Enantioselective reactions nitrogen

Enantioselective -Functionalization of Aldehydes and Ketones The direct and enantiosective functionalization of enolates or enolate equivalents with carbon-, nitrogen-, oxygen-, sulfur- or halogen-centered electrophiles represents a powerful transformation of chemical synthesis and of fundamental importance to modem practitioners of asymmetric molecule constmction. Independent studies from List, J0rgensen, Cordova, Hayashi, and MacMiUan have demonstrated the power of enamine catalysis, developing catalytic enantioselective reactions such as... 

Seebach, D., Hayakawa, M., Sakaki, J. and Schweizer, W.B. (1993) Derivatives of tetraaryl-2,2-dimethyl-1,3 -dioxolane-4,5 -dimethanol (TADDOL) containing nitrogen, sulfur, and phosphorus atoms. New ligands and auxiliaries for enantioselective reactions. Tetrahedron, 49, 1711-1724. 

Asymmetric Mannich reactions provide useful routes for the synthesis of optically active p-amino ketones or esters, which are versatile chiral building blocks for the preparation of many nitrogen-containing biologically important compounds [1-6]. While several diastereoselective Mannich reactions with chiral auxiliaries have been reported, very little is known about enantioselective versions. In 1991, Corey et al. reported the first example of the enantioselective synthesis of p-amino acid esters using chiral boron enolates [7]. Yamamoto et al. disclosed enantioselective reactions of imines with ketene silyl acetals using a Bronsted acid-assisted chiral Lewis acid [8]. In all cases, however, stoichiometric amounts of chiral sources were needed. Asymmetric Mannich reactions using small amounts of chiral sources were not reported before 1997. This chapter presents an overview of catalytic asymmetric Mannich reactions. 

The effect of (i) the distance between the side-chain phenyl and the a-chiral reaction centre, (ii) the distance between the 4-methoxyphenyl ring and the nitrogen atom, and (iii) the effect of adding TADDOL in the BTPP base-catalysed formation of the /3-lactam (83) from (82) was investigated.132 The most enantioselective reaction (74% ee) occurred when n = 0 and m = 1. TADDOL had a variable effect on the enantioselectivity but had a negative effect on the enantioselectivity in the reaction with n = 0 and m = 1. Reasons for the observed enantioselectivities are presented. 

Nitrogen-Containing Ligands Anchored onto Polymers as Catalyst Stabilizer for Catalytic Enantioselective Reactions... 

Enantioselective allylic substitutions of cyclic allylic esters have been more challenging to develop than enantioselective reactions of symmetrical, acyclic allylic esters. In one set of reactions, racemic allylic esters react to form non-racemic products by addition of carbon or nitrogen nucleophiles in the presence of palladium catalysts. In these cases, attack at the two termini of the allylic intermediate generates the two enantiomers. Only a handful of ligands have generated catalysts that form products from the substitution of aliphatic. 

Due to their importance for research but also for industrial chemistry, transition metal based catalysts are intensively investigated. Ananikov et al. [684] reviewed various appUcatimis of hybrid ONIOM methods within this field. This review involves reaction mechanisms and enantioselective reactions of transition metal complexes, e.g. Ti-catalyzed cyanation of benzaldehyde [685], Cu-catalyzed cyclopropanation [686], Mn-porphyrin catalyzed epoxidation of alkene [687], and Mo-catalyzed nitrogen activation [688]. These approaches involve QM/QM as well as QM/MM approaches. 

The amidation of esters and amino alcohols is a less widely investigated area with relatively few literature examples. In 2005, nitrogen-heterocyclic carbenes (NHCs) were reported to be catalytic in this transformation." l,3-Bis(2,4,6-trimethylphenyl)-l,3-dihydro-2i -imidazol-2-ylidene (IMes) was chosen as the most suitable carbene, being readily available, reactive and easy to store. It is required in low catalytic loadings of 5 mol% in THF at 23 °C. These mild conditions are highly desirable so that the reaction is compatible with other functional groups and can potentially be used for enantioselective reactions. Reaction times varied from 1.5-24 hours depending on steric bulk and electrophilicity of the ester. 

The two 3,5-dimethylbenzyl substituents on the nitrogen atom of the ligand are important determinants of the enantioselectivity. The reaction is thought to proceed... 

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