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

在手性醇试剂中引入硫醇基团进行不对称Meerwein-Ponndorf-Verley（MPV）还原，可以通过新型串联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-不饱和酮与（-）-10-巯基异冰片在二甲基氯化铝作用下反应，非对映选择性地得到MPV还原产物，产率高达96%。机制研究阐明：（1）与（-）-异冰片和dimethylalumium chloride的螯合络合物的结构，（2）不对称的1，7-氢化物位移，和3）通过可逆Michael加成的动态动力学拆分。MPV产物经改性Raney镍还原脱硫后，α，β-不饱和酮高度对映选择性地还原为饱和仲醇（96- 98%ee），相应的亚砜经β-消除反应生成烯丙醇（86- 98%ee）。 关于我们 以α，β-不饱和酮为原料，经（-）-2-巯基甲基异黄酮两步反应合成了光学活性的1，3-巯基醇。转化涉及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产生的碳原子被对映选择性地控制到了很高的程度。利用上述转化，发展了底物与手性试剂之间的不对称双官能基团交换反应，发现使用手性巯基醇对α-取代的α，β-不饱和酯进行硫醇迈克尔加成反应存在高度不对称质子化，随后从产物中裂解出手性助剂，将正式提供硫化氢对α-取代的α，β-不饱和酯的不对称迈克尔加成反应。在α-取代α，β-不饱和酮的串联反应中，新生成的三个连续碳的构型也受到高度控制。然而，从产物中除去手性助剂的尝试迄今为止是不成功的。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