Pergamon Tetrahedron 54 (1998) 10449-10456 TETRAHEDRON First Enantioselective Synthesis of (+)-(3R,3aS,6aS)-3-Hydroxy-3,3a,4,6a-tetrahydrocyclopenta[blfuran-2-one - a Versatile Chiral Heterocyclic Building Block Steffen Kudis and Giinter Heimchen* Organisch-Chemisches Institut der Umversit~t Heidelberg,Im Neuenheirner Feld 270, D-69120Heidelberg,Germany Received 2 February 1998; accepted 11 February 1998 Abstract: Asymmetric Pd-catalyzed allylic alkylations of 2-acetoxymalonates with 2-cyclopentenyl chloride are described. With the cymantrene based phosphinooxazoline 2 as chiral ligand enantio- meric excess of> 99 % and > 90 % yield were obtained. Alkylation products were transformed in three steps to ( + )-(3 R,3aS, 6aS)- 3-hydroxy- 3,3a, 4, 6a-tetrahydrocyclopenta [b]furan- 2-one (l a) in up to 52 % yield. © 1998ElsevierScienceLtd. All rights reserved. The bicyclic lactone I a (Scheme 1) is a versatile building block for syntheses of a variety of important natural products, e.g. brefeldin A, 'a mevinolin) aristeromycin and carbodine, 4 5'-homo-carbocyclic nucleo- sides, 5 carbocyclic analogs of polyoxins and nikkomycins, 6 the anti-HIV agent carbovir7 and the antitumor agents sesbanimide A and B. s The key building block la has so far been prepared by enzyme catalyzed kinetic resolution of the racemic compound which was obtained via Diels-Alder reaction of cyclopentadiene and glyoxylic acid. 9 In view of the importance of the lactone la a catalytic asymmetric synthesis appears highly desirable. OH H OH U ~ 4 " 3 HO .... ) s 0 6 - v 1 H H Brefeldin A Scheme 1 (+ )-(3R,3aS,6aS)-la * Corresponding author. Email: en4@ix.urz.uni-heidelberg.de. Fax: 0049 6221 544205. 0040-4020/98l$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved. Plh S0040-4020(98)00497-9