Carbo metallation

Another unusual three-component coupling reaction involving an imine as intermediate has been developed by Ishii who has shown that a C-H bond adjacent to the nitrogen atom of an imine can be activated by an iridium complex. Carbo-metallation reactions of acetylenic compounds may then be achieved, which lead to unsaturated imines 155 (Scheme 8.67) [122]. 

B. H. Lipshutz, S. Sengupta, Organocopper Reagents Substitution, Conjugate Addition, Carbo/Metal-locupration, and Other Reactions, Org. React. 1992, 41, 135-631. 

The required iodochlorides can be prepared from propargylic alcohols by carbo-metallation followed by iodinolysis ... 

Hydrosilylation of alkynes catalysed by Lewis acids Hydrosilylation of alkynes catalysed by transition metals Hydrozirconation Carbo-Metallation... 

A recent application to the synthesis of the macrolide antibiotic concanamycin used carbo-metallation of the alkyne 141 to give the vinyl iodide -142 followed by a palladium-catalysed coupling with a vinyl stannane, also created from an alkyne, to give the diene34 , -143. 

Functionalized cyclopropenes have been prepared by a cyclization reaction of an alkenyl-lithium (52) (Scheme 14). Hydro- and carbo-metallation reactions of the trimethylsilylcyclopropenes (53) have also been described. 

Generally speaking, other cyclopentadienylmetal complex catalyzed carbo-metallations of alkynes are rather rare but a few interesting examples have been reported. The first one is the zirconocene 1 catalyzed ethylmagnesation of dialkyldiynes with ethylmagnesium bromide to afford a mixture of isomeric enynes 34 (Scheme 14). The ethylation proceeds regioselectively on the terminal carbon atom of the diyne moiety. However, the addition is not stereoselective a mixture of cis and trans isomers is obtained [22]. 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

This chapter will try to cover some developments in the theoretical understanding of metal-catalyzed cycloaddition reactions. The reactions to be discussed below are related to the other chapters in this book in an attempt to obtain a coherent picture of the metal-catalyzed reactions discussed. The intention with this chapter is not to go into details of the theoretical methods used for the calculations - the reader must go to the original literature to obtain this information. The examples chosen are related to the different chapters, i.e. this chapter will cover carbo-Diels-Alder, hetero-Diels-Alder and 1,3-dipolar cycloaddition reactions. Each section will start with a description of the reactions considered, based on the frontier molecular orbital approach, in an attempt for the reader to understand the basis molecular orbital concepts for the reaction. 

Application of the reaction to the 2-azidobenzoyl derivative of diethylene glycol monomethyl ether 92, in a mixture of tetrahydrofuran and diethylene glycol monomethyl ether as the nucleophile, affords 2-(2-methoxyethoxy)ethyl 2-[2-(2-methoxyethoxy)ethoxy]-37/-azepine-3-carbo-xylate (93), which displays metal cation complexing properties towards lithium, potassium, and. to a lesser extent, barium and calcium cations.198... 

Despite the fact that transition metal complexes have found wide application in the synthesis of carbo- and heterocycles, [3+3] cyclisation reactions mediated or assisted by transition metals remain almost unexplored [3, 86]. However, a few examples involving Fischer carbene complexes have been reported. In all cases, this complex is a,/J-unsaturated in order to act as a C3-synthon and it reacts with different types of substrates acting as C3-synthons as well. 

Hence, the rate depends only on the ratio of the partial pressures of hydrogen and n-pentane. Support for the mechanism is provided by the fact that the rate of n-pentene isomerization on a platinum-free catalyst is very similar to that of the above reaction. The essence of the bifunctional mechanism is that the metal converts alkanes into alkenes and vice versa, enabling isomerization via the carbenium ion mechanism which allows a lower temperature than reactions involving a carbo-nium-ion formation step from an alkane. 

Cycloaddition reactions catalysed by transition metal complexes are an important tool in the construction of a wide range of carbo- and hetero-cyclic systems, such as benzene, pyridines, triazoles, etc. [7]. In general, these reactions are extremely atom-efficient and involve the formation of several C-C bonds in a single step. Among the innumerable possible catalytic systems for the cycloaddition reaction the NHC-metal complexes have received special attention [7c]. 

Structurally related complexes are also active initiators for the living polymerization of carbo-diimides (which are isoelectronic to isocyanates).1003 The proposed intermediate for this polymerization process is a metal amidinate (Scheme 29), and the model complex (349) has been reported to be a highly efficient catalyst, polymerizing 500 equivalents of di- -hexylcarbodiimide in less than 10 s. A more hydrolytically robust series of initiators has also been developed, based upon copper(I) and copper(II) amidinates.1004... 

In summary, transifion-metal-catalyzed alkene-polymerization reactions highlight the metal-induced electrophilic activation of C—C n bonds to form carbo-cation-like alkene complexes. Considerations involving substituent pi-donor or pi-acceptor strength (i.e., tendency toward carbocation formation) will be useful in similarly rationalizing polymerization reactions (4.105) for more general alkenes. 

Transition metal-mediated C-C bond formation through reaction of C02 with acetylenes and dienes can serve as a useful method for the construction of various carbon skeletons, such as linear and cyclic carboxylic acids, and esters and lactams. Enantioselective incorporation of C02 can also be achieved, especially when combined with sterically controlled formation of cyclic carbo- or heterocyclic skeletons. In perspective of the future in this area, development of more efficient and more selective catalytic systems for incorporation or transformation of C02 into useful fine chemicals and polymer materials will continue to be an important and attractive research target. 

Under typical freshwater conditions, at pH 7-9 and in presence of millimolar concentrations of carbonate, most transition metals in solution (Cu(II), Zn(II), Ni(II), Co(II), Cd(II), Fe(TII), etc.) occur predominantly as hydroxo or carbo-nato complexes. For a few metals, chloro complexes may be predominant (Ag(I), Hg(II)), if chloride is in the range 10-4—10-3 mol dm-3 or higher. Alkali and alkali-earth cations occur predominantly as free aquo metal ions [29], At lower pH values, the fraction of free aquo metal ions generally increases. Strong sulfide complexes of several transition metals have recently been shown to occur even under oxic conditions [32,33]. 

Five-membered carbo- or heterocycles can be prepared with the aid of heteroatom-substituted carbene complexes in several different ways. In the following sections the focus will be on cyclization reactions in which the carbon-metal double bond plays a decisive role. 

In laboratory-scale homogeneous catalysis applications, in the last decade further investigations have been carried out in which a less soluble organo-metallic catalyst system was utilized for metathesis reactions [46]. Under RCM-conditions, it was possible to convert substrates with functional groups that were problematic due to their potential to inactivate the rutheniiun catalyst here, the conversion in supercritical carbon dioxide avoids the protection of critical amino groups as an additional synthetic step. Consequently, it was possible to synthesize a number of carbo- and heterocyclic products with varying ring size (C4 to Cie). 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

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