Homoallylic esters are obtained in a single transformation from allyl 2,2,2-trifluoroethyl malonates by using a Pd(0)-catalyst. Facile decarboxylation of allyl 2,2,2-trifluoroethyl malonates is attributed to a decrease in pK a compared to allyl methyl malonates. Subsequent reduction of the homoallylic 2,2,2-trifluoroethyl ester provides a (hydroxyethyl)cyclopentenyl derivative that represents a key intermediate in the synthesis of carbocyclic nucleosides. A select allyl 2,2,2-trifluoroethyl malonate undergoes a decarboxylative Claisen rearrangement to provide a regioisomeric homoallylic ester.Homoallylic esters are embedded in the core structures of several classes of natural products including macrolide polyketides, 1 α-linolenic acid metabolites and derivatives 2 and cyclopentenone prostaglandins. 3 Although homoallylic esters may be synthesized in several steps by functional group manipulation, 2a direct access to homoallylic esters has been achieved by Krapcho decarboxylation of malonates, 4 addition of vinyl radicals to α,β-unsaturated esters 5 and 1,4-addition of alkenylcopper reagents. 6 We considered metal-catalyzed decarboxylative allylations as an alternative method to directly prepare homoallylic esters under mild conditions. 7 Although α-cyano, α-nitro, α-keto 8 and α-sulfonyl 9 allyl esters readily undergo Pd(0)-catalyzed decarboxylative rearrangements to afford the corresponding homoallylic derivatives, allyl methyl malonates are much less reactive. Their diminished reactivity is attributed to the less stable methoxyethenolate that forms upon decarboxylation. α,α-Dialkyl allyl methyl malonates require harsh conditions (i. e., 120 °C in DMF) to effect Pd(0)-decarboxylative rearrangements. 8 Diallyl malonates undergo decarboxylative allylation at room temperature, but must possess an aryl group at the α-position. 10 To our knowledge, Pd(0)-decarboxylative rearrangements of α,α-unsubstituted allyl alkyl malonates have not been reported. In order to achieve decarboxylation, we envisioned replacement of the allyl methyl malonate with an allyl 2,2,2-trifluoroethyl malonate. The strong electron-withdrawing ability of the trifluoroethyl group would improve the stability of the transient alkoxyethenolate and promote decarboxylation. Herein, we disclose that α,α-unsubstituted allyl 2,2,2-trifluoroethyl malonates are suitable substrates for Pd(0)-catalyzed decarboxylative allylations and provide desired homoallylic 2,2,2-trifluoroethyl esters in high yields. Our group has previously reported Pd(0)-catalyzed allylic alkylations with cycloadduct 3 11 and related substrates as key steps en route to targeted carbocyclic nucleosides. 12 In order to access carbonucleoside targets 5′-homocarbovir 1b 13 and 5′-homoaristeromycin 2b ,14 we required a reliable method to install the requisite 5′-hydroxyethyl side chain. We envisioned a Pd(0) decarboxylative rearrangement to afford an α-allyl ester and subsequent reduction to the (hydroxyethyl)cyclopentyl core structure. Further elaboration would furnish 1b and 2...
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