Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 26, 2011
Douglass F. Taber
University of Delaware

Stereoselective Carbocyclic Construction: The Metz Synthesis of (±)-Codeine

Jeffrey M. Kallemeyn of Abbott Laboratories showed (Synlett 2011, 535. DOI: 10.1055/s-0030-1259535) that 1, prepared by Itsuno-Corey reduction of the corresponding ketone, could be cyclized to 2 with high diasteroselectivity. Gérard Audran of the Université Paul Cézanne developed (Tetrahedron Lett. 2011, 52, 1082. DOI: 10.1016/j.tetlet.2010.12.097) a practical preparation of 3, then optimized the enzymatic resolution. David J. Aitken of Université Paris-Sud prepared (Tetrahedron Lett. 2011, 52, 1253. DOI: 10.1016/j.tetlet.2011.01.013) a 1:1 mixture of the readily separable diastereomers of 8 by the photochemical addition of ethylene 7 to 6. Rick L. Danheiser of MIT observed (Tetrahedron Lett. 2011, 52, 2111. DOI: 10.1016/j.tetlet.2010.11.002) high regioselectivity in the addition of ketene ketene 10 to the ynamide 9.

Wesley J. Moran of the University of Huddersfield originated (Org. Lett. 2011, 13, 2220. DOI: 10.1021/ol200471w) a protocol for the oxidative cyclization of 12 to 13. Kevin R. Campos of Merck Process effected (Org. Lett. 2011, 13, 1004. DOI: 10.1021/ol1030348) diastereoselective conjugate addition to the nitrile 14, prepared by enzymatic reduction of the corresponding enone. Qizheng Yao of China Pharmaceutical University and Ao Zhang of the Shanghai Institute of Materia Medica devised (J. Org. Chem. 2011, 76, 2820. DOI: 10.1021/jo200243d) the condensation of 18 with the carbohydrate-derived 17, to give the racemic cyclopentenone 19. Erick M. Carreira of ETH Zürich effected (Org. Lett. 2011, 13, 78. DOI: 10.1021/ol102577q) unsymmetrical ozonolysis of the enantiomerically-pure 20 to give 21 as the only isolable regioisomer.

Isabelle Chataigner and Serge R. Piettre of the Université de Rouen observed (Angew. Chem. Int. Ed. 2011, 50, 472. DOI: 10.1002/anie.201005779) smooth addition of the dipole precursor 23 to 22, leading to the dearomatized 24. En route (Org. Lett. 2011, 13, 2015. DOI: 10.1021/ol200376z) to Clavolonine, Hiromichi Fujioka of Osaka University converted 25, readily prepared via Birch reduction of benzoic acid, to the highly-substituted cyclohexanone 26. Tony K. M. Shing of the Chinese University of Hong Kong devised (Synlett 2011, 1318. DOI: 10.1055/s-0030-1260547) an efficient protocol for the conversion of the carbohydrate-derived 27 into 29, with preservation of the enantiomeric purity.

The development of general strategies for the assembly of angularly-substituted polycarbocyclic systems is one of the continuing challenges of organic synthesis. Samir Z. Zard of Ecole Polytechnique used (Org. Lett. 2011, 13, 1230. DOI: 10.1021/ol2001182) the ketone of 30 to direct the substitution of the proximal alkene, leading to 31.

Peter Metz of the Technische Universität Dresden prepared (Angew. Chem. Int. Ed. 2011, 50, 3892. DOI: 10.1002/anie.201007448) the prochiral 32 by Suzuki coupling followed by oxidation. Intramolecular dipolar cycloaddition then closed the last carbocyclic ring, leading to (±)-Codeine 35.

D. F. Taber, Org. Chem. Highlights 2011, December 26.