Overman synthesis

Scheme 3. Overman s intramolecular Heck strategies for the synthesis of (-)-morphine (9).

Scheme 4. Overman s sequential Heck cyclization approach to the synthesis of the scopadulcic acids.

The prerequisite for an evaluation of the utility of the aza-Cope/ Mannich strategy for a synthesis of strychnine has now been satisfied. Using unsaturated azabicyclo[3.2. ljoctanols closely related to 14, the Overman group had previously demonstrated the impressive facility with which the aza-Cope/Mannich reaction can construct the complex molecular frameworks of ( )-dehydrotubifoline and... 

E. F. Kleinman, R. A. Volkmann, L. Overman, D. J. Ricca in Comprehensive Organic Synthesis,... 

For overviews of applications of the Heck reaction in natural products synthesis, see (a) Link, J. T. Overman, L. E. In Metal-Catalyzed Cross-Coupling Reactions, Diederich, F., Stang, P. J., Eds. Wiley-VCH New York, 1998 Chapter 6. (b) Brase, S. de Meijere, A. In Metal-Catalyzed Cross-Coupling Reactions Diederich, F., Stang, P. J., Eds. Wiley New York, 1998 Chapter 3.6. (c) Nicolaou, K. C. Sorensen, E. J. Classics in Total Synthesis VCH New York, 1996 Chapter 31. These authors refer to the Heck reaction as "one of the true "power tools" of contemporary organic synthesis" (p. 566). 

Anderson CE, Donde Y, Douglas CJ, Overman LE (2005) Catalytic asymmetric synthesis of chiral allylic amines. Evaluation of ferrocenyloxazoline palladacycle catalysts and imidate motifs. J Org Chem 70 648-657... 

Prasad RS, Anderson CE, Richards CJ, Overman LE (2005) Synthesis of tert-leucine-derived cobalt oxazoline palladacycles. Reversal of palladation diastereoselectivlty and application to the asymmetric rearrangement of N-aryl trifluoroacetimidates. Organometallics 24 77-81... 

Hong, C.Y, Kado, N., Overman, L.E. (1993) Asymmetric Synthesis of Either Enantiomer of Opium Alkaloids and Morphinans. Total Synthesis of (—)- and (-f)-Dihydrocodeinone and (—)- and (-F)-Morphine. Journal of the American Chemical Society, 115, 11028-11029. 

A beautiful example of a domino [3+3]-sigmatropic rearrangement is the synthesis of the enantiopure antifungal antibiotic (-)-preussin (4-14) by Overman [5], which starts from the amine 4-10 and decanal to give the iminium ion 4-11 (Scheme 4.3). This undergoes a [3+3]-sigmatropic rearrangement to provide 4-12, followed by a Mannich reaction with the formation of 4-13. 

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