title: Intramolecular photochemical dioxenone-alkene [2 + 2] cycloadditions as an approach to the bicyclo[2.1.1]hexane moiety of solanoeclepin A.
abstract: A synthesis of the bicyclo[2.1.1]hexane substructure of solanoeclepin A (1), the most active natural hatching agent of potato cyst nematodes, was approached via an intramolecular [2 + 2] photocycloaddition. Aldehyde 12 containing the dioxenone chromophore served as a useful starting material, allowing the synthesis of a variety of photocycloaddition substrates via Grignard addition or via a Nozaki-Hiyama-Kishi reaction. Photolysis of the unsubstituted alkene 14 led to the expected crossed cycloadduct bicyclo[2.1.1]hexane 15 according to the so-called rule of five. However, several functionalized alkenes 18, 20, and 31 exhibited a complete reversal of cycloaddition regioselectivity, providing straight cycloadducts bicyclo[2.2.0]hexanes 21-26 and 4, respectively. Their structures were proved by a combination of extensive NMR measurements, X-ray analyses, and subsequent retro-aldol reactions. The latter de Mayo process allowed the formation of spiro-[3.5]nonane 35 and spiro[3.4]octane 36 as well as the cyclobutanes 37 and 38. Finally, the cyclization of the more rigid lactone precursor 28 occurred in high yield in the desired fashion with complete regio- and stereoselectivity to give 3 containing the core bicyclo[2.1.1]hexane skeleton of the natural product.
authors: Institute of Molecular Chemistry, Laboratories of Organic Chemistry and Crystallography, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands.
authors: R H
authors: RH
authors: Blaauw
authors: J F
authors: JF
authors: Brière
authors: R
authors: R
authors: de Jong
authors: J C
authors: JC
authors: Benningshof
authors: A E
authors: AE
authors: van Ginkel
authors: J
authors: J
authors: Fraanje
authors: K
authors: K
authors: Goubitz
authors: H
authors: H
authors: Schenk
authors: F P
authors: FP
authors: Rutjes
authors: H
authors: H
authors: Hiemstra
mesh_terms: D000969:Antinematodal Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D003500:Cyclization; D006586:Hexanes / Q000138:chemical synthesis / Q000737:chemistry*; D010777:Photochemistry
chemical_list: D000969:Antinematodal Agents; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D006586:Hexanes; C431673:solanoeclepin A