Highly Enantioselective Asymmetric Michael Addition Reactions with New Chiral Multisite Phase-Transfer Catalysts

Abstract

Highly enantioselective Michael addition reactions of diethyl malonate to various chalcones have been achieved under mild chiral multisite phase-transfer reaction conditions by the successful utilization of 2,4,6-(triscinchoniummethyl)phenyl-1,3,5-triazines as new chiral quaternary ammonium catalysts. This simple asymmetric Michael addition process was found to be quite effective and to obtain Michael adducts with very good yields and enantiomeric excesses.Phase-transfer catalysis is a versatile, well-established synthetic technique applicable to a number of organic biphase reactions. 1 This technique has become one of the most interesting and fascinating topics of research during the last few years being successful for a multitude of organic transformations. 2 One of the most general, efficient, and environmental benign methodologies that can successfully be employed to solve the predicament of insolubility of aqueous phase with organic phase is phasetransfer catalysis. 3 As the chemical reactants reside in immiscible phases, phase-transfer catalysts have the ability to carry one of the reactants as a highly active species for penetrating the interface, into the other phase where the reaction takes place, and to give a high conversion and selectivity for the desired product under mild reaction conditions. Since the mid 1880's the Michael addition reaction has been extensively investigated and applied in organic chemistry. 4 During the past two decades, a large progress has been made in the development of asymmetric catalyzed Michael addition reactions in the presence of cinchona-based chiral catalysts with very good yield and high enantiomeric excesses. In recent years most of the researchers concentrated on the catalysis of asymmetric Michael reaction using chiral metal complexes and cinchona alkaloid based chiral catalysts, they have been developed as an efficient method for the enantioselective construction of carbon-carbon bonds. 5 Recently, Corey et al. 6a and Kim et. al. 6b have reported the enantioselective Michael addition of nitromethane and nitroalkane to α,β-enone using a chiral quaternary ammonium salt as chiral catalyst, respectively. Shishido et al. has reported on the synthesis of (+)-triptoquinone using the chiral cinchonidine-based quaternary ammonium bromide as catalyst. 7 All the previously reported Michael addition reactions are using single-site quaternary ammonium chiral catalysts also they have achieved moderate yield and enantiomeric excesses. In our study for the first time we reported the multisite-containing chiral quaternary ammonium catalysts for the Michael addition reaction under mild basic conditions with very good yield and enantiomeric excesses (Figure 1, 1-3). As part of our research program related to the development of effective cinchona alkaloid derived chiral multisite phase-transfer catalysts (CMPTC), 8 we reported the catalytic enantioselective Michael reaction promoted by quaternary ammonium salts from cinchonine as phasetransfer catalysts 11a and 11b. 9 Figure 1 Cincho...

Synthesis of C3-Symmetric Cinchona-Based Organocatalysts and Their Applications in Asymmetric Michael and Friedel–Crafts Reactions

“…Jew et al demonstrated the high enantioselectivity of a novel trimeric cinchona alkaloid ammonium salt as a phase-transfer catalyst (PTC) in the catalytic asymmetric alkylation of the N-(diphenylmethylene)glycine tert-butyl ester [21]. Later, the C 3 -symmetric cinchona PTC catalyzed asymmetric synthesis of α-amino acids and the highly enantioselective Michael reaction of chalcones and diethyl malonate were performed by Siva et al [22][23][24][25]. Csámpai and co-workers examined the in vitro antitumor activity of acylated mono-, bis-, and tris-cinchona-based amines [26].…”

Synthesis of C3-Symmetric Cinchona-Based Organocatalysts and Their Application in Asymmetric Michael and Friedel–Crafts Reactions

“…Jew et al demonstrated the high enantioselectivity of a novel trimeric cinchona alkaloid ammonium salt as phase-transfer catalyst (PTC) in the catalytic asymmetric alkylation of N-(diphenylmethylene)glycine tert-butyl ester [21]. Later, the C3-symmetric cinchona PTC catalyzed asymmetric syntheses of α-amino acids and the highly enantioselective Michael reaction of chalcones and diethyl malonate were performed by Siva et al [22][23][24][25]. Csámpai and co-workers examined the in vitro antitumor activity of acylated mono-, bis-, and tris-cinchona-based amines [26].…”