Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 11, 2006
Douglass Taber
University of Delaware

Transition-Metal Catalyzed Enantioselective Ring Construction

Powerful transition metal-catalyzed methods for the conversion of prochiral alkenes and alkynes to carbocyclic rings have been developed over the past several years. Three recent reports are representative. P. Andrew Evans, now at the University of Liverpool, has shown (J. Am. Chem. Soc. 2005, 127, 12466. DOI: 10.1021/ja053123y) that on exposure to an enantiomerically-pure Rh catalyst, the sulfonamide 1 added to the alkyne 2 to give 3 in high ee. Ken Tanaka of the Tokyo University of Agriculture and Technology has found (Angew. Chem. Int. Ed. 2005, 44, 7260. DOI: 10.1002/anie.200502380) that 4, again with an enantiomerically-pure Rh catalyst, added to 5 to give 6 in high ee.

F. Dean Toste of the University of California at Berkeley has developed (J. Am. Chem. Soc. 2005, 127, 17168. DOI: 10.1021/ja055059q) an enantioselective Pd-catalyzed Conia ene reaction. The β-ketoester 7 is cyclized to 8 in high ee.

Alexandre Alexakis of the University of Geneva has devised powerful methods for enantioselective conjugate addition. He has now (Tetrahedron Lett. 2005, 46, 8019. DOI: 10.1016/j.tetlet.2005.09.065) applied those methods to dienes such as 9. The intermediate enolate from the initial conjugate addition effects Michael addition to the α,β-unsaturated ester, leading to the product 10 in high ee.

Enantiomerically-pure ring systems can also be prepared by the asymmetric transformation of performed prochiral rings. Masakatsu Shibasaki of the University of Tokyo had developed La catalysts for the enantioselective addition of acetoacetate 11 to cyclohexenone 12. He has now shown (Tetrahedron Lett. 2005, 46, 5377. DOI: 10.1016/j.tetlet.2005.05.139) that commercial, easily-handled La(OTf)3 in conjunction with an amine base and the same Binol-derived ligand gives equally good results.

Three-component conjuate addition-enolate trapping, pioneered by Gilbert Stork, is a powerful strategy for the rapid assembly of complex structures. K. C. Nicolaou of Scripps-La Jolla has developed (Angew. Chem. Int. Ed. 2005, 44, 3874. DOI: 10.1002/anie.200500789) a chiral catalytic version of this approach. The enolate from Rh-mediated conjugate addition of the alkyne 14 to cyclohexenone 11 was trapped with n-butanal, leading to the aldol product 15 in high ee.

In a variant on this approach, Liu-Zhu Gong of the Chengdu Institute of Organic Chemistry has described (Org. Lett. 2005, 7, 4285. DOI: 10.1021/ol051795n) enantioselective conjugate addition of the boronic acid 18 to the racemic acetate 17. Spontaneous elimination of acetic acid led to the nitroalkene 19 in high ee. Conjugate addition of acetate delivered the all-cis product 20, the relative and absolute configuration of which were confirmed by conversion to (+)-γ-lycorane (21).

D. F. Taber, Org. Chem. Highlights 2006, September 11.