Ramachary Dhevalapally B, Shruthi Kodambahalli S
Catalysis Laboratory, School of Chemistry, University of Hyderabad, Central University (PO) , Hyderabad 500 046, India.
J Org Chem. 2016 Mar 18;81(6):2405-19. doi: 10.1021/acs.joc.5b02896. Epub 2016 Mar 3.
Herein, for the first time, a combination of L-amino acid, (R)-5,5-dimethyl thiazolidinium-4-carboxylate (L-DMTC) with simple Brønsted acid TFA is reported as the suitable synergistic catalyst for the List-Lerner-Barbas aldol (LLB-A) reaction of less reactive 2-azidobenzaldehydes with various ketones at ambient temperature to furnish the optically active functionalized (2-azidophenyl)alcohols with very good yields, dr's, and ee's. This method gives first time access to the novel azido-containing multifunctional compounds, which are applicable in material to medicinal chemistry. Chiral functionalized (2-azidophenyl)alcohols were transformed into different molecular scaffolds in good yields with high selectivity through Lewis acid mediated NaBH4 reduction, aza-Wittig and Staudinger reaction (azide reduction), followed by oxidative cyclizations, allenone synthesis, and click reaction, respectively. Chiral LLB-A products might become suitable starting materials for the total synthesis of natural products, ingredients, and inhibitors in medicinal chemistry. The mechanistic synergy of L-DMTC with TFA to increase the rate and selectivity of LLB-A reaction in DMSO-D6 is explained with the controlled and online NMR experiments.
在此，首次报道了L-氨基酸、(R)-5,5-二甲基噻唑烷-4-羧酸盐（L-DMTC）与简单的布朗斯特酸三氟乙酸（TFA）的组合，作为在室温下使反应活性较低的2-叠氮基苯甲醛与各种酮进行List-Lerner-Barbas醛醇缩合（LLB-A）反应的合适协同催化剂，以高收率、高非对映体过量（dr）和高对映体过量（ee）得到光学活性的官能化（2-叠氮基苯基）醇。该方法首次获得了新型含叠氮基的多功能化合物，其适用于从材料到药物化学等领域。通过路易斯酸介导的硼氢化钠还原、氮杂维蒂希反应和施陶丁格反应（叠氮还原），随后分别进行氧化环化、联烯酮合成和点击反应，手性官能化（2-叠氮基苯基）醇以高选择性、高收率转化为不同的分子骨架。手性LLB-A产物可能成为天然产物、成分和药物化学中抑制剂全合成的合适起始原料。通过可控的在线核磁共振实验解释了L-DMTC与TFA在DMSO-D6中提高LLB-A反应速率和选择性的机理协同作用。
