Synthesis of Echinopines A and B

1. Synthesis of Echinopines A and B James Bull Louis-Philippe Beaulieu Olga Lifchits Frederic Vallée Kim Laberge

2. Synthesis Plan

3. Synthesis Plan

4. Synthesis Plan Stereochemistry unimportant

5. Synthesis Plan Stereochemistry unimportant Use stereochemistry to control diastereoselectivity Simmons-Smith Homologation

6. Diastereoselective Pauson Khand For a recent review on the Pauson-Khand reaction: Perez-Castells, J. et al., Chem. Soc. Rev., 2004, 33, 32-42

7. Diastereoselective Pauson Khand

8. Diastereoselective Pauson Khand Oxidation to b-g unsaturated aldehyde: Viala, Synthesis, 2001, 326 For S containing Pauson-Khand: Moyano et al. J. Org. Chem. 1998, 63, 3346. Dithiolane protection: D. A. Evans, et al, J. Am. Chem. Soc., 1977, 99, 5009. Also Perkin 1, 1998, 149

9. Chemoselective Cyclopropanation Martin et al. JACS 1974, 4604 Grignard: Synth. Comm. 1990, 20, 1175-1179; Heterocycles, 1998, 48, 1423-1430 For a similar example of Grignard addition/dehydration: Aust. J. Chem. 1995, 48, 515.

10. Alkyne formation Ohira-Bestmann: see Synlett, 1996, 521

11. Radical Cyclisation End Game Echinopine B 17 Steps Echinopine A 18 Steps