Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 18, 2006
Douglass Taber
University of Delaware

Enantioselective Carbocyclic Construction

Richard P. Hsung, now of the University of Wisconsin, has reported (Org. Lett. 2006, 8, 231. DOI: 10.1021/ol052487s) the intramolecular addition of ynamides to aldehydes. One might classify this as an intramolecular aldol condensation. It is known that the conjugate addition of organometallics to chiral imides such as 2 proceeds with high facial control.

Many methods have been developed for the enantioselective transformation of preexisting prochiral rings. The work (Angew. Chem. Int. Ed. 2006, 45, 947, DOI: 10.1002/anie.200502658; Angew. Chem. Int. Ed. 2006, 45, 4301, DOI: 10.1002/anie.200600867) of Li Deng of Brandeis University is particularly noteworthy. He has shown that in the presence of a catalytic amount of enantiomerically-pure base, Michael donors such as 3 add to Michael acceptors with high facial selectivity.

The “cycloaddition” of 5 to 6 developed by Gregory C. Fu of MIT (Angew. Chem. Int. Ed. 2006, 45, 1426. DOI: 10.1002/anie.200503312) is in fact a stepwise ionic process. An enantiomerically-pure phosphine catalyst directs the absolute sense of the reaction. The cycloaddition works equally well if the alkyne of 6 is replaced by another aromatic ring.

Keisuke Suzuki of the Tokyo Institute of Technology has found (Angew. Chem. Int. Ed. 2006, 45, 3492. DOI: 10.1002/anie.200600268) that the Rovis triazolium salt 9 nicely catalyzes the intramolecular benzoin condensation of keto aldehydes such as 8, with high ee.

A truly spectacular approach to organocatalytic carbocyclic construction has been reported (J. Am. Chem. Soc. 2006, 128, 5475. DOI: 10.1021/ja058490o) by Karl Anker Jorgensen of Aarhus University. Condensation of the commercially-available chloroester 12 with an α,β-unsaturated aldehyde such as 11 proceeds, via a series of three bond-forming steps, to give the epoxy ketone 14 in high ee.

A long-standing problem in the synthesis of Vitamin D and its metabolites has been the establishment of the requisite angularly-substituted trans 6/5 C-D ring fusion. Jerzy Wicha of the Polish Academy of Sciences in Warsaw has now put forward (Org. Lett. 2006, 8, 2551. DOI: 10.1021/ol060775y) an elegant solution to this problem. Peracid oxidation of 15 gave the epoxide 16. Reduction of 16 by the Hutchins protocol proceeded with inversion, as expected, to give 17.

Schering-Plough isolated the macrolactone (+)-Sch 642305 (20) from a soil sample collected near Tucson, Arizona. Barry B. Snider of Brandeis University (Org. Lett. 2006, 8, 1283. DOI: 10.1021/ol052948+) reasoned that the substituents on 18 would set the conformation of the medium ring, so that intramolecular Michael addition would proceed selectively across one face of the acceptor. Indeed, on exposure to NaH 18 cyclized to 19 as a single diastereomer. Acid-catalysed epimerization followed by desilylation then delivered 20.

D. F. Taber, Org. Chem. Highlights 2006, December 18.