Ahlke Hayen et.al.: 1,3-Stereoinduction in Radical Reactions: Radical Additions to Dialkyl 2-Alkyl-4-methyleneglutarates

Author(s): Ahlke Hayen, Rainer Koch, Wolfgang Saak, Detlef Haase, Juergen O. Metzger

Title: 1,3-Stereoinduction in Radical Reactions: Radical Additions to Dialkyl 2-Alkyl-4-methyleneglutarates

Date of Upload: 2000

Article: J. Am. Chem. Soc. 2000, 122, 12458-12468, Contribution from the Department of Chemistry, UniVersity of Oldenburg, P.O. Box 2503, 26111 Oldenburg, Germany

Keywords: radical reactions, selectivity, stereoselectivity, enentioselectivity,

Abstract:
Tin hydride-mediated radical additions to a series of R-methylene-glutarates 1, furnishing 2,4-dialkylsubstituted glutarates 3 are reported. The diastereoselectivity of hydrogen transfer to the intermediate adduct radicals 2, possessing a stereogenic center in c-position, was disappointing in the temperature range of -78 to 80 °C. However, the reactions proved to be able to proceed with excellent 1,3-diastereoselectivities under chelation-controlled conditions, depending on the steric impacts of 2- and 4-alkyl substituents as well as on the ester-alkyl moiety and choice of Lewis acid. Using MgBr2aOEt2 as additive, syn-selectivities of 98:2 were achieved upon initial tert-butyl radical addition at -78 °C. High anti-diastereoselectivities were observed in the MgBr2aOEt2-controlled pathway at 70 °C when smaller alkyl radicals such as cyclohexyl, ethyl, and methyl were applied. Interesting and uncommon temperature dependences were observed in the temperature range of -78 to 100 °C, revealing strong entropic effects in the transition states. A model that accounts for the opposed stereochemical outcomes under chelation-controlled conditions is presented.

URL: http://www.chemie.uni-oldenburg.de/oc/metzger/publikationen/pdf/89.pdf (application/pdf)


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