Über die Autorin bzw. den Autor

SCOTT E. DENMARK is the R. C. Fuson Professor of Chemistry at the University of Illinois at Urbana-Champaign. In addition to his editor-in-chief role for Organic Reactions, he is an editor for Organic Syntheses and for the Encyclopedia of Reagents for Organic Synthesis, both available from Wiley.

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Since it was first published in 1967, the highly regarded Topics in Stereochemistry series has consistently reflected the state of the art in the field and provided readers with a coherent framework for the conceptual, theoretical, and practical aspects of modern stereochemistry.

With the new series editor, Scott E. Denmark, at the helm, Volume 22 continues to offer important insights into the evolution of stereochemistry and its future directions. Written by internationally recognized leaders in their respective fields, this volume introduces readers to some of the most intensely studied topics in research laboratories today.

Along with the fundamental principles of chirality, the authors describe exciting new applications of stereochemistry in synthetic organic, physical organic, and bioorganic chemistry. They cover cutting-edge research in areas such as asymmetric catalysis, reactions with catalytic antibodies, and stereoelectronic control of organic reactions. In addition, a feature chapter provides a critical analysis of the concepts of molecular chirality.

Timely and authoritative, Topics in Stereochemistry, Volume 22, features over 120 illustrations and a cumulative index covering Volumes 1 through 22. It is an essential resource for organic chemists involved in synthesis as well as those in the physical and bioorganic areas of organic chemistry.

"This excellent series is highly recommended to all chemists and is a requisite for all chemistry libraries."―Journal of Medicinal Chemistry

Volume 22 of Topics in Stereochemistry relaunches this highly respected series, providing a timely, valuable reference to the theory and practice of stereochemistry. Cutting-edge topics include:

• Foundations of molecular and topological chirality
• Stereoselective reactions with catalytic antibodies
• Stereoelectronic effects of the group 4 metal substituents in organic chemistry
• Asymmetric catalysis with the new class of chiral lanthanoid complexes
• Basic principles of the exciting new area of asymmetric amplification

Aus dem Klappentext

Since it was first published in 1967, the highly regarded Topics in Stereochemistry series has consistently reflected the state of the art in the field and provided readers with a coherent framework for the conceptual, theoretical, and practical aspects of modern stereochemistry. With the new series editor, Scott E. Denmark, at the helm, Volume 22 continues to offer important insights into the evolution of stereochemistry and its future directions. Written by internationally recognized leaders in their respective fields, this volume introduces readers to some of the most intensely studied topics in research laboratories today. Along with the fundamental principles of chirality, the authors describe exciting new applications of stereochemistry in synthetic organic, physical organic, and bioorganic chemistry. They cover cutting-edge research in areas such as asymmetric catalysis, reactions with catalytic antibodies, and stereoelectronic control of organic reactions. In addition, a feature chapter provides a critical analysis of the concepts of molecular chirality. Timely and authoritative, Topics in Stereochemistry, Volume 22, features over 120 illustrations and a cumulative index covering Volumes 1 through 22. It is an essential resource for organic chemists involved in synthesis as well as those in the physical and bioorganic areas of organic chemistry.

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Topics in Stereochemistry

Wiley-Interscience

Chapter One

FUMIO TODA

Department of Chemistry, Okayama University of Science, Ridia-cho1-1, Okayama 700-0005, Japan

I. Introduction

II. Separation of Stereoisomers

A. Separation of a Component of an Equilibrium Mixture

B. Separation of Conformational Isomers of [alpha]- and ?-Ionones, Acrylic Acid, and 1,2-Dichloroethane

C. Separation of Conformational Isomers of Cyclohexane Derivatives

III. Chiral Conformers of Achiral Molecules in Their Own Crystals

IV. Control of Stereochemistry of Molecules in Crystals for Selective Reactions

Acknowledgments

References

I. INTRODUCTION

A stereoisomer can be studied precisely if it is isolated in a pure state from a mixture of stereoisomers. When the stereoisomer is a component of an equilibrium mixture, its isolation in a pure state is more difficult. The usual method is X-ray crystallographic analysis for the structural study of molecules whereby the stereoisomers are isolated as inclusion crystals with a host compound. By the inclusion method the isomeric molecule of gas, liquid, or solid can be isolated as an inclusion complex in a pure state. The separation of one enantiomer of a racemic compound can be accomplished by using a chiral host compound. In some cases the racemic compound easily forms a conglomerate by complexation with an achiral host compound and thus is separated into enantiomers very efficiently. Once the stereoisomer is trapped in on inclusion crystal, a stereoselective reaction of a symmetrical molecule can be accomplished by carrying out the reaction within a host compound that controls the steric course of the reaction in the solid state. In some cases achiral molecules can be arranged in chiral form in their own crystal, and their reaction in the solid state proceeds stereoselectively to give an optically active product. Stereochemical study of the absolute asymmetric reaction in a crystal is an interesting subject as well.

In this chapter separation of stereoisomers in a pure state by inclusion complexation with a host compound, and stereochemical study of these stereoisomers in inclusion complexes by X-ray analysis are described. The solid state reactions in the inclusion complex that give stereoselective reaction products is also described.

II. SEPARATION OF STEREOISOMERS

A. Separation of a Component of an Equilibrium Mixture

We developed a method to separate one stereoisomer from a mixture based on inclusion complexation with a host compound. We began by testing whether the method is useful for separation of one component of an equilibrium mixture.

Since 1,2,4-triazole (1) exists as an equilibrium mixture of the two tautomers, 1,2,4-triazacyclopenta-3,5-diene (1a) and 1,2,4-triaza-2,5-diene (1b), we had trouble isolating a single tautomer in a pure state in order to study its structure. We succeeded in freezing out the equilibrium by inclusion complexation with 1,1-di(2,4-dimethylphenyl)but-2-yn-1-ol host (2). We could thus isolate the more stable 1a in a pure state as a 1:1 complex with 2. X-ray crystallographic analysis of the 1:1 complex showed that 1a is included by formation of a hydrogen bond between its N(84) and the hydroxyl group of 2.

1,2,3-Triazole (3) and 3(5)-methylpyrazole (4) also exist as an equilibrium mixture of two tautomers whose stability as not very different, 1H- (3a) and 2H-1,2,3-triazole (3b) and 3- (4a) and 5-methylpyrazole (4b), respectively. Likewise the structures of these tautomers have not been studied because of difficulty in obtaining them in a pure state. By inclusion complexation of 3 with 2, we isolated the relatively unstable 3a in a pure state as a 1:1 complex with 2. In the case of 4, both 4a and 4b were isolated as a 1:1:1 complex of 4a, 4b, and 2. These are the first isolations of tautomers having almost the same stability. X-ray crystallographic analysis showed that hydrogen bond networks and cyclic hydrogen bonding play an important role in constructing the former and the latter inclusion crystalline lattices, respectively (Figure 1.1).

Of the two possible tautomers, 2-phenyl-5-methylimidazole (5a) and 2-phenyl-4-methylimidazole (6a), the isomer 5a was isolated in a pure state as a 1:1 inclusion complex with the rac-2,2'dihydroxy-1,1'-binaphthyl (7a). X-ray analysis of the crystalline complex showed that 5a is accommodated in the inclusion cavity by formation of a hydrogen bond between the hydroxyl group of 7a and the [sp.sup.2]-nitrogen atom of 5a. This hydrogen bond formation is more favorable than that between 7a and the [sp.sup.2]-nitrogen atom of 6a because the latter atom is more sterically hindered due to the methyl substituent.

In the case of the equilibrium mixture of 2-ethyl-5-methylimidazole (5b) and 2-ethyl-4-methylimidazole (6b), the tautomer 5b was included by the host 1,1,6,6- tetraphenylhexa-2, 4-diyne-1,6-diol (8) on recrystallization from ether as a 2:1:1 complex of 5b, 8, and ether. X-ray analysis showed that hydrogen bond formation between the hydroxyl group of 6 and the [sp.sup.2]-nitrogen atom of 5b is also favored due to steric factors. In the case of 3-methylimidazole, however, 7a trapped 6c to form a 1:1 inclusion complex.

We were able to isolate an enol form of acetylacetone (9b) in a pure state. By recrystallization of 1,1-di(p-hydroxyphenyl)cyclohexane (10) from acetylacetone, a 1:1:1 inclusion complex of 9b, [H.sub.2]O and 10 was formed as colorless plates. X-ray crystallographic analysis of the complex showed that the C=O, C-O, C=C and C-C bond lengths are 1.258(5), 1.284(5), 1.361(5), and 1.398(6) A, respectively. From these data it is clear that the enol form (9b) isolated as an inclusion complex with 10 is in a pure state. A 2:2 inclusion complex of 9 and (R,R)-(-)-trans-4, 5-bis(hydroxyldiphenyl)-2,2-dimethyl-1,3-dioxacyclopentane (11) was obtained by recrystallization of 11 from 9 as colorless crystals. X-ray crystallographic analysis showed that two independent acetylacetone molecules are accommodated in the complex. The two independent enolic molecules (9b) have the same geometry, first molecule: C=O 1.263(3), C-O 1.323(3), C=C 1.365(3), and C-C 1.419(3) A; second molecule: C=O 1.258(3), C-O 1.321(3), C=C 1.357(3), and C-C 1.415(3) A.

Cyanohydrins exist as an equilibrium mixture of enantiomers in the presence of base as indicated, for 1-cyano-2,2-dimethyl-1-phenylpropanol (12) in Scheme 1.1. When (+)-12 is trapped out of the equilibrating mixture, excess (-)-12 is transformed into rac-12 through the equilibrium, and thus more (+)-12 of the rac-12 is trapped. As the processes continue, rac-12 is completely transformed into (+)-12 by a 1st order asymmetric transformation.

The transformation of rac-12 into (+)-12 was accomplished...