Organic chemists have always been fascinated by the cyclopropane subunit.1 The smallest cycloalkane is found as a basic structural element in a wide range of naturally occurring compounds.2 Moreover, many cyclopropane-containing unnatural products have been prepared to test the bonding features of this class of highly strained cycloalkanes3 and to study enzyme mechanism or inhibition.4 Cyclopropanes have also been used as versatile synthetic intermediates in the synthesis of more functionalized cycloalkanes5,6 and acyclic compounds.7 In recent years, most of the synthetic efforts have focused on the enantioselective synthesis of cyclopropanes.8 This has remained a challenge ever since it was found that the members of the pyrethroid class of compounds were effective insecticides.9 New and more efficient methods for the preparation of these entities in enantiomerically pure form are still evolving, and this review will focus mainly on the new methods that have appeared in the literature since 1989. It will elaborate on only three types of stereoselective cyclopropanation reactions from olefins: the halomethylmetal-mediated cyclopropanation reactions (eq 1), the transition metal-catalyzed decomposition of diazo compounds (eq 2), and the nucleophilic addition-ring closure sequence (eqs 3 and 4). These three processes will be examined in the context of diastereoand enantiocontrol. In the last section of the review, other methods commonly used to make chiral, nonracemic cyclopropanes will be briefly outlined.

Stereoselective Cyclopropanation Reactions

Recent Advances in Asymmetric Catalytic Metal Carbene Transformations.

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.

C2-Symmetric Chiral Bis(Oxazoline) Ligands in Asymmetric Catalysis

The development of methodologies for efficient asymmetric synthesis is one of the most important areas of synthetic organic chemistry.1 The syntheses of biologically relevant natural and unnatural organic molecules in optically pure form are of central interest in medicinal chemistry and related disciplines. Variations in the stereochemistry of molecular probes for a target enzyme or receptor sites very often display dramatic differences in their binding properties and biological activities. For meaningful biological studies it is important, if not mandatory, to synthesize such agents in enantiomerically pure form. Recent advances in molecular biology and modern instrumentation techniques have led to a better understanding of many complex human diseases at the molecular level. Concurrent with these remarkable achievements have come new challenges and opportunities for asymmetric synthesis. Thus, from the design of enzyme inhibitors to the synthesis of receptor agonists or antagonists and bioactive natural products, asymmetric synthesis is of fundamental significance in biology and medicine.

The advances in asymmetric synthesis have now reached the point that many organic molecules can be prepared with near complete enantioselectivity. This technology is particularly sophisticated in the generation of new stereogenic centers in the presence of existing chiral centers. A number of asymmetric catalysts or so called ‘abiological catalysts’ are approaching an efficiency and selectivity comparable to enzymes such as in the asymmetric hydrogenation of dehydroamino acids utilizing chiral bisphosphine–rhodium complexes,2 asymmetric isomerization of allylic amines with rhodium(I)–BINAP complexes,3 asymmetric epoxidation of allylic alcohols,4 asymmetric epoxidation of unfunctionalized olefins,5 asymmetric reductions with chiral oxazaborolidenes6 and asymmetric dihydroxylation reactions.7 The advantage of abiological catalysts, however, is the availability of either enantiomer of the catalyst which enables one to synthesize either enantiomer of the target molecule. Today there is enormous emphasis on the design and development of efficient chiral catalysts for enantioselective synthesis and this field has become one of the most intense areas of organic chemical research.

In recent years, C2-symmetric chiral bis(oxazoline) ligand–metal complexes have received a great deal of attention through their use in various catalytic process.1c The bis(oxazoline) ligands are structurally related to C2-symmetric semicorrins pioneered by Pfaltz and co-workers.8a–c The inception of bis(oxazoline) ligands, however, added a new dimension in terms of flexibility in ligand design, convenient synthesis and availability of ligands in both enantiomeric forms. Since the early 1990s, many impressive enantioselective carbon–carbon bond forming reactions, aziridination reactions, hydrosilylations, oxidations and reductions have been recorded using bis(oxazoline)–metal complexes. The present review is intended to focus on the recent developments of bis(oxazoline) ligand–metal catalyzed asymmetric reactions and their applications in organic synthesis. The authors do not intend to provide an exhaustive review of this area since earlier developments have been reviewed by Pfaltz8a–c and Bolm.9 Applications of mono- and tris(oxazoline) ligand–metal complex catalyzed reactions are not included in this review.

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C2-Symmetric chiral bis(oxazoline)-metal complexes in catalytic asymmetric synthesis.

The first enantioselective synthesis of the chemotactic factor sirenin by an intramolecular [2 + 1] cyclization using a new chiral catalyst

A catalytic enantioselective synthetic route to the important antidepressant sertraline

Summary A simple, highly enantioselective synthesis of sirenin ( 1 ) (bioactive form) has been developed which depends on the intramolecular [2 +1] cycloaddition reaction of diazo ester 5 to form bicyclic ester 6 (95 : 5 enantioselectivity) using a new and remarkably stable monomeric chiral Cu(I) complex ( 2 ) whose structure was proven by X-ray diffraction analysis.

The First Enantioselective Synthesis of the Chemotactic Factor Sirenin by an Intramolecular (2 + 1) Cyclization Using a New Chiral Catalyst.

A Catalytic Enantioselective Synthetic Route to the Important Antidepressant Sertraline (VII).

L'invention concerne des composes de la formule (1), ainsi que des sels pharmaceutiquement acceptables, des promedicaments et leurs solvates. Z, X, X?1, R1, R2 et R3? sont tel que definis dans le descriptif qui porte sur des compositions pharmaceutiques contenant lesdits composes pour le traitement de troubles induits par l'angiogenese chez les mammiferes par administration desdits composes.

Thomas George Gant

Papers

The first enantioselective synthesis of the chemotactic factor sirenin by an intramolecular [2 + 1] cyclization using a new chiral catalyst

A catalytic enantioselective synthetic route to the important antidepressant sertraline

The First Enantioselective Synthesis of the Chemotactic Factor Sirenin by an Intramolecular (2 + 1) Cyclization Using a New Chiral Catalyst.

A Catalytic Enantioselective Synthetic Route to the Important Antidepressant Sertraline (VII).

Derives heterocycliques servant d'agents anticancereux