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

在用于不对称Meerwein-Ponndorf-Verley(MPV)还原的手性醇试剂中引入硫醇基团，可以通过一种新颖的串联Michael加成/MPV还原将α，β-不饱和酮不对称还原为仲醇和烯丙醇。无环α，β-不饱和酮和(-)-10-甲基异冰片与二甲基氯化铝反应，以非常高的产率(高达96%)获得了MPV非对映选择性还原产物。机理研究阐明：(1)与(-)-异冰片和氯化二甲基铝形成的络合物的结构；(2)1，7-氢化物的不对称移动；(3)通过可逆的Michael加成反应实现的动态动力学拆分。MPV产物随后用改进的Raney镍体系进行还原脱硫，在96-98%ee中将α，β-不饱和酮高度对映选择性还原为饱和仲醇。β-消除相应的亚硫醚得到86-98%ee的烯丙醇。应用程序…开发了前列腺素合成中间体的不对称还原反应和(+)-甲虫信息素的不对称合成新方法。以α，β-不饱和酮为原料，以(-)-2-硫代甲基异冰片为原料，经两步反应合成了光学活性1，3-巯基醇。该转化包括上述串联反应和碱催化消除。反式查尔酮衍生物中的两个新生成的碳被高度对映选择性控制。通过上述转化，在底物和手性试剂之间发生了不对称的双官能团交换反应，发现在手性巯基醇的作用下，硫醇与α取代的α，β不饱和酯的Michael加成反应具有高度的不对称质子化反应。随后将手性助剂从产物中切割出来，将正式地将硫化氢不对称地加成到α取代的α，β不饱和酯上。在α-取代α，β-不饱和酮的串联反应中，新生成的三个顺序碳的构型也得到了高度控制。然而，从产品中去除手性助剂的尝试到目前为止都是不成功的。较少

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