Simple and Facile l -Prolinamides Derived from Achiral Cycloalkylamines as Organocatalysts for the Highly Efficient Larg
- PDF / 690,290 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 54 Downloads / 155 Views
Simple and Facile L-Prolinamides Derived from Achiral Cycloalkylamines as Organocatalysts for the Highly Efficient Large-Scale Asymmetric Direct Aldol Reactions Jiang-Wei Xu • Xiang-Kai Fu • Xiao-Yan Hu Chuan-Long Wu
•
Received: 22 February 2011 / Accepted: 17 March 2011 / Published online: 7 April 2011 Ó Springer Science+Business Media, LLC 2011
Abstract A series of N-cycloalkylprolinamides have been designed and synthesized from achiral cycloalkylamines in a facile manner. They promoted high stereoselectivity in the cross-aldol reaction. N-cyclopropylprolinamide performed best with a smallest carbocyclic ring, and the anti-aldol products could be obtained with up to 99:1 anti/syn and 99% ee. Carbocyclic ring was found to play a significant role in the formation of the aldol products. This simple catalyst can be efficiently used in large-scale reactions with the enantioselectivity being maintained at the same level, which offers great possibility for applications in industry. Keywords N-cycloalkylprolinamides Stereoselectivity Cross-aldol Carbocyclic ring Organocatalyst Largescale
1 Introduction Asymmetric organocatalysis has emerged as a rapidly growing and important field in organic chemistry [1–9]. Small molecules as organocatalysis brought the prospect of a complementary mode of catalysis, with the potential for
J.-W. Xu X.-K. Fu (&) X.-Y. Hu C.-L. Wu College of Chemistry and Chemical Engineering, Southwest University, Institute of Applied Chemistry Southwest University, The Key Laboratory of Applied Chemistry of Chongqing Municipality, Chongqing 400715, People’s Republic of China e-mail: [email protected] J.-W. Xu X.-K. Fu X.-Y. Hu C.-L. Wu The Key Laboratory of Ecoenvironments in Three Gorges Reservoir Region Ministry of Education, Chongqing 400715, People’s Republic of China
123
savings in cost, time and energy, an easier experimental procedure, and reductions in chemical waste [10, 11]. Not surprisingly, aldol reaction constitutes one of the immensely investigated amongst C–C bond forming reactions in the realm of organocatalysis [12–15]. Since the pioneering work of List et al. [16–18] who demonstrated the use of proline in catalyzing the direct aldol reaction of p-nitrobenzaldehyde with acetone, a number of organocatalysts that function based on the principle of the so-called ‘‘enamine catalysis’’ have been reported [15]. Although the acidic proton of the carboxylic group of proline is responsible for enantioselectivity in aldol reactions, it is sufficiently clear that the carboxylic acid group is not indispensable for catalysis. A variety of pyrrolidine-based organocatalysts that are devoid of carboxyl groups have been designed and shown to be efficient. These compounds are generally prolinamide derivatives that differ in the nature of the amine component attached to the carboxylic functionality of proline, and generally contain additional stereogenic center and hydrogen-bonding site [19–23]. Therefore, these catalysts not only complex but also expensive as a rule. Barbas, [24–27
Data Loading...
