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

22 Synthesis Plan

33

44 Stereochemistry unimportant

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

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

77 Diastereoselective Pauson Khand

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

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

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

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