Heteroatom-carbon multiple bonds

In contrast to the related organoboranes, which are mostly used in the addition to non-polar carbon-carbon multiple bonds, aluminum hydrides have found their widest use in organic synthesis in the addition reaction to polar carbon-carbon and carbon-heteroatom multiple bonds including carbonyl, nitrile and imino groups as well as their a,(J-unsaturated analogs. Although these reduction reactions are also sometimes referred as hydroalumination reactions in the Hterature, they are outside the scope of this review. 

In the scope of this subsection, competitive 1,3-cycloaddition of nitrile oxides to carbon-carbon and carbon-heteroatom multiple bonds are of special interest. Competition between carbon-carbon and carbon-nitrogen double bonds in... 

Kumada s use of a ferrocene moved away from the C2-symmetrical motive, as planar chirality can result from the two ferrocene rings having different substituents. The development of this class of ligand is well documented [5, 125-127]. The best-known uses of these ligands are for reductions of carbon-heteroatom multiple bonds, as in the synthesis of the herbicide, Metolachlor [128, 129]. 

Addition of radicals to carbon-carbon or carbon-heteroatom multiple bonds followed by the trapping of resulting radicals with a hydrogen atom source... 

Carbon-heteroatom multiple bonds can also participate in cycloaddition reactions with carbonyl ylides leading to the synthesis of interesting heterocycles (Scheme 4.18). 

In addition to olefins, carbon heteroatom multiple bonds can also participate in the cycloaddition with various carbonyl ylides (Scheme 4.28). 

Due the nature of the substituents, all the stable singlet carbenes exihibit some carbon-heteroatom multiple-bond character and for some time their carbene nature has been a subject of controversy. One has to keep in mind that apart from dialkyl-carbenes, all the transient singlet carbenes present similar electronic interactions. As early as 1956, Skell and Garner drew the transient dibromocarbene in its ylide form based on the overlap of the vacant p-orbital of carbon with the filled p orbitals of the bromine atoms (Scheme 8.31). 

Addition reactions to other carbon-heteroatom MULTIPLE BONDS (see also Grignard reaction, Hydrolysis, Reduction reactions)... 

Addition reactions of carbon radicals to C—O and C—N multiple bonds are much less-favored than additions to C—C bonds because of the higher ir-bond strengths of the carbon-heteroatom multiple bonds. This reduction in exothermicity (additions to carbonyls can even be endothermic) often reduces the rate below the useful level for bimolecular additions. Thus, acetonitrile and acetone are useful solvents because they are not subject to rapid radical additions. However, entropically favored cyclizations to C—N and C—O bonds are very useful, as are fragmentations (see Chapter 4.2, this volume). 

The following introduction will briefly recount some of the key features of radical cyclizations with an emphasis on basic concepts that control regio- and stereo-selectivity. More details will be provided in the following sections, which describe specific types of reactions. The factors affecting the cyclization reactions to carbon-heteroatom multiple bonds are treated separately in Section 4.2.5, and the cyclizations of heteroatom-centered radicals are contained in Section 4.2.4. 

L. Miginiac, Nucleophilic Addition to Carbon-Heteroatom Multiple Bonds O, S, N, P, in Handbook of Grignard Reagents (G. S. Silverman, P. E. Rakita, Eds.), Marcel Dekker Inc., New York, 1996, 361-372. 

Meerwein type arylations involving radical additions to carbon-heteroatom multiple bonds such as in isothiocyanates have been further extended to tandem reactions leading to heterocycles [117, 118]. 

Co-Cyclotrimerizations of Alkynes with Carbon-Heteroatom Multiple Bonds... 

Carbocations can be generated by the protonation of unsaturated hydrocarbons such as alkenes and cycloalkenes [49,52], cyclopentadienes [57], benzenes and naphthalenes (Eq. 24) [58], pyrenes and cyclophanes [59], unsaturated heterocycles [60], and their derivatives with carbon-heteroatom multiple bonds [2], including carbonyl and nitrile compounds and diazoalkanes [61]. 

The electrophile shown in step 2 is the proton. In almost aU the reactions considered in this chapter, the electrophihc atom is either hydrogen or carbon. Note that step 1 is exactly the same as step 1 of the tetrahedral mechanism of nucleophilic substim-tion at a carbonyl carbon (p. 1255), but carbon groups (A, B = H, alkyl aryl, etc.) are poor leaving groups so that substitution does not compete with addition. For carboxylic acids and their derivatives (B = OH, OR, NH2, etc.) much better leaving groups are available and acyl substitution predominates (p. 1254). It is thus the nature of A and B that determines whether a nucleophilic attack at a carbon-heteroatom multiple bond will lead to substitution or addition. 

Reactivity factors in additions to carbon-heteroatom multiple bonds are similar to those for the tetrahedral mechanism of nucleophilic substitution. If A and/or B are electron-donating groups, rates are decreased. Electron-attracting substituents increase rates. This means that aldehydes are more reactive than ketones. Aryl groups are somewhat deactivating compared to alkyl, because of resonance that stabilizes the substrate molecule, but is lost on going to the intermediate ... 

Double bonds in conjugation with the carbon-heteroatom multiple bond also lower addition rates, for similar reasons but, more important, may provide competition from 1,4-addition (p. 1008). Steric factors are also quite important and contribute to the decreased reactivity of ketones compared with aldehydes. Highly hindered ketones like hexamethylacetone and dineopentyl ketone either do not undergo many of these reactions or require extreme conditions. 

Nucleophilic Addition to Carbon-Heteroatom Multiple Bonds O, S, N, P... 

A very powerful and elegant methodology intensely developed in recent years for the construction of five-membered ring systems, e.g. of cyclopentanoid natural products, is based on the in situ formation of highly reactive Cj intermediates from a variety of synthetic precursors. These intermediates 1 can then serve as three-earbon, 2n-electron (Y = Hj) or 4 -electron (Y = CH, O) components in cycloaddition reactions, specifically of the [3-1-2] type, with various carbon-carbon - or carbon-heteroatom multiple bonds as 2rt-components. 

One must be well aware of the characteristic features concerning the addition of organometallic reagents to carbon-heteroatom multiple bonds such as the carbon-oxygen and the carbon-nitrogen double bonds in order to develop a catalytic asymmetric process for this type of reaction. 

The hydrosilylation of carbon-heteroatom multiple bonds had received little attention until it was found in 1972 that Rh(PPh3)3Cl is an extremely effective catalyst for the hydrosilylation of carbonyl compounds. This is a new and unique reduction method since the resulting silicon-oxygen bond can easily be hydrolyzed. Other transition metal complexes including platinum, ruthenium , and rhodium also have good catalytic activity in the selective and asymmetric hydrosilylation of carbonyl compounds "". 

As a facile method of carbon-carbon bond formation, the insertion of carbon-carbon multiple bonds into carbon-transition-metal bonds is a very important fundamental reaction in organotransition-metal chemistry. However, in contrast to the tremendous number of reports about the insertion of carbon-carbon multiple bonds into carbon-transition-metal bonds, direct insertion of carbon-heteroatom multiple bonds, such as carbonyl and nitrile groups, without using stoichiometric organometallic reagents, has received scant attention.111 A palladium(II)-catalysed cycliza-tion reaction of alkynes with carbon-heteroatom multiple bonds under mild conditions has been developed, using insertion of carbon-heteroatom multiple bonds into the carbon-palladium bond as the key step.[2]... 

This is a reaction with high atom economy and without the use of organometallic reagents, additives, or redox systems. Such an acetoxypalladation-initiated carbon-heteroatom multiple bond insertion-protonolysis system may extend the scope of transition metal-catalysed reactions pertaining to the insertion of carbon-heteroatom multiple bonds into metal-carbon bonds, and provide a new methodology in organic synthesis. The generality of the present catalytic system is shown in Table 10.2.[3]... 

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