Current Organic Chemistry - Volume 15, Issue 14, 2011

Polar Organometallic compounds, a term coined by professor Manfred Schlosser, became reagents of choice to ascertain a high degree of structural diversity with applications in organic synthesis, material science and industrial applications in pharmaceutical and agrochemical fields. The subtle interplay between a metal (the alkali metals, the alkaline earth metals and even organozinc compounds) with a carbon backbone and the coordination of the metal counterion with solvent molecules or coligands allow the fine-tuning of their properties. Although a polar carbon-metal bond characterizes these compounds, the degree and pattern of polarity varies with the nature of the metal. As outlined by professor Schlosser: “…the individuality of the metal involved is the most critical parameter for designing tailor-made organometallic reactions”. Most frequently alkyllithium reagents and lithium amides have been used. More recently, due to new insight and techniques, new homoand hetero-bimetallic reagents have been developed allowing the metalation of substrates with a greater functional group tolerance and the work under non-cryogenic conditions. The aim of this special issue “Polar Organometallic Chemistry” is to highlight the current activity of the research groups working in this area reflecting the state of the art of polar organometallic chemistry in the synthesis of complex organic molecules. The Editors are extremely grateful to all the authors contributing to this Issue and the submission of high quality manuscripts befitting this Special Issue.

Trimethylsilylmethyllithium (TMSCH2Li) is well-known as a nucleophilic reagent in methylation and methylenation reactions but its application in deprotonation or halogen-metal exchange has been underexploited to date. The present review covers new applications of TMSCH2Li and TMSCH2Li-LiDMAE (LiDMAE=Lithium 2-dimethylamino ethoxide) in selective metallation of pyridine derivatives focusing on the design of more applicable bromine-lithium exchange and deprotonation processes as well as new selectivities.

Efficient deprotonative cadmiation reactions of functionalized aromatics including heterocycles have been realized using TMP-cadmiate, (TMP)3CdLi (TMP = 2,2,6,6-tetramethylpiperidino). The reagent is compatible with reactive functional groups (amide, ester, nitrile and even ketone functions), heavy halogens (Br, I), five-membered aromatic heterocycles (furan, thiophene, oxazole, thiazole, and pyrrole derivatives) and even aromatic aza-heterocycles (pyridine, diazine compounds). Some heterocycles benefiting from doubly activated positions can be dimetallated at room temperature. The deprotonative cadmiation pathways/mechanisms have been studied using computational/theoretical techniques. Such generated lithium arylcadmiates have been evidenced using iodine. Alternative trappings of the species are palladium-catalyzed cross-coupling reactions or simple quench with acid chlorides.

The recent publications on the topic of the preparation of organolithium reagents by non-deprotonating methodologies and starting from non-halogenated substrates have been covered in the present revision. In this second part, transmetallation processes, mainly tin-lithium exchange, and addition to multiple bonds have been considered. Moreover, other procedures, such as carbon-carbon bond scission and the Shapiro reaction, have been included.

The advice of professor Dieter Seebach “Thinking of polar organometallics compounds as carbanions is an impoverishment rather that a simplification” (ISCC, Durham 1984), perfectly fits the statement of professor Manfred Schlosser, who coined the term polar organometallic”, according which no difference in reactivity patterns of organometallic reagents can be rationalized without taking into account the metal counterion and its specific interactions with the accompanying carbon backbone. Both statements stress the need of considering the metal as a key component of these reagents, that can initiate and govern the subsequent reactions. The class of the socalled polar organometallics comprises the reagents of the most common alkali and alkaline earth metals and extend into the area of organozinc derivatives. All these reagents are characterized by a polar carbon-metal bond and the pattern of polarity vary significantly with the metal. Metalation is one of the widely used synthetic routes in order to obtain a labile and reactive carbon-metal bond from the relatively inert carbon-hydrogen bond. Until recently, alkyllithium reagents and bulky lithium amides have been commonly employed for this purpose. More recently, some groups have pioneered alternative metalating agents made up of two or more distinct compound types. Several examples include Schlosser's superbases, Kondo and Uchiyama's 2,2,6,6-tetramethylpiperidide (TMP)-zincate complexes, and Knochel's turbo-Grignard reagents. In this review, we wish to report the most recent contributions appeared in the literature from 2005 to date, concerning the use of polar organometallics in synthesis. The topic has been divided into three sections, the first of which deals with metalated 1,2-dienes and the second one with metalated 1,3-dienes (the metal is in turn lithium, potassium or magnesium). The third section is dedicated to miscellaneous applications that cannot be comprised into the previous classification.

The Meyers reaction, i.e. the nucleophilic aromatic substitution reaction between aryloxazolines with organolithium and organomagnesium reagents is a very efficient and reliable method for the formation of new carbon-carbon and carbon-heteroatom bonds. The aim of this review is to present a general overview of this reaction in chiral and racemic form, emphasizing its scope and limitations. The literature is covered since 1994.

In this review, the use of molecular iodine as a catalyst in the synthesis of heterocyclic compounds is presented and reviewed. In recent years, the use of molecular iodine in organic chemistry has received considerable attention because the chemical (a) is inexpensive and readily available, (b) is less toxic than alternatives, (c) has an easy workup method, and (d) is a moisture-stable, mild Lewis acid. Many of the reactions using iodine are associated with mild conditions, greater stero- and regioselectivities, short reaction times, and simplicity in their operation.

This review deals with synthesis of thiophosphinic acids. Some of these reactions have been applied successfully to the synthesis of chemically or biologically interesting compounds. The main purpose of this review is to cover the literature on thiophosphinic acids from the first report up to date since such compounds have not been previously reviewed.

Pyrazolo[1,5-a]pyridines have become subject to growing interest by both synthetic and medicinal chemists, and as such new and simple methods for their synthesis are becoming increasingly more important. They exhibit reactivity which permits substitution at various positions, allowing many diverse chemical structures to be made. This review briefly discusses the medicinal uses of pyrazolo[1,5-a]pyridines, it outlines the synthetic methods which have been used to make them and discusses the chemistries which have been carried out to further functionalise the ring system.

Herein we give a brief account of the efforts our group made in recent years to discover novel enzymes and utilize them by bioprocess engineering techniques for stereoselective synthesis of various enantiomerically pure chiral chemicals with high value in a greener manner. Included are discussions on oxidoreductases, expoxide hydrolases and glucosidases in whole cells or isolated form from microorganisms or plants.

Microwave-assisted [2+2] cycloadditions of (E)-3-dimethylamino-1-substituted prop-2-en-1-ones, prepared from carbocyclic, aromatic and heteroaromatic methyl ketones, ethyl acetate, diethyl malonate, ethyl methoxyacetate, methyl phenoxyacetate and dietyl acetylenedicarboxylate give substituted dimethyl 2-[(dimethylamino)methylene]succinates.