Table 1. One-pot routes to rac-2, (S)-trolline 2 and analogues via step a and steps a + b.

Aldehyde	Solvent	Step a a or f		Steps a + b b
		Linear product yield c (para : ortho)	Cyclised product yield c (para : ortho)	Product yield c (para : ortho)	Isolated product yield (para : ortho)	Product ee h
KPi step a a
5	50% CH3CN/KPi	6 32% (15 : 1)	2 68% (22 : 1)	2 97% (18 : 1)	2 81% (34 : 1) d	na
7	50% CH3CN/KPi	8 75% (8 : 1)	9 14% (13 : 1)	9 89% (9 : 1)	9 69% (50 : 1) e	na
10	50% CH3CN/KPi	11 72% (7 : 1)	Only 11	11 72% (7 : 1)	11 26% (7 : 1) e	na
Enzymatic step a f
5 g	10% CH3CN/HEPES	6 35%	2 3%	na	na	nd
5 g	10% DMSO/HEPES	6 61%	2 7%	na	na	nd
5	10% DMSO/HEPES	6 71%	2 15%	na	na	nd
5	1% DMSO/HEPES	6 67%	2 19%	2 75%	2 74% d	95%
7	1% DMSO/HEPES	8 82%	9 15%	9 96%	9 87% d	96%
10	1% DMSO/HEPES	11 92%	only 11	11 92%	11 63% e	>99%

^a 1 and aldehyde (1 : 1.5) in KPi buffer (0.3 M)/CH₃CN (1 : 1), 18 h, under Ar, 60 °C, pH 6, and ascorbic acid (1 equiv.).

^bNa₂CO₃ (1 M), pH 7.5, and 4 h.

^cHPLC yields: calculated by analytical HPLC.

^dIsolated in high purity by a basic and then acidic extraction procedure using EtOAc and then MeOCO₂Me.

^eIsolated by preparative HPLC.

^f 1 and aldehyde (ratio 1 : 1.5) in co-solvent/HEPES buffer (pH 7.5 and 0.1 M), 37 °C, WT-TfNCS (0.1 mg mL^–1), sodium ascorbate (1 equiv.), and 6 h.

^gAs for f but 1 : 5 in a ratio of 1.5 : 1, and 3 h reaction.

^hThe ees determined by chiral HPLC: for trolline the absolute stereochemistry was confirmed by the optical rotation. na, not applicable. nd, not determined.