Addition to C-N multiple bonds

The objective of most Reformatsky syntheses is, however, not the hydroxy ester but the unsaturated ester. If the latter is not formed spontaneously during the synthesis, the hydroxy ester can be dehydrated by one of the methods described on pages 818-19 if so, it is often unnecessary to isolate the hydroxy ester it suffices to heat the crude product with phosphorus oxychloride or to distil it from phosphoric oxide. 

For example, after acetophenone (72 g) has been allowed to react with ethyl bromo-acetate (100 g), and zinc turnings (41 g) in benzene (250 ml), the solvent is distilled off and the residue is treated with phosphorus oxychloride (20 drops). Distillation then gives ethyl -methylcinnamate (80 g) as the fraction boiling at 155-165°/28 mm.221 

The poor yields often obtained in Reformatsky syntheses are due to side reactions for instance, the basic zinc salts may cause aldol condensation of aldehydes and coupling of 2 molecules of the bromo ester has been observed to give the succinic ester. An indication of how to avoid these side reactions has been provided by Lipkin and Stewart.222 

Other halides may be used in place of the bromo ester. Reaction of a pro-pargyl halide, for example, with various carbonyl compound gives y,d-acetylenic alcohols of type (6) in good yield.223 Also the carbonyl component may be replaced by an orthoformic ester, which leads to a malonic monoester monoaldehyde acetal of type (7) in 44-58% yield.224 

Reformatsky reactions have been used in the total synthesis of various important natural products such as phytol,225 naturally occurring polyenes,226 and vitamin A (from / -ionylideneacetaldehyde).227 

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On treatment with sulfur tetrafluoride, primary amines and compounds containing C-N multiple bonds are converted into iminosulfur difluorides. Sulfur tetrafluoride also undergoes addition to pcrfluoroalkenes and polyfluorovinyl ethers. 

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). 

Additions to the C=0 double bonds of various ketones66 as well as to a C=N multiple bond of isoquinoline107 afford the compounds 85 and 86, respectively. The reaction of 41 with the racemic 3-thiazoline 92 is diastereoselective and yields the azadisilacyclobutane 93 (equation 15)72. 

Triethylborane or diethylzinc has been proposed to have multiple roles in radical additions to C=N bonds, including both initiation and chain propagation, offering the potential for a radical chain process without tin hydride [6, 7]. Accordingly, we attempted triethylborane mediated tin free additions of various halides, simply deleting BujSnH from the conditions outlined in Table 2.3 and using InCb as the Lewis acid (Table 2.5). As in the case of tin mediated additions, the secondary iodides worked quite well in additions to the propionaldehyde hydrazone (entries 2 4). Although other primary radicals were ineffective, chloroiodomethane did lead to... 

In agreement with this principle, Gilman,18 studying the addition of organometallic compounds to C-0 and C-N multiple bonds and to C=C bonds of unsymmetrical olefins, found the reactivity of carbon compounds of the... 

Allylic, benzylic and propargylic bromides will also react with zinc to give the corresponding organozinc bromides. Reaction with both C—C and C—N multiple bonds has already been shown to provide a potentially useful route to some Olefinic compounds [135]. However, the reaction with terminal acetylenes produces mixtures of mono- and bis-addition products (27) and (28) in low yields [136] (Scheme 57). 

No structure of a stable monomeric iminoalane is currently available. However, the p-diketiminate stabilized monomeric [(L)]AINC6H3(C6H2Pr 3-2,4,6)2-2,6] (L = HC C-(Me)N(Dipp) 2) is believed to have a very similar structure to its gallium analogue (cf. Section 8.3.5) which has a very short Ga—N distance of 1.701 A consistent with Ga—N multiple bonding. It readily underwent intramolecular additions to the Al—N bond to give crystalline products. For an account of the chemistry of A1(L), see Ref. 184. 

Intramolecular nucleophilic displacements are sometimes better suited to difficult cyclizations than additions to C-C multiple bonds, because nucleophilic substitutions are usually irreversible. Some metalated 4-halobutyl imines cydize to yield cydobutanes rather than six-membered cydic enamines (Scheme 9.22). If alkoxides are used as bases, however, exclusive N-alkylation is observed. No examples could be found of the cydization of 4-halobutyl ketones to cyclobutyl ketones, but 5-halopen-... 

Early examples of intramolecular aryl radical addition reactions to heteroatom containing multiple bonds included cyclizations on N=N and C=S moieties [52, 53]. Recently, cyclizations to imines have been used as part of a new enantio-selective approach to indolines (Scheme 8). In the first step of the sequence, the required ketimines 19 were obtained by phase-transfer catalyzed alkylation of 2-bromobenzyl bromides 20 with glycinyl imines 21 in the presence of a cincho-nidinium salt [54], Due to the favorable substitution pattern on the imine moiety of 19, the tributyltin hydride mediated radical cyclization to 22 occurred exclusively in the 5-exo mode. The indoline synthesis can therefore also be classified as a radical amination. 

Recently, the transition-metal-catalyzed addition of active methylene C-H bonds to electron-deficient olefins having a carbonyl, a nitrile, or a sulfonyl group has been extensively studied by several research groups. In particular, the asymmetric version of this type of catalytic reaction provides a new route to the enantioselective construction of quaternary carbon centers [88]. Another topic of recent interest is the catalytic addition of active methylene C-H bonds to acetylenes, allenes, conjugate ene-ynes, and nitrile C-N triple bonds. In this section, the ruthenium-catalyzed addition of C-H bonds in active methylene compounds to carbonyl groups and C-C multiple bonds is described. 

Germylenes have long been known to react with multiple bonds such as C=C, C C, and C=0. In addition, insertion reactions into carbon halogen, O H, and N H bonds, are well precedented. In the last 10 years, substantial progress has been made in the reaction with C H bonds. 

Some remarkable N-substituted derivatives of SeCU with significant Se-N multiple bonding have been obtained from the reaction of (CeHsIsP-N-SKCHala with SeCU. The first product to be isolated is (CeHslaP-N-SeCU, in which another chlorine is replaced to give [(CeHslaP NlaSeCU. On addition of SbCU at -78°C, one Cl is abstracted and [(CeHslaP NlSeCr ][SbCl6"] is formed (389). A Se-N dou-... 

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