Table 1. Optimization of the 1,6-addition of glycine Schiff base 1 to p-QM 7a.^a.

Entry	ITU	Base	T [°C]	Yield[%]b	drc	erd,e
1	–	Et3N	25	70	75:25	–
2	ITU-1	Et3N	25	53	75:25	–
3	ITU-2	Et3N	25	85	70:30	42:58 (45:55)
4	ISeU-2	Et3N	25	73	60:40	26:74 (44:56)
5	ITU-3	Et3N	25	79	75:25	38:62 (40:60)
6	ITU-4	Et3N	25	66	65:35	18:82 (69:31)
7	ITU-5	Et3N	25	66	75:25	84:16 (40:60)
8	ITU-5	DIPEA	25	67	75:25	90:10 (45:55)
9	ITU-5	DABCO	25	58	70:30	90:10 (40:60)
10	ITU-5	K2CO3	25	73	70:30	87:13 (40:60)
11f	ITU-5	DIPEA	25	41	60:40	89:11 (59:41)
12g	ITU-5	DIPEA	25	78	65:35	89:11 (38:62)
13	ITU-5(5%)	DIPEA	25	71	75:25	80:20 (46:54)
14	ITU-5 (20%)	DIPEA	25	60	70:30	90:10 (43:57)
15	ITU-5	DIPEA	− 20	72	80:20	93:7 (52:48)
16	ITU-5	DIPEA	− 40	77	85:15	93:7 (56:44)

^aAll reactions were run using 0.05-0.1 mmol 1, 7a (1 equiv.) and base (1 equiv.) in acetonitrile under the given conditions unless otherwise stated.

^bIsolated yields of the mixture of diastereomers.

^cDetermined by 1^H NMR of the crude product.

^dDetermined by HPLC using a chiral stationary phase (values in brackets refer to the er of the minor diastereoisomer).

^eFor the major stereoisomer the depicted (R,R)-configuration was assigned in analogy to the results obtained by single crystal X-ray analysis of derivative 9d (see below) and comparison of the analytical details of products 8 (Scheme 3) and derivatives thereof (Scheme 4) with reported data.^[29]

^fCH₂Cl₂ as the solvent.

^gAcetone as the solvent.