%0 Journal Article
%T A Conformational Model for MTPA Esters of Chiral N-(2-Hydroxyalkyl)acrylamides
%A Eduardo M. Rustoy
%A Alicia Baldessari
%A Leandro N. Monsalve
%J Advances in Chemistry
%D 2014
%R 10.1155/2014/736417
%X The absolute stereochemistry of novel chiral N-(2-hydroxylalkyl)acrylamides prepared by a lipase-catalyzed resolution was successfully determined by 1H NMR of their MTPA esters. The method was validated for this particular case by computational experiments. 1. Introduction It is well known that chiral acrylamides are useful compounds in organic synthesis [1每3]. The absolute stereochemistry of chiral compounds is determined by using several methods [4]. Among the methods available, NMR spectroscopy using chiral derivatizing agents such as 2-methoxy-2-(trifluoromethyl)phenylacetic acid (MTPA) has been widely used in the determination of configuration of stereogenic centers bearing either hydroxyl or amine groups. More recently, this methodology has been applied for the derivatization of chiral primary alcohols thus determining the absolute configuration of stereogenic centers at a two- and three-bond distance from the hydroxyl group [5每8]. Moreover, the modified Mosher＊s method has been used to determine the absolute configuration of primary alcohols with chiral methyl groups at C-2 [9]. However, it should be noted that this modification of Mosher＊s method seemed to be unsuccessful for determining their stereochemistry of MTPA esters of some simple C-2 branched primary alcohols with conjugated groups or a consecutive chiral centre at C-3. According to Tsuda et al. the difference in chemical shift between diastereotopic oxymethylene protons is similar for both diastereomers [9]. We have previously performed a lipase-catalyzed synthesis of nonchiral and chiral N-(2-hydroxyalkyl)acrylamides (Scheme 1) [10, 11]. Scheme 1: Lipase-catalyzed synthesis of 2a每 d. We employed the modified Mosher＊s method for the determination of %ee. The absolute configuration of products was found to be (S). However, a report by Puertas et al. [12] describes the enantioselective behavior of Candida antarctica lipase B (CAL B) affording the (R)-acrylamides instead of (S)-acrylamides as products, using racemic amines as starting materials. Considering the absence of a conformational model for MTPA esters of -chiral primary alcohols and the results of our experiments showing opposite selectivity to previous experience, we decided to test the reliability of the method for our case. The aim of this work was to validate the results by conformational analysis of MTPA esters and thus obtain a reasonable explanation for NMR data on a molecular basis. 2. Results and Discussion We performed the synthesis of chiral N-(2-hydroxyalkyl)acrylamides 2a每d and their corresponding MTPA esters 3a每d
%U http://www.hindawi.com/journals/ac/2014/736417/