An asymmetric, SmI 2 -mediated approach to g-butyrolactones using a new, fluorous-tagged auxiliary Johannes C. Vogel a , Rebecca Butler b , David J. Procter a, * a School of Chemistry, University of Manchester, Manchester M13 9PL, UK b Novartis, Horsham, UK article info Article history: Received 29 July 2008 Accepted 12 August 2008 Available online 20 September 2008 Keywords: Samarium Radicals Asymmetric Fluorous Lactones abstract A new, fluorous-tagged chiral auxiliary has been developed for the asymmetric, SmI 2 -mediated coupling of aldehydes and a,b-unsaturated esters. g-Butyrolactones are obtained in moderate to good isolated yield and in high enantiomeric excess. The fluorous tag allows the auxiliary to be conveniently recovered by fluorous solid-phase extraction (FSPE) and reused. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Samarium(II) iodide (SmI 2 ) continues to be used widely in or- ganic synthesis. 1 This mild, single-electron reductant has been used to mediate a broad range of radical and anionic transformations ranging from functional group interconversions to complex car- bon–carbon bond-forming sequences. 1 The reductive coupling of carbonyl compounds with olefins represents one of the most im- portant classes of SmI 2 carbon–carbon bond-forming reaction. In 1986, Fukuzawa 2 and Inanaga 3 described the SmI 2 -mediated, in- termolecular coupling of aldehydes and ketones with a,b-un- saturated esters to give substituted g-butyrolactones. In 1997, Fukuzawa reported a useful, asymmetric variant in which acrylates and crotonates derived from ephedrine are coupled with aldehydes and ketones. 4 We have applied Fukuzawa’s approach in a short asymmetric synthesis of an antifungal, g-butyrolactone natural product. 5 We have also adapted Fukuzawa’s methodology in the development of a solid-phase asymmetric catch and release ap- proach to g-butyrolactones using acrylates and crotonates linked to resin through an ephedrine chiral linker. 6 Lin 7 and Dai 8 have also reported the use of new chiral auxiliaries in asymmetric, SmI 2 - mediated approaches to g-butyrolactones (Fig. 1). Here, we describe the design and synthesis of a new, fluorous- tagged 9 auxiliary for the asymmetric, SmI 2 -mediated coupling of aldehydes and a,b-unsaturated esters to give g-butyrolactones in high enantiomeric excess. The fluorous tag allows the auxiliary to be conveniently recovered by fluorous solid-phase extraction (FSPE) 10 and reused. 2. Results and discussion Our auxiliary design is inspired by Braun’s (R)-2-hydroxy-1,2,2- triphenyl-1,2-diol (HYTRA) auxiliary that has found application in a number of asymmetric reactions. 11 To our knowledge the use of Fukuzawa 1997 aldehydes/ketones 43–99% ee 43–88% GC yield R 3 O OR* R 1 O R 2 SmI 2 , THF ROH O R 3 R 1 R 2 O O N Ph O N Ph Procter 2003 aldehydes/ketones 66–96% ee 37–73% yield O O H H OBn O Lin 2000 ketones 76–99% ee 43–99% yield MeO O N i–Pr i–Pr O Dai 2006 aldehydes 80–99% ee 87–90% yield Figure 1. Asymmetric, SmI 2 -mediated approaches to g-butyrolactones. * Corresponding author. Tel.: þ44 161 275 1425; fax: þ44 161 275 4939. E-mail address: david.j.procter@manchester.ac.uk (D.J. Procter). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2008.08.110 Tetrahedron 64 (2008) 11876–11883