Enantioselective Organocatalyzed Construction of Carbocyclic Rings

Abstract

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 (Organic Lett. 2008, 10, 3425; Organic 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 (Organic 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.