Olefin Metathesis in Cyclic Ether Formation. Direct Conversion of Olefinic Esters to Cyclic Enol Ethers with Tebbe-Type Reagents

Abstract

Department of Chemistry, The Scripps Research Institute 10666 North Torrey Pines Road, La Jolla, California 92037 Department of Chemistry and Biochemistry UniVersity of California, San Diego 9500 Gilman DriVe, La Jolla, California 92093 ReceiVed October 17, 1995 The olefin metathesis reaction1 is rapidly emerging as a powerful tool in organic synthesis.2 Of particular interest are ring forming metathesis reactions catalyzed by transition metal complexes, several elegant examples of which have recently appeared.3 Despite the successes of this general approach to ring construction, much remains to be improved in terms of scope, convenience, and generality. In this communication we report a new strategy, based on the olefin metathesis reaction, for the generation of cyclic enol ethers directly from olefin esters4 using the Tebbe5 or the Petasis reagents.6 Scheme 1 shows the general concept7 for the envisioned Tebbe-reagent-mediated transformation of olefinic esters of type I to cyclic enol ethers of type VI. Thus it was anticipated that the initially formed enol ether II would react with a second molecule of the Tebbe reagent to afford the titanacyclobutane III, fragmentation of which would then lead to titanium alkylidene IV. Intramolecular reaction of IV was then expected to lead to titanacyclobutane V, whose regioselective fragmentation as shown should allow an entry to the desired cyclic enol ethers VI via olefin metathesis. Implementation of this strategy using olefinic ester 1 leads to the formation of cyclic enol ether 3 via the initially formed methylenation product 2 in 71% overall yield (Scheme 2). The intermediacy of compound 2 was proven by isolation and full spectral characterization followed by conversion to 3 under the influence of the Tebbe reagent. The generality and scope of this new process was investigated by employing a variety of substrates. As illustrated in Table 1, the reaction can deliver a series of sixand seven-membered cyclic enol ethers in good yields (entries 1-3 and 10-12, respectively). In addition to these findings, the important observation of the open-chain products shown in entries 6-9 (Table 1) was made. These hydroxy exomethylenic compounds are presumably obtained by sequential hydrolysis and olefination of the initially formed cyclic enol ethers.8 Apparently the lability of the enol ether products depends on their precise environment and the reaction conditions, a circumstance that