TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 11 (2000) 4935–4944 Pergamon Synthesis of 1,1-methylenedi[(1R,1R,3R,3R,5R,5R )- 8-oxabicyclo[3.2.1]oct-6-en-3-ol] and derivatives: precursors of long-chain polyketides Aurelio G. Csa ´ky ¨ † and Pierre Vogel* Section de chimie de l’Universite ´ de Lausanne, BCH, CH 1015 Lausanne -Dorigny, Switzerland Received 30 October 2000; accepted 27 November 2000 Abstract Racemic 1,1-methylene[(1RS,1RS,3RS,3RS,5RS,5RS )-8-oxabicyclo[3.2.1]oct-6-en-3-ol] ((±)-6) derived from 2,2-methylenedifuran has been resolved kinetically with Candida cyclindracea lipase-cat- alysed transesterification giving 1,1-methylenedi[(1R,1R,3R,3R,5R,5R )-8-oxabicyclo[3.2.1]oct-6-en-3-ol] (-)-6 (30% yield, 98% ee) and 1,1-methylenedi[(1S,1S,3S,3S,5S,5S )-8-oxabicyclo[3.2.1]oct-6-en-3-yl] di- acetate (+)-8, (40% yield, 98% ee). These compounds have been converted into 1,1-methylenedi- [(4S,4S,6S,6S )- and (4R,4R,6R,6R )-cyclohept-1-en-4,6-diyl] derivatives. © 2001 Published by Elsevier Science Ltd. 1. Introduction A great variety of natural products of biological interest include polyketides (1,3-polyoxo, 1,3-polyols, aldols). 1 Several approaches for their synthesis have been proposed. 2,3 Inspired by the work of Lautens 4 and Hoffmann et al. 5 who have converted 8-oxabicyclo[3.2.1]oct-6-en-3- one into 7-carbon-1,3-polyols and analogs 6 and by that of Kaku et al. 7 who have transformed cyclohept-3-ene-1,6-diol into 1,3-polyols, we have proposed a new, non-iterative asymmetric synthesis of long-chain 1,3-polyols starting from the now readily available 2,2-methylenedifuran 1. 8 The method implies the double [4+3]-cycloaddition of the 1,1,3-trichloro-2-oxyallyl cation to 1. After reductive work-up a 45:55 mixture of meso -2 and (±)-threo -2 was obtained in 55% yield and separated by fractional crystallization. The meso compound was converted into meso -3 that was desymmetrized into diol (-)-4 (or (+)-4) by means of the Sharpless asymmetric dihydroxyla- tion. 9 Further transformations involving combinations of Evans’ anti 10 and Nasaraka’s syn 11 * Corresponding author. Tel: 0041 21 692 39 71; fax: 0041 21 692 39 75; e-mail: pierre.vogel@ico.unil.ch † On leave of absence from Departamento de Quı ´mia Orga ´nica, Faculdad de Quı ´mica, Universidad Complutense, E-28040 Madrid, Spain. 0957-4166/00/$ - see front matter © 2001 Published by Elsevier Science Ltd. PII:S0957-4166(00)00475-4