Current Organic Chemistry - Volume 6, Issue 11, 2002

Solid-phase organic synthesis has attracted considerable attention from the academic and industrial laboratories throughout the world in the last two decades. From peptides, to heterocycles, and then to the highly complex natural product combinatorial libraries, solid-phase organic synthesis has proven to be one of the most important fields in organic chemistry. One of the areas of exploding research is the use of traceless linkers to generate compounds which do not contain the undesired functional groups normally derived from the solid support.This review summarizes the solid-phase organic reactions published in the literatures and focuses primarily on those utilizing cleavage via traceless linkers or chemical reactions. The general routes to traceless cleavage include:[1] Electrophile- or Nucleophile-Induced Cleavage [2] Electrophile- or Nucleophile-Induced Cleavage with Modifications in Solution [3] Cyclorelease via Intramolecular Nucleophilic Attack [4] Metal-Mediated Cyclorelease [5] Activated Cleavage through Acylation [6] Cleavage via Cycloaddition or Cycloreversion [7] Reductive, Oxidative or Radical Cleavage [8] Photolytic Cleavage [9] Dissociation of Metal ComplexesThe review also describes our continual effort in the generation of cheaper and better traceless linkers, and combinatorial libraries with biological interest.

The progress that has been made in organic synthesis via the reactions of hydrazones with lead tetraacetate, mainly since 1970, is presented in this review. Thus, the synthesis of various compounds, as gem-azoacetates, azo and diazo compounds, acylhydrazines, alkenes, oxadiazolines, triazoles, pyrazoles, indazoles and dibenzazepinones will be discussed. Special emphasis is given in a synthetically useful new rearrangement that takes place in LTA oxidations of N-acylhydrazones of ohydroxyaryl ketones and leads to high yield synthesis of 1,2-diacylbenzenes, oacylarylcarboxylic esters, o-acylbenzoyl bromides, 1,2,3- triacylbenzenes, 1,2,3,4- tetraacylbenzenes, o-acylbenzaldehydes and o-phthalaldehyde. Finally, some of the applications of hydrazones and their derivatives are discussed.

In the last decade, modern synthetic organic chemistry has experienced an enormous progress biocatalytic methodologies. Enzymatic routes and microbial whole-cell bioconversions have become a generally accepted synthetic tool. Recent advances in biocatalytic chemistry focus on unconventional non-protein biocatalysts such as catalytically active RNA-molecules, and biotransformations in ionic liquids. The example of ethyl chloroacetoacetate depicts how whole-cell biocatalysis is developing from rather empirical screening studies towards a technology which selectively elucidates, engineers and employs living cells for bioconversions. This review further discusses the question whether there are natural Diels-Alderases, and gives an overview of novel and unconventional approaches in biodehalogenations and contrathermodynamic reactions. The biotechnological production of hydroquinone demonstrates that the efficiency of biocatalytic routes is not limited to stereoselective synthesis.

This article describes the discovery and recent progresses of cyclobutanonebased free radical ring expansion and annulation reactions. Mechanisms associated with these reaction processes are also discussed. Ring expansion reactions rely on selective β- scission of alkoxy radicals generated from the cyclization of carbon radicals onto carbonyls. Exo-substituted cyclobutanones are employed to construct cis-fused seven- and eight-membered rings, spiro-annulated medium rings, large rings, and cyclopropanecontaining compounds. Endo-substituted cyclobutanones can undergo tandem rearrangements to produce bridged rings. The cyclization of dichlorocyclobutanones followed by TMSI-induced ring opening is another ring expansion strategy for the construction of some novel ring systems. Cyclobutanones used for free radical reactions are readily prepared by well-established [2 + 2] cycloadditions of ketenes with various olefins.