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. 2025 May 21;27(22):5720–5725. doi: 10.1021/acs.orglett.5c01478

1. Optimization of the Reaction Conditions .

graphic file with name ol5c01478_0005.jpg

entry 1 (R)-3 solvent anti/syn, ee (%)
1 1a (R)-3a toluene 60/40 96
2 1a (R)-3a CH2Cl2 64/36 95
3 1a (R)-3a THF 85/15 95
4 1a (R)-3a Et2O 94/6 97
5 1a (R)-3b Et2O 95/5 98
6 1a (R)-3c Et2O 91/9 98
7 1b (R)-3a Et2O 84/16 95
8 1b (R)-3b Et2O 83/17 88
a

Reaction conditions: 1 (0.20 mmol), 2a (0.30 mmol, 1.5 equiv), and (R)-3 (5 mol %, 0.01 mmol) in the indicated solvent (2 mL, 0.1 M) under a nitrogen atmosphere unless otherwise specified.

b

A diastereomeric mixture of 4 was obtained quantitatively in all cases.

c

The diastereomeric ratio was determined by 1H NMR measurements after short path silica-gel column chromatography.

d

The enantiomeric excess of the major anti-diastereoisomer was determined by HPLC analysis using a chiral stationary phase column.

e

A 93% ee for the syn-isomer.

f

A 60% ee for the syn-isomer.