Issue in Honor of Prof. James Bull ARKIVOC 2002 (ix) 37-45 ISSN 1424-6376 Page 37 © ARKAT USA, Inc Synthesis of (2S, 3R)-2-allyl-3-furyl cyclopentanone. An enantioselective strategy towards the synthesis of phorbol Vanida Chairgulprasert, Michael G. B. Drew, Archie Jahans, and Laurence M. Harwood Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK. E-mail: l.m.harwood@reading.ac.uk Dedicated to Professor Jimmy Bull on the occasion of his retirement Abstract (1S, 5R)-5-(2-furyl)-2-oxocyclopentanecarboxylate 10 was synthesised by asymmetric conjugate addition of lithium difurylcyanocuprate to the chiral substrate 9 in high diastereoisomeric excess (>95 %). After transesterification, allylation and subsequent decarbomethoxylation, (2S, 3R)-2- allyl-3-furyl cyclopentanone 13 was obtained in >86 % ee. Keywords: Chiral, cyclopentenone, phorbol Introduction Phorbol 1 and its derivatives are toxic diterpenes found in the sap of plants of the family Euphorbiaceae. 1 The extracts and sap of these plants have been used in folkloric medicine as purgatives but their toxicological properties are very harsh 2 and tetradecanoyl phorbol acetate has been found to be a potent tumour promoter. 3 Wender has succeeded in total synthesis of phorbol, 4 while other routes have yet to be completed. 5 Thus far only Wender 6a and Shibasaki 6b have reported enantioselective strategies. To date, we have made substantial progress in a synthetic approach to phorbol utilising the diastereocontrolled ultra-high pressure promoted intramolecular Diels-Alder reaction of furan (IMDAF) 7 to provide tricyclic adducts 2 with relative stereochemistry at 6 stereocentres and disposed functionality rendering them amenable to access phorbol. The relative stereocontrol in the cycloaddition is a consequence of the trans-2, 3 relative configuration at the cyclopentanone and endo cycloaddtion of the Z-dienophile in the precursor 4 under high pressure conditions and subsequent regiocontrolled epimerisation of the cycloadducts 3 at standard pressure to furnish the desired relative stereochemistry (Figure 1). Thus, stereochemical information in the trans-2-substituted-3-furyl cyclopentanone precursor 4 is relayed and amplified during the sequence and, therefore, development of an enantiocontrolled