Lewis acid catalyzed regio- and stereoselective [1, 3] O to C rearrangements

Abstract

A regioselective Lewis acid-mediated [1, 3] rearrangement of allyl vinyl ethers has been developed. The rearrangement involves Lewis acid coordination to the allyl vinyl ether oxygen, which upon ionization produces a metalloenolate and allyl cation that recombine in a regioselective manner. Substitution about the allyl vinyl ether can be used to control the regioselectivity of the reaction. A diastereoselective [1, 3] ring contraction of 2,5-dihydrooxepins to provide densely functionalized cyclopentenes has been realized. A modular synthesis of the 2,5-dihydrooxepin skeleton combined with the Lewis acid-mediated ring contraction provides access to tri-, tetra- and pentasubstituted cyclopentenes. An enantioselective variant of the reaction has also been developed. A mild and efficient diastereoselective Heck reaction of 1,3-dioxepins is described. The reaction scope is broad with respect to both sp2 iodide and alkene coupling partners. The reaction is also chemoselective for the Z-alkene of the 1,3-dioxepin in the presence of other potentially reactive E-alkenes. The diastereoselectivity is influenced by substitution at the 2- and 4-positions of the 1,3-dioxepin. A Lewis acid-mediated ring contraction of 1,3-dioxepins to provide 2,3,4- and 2,3,4,5-substituted tetrahydrofurans has been investigated. Rearrangement in the presence of TMSOTF-MeCN provides the 2,3-cis/3,4-trans diastereomer, while SnCl4-CH2Cl2 provides the 2,3-trans/3,4-cis diastereomer in good yield and diastereoselectivity. The reaction scope is broad and both conditions are tolerant of a range of functionality including other Lewis basic groups. The utility of the union of the diastereoselective Heck reaction and the Lewis acid-mediated [1, 3] ring contraction of 1,3-dioxepins has been evaluated in the context of total synthesis. These two reactions formulate the core strategy used to accomplish the synthesis of (+/-)-sylvone and as an approach to the core of lophirone H.