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Rita G. Hazell

Bio: Rita G. Hazell is an academic researcher from Aarhus University. The author has contributed to research in topics: Crystal structure & Enantioselective synthesis. The author has an hindex of 37, co-authored 166 publications receiving 4841 citations. Previous affiliations of Rita G. Hazell include National Research Foundation of South Africa.


Papers
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TL;DR: In this paper, a new catalytic enantioselective conjugate addition of nitroalkanes to acyclic α,β-unsaturated enones catalyzed by novel organic catalysts has been developed.
Abstract: A new catalytic enantioselective conjugate addition of nitroalkanes to acyclic α,β-unsaturated enones catalyzed by novel organic catalysts has been developed. A series of chiral amines has been tested as catalysts for the addition of 2-nitropropane to benzylideneacetone, and it is found that a novel imidazoline catalyst, prepared from phenylalanine, can catalyze a highly enantioselective 1,4-addition reaction. The reaction of various acyclic and cyclic nitroalkanes was found to proceed well with enantioselectivities up to 86% ee, and enantiopure products can be obtained by recrystallization. The potential of the reaction is documented by the reaction of a series of substituted α,β-unsaturated enones with different nitroalkanes. Furthermore, the synthetic applicability of the reaction is demonstrated by the formation of optically active functionalized pyrrolines and pyrrolidines by reductive amination of the products. On the basis of the absolute configuration of the conjugate addition products, the mechan...

222 citations

Journal ArticleDOI
TL;DR: The catalytic enantioselective Henry reaction of α-keto esters with nitromethane has been developed in this article, where the reaction conditions have been optimized by the screening of different chiral Lewis acids, solvents, and bases, and it was found that the copper(II)−tert-butyl bisoxazoline complex in combination with triethylamine catalyzed a highly enanti-lective reaction giving optically active β-nitro-α-hydroxy esters in high yields and with excellent enantiomeric excess
Abstract: The catalytic enantioselective Henry reaction of α-keto esters with nitromethane has been developed. The reaction conditions have been optimized by the screening of different chiral Lewis acids, solvents, and bases, and it was found that the copper(II)−tert-butyl bisoxazoline complex in combination with triethylamine catalyzed a highly enantioselective reaction giving optically active β-nitro-α-hydroxy esters in high yields and with excellent enantiomeric excesses. The scope of the reaction is demonstrated by the reaction of a variety of different α-keto esters. The catalytic enantioselective Henry reaction of β,γ-unsaturated-α-keto esters proceeds as a 1,2-addition reaction exclusively, in contrast to the uncatalyzed reaction where both the 1,2- and 1,4-addition products are formed. It is demonstrated that the β-nitro-α-hydroxy esters can be converted into, e.g., Boc-protected β-amino-α-hydroxy esters in high yields and without loss of optical purity. The mechanism for the reaction is discussed, and it i...

214 citations

Journal ArticleDOI
TL;DR: A new catalytic enantioselective synthetic method for the formation of optically active aromatic and heteroaromatic hydroxy-trifluoromethyl ethyl esters is presented, which proceeds in good yield and with high enantiomeric excess.
Abstract: A new catalytic enantioselective synthetic method for the formation of optically active aromatic and heteroaromatic hydroxy-trifluoromethyl ethyl esters is presented. This catalytic enantioselective Friedel-Crafts reaction of trifluoromethyl pyruvate with aromatic and heteroaromatic compounds is catalyzed by a chiral bisoxazoline copper(II) complex and proceeds in good yield and with high enantiomeric excess. For a series of substituted indoles, the corresponding 3-substituted hydroxy-trifluoromethyl ethyl esters are formed in up to 93% yield and 94% ee. Pyrrole and 2-substituted pyrroles also react with trifluoromethyl pyruvate in a highly enantioselective aromatic electrophilic reaction and up to 93% ee and good yields are obtained. Furanes and thiophenes give the corresponding 2-hydroxy-trifluoromethyl ethyl esters in high enantiomeric excess; however, the yields of the products are only moderate. Various types of aromatic compounds react in this catalytic reaction with trifluoromethyl pyruvate to give the aromatic electrophilic addition product in good yield. To obtain high enantiomeric excess (> 80% ee) it is necessary that aromatic amines are protected with sterically demanding protecting groups such as benzyl or allyl. This prevents coordination of the amine nitrogen atom to the catalyst, as aromatic amines having a N,N-dimethyl group probably coordinate to the catalyst, leading to a significant reduction of the enantioselective properties of the catalyst. On the basis of the experimental results and the absolute configuration of the formed chiral center, the mechanism for the catalytic enantioselective Friedel-Crafts reaction is discussed.

165 citations


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TL;DR: Huisgen's 1,3-dipolar cycloadditions become nonconcerted when copper(I) acetylides react with azides and nitrile oxides, providing ready access to 1,4-disubstituted 1,2, 3-triazoles and 3, 4-disubsided isoxazoles, respectively.
Abstract: Huisgen's 1,3-dipolar cycloadditions become nonconcerted when copper(I) acetylides react with azides and nitrile oxides, providing ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted isoxazoles, respectively. The process is highly reliable and exhibits an unusually wide scope with respect to both components. Computational studies revealed a stepwise mechanism involving unprecedented metallacycle intermediates, which appear to be common for a variety of dipoles.

1,486 citations

Journal ArticleDOI
TL;DR: Asymmetric multicomponent reactions involve the preparation of chiral compounds by the reaction of three or more reagents added simultaneously and has some advantages over classic divergent reaction strategies, such as lower costs, time, and energy, as well as environmentally friendlier aspects.
Abstract: Asymmetric multicomponent reactions involve the preparation of chiral compounds by the reaction of three or more reagents added simultaneously. This kind of addition and reaction has some advantages over classic divergent reaction strategies, such as lower costs, time, and energy, as well as environmentally friendlier aspects. All these advantages, together with the high level of stereoselectivity attained in some of these reactions, will force chemists in industry as in academia to adopt this new strategy of synthesis, or at least to consider it as a viable option. The positive aspects as well as the drawbacks of this strategy are discussed in this Review.

1,479 citations

Journal ArticleDOI
TL;DR: This Review emphasizes the achievements in the selective catalytic functionalization of indoles (C-C bond-forming processes) over the last four years.
Abstract: 140 years ago Adolf von Baeyer proposed the structure of a heteroaromatic compound which revolutionized organic and medical chemistry: indole. After more than a century, indole itself and the complexity of naturally occurring indole derivatives continue to inspire and influence developments in synthetic chemistry. In particular, the ubiquitous presence of indole rings in pharmaceuticals, agrochemicals, and functional materials are testament to the ever increasing interest in the design of mild and efficient synthetic routes to functionalized indole derivatives. This Review emphasizes the achievements in the selective catalytic functionalization of indoles (C-C bond-forming processes) over the last four years.

1,141 citations