Topics in Stereochemistry, Volume 22 (Topics in Stereochemistry (Discontinued)) - Hardcover

Hardcover

ISBN 10: 0471253162 ISBN 13: 9780471253167

Publisher: Wiley-Interscience, 1999

Synopsis

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 direction. 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.

Volume 22 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.

About this title

About the Author

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.

From the Back Cover

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

From the Inside Flap

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.

Excerpt. © Reprinted by permission. All rights reserved.

Topics in Stereochemistry

By Scott E. Denmark

Wiley-Interscience

Copyright © 1999 Scott E. Denmark
All right reserved.
ISBN: 9780471253167

Chapter One

Stereochemistry of Molecules in Inclusion Crystals

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 by use of brucine (13) as the host and base. When a solution of rac-12 (1.0 g, 5.3 mmol) and 13 (2.1 g, 5.3 mmol) in MeOH (2 ml) was kept in a capped flask for 12 h, a 1:1 brucine complex of (+)-12 (2.08 g, 67% yield, m.p. 112-114oC) separated out as colorless prisms. Decomposition of the complex with dil HCl gave (+)-12 of 97% ee (0.67 g, 67% yield). A yield of (+)-12 of more than 50% shows a conversion of (-)-12 into (+)-12 through racemization during the complexation. The yield of (+)-12 increased to 100% by leaving the MeOH solution to evaporate gradually during the complexation. For example, when a solution of rac-12 (1.0 g) and 13 (2.1 g) in MeOH (2 ml) was kept in an uncapped flask at room temperature for 24 h, the amount of solvent decreased to 0.6 ml. From the MeOH solution the inclusion complex of (+)-12 and 13 was isolated quantitatively, which upon treatment with dil HCl gave (+)-12 of 100% ee in 100% yield.

Stereochemical study of the inclusion complex with 13 was carried out for the 1:1 complex of tertiary acetylenic alcohol, (S)-(-)-1-(o-bromophenyl)-1-phenylprop-2-yn-1-ol (14a) instead of (+)-12, since the brucine complex of 12 does not form suitable crystals for X-ray crystallographic analysis. The brucine complex of 14a is constructed by formation of a hydrogen bond between the hydroxyl group of 14a and the tertiary amine nitrogen atom of 13. In the complex, mutual chiral recognition between 13 and 14a occurs precisely. We used this inclusion complexation with chiral amines such as 13 and sparteine and obtained 14a and 14b of 100% ee.

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

As we noted in Section A, it is not difficult to isolate one component of an equilibrium mixture by inclusion complexation with a host compound to study its stereochemistry by X-ray analysis. By this method, conformational isomers of [alpha]- and ?-ionones, acrylic acid, and 1,2-dichloroethane have been isolated in a pure state, and their stereochemical structures have been studied.

Conformational study of ?-ionone (15) has long been interesting because 15 is closely related to the retinal chromophore, whose binding within rhodopsin is known to be conformationally dependent. However, no conformational isomer of 15 has yet been isolated in a pure state until 1990, although NMR studies of the solution conformation of 15 have shown it to exist mainly in the s-cis form (15b). The s-trans conformer (15a) and the s-cis conformer (15b) were isolated in pure state as inclusion complexes with the host compounds 10 and (R,R)-(-)-trans-2, 3-bis(diphenylhydroxymethyl)-1,4-dioxaspiro[4.5]decane (16), respectively. The quasi-chair form (17a) of [alpha]-ionone (17) was also isolated in a pure state as an inclusion complex with 9,9'-bianthryl (18).

X-ray crystallographic analysis of a 2:1 inclusion complex of 10 and 15a showed that molecule 15a is accommodated in an almost planar s-trans-form between two molecules of the host 10. Energywise is easier for 10 to form a cavity that accommodates 15a through van der Waals and hydrogen-bonding interactions. Conversely, 16 formed a 1:1 inclusion complex with 15b. Although an X-ray crystal structure analysis of the complex with 15b could not be carried out because of difficulty in obtaining a good crystal, the s-cis conformation was determined spectroscopically. In the IR spectrum, vC=O at 1675 [cm.sup.-1] of 15b in the complex with 16 was at higher frequencies than the vC=O at 1590 [cm.sup.-1] of 15a in the complex with 10. It has been well established that s-cis enones show vC=O at higher frequencies than do the s-trans isomers. In the UV spectrum in the solid state, 15b in the complex with 16 showed [[lambda].sub.max] at shorter wavelengths than did 15a in the complex with 10. It has also been established that s-cis enones absorb in the UV at shorter wavelengths than do s-trans enones.

Interestingly [alpha]-ionone (17) and 18 formed a 1:1 inclusion complex, in which the quasi-chair form with an axial enone group (17a) is present. The X-ray crystal structure analysis of the complex showed that the molecules of 18 are arranged so as to form a channel-type complex with 17a. In a channel, two molecules of 17a of the same chirality face each other and display contacts through their acyl groups. The cavity formed by 18 is suitable to accommodate 17a but not the equatorial quasi-chair form (17b), the axial quasi-boat form (17c), or the equatorial quasi-boat form (17d).

Carboxylic acids exist as cyclic dimers in the gas, liquid, and solid states. For example, acrylic acid (19) has been shown to exist as two different cyclic dimers, s-trans-19...s-trans-19 and s-cis-19...s-cis-19. However, no monomeric rotational isomer of 19, neither s-trans-19 nor s-cis-19, has ever been isolated in a pure state. In 1998 monomeric s-trans-19 was isolated in a pure state as an inclusion complex with 2,2'-bis(hydroxydiphenylmethyl)-1,1'-biphenyl (20). X-ray crystal structure analysis of the complex showed that the s-trans-19 has bond lengths and a dihedral angle between vinyl and carboxylic acid groups as shown in Figure 1.2.

By an inclusion complexation similar to 20, monomeric formic, acetic, propionic, and butanoic acids were isolated in their pure states, and their X-ray crystal structures were studied.

It has been established that the energetically most stable rotational isomer around the C-C bond of 1,2-disubstituted ethane is the trans-form. For example, 1,2-dichloroethane (21) exists in the trans-form (21a), although the energy difference between the trans (21a) and gauche form (21b) is estimated to be small. The existence of 21 in the eclipsed form of the two chlorine atoms (21c, [theta]=0o) is excluded because of its instability, which is due to a strong repulsion between not only the chlorine atoms but also the carbon-hydrogen bonds. Isolation of the eclipsed form has never been reported. In 1997, however, a nearly eclipsed form (21c, [theta] = 32(2)o) was isolated as a 1:1 inclusion complex with the optically active host compound (S)-(-)-2-bromo-3,3a,8-triphenyl-1,2a-dihydrocyclopenta[a]inde n-1-one (22). X-ray analysis of the complex showed that only one enantiomer of 21c, the left-handed helical form (M)-21c, is accommodated, since 22 is an optically active (S)-(-)-host compound.

There is no relatively strong interaction between the host and guest molecules. Isomer 21c is just accommodated through a van der Waals interaction in a small cavity constructed with its host 22, since the cavity is too small to include sterically bulky 21a and 21b. For the same reason 22 includes sterically less bulky cis-1,2-dichloroethane (23) but not its trans isomer (24).

C. Separation of Conformational Isomers of Cyclohexane Derivatives

Stereoisomerism of cyclohexane derivatives can easily be recognized in an inclusion complex with a host compound. By way of this phenomenon, stereoisomers of cyclohexane derivatives can be separated efficiently. For example, the inclusion complexation of a commercially available mixture of three 3,5-dimethylcyclohexanols 25 (63%), 26 (22%), and 27 (15%) in the composition indicated with 1,1,6,6-tetraphenylhexa-2, 4-diyne-1,6-diol (8) gives a 1:2 complex of 8 and 25 as colorless crystals (69% yield, m.p. 90-91oC). Heating of the complex in vacuo gives 25 of 99.7% purity in 65% yield. X-ray analysis of the 1:2 complex of 8 and 25 shows that two 25 molecules are binding to the two OH groups of 8 through hydrogen bond formation. Only the all equatorial isomer 25 is accommodated in the crystalline cavity, and this is probably because of its less bulky structure.

Continues...

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Edition details

• Publisher: Wiley-Interscience
• Publication date: 1999
• Language: English
• ISBN 10: 0471253162
• ISBN 13: 9780471253167
• Binding: Hardcover
• Edition number: 1
• Number of pages: 336
• Editor: Denmark Scott E.