An unusual domino retro-ene-Conia reaction:: Regio- and stereoselective one-carbon ring expansion of Fenchol derivatives

被引:6
作者
Rüedi, G [1 ]
Laikov, DN [1 ]
Hansen, HJ [1 ]
机构
[1] Univ Zurich, Inst Organ Chem, CH-8057 Zurich, Switzerland
关键词
D O I
10.1002/hlca.200490180
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The 2-exo-substituted fenchol derivatives 1-7, easily prepared from (-)-fenchone in good-to-excellent yields, were pyrolyzed by dynamic gas-phase thermo-isomerization (DGPTI). At temperatures of ca. 620degrees, the substrates with a hydroxyallyl (1-4) or a hydroxypropargyl moiety (6) underwent an initial retro-ene reaction under cleavage of the C(2)-C(3) bond to form enol-ene intermediates with no loss of optical activity. These intermediates then experience either tautomerization to the corresponding alpha,beta-unsaturated ketones or subsequent Conia rearrangement under one-carbon ring expansion of the fenchone system to a bicyclof 3.2.1]octane framework. In the case of the isopropenyl substrate 3, the sterically crowded Conia product underwent a new type of 'deethanation' reaction by stepwise loss of two Me radicals, giving rise to the thermodynamically favored enone 21. A similar relaxation behavior was observed in the case of the ethynyl substrate 6, which showed a remarkable 1,3-Me shift after the Conia reaction, leading to the a,alpha,beta-unsaturated cyclic ketone 25. The homolytic cleavage of the weakest single bond in 1-3 turned out to be a competing reaction pathway. Intramolecular H-abstraction within the generated diradical intermediates produced the monocyclic ketones 8, 16, and 19, besides the products obtained by tautomerization and Conia reaction. In contrast, a Ph substituent at C(2) in 7 allowed only the passage through a diradical species to provide phenone 26, which was converted by regioselective Baeyer-Villiger oxidation to the optically active cyclopentanol 29. Both reaction channels, the domino retro-ene-Conia rearrangement and the diradical-promoted H-transfer, have been shown to proceed highly stereoselectively. The absolute configuration of the newly formed stereogenic centers in all compounds was assigned by H-1-NOE experiments. The reaction mechanism of the novel domino retro-ene-Conia reaction was established by both a series of H-2- and C-13-labeling experiments, as well as by a detailed computational analysis.
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页码:1990 / 2021
页数:32
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