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Synthesis of ( R )‐ and ( S )‐ O ‐Methylcannabispirenone by Desymmetrization of O ‐Methylcannabispirone
Author(s) -
Braun Manfred,
Meyer Brigitte,
Féaux de Lacroix Boris
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200204)2002:8<1424::aid-ejoc1424>3.0.co;2-w
Subject(s) - chemistry , enantioselective synthesis , desymmetrization , lithium amide , diastereomer , deprotonation , ketone , lithium (medication) , stereochemistry , enantiomer , enantiomeric excess , medicinal chemistry , amide , base (topology) , organic chemistry , catalysis , medicine , ion , mathematical analysis , mathematics , endocrinology
Abstract O ‐Methylcannabispirenone ( 1c ) is available by a one‐pot protocol that involves enantioselective deprotonation of the ketone 2 , conversion of the lithium enolate thus formed into the β‐keto selenide, oxidation and spontaneous elimination. When the C 2 ‐symmetric lithium base 5b is used for enolate formation, ( S )‐ 1c is obtained in 45−54% ee In contrast, the lithium amide 6b , derived from the diamine 6a , gives the enantiomeric enolate predominantly, thus leading to ( R )‐ 1c . The norephedrine‐derived base 6b , hitherto not applied for enantioselective deprotonations of meso ‐ketones, provides a higher enantioselectivity in the formation of the spirenone 1c (84% ee ) than the amide base 5b . According to known procedures, the dimethyl ether 1c can be converted into the nonhallucinogenic natural products cannabispirenone A ( 1a ) and B ( 1b ). The enantiomeric excess of ( R )‐ and ( S )‐ 1c was determined by treatment with ( R , R )‐diol 8 , leading to the diastereomeric acetals 9 and 10 . (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)