TETRAHEDRON LETTERS Tetrahedron Letters 44 (2003) 4985–4988 Pergamon Stereocontrolled total syntheses of (±)-clovan-3-one and (±)-epi -clovan-3-one and a facile total synthesis of (±)-pseudoclovene-A Tapas Paul and Debabrata Mukherjee* Department of Organic Chemistry, Indian Association for the Cultivation of Science, Calcutta -700 032, India Received 2 April 2003; revised 29 April 2003; accepted 9 May 2003 Abstract—Stereocontrolled total syntheses of the bridged tricyclic ketones (±)-clovan-3-one (5) and (±)-epi -clovan-3-one (6) and a facile total synthesis of the tricyclic sesquiterpene (±)-pseudoclovene-A (3) have been successfully accomplished involving participation of an aryl intramolecular cyclisation of the bromophenol 11 as a key step. © 2003 Elsevier Science Ltd. All rights reserved. Tricyclic sesquiterpenes derived from acid treatment of caryophyllene and caryolan-1-ol possess novel skeletal features and have attracted considerable attention as challenging synthetic targets. Clovene (1) 1 and epi - clovene (2) 2 are acid-catalysed rearrangement products of caryophyllene and caryolan-1-ol, respectively. The sesquiterpenes 1 and 2 incorporate a tricyclo[6.3.1.0 1,5 ]- dodecane ring system as the basic carbocyclic frame- work but differ in the stereochemistry of the A/B ring junction which is cis in 1 and trans in 2 (Fig. 1). Pseudoclovene-A (3), another sesquiterpene hydrocar- bon possessing a similar tricyclo[6.3.1.0 1,5 ]dodecane skeleton was isolated 3 along with several other sesquiterpenes when caryolan-1-ol was treated with polyphosphoric acid. On the basis of chemical and spectroscopic studies, the structure 3 was proposed for pseudoclovene-A and this structure was conclusively established by synthesis 3 as well as through X-ray crys- tallographic analysis 3 of the p -bromobenzenesulfonate ester 4 (Fig. 1) which was prepared from 3. The possi- ble mode of formation of 2 and 3 from caryolan-1-ol was investigated by Parker and co-workers and a plau- sible mechanistic scheme was proposed. 2 The total syn- thesis of the sesquiterpenes 1 and 2 must address the following problems: (i) construction of the tricy- clo[6.3.1.0 1,5 ]dodecane framework with appropriate substituents at C-4 and C-8, (ii) control of the stereo- chemistry of the A/B ring junction, and (iii) introduc- tion of an isolated double bond in ring A. Although clovene (1) has been synthesised 4 a number of times, the synthesis of epi -clovene (2) has not been reported yet in the literature. Starting from 2,5-dimethyl-6-methoxy-1- tetralone (7), 5 we report here an aryl cyclisation strat- egy to accomplish a stereocontrolled total synthesis of the bridged tricyclic ketones (±)-clovan-3-one (5) and (±)-epi -clovan-3-one (6). During the present studies, we have also accomplished a facile total synthesis of (±)- pseudoclovene-A (3) as shown in Scheme 1. The salient Figure 1. Keywords : terpenes; ketones; cyclisation; hydrogenation; alkylation. * Corresponding author. Fax (91)-33-2473-2805; e-mail: ocdm@mahendra.iacs.res.in 0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0040-4039(03)01170-5