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Monday, November 19, 2007
Douglass F. Taber
University of Delaware

Stereoselective C-O Ring Construction

Five-membered cyclic ethers often do not show strong thermodynamic preferences. High diastereocontrol can, however, be achieved. Epoxy alkynes such as 1 can be prepared in high ee by Sharpless epoxidation. Norbert Krause of Dortmund University has shown (Angew. Chem. Int. Ed. 2007, 46, 1650. ) that Cu hydride reduces epoxides such as 1 to the corresponding allene 2. The alcohol 2 was then cyclized with an Au catalyst to the dihydrofuran 3, with high overall diastereocontrol. In a complementary approach, Dennis G. Hall of the University of Alberta has developed (J. Am. Chem. Soc. 2007, 129, 3070. ) a simple procedure for the preparation of the enantiomerically-pure allyl borinate 4 and its enantiomer, which can be purified by column chromatography and stored. Addition of 4 to the aldehyde 5 gave the allyl silane 6 in high ee. Addition of 6 to a second aldehyde 7 then gave the all-cis tetrahydrofuran 8, without loss of ee.

Much energy is going into the development of new methods for the stereocontrolled preparation of 2,6-dialkyl tetrahydropyrans. J. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad, has found (Tetrahedron Lett. 2007, 48, 2205. ) that iodine mediated the Prins coupling of 9 and 10, with high diastereocontrol. Michel R. Gagné of the University of North Carolina developed (J. Am. Chem. Soc. 2007, 129, 1908. ) Negishi conditions for coupling glycosyl chlorides such as 12 with easily-prepared organozinc halides. The coupling tended to give the trans product, and to proceed trans to the adjacent alkoxy substituent.

Intramolecular epoxide opening has also been a reliable method for stereocontrolled cyclic ether construction. Masayuki Inoue and Masahiro Hirama have improved on the usual acid-mediated cyclization of substrates such as 14 by demonstrating (Tetrahedron Lett. 2007, 48, 2171. ) that the transformation is even more efficient with a Rh catalyst.

Following the biosynthetic hypothesis of Koji Nakanashi, the cascade cyclization of polyepoxides to ladder polyethers such as 17 has long been a goal of organic chemistry. With the development of methods for the direct enantioselective epoxidation of alkenes, the preparation of the requisite substrates, such as 16, is now practical. Timothy F. Jamison of MIT found (Science 2007, 317, 1189. ) that merely warming 16 in water for three days delivered the cyclized product 17 in 71% yield. K. N. Houk of UCLA and Paul E. Floreancig of the University of Pittsburgh have reported (J. Am. Chem. Soc. 2007, 129, 7915. ) an alternative approach to such cyclizations.

There are many macrolactone natural products. Tarek Sammakia of the University of Colorado has shown (Org. Lett. 2007, 9, 2103. ) that the conditions developed by Hisashi Yamamoto for intermolecular vinylogous aldol also worked well for the construction of macrolactones, and that the cyclizations proceeded with remarkable diasterocontrol. Helena M. C. Ferraz of the Universidade de São Paulo has reported (J. Org. Chem. 2007, 72, 2945. ) a complementary route to macrolactones, from 20 to 22.

D. F. Taber, Org. Chem. Highlights 2007, November 19.