Stimulating Concepts in Chemistry

Editors: Fritz Vögtle, J. Fräser Stoddart, Masakatsu Shibasaki

©WILEY-VCH Weinheim • New York • Chichester Brisbane • Singapore • Toronto

Table of Contents

New types of Lewis acids as water-stable catalysts have been developed. These Lewis acids activate Sub­strates such as aldehydes efficiently in aqueous media. Furthermore, surfactant-aided Lewis acid catalysis has also been used for reac-tions in water without using any organic solvents.

H2q

FAH

OH2

,-Mn+---OH2

I

OH,

S. Kobayashi,

K. Manabe

Lewis Acid Catalysis

in Aqueous Media

Supercritical fluid (SCF) with the beneficial effects of both liquid- and gas-phase chemistry is an emerging reaction medium for many scientific and technical rea-sons. The reaction rate and selcectivity are readily tun-able by a subtle change in pressure and temperature.

: Solute molecule

O : Solvent molecule

R. Noyori,

T. Ikariya

Supercritical Fluids for Organic Synthesis

13

Methods for workup and purification of organic reac­tion mixtures are beginning to change as synthesis and Separation merge forces. Highly fluorinated, or fluor-ous, molecules offer a num-ber of attractive features in both traditional and parallel synthesis venues.

(FVA+B

(F) = highly fluorinated tag

©-C + D

workup

phase

Phase

D. P. Curran

Fluorous Techniques u (p)_c for the Synthesis of

Organic Molecules: A Unified Strategy for Reaction and Separa­tion

25

Domino reactions present a modern approach in organic synthesis since they allow the preparation of complex molecules starting from sim­ple Substrate in a few steps and in many cases with high stereoselectivity. AAoreover, as multi-component trans-formation they are highly suitable for combinatorial chemistry and give access to libraries of great diversity.

CHO

L. F. Tietze, F. Haunert

Domino Reaction in Organic Synthesis. An Approach to Efficiency, Elegance, Ecological Benefit, Economic Advantage and Preservation of Our Resources in Chemical Transformations

39

VI Table of Contents

Combinatorial chemistry has played an increasingly important role in the field of drug discovery for identifica-tion and optimization of drug leads. Combinatorial methods provide rapid access to large numbers of Compounds for testing. Shown is a general sche-matic of a combinatorial library prepared from a small set of building blocks.

* iH* ++ M O +0 O-O •-© • "*" * - # #-# • - • D +U #-D *-D 4 [4x4 = 16]

D * QO D-# OD

A. Lee,

J. W. Szewczyk, J. A. Ellman

Combinatorial I for Drug Development

65

Theoretical catalytic arrays called "theozymes" can be used to quantitate the effects of specific noncoval-ent catalyst transition State interactions on reaction rates. This strategy has been used to understand and pre-dict catalysis by both biolog-ical and synthetic catalysts.

I-

I

transition

t

State

MPMM

i n wmm , r theozyme

1

{ M M t

product

D. J. Tantillo,

K. N. Houk

Theozymes and Catalyst Design

79

Sterically and electronicaily unsymmetrical P,N-\igands have been designed to incorporate two types of coordinating units, e.g. a phosphine group and a nitrogen-containing hetero-cycle. These hybrid ligands lead to superior results in various metal-catalyzed pro-cesses and allow a system-atic 'fine tuning' of a gener-alized structure to suit a spe­cific process.

A. C. Humphries,

A. Pfaltz

Enantioselective Catalysis using Sterically and Electronicaily Unsymmetrical Ligands

89

The successfui deveiopment of the asymmetric two-center catalysis has opened up a new field in asymmet­ric synthesis. It has bee especially fruitful in Michael additions and aldol reac-tions.

M. Shibasaki

Asymmetric Two-Center Catalysis

105

'~;i^n:Li§!ilp;s£;

Asymmetric phase-transfer catalysis using chiral nonra-cemic onium salts or crown ethers has now grown into a practical method whereby a large number of reactions can be performed and some optically pure Compounds can be produced effectively on a large scale.

(Reactionj Y-CH.-Z R-X, Q^X®

1

OH®, Solvent

R T. Shioiri, Y-CH-z s. Arai

Asymmetric Phase Transfer Catalysis

123

Table of Contents VII

Metal-catalyzed enantiose-lective reactions are used in the synthesis of complex organic molecules. These transformations offer cost-effective, highly selective alternatives to the more classical methods. Additional levels of efficiency are achieved when various cata-lytic reactions are used successively.

20mol% chiral

catalyst 1 cov^cov 10mol% catalyst 2

0 HO»

CT A-Q3 V-f0H

wodesntol

2mol% catalyst 3

A. H. Hoveyda

Asymmetrie Catalysis in Target-Oriented Synthesis

145

The hypothetical fullerene -acetylene hybrid at right symbolizes the exciting prospects that have arisen from the discovery of fuller-enes, and the profound changes they have induced in our view of acetylene and carbon allotrope chemistry. The preparation of molecu-lar and polymeric acetylenic carbon allotropes, as well as carbon-rich nanometer-sized struetures, has opened up new avenues in fundamen­tal and technological research at the interface of chemistry with materials science.

Y. Rubin,

F. Diederich

From Fullerenes to Novel Carbon Allotropes: Exciting Prospects for Organic Synthesis

163

In dendrimer chemistry there are different ways to display functionalities. On the one hand, a central functional unit can be den-drylated to change some of its properties. On the other hand, it is possible to attach functional groups to the periphery of a dendrimer skeleton, i.e., the functional-ity can be multiplied.

s = functional unit

S. Gestermann,

R. Hesse, B. Windisch,

F. Vögtle

Dendritic Architectures

187

Self-assembling capsules are about to leave the play-ground of basic research and begin their career in materials sciences. The long way from the principles of self-organization through noncovalent interactions and the filling of space inside host molecules via chiral recognition and catal­ysis in reaction vessels to hydrogen-bonded liquid crystals and fibers forms the backbone of this review.

C. A. Schalley, J. Rebek

Chemical Encapsulation

in Self-Assembling Capsules

199

VIII Table of Contents

Kinetically stable super-architectures can be assem-bled by relying upon both noncovalent bonds and mechanical coercion. Thus, at elevated temperatures, rotaxane-like complexes (a) are generated when macro-cycles slip over the stoppers of chemical dumbbells, while hemicarceplexes (b) are created when guests squeeze through the portals of hemicarcerands.

© © M. C. T. Fyfe,

F. M. Raymo,

J. F. Stoddart

Slippage and Constrictive Binding

211

Soft and topologically adaptable supramolecular modules that allow host lat-tices to achieve dense pack-ing through low-energy deformations, while retain-ing their inherent dimen-sionality and supramolecular Connectivity, can facilitate the systematic design of molecular inclusion Com­pounds. This is demon-strated by the ability to pre-dict and maintain architec-tural control in a series of lamellar host frameworks.

K. T. Holman,

M. D. Ward

Crystal Engineering with Soft and Topologically Adaptable Molecular Host Frameworks

221

Synthetic routes to precisely defined molecular wires and devices are described along with procedures for testing their electronic properties. 02N^

NH2

J. M. Tour

Molecular Wires and Devices

237

The extension of the con-cepts of device and machine to the molecular level is of great scientific interest since it introduces new ideas into the field of chemistry and stimulates the ingenuity of researchers engaged in the emerging fields of nanosci-ence and nanotechnology.

molecular components

\ 1 • simple acSs

supramolecular System

^ <& Q O ^

V. Balzani,

A. Credi,

M. Venturi

Molecular-Level Devices and Machines

255

cornpiex funciion

Table of Contents IX

Long-range electron and energy transfer may take place over large distances by a through-bond or superex-change mechanism, in which the electron tunnels through the intervening medium. Examples include electron transfer through satured hydrocarbon bridges through solvent molecules and through n-stacks of base pairs in DNA.

e ET over 13.5 A

*MeO

MeO DMN DCV

CN

~CN

electron moves through c* bonds

DMN T 7 T ., DCV a and a bonds,

M. N. Paddon-Row

Electron and Energy Transfer

267

The supramolecular synthon is the supramolecular equi-valent of the functional group and is as useful in supra­molecular chemistry as is the functional group in molecu-lar chemistry. Synthons are small repetitive units that economically, yet fully, cap-ture the essence of a crystal structure.

^ ; Synthoi

G. R. Desiraju

The Supramolecular Synthon in Crystal Engineering

293

Connecting lumophores and receptors with spacers per-mits the build-up of modular Systems of increasing logical complexity. Even the sim-plest of these Systems can be powerful molecular sensors. Light Power Light Output Chemicai input

A. P. de Silva, D. B. Fox, T. S. Moody

Luminescent Logic and Sensing

307

Nanochemistry creates new opportunities for chemistry, since molecular characteris-tics are obtained which no longer resemble an ensemble average. The task of nano­chemistry is to provide an insight into structure and function at a molecular level.

S. Becker, K. Müllen

Nanochemistry -Architecture at the Mesoscale

317

This chapter focuses on mimics based on natural enzymes and other biopoly-mers, synthetic macromole-cules and small-molecule host-guest interactions.

N I M M Pu-PyHM

ff I I • H P y U Ar""1

r G G

C C

TA J G C T A C

5'-ribo

3'-deoxyribo

A. J. Kirby

Enzyme Mimics

341

Recent developments in enzyme inhibitor design are reviewed, with particular emphasis on the "distal binding analog" approach.

distal binding Site

I Enzyme

active site

• Enzyme-Inhibitor Complex

K. D. Kreutter, C.-H. Wong

Asymmetrie Two-Enzyme Inhibitors

355

X Table of Contents

This chapter highlights the interplay between organic synthesis, biophysics and cell biology in the study of protein lipidation and its rel-evance to targeting proteins towards the plasma mem-brane of cells in precise molecular detail.

D. Kadereit, J. Kuhlmann, H. Waldmann

Organic Synthesis and Cell Biology

369

Biopbysical Chemisuy Molecular Biologv