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Monday, August 10, 2009
Douglass F. Taber
University of Delaware

Enantioselective Organocatalyzed Construction of Carbocyclic Rings

One of the most practical ways to construct enantiomerically-enriched carbocyclic systems is to effect asymmetric transformation of preformed prochiral rings. Choon-Hong Tan of the National University of Singapore observed (Chem. Commun. 2008, 5526. ) that allylic halides such as 1 coupled with malonates such as 2 to give the α-methylene ketone 3 in high ee. Xinmiao Liang of the Dalian Institute of Chemical Physics and Jinxing Ye of the East China University of Science and Technology reported (Chem. Commun. 2008, 3302. ) that nitromethane 5 could be added to enones such as 4 to construct cyclic quaternary stereogenic centers such as that of 6. The addition of the cyclohexanone 7 to the acceptor 8 described (Chem. Commun. 2008, 6315. ) by Yixin Lu, also of the National University of Singapore led to the creation of two new cyclic stereogenic centers. Polycarbocyclic prochiral rings are also of interest. Teck-Peng Loh of Nanyang Technological University devised (Tetrahedron Lett. 2008, 49, 5389. ) the steroid AB donor 10, that added to crotonaldehyde 1 to give the single enantiomerically-pure diastereomer 12.

Nitro alkenes are excellent Michael acceptors. Dieter Enders of RWTH Aachen took advantage of this (Angew. Chem. Int. Ed. 2008, 47, 7539. ) in developing the addition of aldehydes such as 14 to the nitroalkene 13. Intramolecular alkylation ensued, to deliver the product 15 as a single diastereomer. Guofu Zhong, also of Nanyang Technological University, established (Org. Lett. 2008, 10, 3425; and Org. Lett. 2008, 10, 3489; ) an approach to cyclopentane construction based on the Michael addition of β-ketoesters such as 16 and 19 to nitroalkenes such as 17 and 20. Intramolecular nitro aldol (Henry) addition led to 18, while an intramolecular Michael addition delivered 21.

Damien Bonne and Jean Rodriguez of Aix-Marseille Université employed (Org. Lett. 2008, 10, 5409. ) intramolecular dipolar cycloaddition to convert the initial adduct between 22 and 23 to the cyclopentane 24. They also prepared cyclohexane derivatives using this approach.

The diketone 25 is prochiral. Benjamin List of the Max-Planck Institut, Mülheim devised (Angew. Chem. Int. Ed. 2008, 47, 7656. ) an organocatalyst that mediated the intramolecular aldol cyclization of 25 to 26 in high ee. Mark J. Kurth of the University of California, Davis developed (Angew. Chem. Int. Ed. 2008, 47, 6407. ) a resin bound organocatalyst that, inter alia, combined 27 with 28 to give the Robinson annulation product 29. Dawei Ma of the Shanghai Institute of Organic Chemistry reported (Org. Lett. 2008, 10, 5425. ) a related Robinson annulation, combining 30 and 14 to give 31.

The most powerful such Robinson annulation reported to date was by (Org. Lett. 2008, 10, 3753. ) Karl Anker Jřrgensen of Aarhus University, Denmark, who showed that α-alkyl acetoacetates such as 32 could be combined with the silyl aldehyde 33 to give the 5-silyl cyclohexenones 34. Conjugate addition to such cyclohexenones is expected to proceed with high diastereocontrol, leading, for instance, after oxidative desilylation to the 5,6-dialkyl cyclohexenone.

D. F. Taber, Org. Chem. Highlights 2009, August 10.