Organic Synthesis—Where now?

Abstract

This review article is an attempt to sketch the important developments in organic synthesis during the past 25 years, and to project them into the future.—The primary motivations that once induced chemists to undertake natural product syntheses no longer exist. Instead of target structures themselves, molecular function and activity now occupy center stage. Thus, inhibitors with an affinity for all the important natural enzymes and receptors have moved to the fore as potential synthetic targets.—New synthetic methods are most likely to be encountered in the fields of biological and organometallic chemistry. Enzymes, whole organisms, and cell cultures for enan‐tioselective synthesis of specific substances have already been incorporated into the synthetic arsenals of both research laboratories and industry. In addition, designing appropriate analogues to transition states and intermediates should soon make it possible, with the aid of the mammalian immune system and gene technology, to prepare catalytically active monoclonal antibodies for almost any reaction; perhaps, more important, such processes will increasingly come to be applied on an industrial scale.‐The discovery of truly new reactions is likely to be limited to the realm of transition‐metal organic chemistry, which will almost certainly provide us with additional “miracle reagents” in the years to come. As regards main group elements (“organoelemental chemistry”), we can surely anticipate further stepwise improvements in experimental procedures and the broader application of special techniques, leading to undreamed of efficiency and selectivity with respect to known procedures. The primary center of attention for all synthetic methods will continue to shift toward catalytic and enantioselective variants; indeed, it will not be long before such modifications will be available with every standard reaction for converting achiral educts into chiral products. Analysis, spectroscopy, structure determination, theory, and electronic data processing have all become indispensable in organic synthesis. Only with the aid of these “tools” will the methods of organic chemistry permit selective syntheses of ever larger and more complex systems on both the molecular and supramolecular levels.—Examples have been introduced throughout this discourse to illustrate its many themes, and a very comprehensive bibliography should help the interested reader become more familiar with important keywords and authors.[ ]—This article will have served its intended purpose if it changes the minds of some of those who claim organic chemistry is a mature science, and if it causes students to discover the vitality and forcefulness with which organic synthesis is meeting new challenges and attempting to fulfill old dreams. Er zeigt uns so in seinem wissenschaftlichen Leben, daß die Chemie nicht von einer Theorie, nicht von einer Methode aus zu erschöpfen ist, und daß Erkenntnis und Nutzen in ihr untrennbar verwoben sind. R. Koch, writing about Louis Pasteur

Chemical Biology of Natural Products on the Basis of Identification of Target Proteins

“…For example, Seebach became suspicious of the "primary motivation" of natural product synthesis as early as 1990. 9 It has become significantly more difficult to find examples of novel natural products or their total syntheses that have provided new concepts in chemistry, as if such conventional structure-based research has been exhausted. This review introduces a new strategy of natural products chemistry on the basis of molecular targets involved in the mode-of-action of naturally occurring ligands.…”

Accuracy of self-reports on donations to charitable organizations

“…Chiral auxiliary based methods have met with high success among the various asymmetric transformations studied. 3 This is mainly due to reliable and often high and predictable absolute stereocontrol. Prerequisites for effective auxiliary based methods are i) diastereomeric excess (d.e.)…”

“…chiral auxiliary recycling. A review of chiral auxiliaries for multistep enantioselective synthesis by Seebach 3 shows that the major part of these compounds is based on aminoacid, hydroxyacid and terpene derivatives and integral enforce conformational rigidity at the crucial stereogenic center forming step. It should be noted that several auxiliaries are still rather expensive or require multistep synthesis.…”

Aromatic Fluorination by Decomposition of Triazenes in Ionic Liquids

“…[1][2][3][4] Although many methods for the synthesis of fluoro aromatic compounds have been developed, such as the Balz-Schiemann reaction, diazotization-fluorination, aromatic nucleophilic and electrophilic substitution, [5][6][7] there are still limitations to practical and efficient application of these chemical processes. Thus, there is considerable interest in developing new and improved methods for aromatic fluorination.…”