Reaction of 2-silylmethylcyclopropyl ketones with in situ oxirane-derived aldehydes and formation of 2-hydroxymethyl tetrahydrofurans Veejendra K. Yadav * , Archana Gupta Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India article info Article history: Received 19 April 2009 Revised 26 May 2009 Accepted 28 May 2009 Available online 2 June 2009 Keywords: (2-Trimethylsilylmethyl)cyclopropyl ketone Oxirane Aldol Oxidative ring closure 2-Hydroxymethyl tetrahydrofuran abstract The enolates formed from Lewis acid treatment of (2-trimethylsilylmethyl)cyclopropyl alkyl and aryl ketones reacted with aldehydes formed in situ from alkoxy-, aryl- and vinyl-substituted oxiranes to gen- erate aldol products in good yields. Selected aldol products were conveniently transformed into highly substituted tetrahydrofurans under oxidative conditions. Ó 2009 Elsevier Ltd. All rights reserved. The ring strain present in a three-membered ring makes it a useful synthon in organic synthesis. Vicinal placement of a donor and an acceptor group on the ring provides dual activation that renders the cleavage of the in-between r C–C bond feasible under mild Lewis acid conditions. A silylmethyl group acts as a donor group for the b-effect of silicon. 1 We have previously reported reactions of enolates generated from the ring cleavage of 2-trim- ethylsilylmethylcyclopropyl alkyl/aryl ketones with aldehydes, ke- tones and imines to deliver aldol and iminoaldol products that were subsequently transformed into tetrahydofurans and pyrrol- idines, respectively, under oxidative conditions. 2 As an extension of this protocol, we envisioned reactions of 2- trimethylsilylmethylcyclopropyl ketones with aldehydes formed in situ from oxiranes to generate aldols in a single step. Applica- tion of oxiranes as in situ precursors to aldehydes appeared appealing because (a) generation of oxiranes from alkenes is sim- ple and (b) alkenes bearing diverse substituents are readily avail- able by following literature methods. 3 We report herein the construction of tetrahydrofuran skeleton through the addition of a cyclopropane-derived enolate to an in situ oxirane-derived alde- hyde followed by ring closure under oxidative conditions. The resultant 2-hydroxymethyltetrahydrofuran constitutes a common structural feature present in acetogenins that have desirable bio- logical properties such as antineoplastic and immunosuppressive activities. 4 The rearrangement of oxiranes to aldehydes in the presence of Lewis acids is known. 5 We commenced our studies with the screening of Lewis acids for the reaction of an isomeric mixture of 1a with the oxirane 2a (Ar = C 6 H 5 , R = CH 2 OBn). TiCl 4 (1.2 equiv, CH 2 Cl 2 , À78 °C), Et 2 AlCl (1.2 equiv, CH 2 Cl 2 , À30 °C), LiClO 4 in CH 3 NO 2 (3 equiv, 0.25 M, 25 °C), ZnCl 2 (1.5 equiv, CH 2 Cl 2 , 25 °C), InCl 3 (1.2 equiv, CH 2 Cl 2 , 25 °C), SnCl 4 (1.2 equiv, CH 2 Cl 2 , À78 °C), Yb(OTf) 3 (5 mol %, CH 2 Cl 2 , 25 °C) and Zn(OTf) 2 (5 mol %, CH 2 Cl 2 , 0?25 °C) were unsatisfactory. These reactions were either compli- cated, leading to the formation of several products, or did not occur at all. In some instances, the cyclopropane had simply transformed into 3-butenyl phenyl ketone, 4, and the oxirane had rearranged to a-benzyloxymethyl-a-phenylacetaldehyde, 5, quantitatively. The use of BF 3 ÁOEt2 (1.5 equiv, CH 2 Cl 2 , À30 °C, 1 h) generated the desired product 3a as a 1:1.2 diastereomeric mixture in 40% overall yield based on the cyclopropyl ketone used. All the cyclo- propyl ketone had reacted; the balance material was transformed into 3-butenyl phenyl ketone. All the oxirane had also reacted. However, the above carbonyl product 5 was not isolated. It is likely that 5 had polymerized under the acidic condition of the reaction. Intense very polar spots were indeed visible on TLC. An experiment with additional suspended K 2 CO 3 (2 equiv) fur- nished the product repeatedly in slightly improved yield (45– 48%). 6,7 Though the diastereomeric ratio had improved to 3:1 with Sc(OTf) 3 (5 mol %, CH 2 Cl 2 , 25 °C, 45 min), the overall yield based on the cyclopropane reactant had reduced considerably to 21% due probably to the predominant transformation of the enolate into 3-butenyl phenyl ketone. Though the reversal in diastereoselectiv- ity is interesting, we do not have an explanation for this observa- tion at present. We considered examining other reactions with the BF 3 ÁOEt 2 –K 2 CO 3 combination to assess the generality of the protocol. 0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2009.05.107 * Corresponding author. Tel.: +91 512 2597439; fax: +91 512 2597436. E-mail address: vijendra@iitk.ac.in (V.K. Yadav). Tetrahedron Letters 50 (2009) 4647–4650 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet