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While this manuscript was being prepared, two reports detailing a similar strategy have appeared: a) for a report disclosing the synthesis of two C-1,2-didehydro cinchonidine/chinchonine-derived variants of 9-epi-DHQT (amongst others) which promoted the efficient addition to thiophenol to α-β-unsaturated imides with low selectivity (up to 17% ee), see: B.-J. Li, L. Jiang, M. Liu, Y.-C. Chen, L.-S. Ding, Y. Wu, Synlett, 2005, 603;
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note
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The prefix "epi" usually refers only to inversion of configuration at a single stereocenter, that is, no functional-group interconversion is implied. The term is adopted in this case for convenient identification of the relative stereochemistry of the catalyst at C8/C9.
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To the best of our knowledge only Deng et al. (ref. [9]) have thus far successfully selectively converted this hindered substrate by using 20 mol % 6′-demethylated quinine.
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MM2 force-field energy-minimization calculations were carried out with CS Chem3D Std v.4.0 software. Conformers were minimized to a minimum RMS gradient of 0.02.
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[12e, 13b].
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This would account for the observed product stereochemistry, and the decrease in catalyst efficiency and selectivity associated with DHQU relative to 9-epi-DHQU. However, it is acknowledged that alternative rationales are possible, for example, reversal of binding selectivity relative to 9-epi-DHQU, etc. It is envisaged that ongoing structural studies will provide more detailed insight into the catalytic behaviour of these C9 diastereomers.
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