Synthesis And Application Of New L-tartrate Derived Chiral Imide

L-(+)-tartaric acid is a kind of natural products with stable structure, widevariety of sources and low cost. The compounds which derived from chiralresource L-(+)-tartaric acid have been widely used in the field of asymmetricsynthesis. As the high activity structure N-H bond, imide compounds are oftenused as the nucleophile which applied on the synthesis of chiral reagents latent.As the introduction of a chiral center in the imide structure, it has the chiralrecognition ability directly. And this has been a new hotspot. In this paper,L-(+)-tartaric acid worked as the chiral source, and then a new class of chiralauxiliary imide is synthetized by seven steps synthesis reaction. Next through thereaction between chiral auxiliary imide and butyryl chloride, a new compoundcalled (2R,3R)-3,4-dialkoxy-N-butyryl-pyrrole-1,4-dione having two chiralcenters is synthetized.The imide synthesis process includes esterification, etherification,hydrolysis, acid hydrolysis, amine solution, dehydration, debenzylation sevensteps reaction. Specific contents are as follows:1. Synthesis of Ⅰintermediate called (2R,3R)-2,3-dialkoxy diethyl tartrate:L-(+)-tartaric acid is worked as raw material, and then L-(+)-diethyl tartrate2issynthetized by the esterification reaction. Next,(2R,3R)-2,3-dimethoxy diethyltartrate3,(2R,3R)-2,3-diethoxy diethyl tartrate4,(2R,3R)-2,3-dibutoxy diethyltartrate5,(2R,3R)-2,3-dibenzyloxy diethyl tartrate6are synthetized fromdimethyl sulfate, diethyl sulfate,1-bromobutane, benzyl bromide respectively.And there is no report about the4and5compounds before. During this process,the influence of protection groups, reaction solvent, temperature, the releaseorder, ratio on the reaction are studied experimentally.2. Synthesis of Ⅱ intermediate called (2R,3R)-2,3-dialkoxy tartrate: it is generated from the Ⅰintermediate by hydrolysis reaction. During this process,the product purity and extraction method have great influence on the experimentresults. After overcoming the low production and extract difficulty by changingand extracting reagents,(2R,3R)-2,3-dimethoxy tartrate7,(2R,3R)-2,3-diethoxytartrate8,(2R,3R)-2,3-dibutoxy tartrate9and (2R,3R)-2,3-dibenzyloxy tartrate10are synthetized eventually.3. Synthesis of imide target products. Four carboxylic acids which areworked as raw materials, react with acetyl chloride through the dehydrationreaction. And four anhydrides, include (2R,3R)-2,3-dimethoxy succinicanhydride11,(2R,3R)-2,3-diethoxy succinic anhydride12,(2R,3R)-2,3-dibutoxysuccinic anhydride13and (2R,3R)-2,3-dibenzyloxy succinic anhydride14aresynthetized. Next,(2R,3R)-2,3-dimethoxy-4-(4-methoxybenzyl)-butyric acidamine15,(2R,3R)-2,3-diethoxy-4-(4-methoxybenzyl)-butyric acid amine16,(2R,3R)-2,3-dibutoxy-4-(4-methoxybenzyl)-butyric acid amine17and (2R,3R)-2,3-dibenzyloxy-4-(4-methoxybenzyl)-butyric acid amine18are synthetizedthrough the ring opening reaction, which occurred between these anhydride andp-methoxy benzylamine. Then,(2R,3R)-2,3-dimethoxy-N-p-methoxy benzylgroup pyrrole-1,4-dione19,(2R,3R)-2,3-diethoxy-N-p-methoxy benzyl grouppyrrole-1,4-dione20,(2R,3R)-2,3-dibutoxy-N-p-methoxy benzyl group pyrrole-1,4-dione21,(2R,3R)-2,3-dibenzyloxy-N-p-methoxy benzyl group pyrrole-1,4-dione22are synthetized through refluxing reaction. At last, using the cericammonium nitrate as deprotection oxidant, four target imide compounds, include(2R,3R)-2,3-dimethoxy-succinimide23,(2R,3R)-2,3-diethoxy-succinimide24,(2R,3R)-2,3-dibutoxy-succinimide25and (2R,3R)-2,3-dibenzyloxy-succinimide26are synthetized. Also there is no literature report about the23,24and25compounds before.Using the four synthetized imide as the chiral synthon react with butyrylchloride respectively.Synthetized last four imide derivatives, include (2R,3R)-2,3-dimethoxy-N-butyryl-pyrrol-1,4-dione27,(2R,3R)-2,3-diethoxy-N-butyryl-pyrrol-1,4-dione28,(2R,3R)-2,3-dibutoxy-N-butyryl-pyrrol-1,4-dione29,(2R,3R)-2,3-dibenzy loxy-N-butyryl-pyrrol-1,4-dione30are synthetized.