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Monday, November 25, 2013
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Lycoposerramine Z (Bonjoch), Esermethole (Shishido), Goniomitine (Zhu), Grandisine (Taylor), Reserpine (Jacobsen)

Josep Bonjoch of the Universitat de Barcelona extended (Org. Lett. 2013, 15, 326. ) the Jřrgensen variation of the Robinson annulation to the amine-substituted β-keto ester 1. The product cis-fused sulfonamide 3, readily brought to high ee by recrystallization, was carried on to (+)-Lycoposerramine Z (4).

Intramolecular ketene 2+2 cycloaddition is underdeveloped as a synthetic method. Kozo Shishido of the University of Tokushima observed (Org. Lett. 2013, 15, 200. ) high diastereoselectivity in the cyclization of 5 to 6. This set the stage for the synthesis of (-)-esermethole (7).

Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne prepared (Angew. Chem. Int. Ed. 2013, 52, 3272. ) the cyclopentene 8 by coupling the alkenyl triflate with the salt of an α-alkyl arylacetic acid. Ozonolysis followed by reductive work up led to a diamino keto aldehyde that cyclized to 9. Benzyl ether cleavage delivered (±)-Goniomitine (10).

Richard J. K. Taylor of the University of York developed (Angew. Chem. Int. Ed. 2013, 52, 1490. ) a powerful tandem conjugate addition-imination-methanolysis protocol. He had already prepared (+)-Grandisine (11) from N-Boc prolinol. Amination-imination converted 11 to (+)-Grandisine (12). This was opened by methanolysis to (+)-Grandisine G (13).

Four diastereomers are possible from the condensation of 14 and 15. Eric N. Jacobsen of Harvard University developed (Org. Lett. 2013, 15, 706. ) an organocatalyst that delivered 16 as the dominant diastereomer. This was readily converted to (+)-Reserpine, the enantiomer of the natural product.

D. F. Taber, Org. Chem. Highlights 2013, November 25.