Current Organic Synthesis - Volume 2, Issue 4, 2005

Room Temperature Ionic Liquids (RTILs) have recently been introduced as new solvents in the chemical and biotechnological arenas. Carbohydrates are important natural products that play important biological and commercial roles as foods, drugs and chemical feedstocks. They have two properties that complicate their use a low solubility in most solvents and complex, highly chiral structures. We are currently witnessing a rapid increase in novel applications for newly discovered RTILs. This account reviews the application of RTILs in carbohydrate chemistry and biochemistry as a mono / biphasic solvent, a solvent / catalyst and a product retrieval media.

this review focuses on the regio- and stereoselective synthesis of β-, γ-, and δ-aminophosphonic derivatives by combining dienophiles and dienes substituted by phosphono- and amino-groups. The initially formed cyclohexene adducts have been further transformed: chemoselective deprotections of masked P, C, and N functions, double bond oxidation and cleavage. Our Diels-Alder strategy has been successfully applied in asymmetric synthesis thanks to the development of a novel chiral 1-aminodiene designed by computational chemistry. The influence of a phosphonate substituent on reactivity in [4+2] cycloadditions has been theoretically studied.

The stereoselective allylation of imines and related compounds is one of the most effective methods for the introduction of an amino group into carbon skeletons. Moreover, by extending the process to other C=N functionalities such as oximes, hydrazones, nitrones and iminium ions, a variety of nitrogen-containing functional groups can be prepared with the concomitant introduction of the allyl moiety. In several instances it is possible to achieve a complete stereocontrol by using different organometallic reagents. In other cases, either the protective group tuning or the reaction time is crucial for the stereoselectivity of the reaction. This review covers the evolution of stereoselective allylation of imines and related compounds, including oximes, hydrazones, nitrones and iminium ions, from the use of allylic organometallic reagents over chiral substrates up to the recent development of enantioselective methods.

2-Amino-2'-hydroxy-1,1'-binaphthyl (NOBIN, 3) can be considered as the analogue of 1,1'-bi-2- naphthol (BINOL, 1) and 1,1'-bi-2-naphthylamine (BINAM, 2) in terms of its functionality and scaffold. Since the first report on the synthesis of NOBIN by Kocovsky, the chemistry of NOBIN has been developed rapidly in the last decade. This article summarizes its synthesis, modification and application of its derivatives as the chiral ligands in asymmetric catalysis. The methods for the preparation of enantiopure NOBIN included asymmetric cross-coupling reaction of 2-naphthol and 2-naphthylamine, optical resolution of its racemic form and transformation from enantiopure BINOL. A variety of chiral ligands could be easily obtained by simple transformation from NOBIN. Their application in various asymmetric reactions, such as diethyl zinc addition to aldehydes, allylation of aldehydes, allylic substitutions, 1,4-addition to α,β-unsaturated ketones, aldol-type reaction, Diels-Alder and hetero-Diels-Alder reactions, transfer hydrogenation of ketones, cyclopropanation, phase-transfer catalysis of alkylations, ring-opening/cross metathesis, α-vinylation/arylation of ketones and Suzuki coupling reactions, clearly demonstrated that NOBIN has become one type of privileged scaffold for construction of various chiral ligands for asymmetric catalysis.

This review introduces the broad general topic of asymmetric organic synthetic reactions and reagents. Reagents containing both frequently used metallic ions, e.g. Zn++, Cu+(++) and Ru++, and rarely used ions, such as Ag+, employed in the construction of designed chiral centers, are updated here. Enantioselective 1,2-additions and 1,4-conjugate additions, transfer hydrogenations, and diasteroselective aldol reaction are discussed. The selectivities induced by chiral β-, δ- or γ-chiral amino alcohols, chiral diols, chiral binaphthyl derivatives, chiral P,N-containing auxiliaries, and other ligands used to prepare chiral metallic complexes, were compared in each reaction system. The use of two or more metallic ions with a single chiral ligand has now become a more popular strategy to catalyze chiral-center-controlled processes. For example, only diethylzinc was used in enantioselective additions to aldehydes in early studies. Recently, the combination of Et2Zn and Cu++ in the selective additions has been used to achieve high ee% values and yields. Finally, quantum calculations have been used to obtain kinetic data to predict a reactions ee% values. For example, the calculated δGcal. values have a strong relationship with the obtained δGfit values which have the direct linkage with the ee% values.