Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 9, 2011
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: (+)-Preussin (Britton), (±)-Xenovenine (Livinghouse), (+)-Subincanadine F (Li), (±)-Strychnine (Reissig), (-)-Virginiamycin M2 (Panek)

Aldehydes such as 1 are readily available by direct enantioselective chlorination. Robert Britton of Simon Fraser University found (Org. Lett. 2010, 12, 4034. DOI: 10.1021/ol101631e) that the addition of the kinetic ketone enolate 2 gave the anti aldol 3. Condensation of the chlorohydrin 3 with a primary amine led to the cyclic pyrrolinium salt, that was reduced with high diastereocontrol to (+)-Preussin (4).

Tom Livinghouse of Montana State University developed Sc catalysts for the cyclization of γ-amino terminal alkenes such as 5. In contrast, addition to internal alkenes was sluggish. He has now shown (Org. Lett. 2010, 12, 4271. DOI: 10.1021/ol101646t) that a thiophene substituent activated the internal alkene for addition, enabling the facile synthesis of (±)-Xenovenine (7).

Chaozhong Li of the Shanghai Institute of Organic Chemistry found (Chem. Commun. 2010, 46, 8436. DOI: 10.1039/C0CC03428B) that ferrocenium ion cleanly oxidized the enolate of the β-keto ester 8, effecting cyclization to 9. The D-tryptophan-derived ester that directed the relative and absolute configuration of the cyclization could readily by removed, delivering (+)-Subincanadine F (10).

In a complementary approach to indole alkaloid synthesis, Hans-Ulrich Reissig of the Freie Universität Berlin devised (Angew. Chem. Int. Ed. 2010, 49, 8021. DOI: 10.1002/anie.201003320) the elegant SmI2-mediated double cyclization of 11 to 12. This set the stage for the assembly of (±)-Strychnine (13).

James S. Panek of Boston University used (Angew. Chem. Int. Ed. 2010, 49, 6165. DOI: 10.1002/anie.201002220) the enantiomerically-pure allylic silanes that he has developed to construct the chloroaldehyde 14. He found that the reductive cyclization to 15 was best carried out with SmI2 in benzene.

SmI2 has the virtue that it is soluble in common organic solvents, so it can readily be deployed even on a micromole scale. It is also versatile, because its reducing power can be tuned by the solvent in which it is dissolved.

D. F. Taber, Org. Chem. Highlights 2011, May 9.