1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

Chiral nitrogen-containing compounds are widely distributed in nature and include many biologically important molecules (Chart 1). In these compounds, the nitrogen-containing units are known to play important roles for their bioactivities. For the synthesis of these chiral nitrogen-containing building blocks, use of imines as electrophiles is the most promising and convenient route.1 While many approaches using chiral imines or chiral nucleophiles have been reported,1 these diastereoselective reactions have some disadvantages. First, the procedures to introduce chiral auxiliaries to substrates and to remove them after the diastereoselective reactions are often tedious. Second, more than stoichiometric amounts of chiral sources are needed to obtain chiral compounds according to these reactions. On the other hand, catalytic enantioselective reactions provide the most efficient methods for the synthesis of chiral compounds,2 because large quantities of chiral compounds are expected to be prepared using small amounts of chiral sources. While much progress has been made recently in catalytic enantioselective reactions of aldehydes and ketones such as aldol,3 allylation,4 Diels-Alder,5 cyanation reactions,6 reduction,1b,2b etc., progress in catalytic enantioselective reactions of imines is rather slow. There are some difficulties in performing catalytic enantioselective reactions of imines. For example, in the cases of chiral Lewis acid promoted asymmetric Shū Kobayashi was born in 1959 in Tokyo, Japan. He studied chemistry at the University of Tokyo and received his Ph.D. in 1988 (Professor T. Mukaiyama). After spending 11 years at Science University of Tokyo (SUT), he moved to Graduate School of Pharmaceutical Sciences, University of Tokyo, in 1998. His research interests include development of new synthetic methods, development of novel catalysts (especially chiral catalysts), organic synthesis in water, solid-phase organic synthesis, total synthesis of biologically interesting compounds, and organometallic chemistry. He received the first Springer Award in Organometallic Chemistry in 1997.

https://chemistry.mdma.ch/hiveboard/picproxie_docs/000499541-cr980414z.pdf

Catalytic enantioselective addition to imines.

II.2.1. Homogeneous Systems 2166 II.2.2. Heterogeneous Systems 2168 II.3. Hydride Transfer Reduction 2169 II.3.1. Homogeneous Systems 2169 II.3.2. Heterogeneous Systems 2171 II.4. Hydrosilylation 2172 III. C−O Bond Formation 2173 III.1. Epoxidation of Unfunctionalized Olefins 2173 III.1.1. Homogeneous Catalysis 2173 III.1.2. Heterogeneous System 2176 III.2. Dihydroxylation of Olefins 2178 III.2.1. Homogeneous Systems 2178 III.2.2. Heterogeneous System 2178 III.3. Ring Opening of Meso Epoxides 2180 III.4. Kinetic Resolution 2180 III.4.1. Terminal Epoxides 2180 III.4.2. Secondary Alcohols 2181 IV. C−H Bond Oxidation 2181 IV.1. Allylic and Benzylic Oxidation 2181 IV.2. Baeyer−Villiger-type Reaction 2181 IV.3. Wacker-type Cyclization 2182 V. S−O Bond Formation 2182 VI. C−N Bond Formation 2183 VI.1. Hydroboration/Amination 2183 VI.2. Enolate Amination 2183 VI.3. Aza-Claisen Rearrangement 2183 VI.4. Azide Synthesis 2184 VI.5. Aminohydroxylation 2184 VI.6. Aziridine Synthesis 2184 VI.7. C−N Bond Formation via S−N Bond Formation 2185

Nitrogen-containing ligands for asymmetric homogeneous and heterogeneous catalysis.

Catalytic Enantioselective Formation of C−C Bonds by Addition to Imines and Hydrazones: A Ten-Year Update

Recent developments in the stereoselective synthesis of α-aminoacids

Asymmetric Addition of Organolithium Reagents to Imines

A series of enantiomerically pure 4-substituted bisoxazolines la-f , 2c, and 2e was prepared from naturally derived or synthetic amino alcohols and malonyl dichloride derivatives. The formation of the bisoxazolines was accomplished in two stages: (1) preparation of the bis-amides of the malonyl derivatives with the amino alcohols and (2) cyclization of the hydroxy amides 4 by either of two general protocols; (1) heating with thionyl chloride in toluene or (2) formation of the bismesylate and then heating with aqueous or alcoholic base. The latter procedure was found to be more reliable especially for bisoxazolines with bulky substitutents at C(4). The C(4) trityl-substituted hydroxy amide 4f produced the bis(acy1aziridine)lO by cyclization on the nitrogen atom using KOWMeOH, but afforded the desired bisoxazoline I f by the action of SOClflt3N. The synthesis of the nonnaturally derived amino alcohols using the Evans asymmetric azidation procedure is also described.

Preparation of Chiral Bisoxazolines: Observations on the Effect of Substituents

Ligand-mediated addition of organometallic reagents to azomethine functions

The reductive cleavage of enantiomerically enriched N-acetylhydrazines can be readily accomplished with lithium in ammonia. In all cases studied, both nitrogens of the hydrazine are bonded to sterogenic carbon centers. The configurational integrity of these centers is fully preserved in the amine products obtained from N−N bond scission

Lithium/ammonia cleavage of the nitrogen-nitrogen bond in N-(methoxycarbonyl)- and N-acetylhydrazines

The effects of reagent stoichiometry on the efficiency and selectivity of organocerium additions to chiral and achiral hydrazones have been investigated. The regent formed in-situ from 1 equiv of CH 3 Li and 0.33 equiv of CeCl 3 adds efficiently (>65% yield) to N,N-dimethylhydrazone 1, but this same regent reacts only sluggishly with chiral SAMEMP hydrazone 2 (<30% yield). The optimal stoichiometry of the organocerium reagent is 1:1 CH 3 Li/CeCl 3 , despite the fact that not all of the CeCl 3 is consumed in the transmetalation

Olivier J.-C. Nicaise

Papers

Asymmetric Addition of Organolithium Reagents to Imines

Preparation of Chiral Bisoxazolines: Observations on the Effect of Substituents

Ligand-mediated addition of organometallic reagents to azomethine functions

Lithium/ammonia cleavage of the nitrogen-nitrogen bond in N-(methoxycarbonyl)- and N-acetylhydrazines

Organocerium Additions to Hydrazones: Effects of Reagent Stoichiometry on Efficiency and Selectivity