Synthesis of Glutamic Acid and Highly Functionalized Pyrrolidine Derivatives by Utilizing Tunable Calcium Catalysts for Chemoselective Asymmetric 1,4-Addition and [3+2] Cycloaddition Reactions

• Published in: Advanced synthesis & catalysis Vol. 355; no. 8; pp. 1561 - 1569
• Main Authors: Hut'ka, Martin, Tsubogo, Tetsu, Kobayashi, Shū
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 17.05.2013; WILEY‐VCH Verlag; Wiley
• Subjects: asymmetric addition reactions; Asymmetry; Calcium; Catalysis; Catalysts; Chemistry; Chemistry, Applied; Chemistry, Organic; chiral calcium complexes; Cycloaddition; Derivatives; Ligands; Physical Sciences; pyrrolidine derivatives; Science & Technology; Synthesis; tuning of the chemoselectivity; β-branched glutamic acid derivatives; ESTER; tuning of the chemoselectivity; IMINES; branched glutamic acid derivatives; EARTH METAL-CATALYSTS; asymmetric addition reactions; MICHAEL ADDITION; KETONES; chiral calcium complexes; pyrrolidine derivatives; AMINO-ACIDS; POLY(L-GLUTAMIC ACID); GLYCINE DERIVATIVES; CONJUGATE ADDITION; AMIDES
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201300171

A current trend in organic chemistry is the development of highly efficient, environmentally friendly and inexpensive catalysts for asymmetric transformations. Alkaline earth metals, due to their specific chemical properties and abundance in nature, provide promising and challenging catalysts in organic synthesis. This article describes the utilization of alkaline earth metals in the development of an effective catalytic system based on calcium salts in combination with Box‐type ligands. We disclose asymmetric 1,4‐addition and [3+2] cycloaddition reactions using simple catalytic systems consisting of calcium chloride dihydrate, chiral ligands and tetramethylguanidine. Various Box ligands were synthesized and the most effective proved to be that bearing an indane chiral backbone and a cyano group. Depending on the structure of both glycine Schiff bases and α,β‐unsaturated compounds, the corresponding Michael adducts or pyrrolidine derivatives were obtained in moderate to high yields with high enantioselectivities. Modification of the catalytic system by using more Lewis acidic calcium salts such as calcium triflate and neutral Pybox‐type ligands allows a tuning of the chemoselectivity and leads to suppression of the [3+2] cycloadition reactions. Various β‐substituted acrylates provided 1,4‐addition adducts exclusively in high yields with moderate to high diastereo‐ and enantioselectivities. This methodology has broadened a synthetic route to β‐branched glutamic acid derivatives and established calcium salts as useful and attractive catalysts for asymmetric catalysis.