Premium
Stereoselective Synthesis of Hexahydroisobenzofuran‐4(1 H )‐ones from Chiral Substituted Cyclohex‐2‐enyl Carbamates via Asymmetric Homoaldol Reaction and THF Cyclocondensation
Author(s) -
Becker Jochen,
Fröhlich Roland,
Kataeva Olga,
Hoppe Dieter
Publication year - 2007
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/ejoc.200700220
Subject(s) - chemistry , transmetalation , stereoselectivity , yield (engineering) , selectivity , lewis acids and bases , stereochemistry , asymmetric induction , enantioselective synthesis , medicinal chemistry , organic chemistry , catalysis , materials science , metallurgy
The diastereofacial selectivity of the homoaldol reaction of metalated substituted cyclohex‐2‐enyl carbamates with aldehydes is controlled by the nature of the metal complex. Allyllithiums yield syn ‐configured products whereas transmetallation to Ti(NEt 2 ) 3 gives access to anti ‐configured 3‐(1‐hydroxyalkyl)cyclohexenes. The syn ‐configured homoaldol products were transformed into annulated all ‐ cis ‐tetrahydrofurans by Lewis acid‐mediated cyclocondensation with aldehydes. Analogous cis , trans , cis‐ substituted hexahydroisobenzofuran‐4(1 H )‐ones, the core structure of many biologically active natural products, were synthesized starting from anti ‐configured homoaldol products. The configurations of the products were determined by 1 H NMR coupling constants, nOe‐studies, and X‐ray crystal structure analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)