Studies on the Development of Novel Asymmetric Multi-Functional MPV Reduction

新型非对称多功能MPV减速器的研制研究

基本信息

批准号：
09470489
负责人：
NODE Manabu
金额：
$ 2.69万
依托单位：
Kyoto Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470489/
关键词：
α,β-Unsaturated Compounds Chinal Mercapto Alcohols Asymmetric Tandem Michael-MPV Reaction Anymmetric 1,7-Hydride Shift Dynamic Kinetic Resolution Asymmetric Protonation Asymmetric Bifunctional Group Exchange Reaction Optically Active Alcohol

项目摘要

The introduction of a thiol group into a chiral alcohol regent for asymmetric Meerwein-Ponndorf-Verley (MPV) reductions allows asymmetric reduction of α,β-unsaturated ketones to secondary alcohols and allylic alcohols via a novel tandem Michael addition/MPV reduction. The reaction of acyclic α,β-unsaturated ketones and (-)-10-mecaptoisoborneol using dimethylaluminum chloride afforded the MPV reduction products diastereoselectively in very high yields (up to 96%). Mechanistic studies elucidated : (1) the structure of the chelation complex with (-)-isoborneol and dimenthylalumium chloride, (2) an asymmetric 1,7-hydride shift, and 3) dynamic kinetic resolution via reversible Michael addition. Subsequent reductive desulfurization of the MPV products with a modified Raney nickel system led to the highly enantioselective reduction of α,β-unsaturated ketones to saturated secondary alcohols in 96-98% ee. β-Elimination of the corresponding sulfoxides gave the allylic alcohols in 86-98% ee. Appl … More ications to the asymmetric reduction of a synthetic intermediate of prostaglandins and to a new asymmetric synthesis of the (+)-Rove beetle pheromone was developed.Optically active 1,3-mercapto alcohol were synthesized from α,β-unsaturated ketones using (-)-2-mercaptomethylisoborneol in two steps. The transformation involved the above tandem reaction and a base catalyzed elimination. The two newly created carbons in tras-chalcone derivatives were enantioselectively controlled to a high degree. Using the above transformation, an asymmetric bifunctional group exchange reaction between the substrate and chiral reagent was developed.A highly asymmetric protonation of Michael addition of thiol to α-substituted α,β-unsaturated esters using a chiral mercapto alcohol was found. Subsequent cleavage of the chiral auxiliary from the product would formally furnish an asymmetric Michael addition of hydrogen sulfide to α-substitute α,β-unsaturated esters. In the tandem reaction of α-substituted α,β-unsaturated ketones, configurations of the newly generated three sequential carbons were also highly controlled. However, attempts to remove the chiral auxiliary from the product are unsuccessful to far. Less

将硫醇基团引入手性酒精调节剂，以减少非对称Meerwein-ponndorf-verley（MPV）减少，允许通过新颖的串联迈克尔添加/MPV减少来减少α，β-不饱和酮对二次酒精和sellic醇。使用二甲基铝氯化二甲基铝的丙烯，β-β-不饱和酮和（ - ） - 10-蛋白异豆菌的反应可为MPV还原产物映射，以非常高的产率（高达96％）。机械研究阐明了：（1）与（ - ） - 异荷酚和二硫酰亚胺的结构，（2）通过可逆的Michael Addafe进行动态动力学分辨率。随后使用改良的Raney镍系统减少了MPV产物的脱硫产品，导致α，β-不饱和酮的高度对映选择性还原为96-98％EE中的饱和二级醇。相应的亚氧化甲基的β-脱颗合含量为86-98％EE。提高了前列腺素合成中间体的不对称还原以及（+） - rove甲虫信息素的新不对称合成。使用（ - ） - 2-羟基甲基异位酚醇从α，β-饱和酮中合成光学活性1,3-羟基醇。转化涉及上述串联反应和碱催化的进化。在Tras-chalcone衍生物中，新创建的两个新创建的碳被高度控制。使用上述转化，开发了底物和手性试剂之间的不对称双功能组交换反应。发现，使用手性墨托酒精，将迈克尔添加到α-取代的α，β-不饱和酯中的高度不对称质子化。随后从产物中手性辅助的裂解将正式提供不对称的迈克尔硫化氢添加到α-替补α-β-β-不饱和酯中。在α-取代α的串联反应中，β-不饱和酮，新生成的三个顺序碳的构型也受到了高度控制。但是，尝试从产品中删除手性辅助的尝试是不成功的。较少的

项目成果

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Kiyoharu Nishide, Uukihiro Shigeta, Kenichi Obata, and Manabu Node: "Asymmetric 1,7-Hydride Shift : The Highly Asymmetric Reduction of α,β-Unsaturated Ketones to Secondary Alcohols via a Novel Tanden Michael Addition - Meerwein-Ponndrof-Verley Reduction."

Kiyoharu Nishide、Uukihiro Shigeta、Kenichi Obata 和 Manabu Node：“不对称 1,7-氢化物转变：通过新型 Tanden Michael 加成 - Meerwein-Ponndrof-Verley 还原将 α,β-不饱和酮高度不对称还原为仲醇。 ”