Pyrrolidine-2-carboxylic Acid
(l-Proline)

Biographical Sketches

Abhimanyu S. Paraskar obtained his Masters degree in chemistry from Amravati University, Maharastra, India. He is currently working on his PhD thesis under the supervision of Dr. Arumugum Sudalai at National Chemical Laboratory, Pune, India.

Introduction

Pyrrolidine-2-carboxylic acid commonly known as l-Proline (I) has shown, in recent times, excellent catalytic activity, in catalyzing a wide variety of reactions such as aldol, [1] [2] Mannich, [3-5] [10-12] Michael, [6-9] in a highly enantio­selective manner. These reactions have produced a variety of useful chiral materials for organic synthesis.

Most of the l-Proline (I) catalyzed reactions are believed to involve enamine (II) as key intermediate in its catalytic cycle (Scheme [1] ).

Scheme 1 Proline - catalytic cycle for aldol reaction.

Abstracts

l-Proline (I) catalyzes the asymmetric aldol reaction between acetone and various aldehydes. In the case of hydroxy acetone, it gives anti-diols in excellent diastereo- and enantioselectivities. [1] [2]
l-Proline catalyzes the Michael reaction of ketones with nitro olefins to provide a variety of chiral Michael addition products. [6-9]
l-Proline catalyzes asymmetric the three component coupling involving Mannich reaction of acetone aldehydes and aryl amines to give β-amino ketones. In case of hydoxyacetone it gives α-hydroxy β-amino ketones in good to excellent ee. This reaction complements the Sharpless asymmetric aminohydroxylation. [3-5] [10]
l-Proline catalyzes Mannich type reaction of protected α-imino ethyl glyoxylate with a variety of ketones to provide functionalized α-amino acids in high enantioselectivities. [11] [12]
l-Proline catalyzes α-amination of ketones by applying azodicarboxylate as nitrogen source to give chiral α-hydrazino, α-amino ketones, and alcohols. [13]
Recently, I has proved to be the best catalyst for asymmetric Robinson annulation. [5]

References

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4 Sakthivel K. Notz W. Bui T. Barbas III CF. J. Am. Chem. Soc.  2001,  123:  5260 

5 Groger H. Wilken J. Angew. Chem. Int. Ed.  2001,  40:  529 

6 Yamaguchi M. Shiraishi T. Hirama M. J. Org. Chem.  1996,  61:  3520 

7 Hanessian S. Pham V. Org. Lett.  2000,  2:  2975 

8 List B. Pojarliev P. Martin HJ. Org. Lett.  2001,  3:  2423 

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11 Cordova A. Notz W. Zhong G. Betancort JM. Barbas III CF. J. Am. Chem. Soc.  2002,  124:  1842 

12 Cordova A. Watanabe S. Tanaka F. Notz W. Barbas III CF. J. Am. Chem. Soc.  2002,  124:  1866 

13 Kumaragurubaran N. Juhl K. Zhuang W. Bogevig A. Jorgensen KA. J. Am. Chem. Soc.  2002,  124:  6254