Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 15, 2008
Douglass F. Taber
University of Delaware

Transition Metal-mediated Ring Construction: The Yu Synthesis of 1-Desoxyhypnophilin

Both 1 and 3 are inexpensive prochiral starting materials. Tae-Jong Kim of Kyungpook National University devised (Organomet. 2008, 27, 1026. DOI: 10.1021/om700935m) a chiral Cu catalyst that efficiently converted 1 (other ring sizes worked as well) to the enantiomerically pure ester 2. Alexandre Alexakis of the University of Geneva found (Adv. Synth. Catal. 2008, 350, 1090. DOI: 10.1002/adsc.200800086) a chiral Cu catalyst that mediated the enantioselective coupling of 3 with Grignard reagents such as 4. The π-allyl Pd complex derived from 6 is also prochiral. Barry M. Trost of Stanford University showed (Angew. Chem. Int. Ed. 2008, 47, 3759. DOI: 10.1002/anie.200800282) that with appropriate ligand substitution, coupling with the phthalimide 7 proceeded to give 8, readily convertible to (-)-oseltamivir (Tamiflu) (9), in high ee.

Jonathan W. Burton of the University of Oxford found (Chem Commun. 2008, 2559. DOI: 10.1039/b802473a) that Mn(OAc)3-mediated cyclization of 10 delivered the lactone 12 with high diastereocontrol. John Montgomery of the University of Michigan observed (Org. Lett. 2008, 10, 811. DOI: 10.1021/ol702961v) that the Ni-catalyzed cyclization of 12 also proceeded with high diastereocontrol. Ken Tanaka of the Tokyo University of Agriculture and Technology combined (Angew. Chem. Int. Ed. 2008, 47, 1312. DOI: 10.1002/anie.200704758) Rh-catalyzed ene-yne cyclization of 14 with catalytic ortho C-H functionalization, leading to 16 in high ee.

Eric N. Jacobsen of Harvard University designed (Angew. Chem. Int. Ed. 2008, 47, 1469. DOI: 10.1002/anie.200704439) a chiral Cr catalyst for the intramolecular carbonyl ene reaction, that converted 17 to 18 in high ee. Using a stoichiometric prochiral Cr carbene complex 20 and the enantiomerically-pure secondary propargylic ether 19, Willam D. Wulff of Michigan State University prepared (J. Am. Chem. Soc. 2008, 130, 2898. DOI: 10.1021/ja077579m) a facially-selective Cr-complexed o-quinone methide intermediate, that cyclized to 21 with high ee.

A variety of methods have been put forward for the transition metal-mediated construction of polycarbocyclic systems. One of the more powerful is the enantioselective Rh-catalyzed stitching of the simple substrate 22 into the tricycle 23 devised (J. Am. Chem. Soc. 2008, 130, 3451. DOI: 10.1021/ja0762083) by Takanori Shibata of Waseda University. Inter alia, ozonolysis of 23 delivered the cyclopentane 24 containing two all-carbon quaternary centers. Zhi-Xiang Yu of Peking University has devised both carbonylative (J. Am. Chem. Soc. 2008, 130, 4421. DOI: 10.1021/ja7100449), illustrated, and non-carbonylative (J. Am. Chem. Soc. 2008, 130, 7178. DOI: 10.1021/ja8008715) Rh-catalyzed cylization of alkenyl cyclopropanes such as 26. Intramolecular aldol condensation followed by further functionalization converted 27 into 1-desoxyhypnophilin (28).

D. F. Taber, Org. Chem. Highlights 2008, December 15.