WestCHEM, School of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
J Org Chem. 2012 Nov 16;77(22):10001-9. doi: 10.1021/jo3022583. Epub 2012 Nov 8.
A base-mediated 6-endo-trig cyclization of readily accessible enone-derived α-amino acids has been developed for the direct synthesis of novel 2,6-cis-6-substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains were tolerated by this mild procedure to give the target compounds in good overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some insight as to how these compounds were formed, with the enolate intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-l-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed.
现已开发出一种基于碱的易接近的烯酮衍生的α-氨基酸的 6-endo-trig 环化反应，用于直接合成新型 2,6-顺式-6-取代-4-氧代-L-哌啶酸。该温和的方法可以容忍各种脂肪族和芳基侧链，以良好的总收率得到目标化合物。通过 6-endo-trig 环化的分子建模，可以了解这些化合物的形成方式，其中烯醇盐中间体通过平衡过程生成，然后不可逆的互变异构/中和提供了产物形成的驱动力。还对得到的 2,6-顺式-6-取代的 4-氧代-L-哌啶酸进行立体选择性还原和脱保护，得到相应的 4-羟基-L-哌啶酸。
