Oxazolines. XXI. Kinetic resolution of sec-alkyl halides and simultaneous asymmetric synthesis of 3-alkylalkanoic acids using a chiral oxazoline. A method for determining absolute configurations and maximum optical rotations
Oxazolines. XXI. Kinetic resolution of sec-alkyl halides and simultaneous asymmetric synthesis of 3-alkylalkanoic acids using a chiral oxazoline. A method for determining absolute configurations and maximum optical rotations
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恶唑啉类。
DOI：
10.1021/ja00424a049
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发表时间：
1976
影响因子：
15
通讯作者：
K. Kamata
中科院分区：
文献类型：
--
作者：
A. Meyers;K. Kamata
在低温（-60至-70）下，用手性锂恶唑啉5对外消旋仲烷基碘和溴进行了动力学拆分。结果提供了富含R对映体的光学活性卤化物2，其对映体纯度在30-49%范围内。水解后，同时形成的烷基化恶唑啉3得到3-烷基链烷酸4，其也富含R对映异构体并具有30-47%的对映异构体纯度。该技术允许建立仲烷基卤化物和3-取代羧酸的绝对构型，而不需要除手性恶唑啉试剂之外的任何光学活性物质。在某些情况下，只要可靠地知道其中之一，该方法就能够预测对映体烷基卤或羧酸的最大旋转。手性试剂（例如（-）-（R））与外消旋底物（±）-A的优先反应，使得外消旋体中只有一种对映体受到影响，通常称为动力学拆分。该方法依赖于（-）-R显示手性识别，使得其具有区分外消旋混合物的对映体形式的能力。从动力学上讲，这意味着相对速率常数k1和k2的差异很大，使得非对映体过渡态以不同的速率达到，因此每种途径的产物以不等量形成。这也将导致在反应结束时回收过量的对映异构体之一A。这种过量的对映体回收的程度将取决于竞争途径中的β。1
Racemic sec-alkyl iodides and bromides are kinetically resolved at low temperature (—60 to—70) with a chiral lithiooxazoline, 5. The results furnish optically active halides 2 enriched in the R enantiomer in the range of 30-49% enan-tiomeric purity. The concurrently formed alkylated oxazoline 3 after hydrolysis, affords 3-alkylalkanoic acids 4 also enriched in the R enantiomer and possessing 30-47% enantiomeric purity. This technique allows the establishment of absolute configurations for sec-alkyl halides and 3-substituted carboxylic acids, without the need for any optically active materils other than the chiral oxazoline reagent. In severalcases, the method demonstrates the ability to predict the maximum rotation of enan-tiomeric alkyl halides or carboxylic acids provided one of the two are reliably known.The preferential reaction of a chiral reagent, eg,(—)-(R), with a racemic substrate (±)-A such that only one of the enantiomers in the racemate is affected is generally termed a kinetic resolution. The process depends upon (—)-R displaying chiral recognition so that it has the ability to distinguish between the enantiomeric forms of a racemic mixture. Kinetically this means that the relative rate con-stants, k\and &2, are sufficiently different that the diastereomeric transition states are reached at different rates and hence the productsfrom each pathway are formed in unequal amounts. This would also result in one of the enan-tiomers, A, being recovered in excess at the end of the reac-tion. The extent of this excess of enantiomeric recovery will depend upon the (7 of the competing pathways. 1