THE DEVELOPMENT FOR STEREOSELECTIVE CONSTRUCTION OF FUSED HETEROCYCLES BY A NEW METHODOLOGY OF INTRAMOLECULAR HETERO DIELS-ALDER REACTION

分子内杂杂狄尔斯-阿尔德反应新方法制备稠合杂环的立体选择性研究进展

• 批准号: 11640540
• 负责人: WADA Eiji
• 金额: $ 2.5万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11640540/
• 关键词: catalytic asymmetric reaction; tandem reaction; Intramolecular Diels-Alder; transetherification; optical active fused heterocycles; hetero 1, 3-diene; unsaturated carbonyl compound; unsaturated alcohol; 環状付加; 立体選択的縮合複素環合成; ヘテロ1,3_-ジエン

The stereoselective construction of fused heterocycles was developed by tandem transetherification/intramolecular hetero Diels-Alder reaction as new type of intramolecular hetero Diels-Alder reaction. Furthermore the high enantioselective tandem reaction of activated bidentate enone with δ, ε-unsaturated alcohols was achieved by using cationic C2-symmetric chiral catalyst bearing bis(oxazoline). The following results were obtained.1) Alkoxy-substituted unsaturated carbonyl compounds such as methoxy-methyleneacetylacetone, butoxymethylenecyanoacetaldehyde, and methyl (E)-4-methoxy-2-oxo-3-butenoate, underwent stereoselective intramolecular hetero Diels-Alder reaction to afford corresponding hydropyranopyrans in the presence of δ, ε-alkenyl alcohols under thermal conditions. The reactions involve the transetherification process between alkoxy-substituted unsaturated carbonyl compounds and δ, ε-alkenyl alcohols as the key step. 2) These tandem reactions also proceeded with sec- and tert-δ, ε-alkenyl alcohols 3) With E, Z-unsaturated alcohols, the reaction proceed stereospecificly to provide correspoding adducts. 4) This tandem reaction proceeds stereoselectively under mild conditions in the presence of catalytic amount of Lewis acid. 5) This tandem reaction proceed in one flask. Furthermore the tandem reaction of bidentate enone such as methyl (E)-4-methoxy-2-oxo-3-butenoate with δ, ε-alkenyl alcohols proceeds in high enantioselectivity (over 97% ee) to afford corresponding optically active hydropyranopyrans in the presence of C2-symmetric (S,S)-tert-butyl-bis (oxazolynyl) Cu (SbF6) 2 as chiral Lewis acid.

串联醚交换/分子内杂Diels-Alder反应是一种新型的分子内杂Diels-Alder反应，可立体选择性地构建稠杂环化合物。此外，在带有双恶唑啉的阳离子C2对称手性催化剂作用下，实现了活化双齿烯酮与δ，ε-不饱和醇的高不对称串联反应. 1）烷氧基取代的不饱和羰基化合物如甲氧基亚甲基乙酰丙酮、丁氧基亚甲基乙醛和（E）-4-甲氧基-2-氧代-3-丁烯酸甲酯在δ，ε-烯基醇存在下，在热条件下发生立体选择性的分子内杂Diels-Alder反应，生成相应的氢化吡喃吡喃。反应的关键步骤是烷氧基取代的不饱和羰基化合物与δ，ε-烯基醇的醚交换反应。2)3）与E，Z-不饱和醇的反应是立体专一的，生成相应的加成物。4)在催化量的刘易斯酸存在下，该串联反应在温和条件下立体选择性地进行。5)该串联反应在一个烧瓶中进行。此外，双齿烯酮如（E）-4-甲氧基-2-氧代-3-丁烯酸甲酯与δ，ε-烯基醇在手性刘易斯酸（C2-对称的（S，S）-叔丁基-双（恶唑啉基）Cu（SbF 6）2）存在下的串联反应具有较高的对映选择性（97%ee），得到了相应的光学活性氢化吡喃.