. Author manuscript; available in PMC: 2017 Nov 3.

Published in final edited form as: J Org Chem. 2017 Aug 4;82(16):8514–8526. doi: 10.1021/acs.joc.7b01274

Table 1.

Optimizations To Synthesize the Pivotal α-Chloroglycin Ester 6a



entry	solvent, temp^a	activator	time (h)	conversion (%)^b
1	CHCl₃, rt		12	5a (62)^c
2	CHCl₃, rt	AcCl	18	5a (76); 6a (4)
3	CH₃CO₂Et, rt		12	5a (82)^c
4	CH₃CO₂Et, rt	AcCl	18	5a (59); 6a (19)
5	CH₃CO₂Et, 60 °C	AcCl	9	6a (100)
6	CHCl₃, 60 °C	AcCl	12	6a (100)
7	THF, 60 °C	AcCl	12	5a (61); 6a (25)^d
8	toluene, 60 °C	AcCl	12	5a (44); 6a (56)
9	CH₃CN, 60 °C	AcCl	24	6a (100)

Reactions were performed with 2a (1.0 mmol), 3a (1.3 mmol), acetyl chloride (2.5 mmol), and acetic acid (10 mol %).

Conversions were reported due to the innate instability of chloroaminal 6a, using a quantitative 1H NMR technique²¹ with mesitylene as an internal standard.

Isolated yields of pure hemiaminal 5a were 60% and 81% for entries 1 and 3, respectively.

Decomposition and possible polymerization were observed.