Irreversible endo-Selective Diels-Alder Reactions of Substituted Alkoxyfurans: A General Synthesis of endo-Cantharimides

被引:22
作者
Foster, Robert W. [1 ]
Benhamou, Laure [1 ]
Porter, Michael J. [1 ]
Bucar, Dejan-Kresimir [1 ]
Hailes, Helen C. [1 ]
Tame, Christopher J. [2 ]
Sheppard, Tom D. [1 ]
机构
[1] UCL, Dept Chem, Christopher Ingold Labs, London WC1H 0AJ, England
[2] GlaxoSmithKline, Med Res Ctr, Stevenage SG1 2NY, Herts, England
基金
英国工程与自然科学研究理事会;
关键词
cantharimides; cycloadditions; dienes; furans; phthalimide; MALEIC-ANHYDRIDE; SMALL MOLECULES; OPTICALLY PURE; FURAN; ANALOGS; DISCOVERY; OXETANES; CYCLOADDUCTS; DERIVATIVES; INHIBITION;
D O I
10.1002/chem.201406286
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides the first general route for preparing endo-cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead-like properties for medicinal chemistry programs. Furthermore, the electron-rich furans are shown to react with a variety of alternative dienophiles to generate 7-oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3-alkoxy group on a furan Diels-Alder reaction.
引用
收藏
页码:6107 / 6114
页数:8
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