Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 22, 2010
Douglass F. Taber
University of Delaware

Synthesis of C-N Natural Products: (-)-α-Kainic Acid (Helmchen), (+)-Tylophorine (Opatz), (-)-Lycoperine A (Rychnovsky), Fluvirucidine A2 (Suh), Complanidine A (Sarpong)

Günter Helmchen of the Ruprecht-Karls-Universität Heidelberg set (Org. Lett. 2010, 12, 1108. DOI: 10.1021/ol1001076) the absolute configuration of 3 by Ir*-mediated coupling of 1 with 2. Diastereoselective Pauson-Khand cyclization then led to (-)-α-Kainic Acid (5).

Till Opatz, now at the Johannes Gutenberg-Universität Mainz, showed (Org. Lett. 2010, 12, 2140. DOI: 10.1021/ol100652b) that the product from the Dibal reduction of 6 could be condensed with the amine 7 without epimerization. Kim cyclization then directly delivered the pentacyclic alkaloid (+)-Tylophorine (9).

The interesting dimeric alkaloid Lycoperine A (13) was recently isolated from the Japanese club moss Lycopodium hamiltonii. Scott D. Rychnovsky of the University of California, Irvine prepared (Org. Lett. 2010, 12, 72. DOI: 10.1021/ol902389e) 12 by double alkylation of the bis-nitrile 11 with the enantiomerically-pure allylic bromide 10. While the projected reductive decyanation of 12 failed, hydrolysis followed by diastereoselective reductive amination successfully gave 13.

Retrosynthetic analysis of Fluvirucinine A2 (16) could lead to an acyclic amino acid, that could be cyclized to the macrolactam. Young-Ger Suh of Seoul National University took (Org. Lett. 2010, 12, 2040. DOI: 10.1021/ol100521v) a different approach, building up the fourteen-membered ring system by two four-carbon ring expansions, beginning with an enantiomerically-pure piperidine precursor. The second of these enolate-based aza-Claisen ring expansions is illustrated in the conversion of 14 to 15.

Richmond Sarpong of the University of California, Berkeley faced (J. Am. Chem. Soc. 2010, 132, 5926. DOI: 10.1021/ja101893b) a different sort of challenge in the synthesis of the dimeric Lycopodium alkaloid Complanadine A (19). Even with established access to monomers such as 17 and its precursors, it was not clear how the 5-position of the pyridine ring could be selectively activated for bond formation. The solution to this dilemma was found in the work of Hartwig. Following that precedent, Ir-catalyzed activation of 17 converted it cleanly into the boronate 18, that could then be coupled with a pyridone triflate to complete the synthesis of 19.

D. F. Taber, Org. Chem. Highlights 2010, November 22.