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Monday, February 23, 2009
Douglass F. Taber
University of Delaware

Enantioselective Construction of Alkylated Centers

Unsaturated half acid esters such as 1 are readily prepared by Stobbe condensation between dialkyl succinate and an aldehyde. Johannes G. de Vries of DSM and Floris P. J. T. Rutjes of Radboud University Nijmegen observed (Adv. Synth. Catal. 2008, 350, 85. ) that these acids were excellent substrates for enantioselective hydrogenation. Kazuaki Kudo of the University of Tokyo designed (Org. Lett. 2008, 10, 2035. ) a resin bound peptide catalyst for the transfer reduction of unsaturated aldehydes such as 3, using 4 as the net H2 donor. Note that 5 was produced with high enantiocontrol from 3 that was a ~ 2:1 mixture of geometric isomers.

Motomu Kanai and Masakatsu Shibasaki of the University of Tokyo devised (J. Am. Chem. Soc. 2008, 130, 6072. ) a chiral Gd catalyst that mediated the conjugate cyanation of enones such as 6 with high ee. Eric N. Jacobsen of Harvard University prepared (Angew. Chem. Int. Ed. 2008, 47, 1762. ) a dimeric Al salen catalyst that showed improved activity over the monomeric catalysts. Even congested imides such as 8 could be cyanated efficiently, delivering alkylated quaternary stereogenic centers.

Takahiro Nishimura and Tamio Hayashi of Kyoto University optimized (J. Am. Chem. Soc. 2008, 130, 1576. ) the Rh*-catalyzed enantioselective conjugate addition of silyl acetylenes to enones such as 10, to give 12. Adriaan J. Minnaard and Ben L. Feringa of the University of Groningen devised (Angew. Chem. Int. Ed. 2008, 47, 398. ) conditions for the enantioselective 1,6-conjugate addition of alkyl Grignard reagents to diene esters such as the inexpensive ethyl sorbate 14. The product 16 incorporated, in addition to the newly formed stereogenic center, a geometrically defined E alkene.

William S. Bechara and André B. Charette of the Université de Montréal found (Org. Lett. 2008, 10, 2315. ) that alkyl Grignard reagents could be induced to add with high enantioselectivity to pyridyl sulfones such as 17. In a different approach, Gregory C. Fu of MIT developed (J. Am. Chem. Soc. 2008, 130, 3302, ; J. Am. Chem. Soc. 2008, 130, 2756, ) conditions for the enantioselective alkenylation of racemic bromo esters such as 19, The latter reference is to the analogous enantioselective coupling of organozinc bromides with racemic allylic chlorides.

Organocatalyst-mediated coupling has also been used to prepare alkylated stereogenic centers. Benedek Vakulya and Tibor Soós of the Hungarian Academy of Sciences, Budapest devised (J. Org. Chem. 2008, 73, 3475. ) a Cinchona alkaloid-based catalyst for the addition of nitromethane 23 to activated amides such as 22. Benjamin List of the Max-Planck-Institut, Mülheim showed (Angew. Chem. Int. Ed. 2008, 47, 4719. ) that with the versatile catalyst 27, acetaldehyde itself could be added with high ee to nitroalkenes such as 25. In a continuation of his work with single-electron chemistry, David W. C. MacMillan of Princeton University effected (J. Am. Chem. Soc. 2008, 130, 398. ) enantioselective alkenylation of aldehydes, using catalytic 31 and the stoichiometric oxidant ceric ammonium nitrate.

Using a designed catalytic peptide, Helma Wennemers of the University of Basel alkylated (J. Am. Chem. Soc. 2008, 130, 5610. ) aldehydes such as 33 with nitroethylene. Samuel H. Gellman of the University of Wisconsin effected (J. Am. Chem. Soc. 2008, 130, 5608. ) the same transformation using the catalyst 27. Professor Wennemers showed that reduction of 35 followed by Mioskowski oxidation of the nitro group to the acid delivered the γ-lactone 36. Enantiomerically-pure γ-lactones such as 36 are powerful intermediates for the enantioselective construction of natural products.

D. F. Taber, Org. Chem. Highlights 2009, February 23.