TETRAHEDRON LETTERS Tetrahedron Letters 44 (2003) 6483–6486 Pergamon Sequential isomerization and ring-closing metathesis: masked styryl and vinyloxyaryl groups for the synthesis of benzo-fused heterocycles Willem A. L. van Otterlo,* E. Lindani Ngidi and Charles B. de Koning Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, Johannesburg, South Africa Received 6 May 2003; accepted 20 June 2003 Abstract—The use of an aryl allyl ether and an arylallyl group as masked vinyl ether and 1-propenylphenyl groups for ring-closing metathesis (RCM) leading to the synthesis of benzo-fused heterocycles was demonstrated by using a ruthenium-mediated isomerization followed by a ruthenium-mediated RCM reaction. This resulted in the syntheses of a variety of products including two substituted benzo[1,4]dioxins, a naphtho[2,3-b ][1,4]dioxin, a 2H-chromene and a benzo[b ]furan. © 2003 Elsevier Ltd. All rights reserved. The recent literature contains a myriad of examples of the application of ruthenium-mediated ring-closing metathesis (RCM). 1–5 The RCM catalyst of choice for this transformation is the Grubbs’ second-generation catalyst 1 owing to its activity, stability and tolerance to various functional groups and solvent impurities. However, amongst the large numbers of examples described in reviews, very few utilize RCM for the metathesis of vinyl ether 6–8 or silyl enol ether 9,10 groups. RCM using Grubbs’ catalysts on substrates containing electron-rich vinylic olefins are known to be problematic 7,8 and earlier this year we communicated the first examples of high-yielding metathesis reactions with aryl vinyl ethers (e.g. the conversion of precursor 2 into 4H -chromene 3.) 11 Nishida and co-workers also recently published the related intramolecular RCM of substituted enamines 4 to give indoles 5 in excellent yields. 12 This paper has prompted us to divulge our successes in the RCM of other substrates containing electron-rich olefins. Furthermore, we demonstrate the in situ isomerization of aryl allyl ethers or arylallyl groups into aryl 1-propenyl ethers or 1-propenylben- zenes, respectively, prior to RCM. This strategy thus obviates the need to synthesize the required aryl vinyl ethers or styrenes directly, the synthesis of which can be problematic. 1. Benzo[1,4]dioxins Previously we have shown that as part of our ongoing interest in the synthesis of benzo-fused bicyclic molecules, 13–16 we were able to use RCM to synthesize 4H -chromenes, naphthols and indenols, 11 all of which are found as structural units in natural products. Firstly, following our success in accomplishing RCM on the vinyl ether-containing substrates, we decided to test the boundaries of this methodology by the intramolecular RCM of molecules containing aryl-bis- O -vinylic olefins. This would then give us benzo[1,4]dioxins, 17 which are interesting compounds with promising anti-tumour activity. Coudert has recently published an approach to their synthesis. 18 Our methodological approach is shown in the disconnection of compound 6 to the bis(vinyloxy)aryl precursors 7. Figure 1. * Corresponding author. Tel.: Int+27+11+717-6707; fax: Int+27+11+ 717-6749; e-mail: willem@aurum.chem.wits.ac.za 0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0040-4039(03)01545-4