title: Stereoselectivity and regioselectivity in the segment-coupling Prins cyclization.
abstract: The scope of the segment-coupling Prins cyclization has been investigated. The method is outlined in Scheme 1 and involves esterification of a homoallylic alcohol (1), reductive acetylation to give the alpha-acetoxy ether (3), and cyclization on treatment with a Lewis acid to produce a tetrahydropyran (4). Alkene geometries dictate the product configurations, with E-alkenes leading to equatorial substituents and Z-alkenes leading to axial substituents (Table 1). Not unexpectedly, applying the method to allylic alcohols leads to fragmentation rather than a disfavored 5-endo-trig cyclization. Dienols in which one alkene is allylic and the other alkene is homoallylic cyclize efficiently and produce the tetrahydropyrans 49-54, Table 3. Dienols with two homoallylic alkenes cyclize with modest to high regioselectively, generating tetrahydropyrans 40-45, Table 2. The relative rates for cyclization decrease in the order of vinyl > Z-alkene > E-alkene > alkyne. The configurations of the products are consistent with cyclization via a chair conformation, Figure 1. The 2-oxonia Cope rearrangement may be a factor in the regioselectivity of diene cyclizations and in the erosion of stereoselectivity with Z-alkenes. This investigation establishes the stereoselectivity and regioselectivity for a number of synthetically useful segment-coupling Prins cyclizations.
authors: Department of Chemistry, University of California, Irvine, CA 92697-2025, USA.
authors: J J
authors: JJ
authors: Jaber
authors: K
authors: K
authors: Mitsui
authors: S D
authors: SD
authors: Rychnovsky
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D003500:Cyclization; D004987:Ethers / Q000737:chemistry; D008968:Molecular Conformation; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000475:Alkenes; D004987:Ethers; D011714:Pyrans