde	–
2	L-4	A-2	P-11	LAP 4-2-11	24	nd	–
3	L-4	A-3	P-11	LAP 4-3-11	24	nd	–
4	L-4	A-4	P-11	LAP 4-4-11	24	nd	–
5	L-4	A-5	P-11	LAP 4-5-11	24	76	41 : 59f
6	L-4	A-6	P-11	LAP 4-6-11	18	ndg	–
7	L-4	A-7	P-11	LAP 4-7-11	48	82	57 : 43
8	L-1	A-5	P-11	LAP 1-5-11	36	60	47 : 53f
9	L-10	A-5	P-11	LAP 10-5-11	40	9h	44 : 56f
10	L-11	A-5	P-11	LAP 11-5-11	24	37	55 : 45
11	L-12	A-5	P-11	LAP 12-5-11	43	30	55 : 45
12	L-13	A-5	P-11	LAP 13-5-11	24	trace	–

^aUnless otherwise specified, all reactions were carried out at 0.2 M in 1a (0.25 mmol) in toluene with 2.0 equiv amine and 1.5 equiv of 2 at rt for the indicated time with 20 mol % of the catalyst. The pre-catalyst was prepared by heating 20 mol% of the (R)-ligand, 40 mol% of the phenol or alcohol, 60 mol% H₂O, 60 mol% of BH₃·SMe₂ in toluene at 100 °C for 1 h. After removal of all volatiles, the BOROX catalyst was generated in-situ by the addition of the amine at rt and this was followed by the addition of aldehyde and then the isonitrile.

^bP-11 is phenol (Table 2).

^cIsolated yield after chromatography on silica gel. nd = not detected.

^dDetermined by HPLC.

^eThe aminal 5 was formed in 50% yield (¹H NMR) and amide 3 could not be detected. Heating this mixture at 80 °C for 18 h resulted in a complex mixture with 3 still not detectable.

^fCatalyst was generated from (S)-ligand.

^gThe imine 4 was formed in 100% yield as determined by ¹H NMR yield with an internal standard. After 89 h, a 100% yield of imine was still observed.

^h1H NMR yield with internal standard.