非功能化的,可对α-epimerizable的非血性和化物可以通过结晶诱导的imines的动态分辨率来获取
Janez Kosmrlj1, Leland O Weigel, David A Evans
1Chemical Process R&D, Lilly Research Laboratories, Indianapolis, IN 46285-4813, USA. janez.kosmrlj@uni-lj.si
Journal of the American Chemical Society
|March 13, 2003
概括
这项研究引入了一种简单的结晶诱导动态分辨率 (CIDR) 方法,以有效地将赛米和转化为单个反体. 该工艺实现了高产量和反体过剩,为奇拉化合物合成提供了实用方法.
科学领域:
- 有机化学 有机化学
- 不对称的合成方法
- 结晶化 结晶化 结晶化
背景情况:
- 性化合物的脱血对于合成性纯物质至关重要.
- 现有的方法可能是复杂的或缺乏广泛基质范围的效率.
研究的目的:
- 开发一种操作上简单且高效的化和的脱血协议.
- 研究新型结晶诱导动态分辨率 (CIDR) 过程的机制和范围.
主要方法:
- 伊米因的形成来自于拉塞姆类化物/和一种性氨基辅助物 (转介-1R,2R) -1-amino-6-nitroindan-2-ol).
- 伊米因衍生物的灾难选择性结晶.
- 双相水解以回收性辅助物并获得性丰富的产品.
主要成果:
- 实现了几乎完全的转化racemic混合物到单个反体.
- 对于各种基质,包括2-甲基环合 (97%/92% ee) 和2-乙基合 (94%/98% ee) 观察到高产量和反体过量 (ee).
- 该过程证明了对一系列和甲的有效性.
结论:
- 开发的CIDR协议是一种强大而实用的脱血方法.
- 这种高效率归因于 imine 和 chiral 辅助器之间的特定固态相互作用 (pi 堆积和键).
- 该工艺具有在合合成中的工业应用的潜力.
相关概念视频
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
Primary amines react with carbonyl compounds—aldehydes and ketones—to generate imines. Imines consist of a C=N double bond and are named Schiff bases after its discoverer—the German chemist Hugo Schiff. On the other hand, secondary amines react with carbonyl compounds to give enamines. In enamines, the presence of a C=C double bond adjacent to the nitrogen atom leads to the delocalization of the lone pair.
Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
Preparation of Amines: Reductive Amination of Aldehydes and Ketones
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
NMR Spectroscopy Of Amines
In proton NMR spectroscopy, primary amines and secondary amines showcase their N–H protons as a broad signal in the chemical shift range between δ 0.5 and 5 ppm. The exact position in this range depends on several factors, including sample concentration, hydrogen bonding, and the type of solvent used. Since amine protons undergo fast proton exchange in solution, the protons are labile and therefore do not participate in any splitting with adjacent protons. Thus, the observed peak is broad and...
Determination of Crystal Structures
In the late 1800s, the revelation that light extended beyond visible wavelengths led to the discovery of X-rays by Wilhelm Roentgen. Recognized as high-energy electromagnetic radiation with short wavelengths, X-rays prompted exploration into their interaction with crystals. Max von Laue proposed in 1912 that the periodic arrangement of atoms, ions, or molecules in crystals would cause them to diffract X-rays, a hypothesis confirmed through experiments with copper sulfate and zinc sulfide...


