|Alternative Title||Highly Asymmetric Addition of Grignard Reagents To Aldehydes Catalyzed by BINOL-Ti Ate-complex
|Place of Conferral||兰州
我们通过利用Ti(Oi-Pr)4使格氏试剂转化成烷基钛，同时产生具有亲核加成促进作用的副产物MgBr(Oi-Pr)，由于BDMAEE能与MgBr(Oi-Pr)络合降低其路易酸活性，所以不需要离心或者借助络合试剂完全除去镁盐，而使用原位生成的烷基钛在BINOL-Ti诱导下对醛进行不对称加成。BDMAEE在络合MgBr(Oi-Pr)的同时也能和格氏试剂中的Mg原子配位，从而也降低了格氏试剂的活性，所以该反应不需要大于格氏试剂量的Ti(Oi-Pr)4使格氏试剂完全转化成烷基钛。研究显示，BINOL，Ti(Oi-Pr)4，格氏试剂的量等条件对对映选择性有很大影响，在最优条件下，10% BINOL催化不同格氏试剂对苯甲醛加成可以得到中等到优秀ee值的对映选择性产物。其中，异丁基格氏试剂加成产物ee值最高，为94%。在BINOL量为15% 条件下，异丁基格氏试剂对多种取代芳香醛加成也取得很好的结果：产物ee值最低为97%，最高大于99%；对脂肪族醛、杂环醛和α,β-不饱和醛肉桂醛也取得了很好的结果，ee值均大于90%。|
|Other Abstract||Grignard reagents are among the most important and traditional organometal reagents. Addition of Grignard reagents to double bonds is one of most reliable methods for forming Carbon-Carbon bonds. Catalytic asymmetric addition of Grignard reagents to aldehydes can produce numerous chiral sec-alcohols, many of them have different biologically activities. However, there are few success report on asymmetric alkylation by Grignard reagents to carbonyl compounds due to the intrinsic high reactivities of Grignard reagents.
For very long time, many research groups focus on using more than a stoichiometric amount of a chiral auxiliaries to obtain high enantioselectivity. There were mainly two sorts of processes reported on highly catalytic asymmetric addition of Grignard reagents to aldehydes. The former case was to transform Grignard reagent RMgX into other organometal reagents such as R2Zn and R-Ti derivatives via complicated procedures at extremely low temperature. The later case was to link a chiral ligand to Mg in the form of organomagnesium amides or use chiral amine ligand catalyzing the alkylation of aldehydes. As a result, realizing the highly asymmetric addition of real Grignard reagents to aldehydes at mild conditions is more fascinating and challenging.
We transformed RMgBr into R-Ti derivatives with the production of byproduct MgBr(Oi-Pr) at the same time, but we didn,t need romove the Mg salt by centrifugation or chelating reagents, for bis[2-(N,N-dimethylamino)ethyl] ether (BDMAEE) could chelate with Mg atom and thereby reduced the Louis acidity of Mg salt, so we used R-Ti derivatives produced in situ to alkylate the aldehydes induced by BINOL-Ti complexes.. At the same time BDMAEE could chelate with Mg atom of RMgBr so as to reduce the reactivity of RMgBr, so this reaction didn,t need much excess of Ti(Oi-Pr)4 to transform RMgBr into R-Ti derivatives. The amounts of (S)-BINOL, Ti(Oi-Pr)4 and RMgBr have great effects on the enantioselection. Under the optimized reaction condition, moderate to good enantioselection in the alkylation of aldehydes using 10% BINOL were achieved. i-BuMgBr was the best Grignard reagent and its enantioselection was up to 94%. Under 15% BINOL conditions, varieties of aryl aldehydes were used to test this reaction, and their enantioselections were all over 97% and the highest two samples were over 99%. High enantioselection with ee>90% were gained for alphatic aldehydes, heterocyclic aldehydes as well as α,β-unsatu...|
王俊蕊. BINOL-Ti复合物催化的格氏试剂对醛的高效不对称加成[D]. 兰州. 兰州大学,2009.
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