Diastereoselective Ammonium-Directed Epoxidation in the Asymmetric Syntheses of Dihydroconduramines (+)-C-2, (−)-C-2, (+)-D-2, (+)-E-2, (+)-F-2, and (−)-F‑2

• Published in: Journal of organic chemistry Vol. 83; no. 17; pp. 9939 - 9957
• Main Authors: Da Silva Pinto, Solange, Davies, Stephen G, Fletcher, Ai M, Roberts, Paul M, Thomson, James E
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.09.2018; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; GLYCOSIDASE INHIBITORS; DERIVATIVES; PURE; STRATEGY
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.8b01359

Epoxidations (40% aq HBF4 then m-CPBA) of racemic cis-2-(N-benzylamino)­cyclohex-3-en-1-ol and racemic cis-2-(N,N-dibenzylamino)­cyclohex-3-en-1-ol proceed with very high levels of diastereoselectivity (>95:5 dr). The latter is in direct contrast to the epoxidation of the corresponding trans-diastereoisomer (which proceeds with essentially no selectivity), showing that the relative configuration of the substrate dramatically influences the diastereoselectivity in these instances. Meanwhile, epoxidations of enantiopure (1R,2S,αR)-2-[(N-α-methylbenzyl)­amino]­cyclohex-3-en-1-ol and (1S,2R,αR)-2-[(N-α-methylbenzyl)­amino]­cyclohex-3-en-1-ol [surrogates for the enantiomers of cis-2-(N-benzylamino)­cyclohex-3-en-1-ol] proceed with complete diastereoselectivity (>95:5 dr) under the same conditions, showing that neither the presence of the α-methyl group nor the relative configuration of the α-methylbenzyl stereocenter have an effect upon the established level of diastereoslectivity in these cases. In contrast, epoxidations of enantiopure (1R,2S,αR)-2-[N-benzyl-N-(α-methylbenzyl)­amino]­cyclohex-3-en-1-ol and (1S,2R,αR)-2-[N-benzyl-N-(α-methylbenzyl)­amino]­cyclohex-3-en-1-ol [surrogates for the enantiomers of cis-2-(N,N-dibenzylamino)­cyclohex-3-en-1-ol] proceed with lower diastereoselectivity (∼70:30 dr). Thus, the presence of the α-methyl group has a detrimental effect on the established level of diastereoselectivity in these cases (although again the relative configuration of the α-methylbenzyl stereocenter is unimportant). The diastereoselective epoxidation pathway is used to enable the asymmetric syntheses of six hitherto unknown, enantiopure dihydroconduramines (+)-C-2, (−)-C-2, (+)-D-2, (+)-E-2, (+)-F-2, and (−)-F-2 (>99% ee in each case).