Multiple bonding amide derivatives

Hydrazides of vicinal acetylene-substituted derivatives of benzoic and azole carboxylic acids are important intermediate compounds because they can be used for cyclization via both a- and /3-carbon atoms of a multiple bond involving both amine and amide nitrogen atoms (Scheme 131). Besides, the hydrazides of aromatic and heteroaromatic acids are convenient substrates for testing the proposed easy formation of a five-membered ring condensed with a benzene nucleus and the six-membered one condensed with five-membered azoles. 

Besides the activation of the olefinic partner by a metal, the unfavorable thermodynamics associated with the addition of an enolate to a carbon—carbon multiple bond could be overwhelmed by using a strained alkene such as a cyclopropene derivative286. Indeed, Nakamura and workers demonstrated that the butylzinc enolate derived from A-methyl-5-valerolactam (447) smoothly reacted with the cyclopropenone ketal 78 and subsequent deuterolysis led to the -substituted cyclopropanone ketal 448, indicating that the carbometallation involved a syn addition process. Moreover, a high level of diastereoselectivity at the newly formed carbon—carbon bond was observed (de = 97%) (equation 191). The butylzinc enolates derived from other amides, lactams, esters and hydrazones also add successfully to the strained cyclopropenone ketal 78. Moreover, the cyclopropylzincs generated are stable and no rearrangements to the more stable zinc enolates occur after the addition. 

This survey is confined to an overview of group 13 amides containing M-NR2 (R = H, alkyl, aryl, silyl, etc.) groups derivatives where nitrogen is part of a delocalized or polydentate ligand, are not generally covered. However, as in the 1980 book, iminome-tallanes (metal imides) of formula (RMNR ) are treated because of their close relationship to amides and also because of the relevance of the lower derivatives (n= 1, 2 or 3) for possible M N multiple bonding. 

Because C-H bonds are usually less reactive towards dioxirane oxidation than heteroatoms and C-C multiple bonds, it is instructive to give a few general guidelines on the compatibility of functional groups within the substrate to be submitted to oxidative C-H insertion Substances with low-valent heteroatoms (N, P, S, Se, I, etc.), C-C multiple bonds, and C=X groups (where X is a N or S heteroatom) are normally not suitable for C-H insertions, because these functionalities react preferably. Even heteroarenes are more susceptible to dioxirane oxidation than C-H bonds, whereas electron-rich and polycyclic arenes are only moderately tolerant, but electron-poor arenes usually resist oxidation by dioxiranes. N-oxides and N-oxyl radicals are not compatible because they catalyze the decomposition of the dioxirane. Oxygen insertion into Si-H bonds by dioxirane is more facile than into C-H bonds and, therefore, silanes are not compatible. Substance classes normally resistant towards dioxirane oxidation include the carboxylic acids and their derivatives (anhydrides, esters, amides, and nitriles), sulfonic acids and their de-... 

A major distinction for nucleophilic reactions with ambident anions is whether they proceed with kinetic or thermodynamic control.80 N-Substituted saccharins (10) should be thermodynamically more stable because of amide character than the isomeric pseudosaccharin (3) of imidate structure. In fact 3 may be rearranged thermally to 10 in an irreversible reaction.96 The threshold for thermodynamic control appears to be lowered for electrophiles with multiple bonds, e.g., formaldehyde, reactive derivatives of carboxylic acids, but also quaternary salts of N-heterocyclic compounds.80 It will be seen that in those cases substitution indeed occurs at the nitrogen, not necessarily through thermodynamic control. 

C = Y l Polarized multiple bond with L Acyl halides RCOCl Anhydrides RCOOCOR Thioesters RCOSR Esters RCOOR Amides RCONRj The poorer donor L is, the more reactive Addition-Elimination Add a second Nu after add-elim (9.2) Carbonate derivatives L2C=Y L on triple bonds L-C=Y... 

M. Meot-Ner (Mautner), J. Am. Chem. Soc., 106, 278 (1984), The Ionic Hydrogen Bond, 4. Intramolecular and Multiple Bonds. Protonation and Comple.xes of Amides and Amino Acid Derivatives. 

Aromatic hydrocarbons also react smoothly with an equimolar amount of chlorosulfonic acid or an excess of the reagent to yield either the sulfonic acid or the sulfonyl chloride (Equations 6 and 7). The direct conversion of aromatic compounds into their sulfonyl chlorides (chlorosulfonation or chlorosulfonylation) is probably the most important reaction of chlorosulfonic acid because sulfonyl chlorides are intermediates in the synthesis of a wide range of sulfonyl derivatives. The process is of wide application because many substituents on the aromatic ring, e.g. alkyl, alkoxy, amide, carboxy, cyano, hydroxy, nitro and multiple bonds are unaffected by the reagent. 

A novel route to synthesize phthahmide derivatives through ruthenium-catalyzed C-H bond functionalization of aromatic amides was developed by Ackermann and coworkers (Eq. (7.57)) [66]. This method is applicable to generate a potent COX-2 enzyme inhibitor in step-economical way. The reaction features by the insertion of a cycloruthenated species into a C—Het multiple bond of isocyanate and cleavage of pyrrolidinyl group. Electron-rich amides were found to favor the reaction, and an initial reversible C-H bond metalation step was also observed. 

Amine activatitMi pathway has been well studied in catalysis by lanthanides, early transition metals, and alkali metals. In metal amide chemistry of late transition metals, there are mainly two pathways to synthesize metal amide complexes applicable under hydroamination conditions [54], One is oxidative addition of amines to produce a metal amide species bearing hydride (Scheme 8a). The other gives a metal amide species by deprotonation of an amine metal intermediate derived from the coordination of amines to metal center, and it often occurs as ammonium salt elimination by the second amine molecule (Scheme 8b). Although the latter type of amido metal species is rather limited in hydroamination by late transition metals, it is often proposed in the mechanism of palladium-catalyzed oxidative amination reaction, which terminates the catalytic cycle by p-hydride elimination [26]. Hydroamination through aminometallation with metal amide species demands at least two coordination sites on metal, one for amine coordination and another for C-C multiple bond coordination. Accordingly, there is a marked difference between the hydroamination via C-C multiple bond activation, which demands one coordination site on metal, and via amine activation. 

QUINAPHOS ligands are usually synthesized in a one-pot-procedure from readily available 8-substituted quinolines [8] via nucleophilic addition of a lithium reagent [9] to the azomethinic double bond and direct quenching of the resulting 1,2-dihydroquinoline amide 1 with a phosphorochloridite derived from enantio-merically pure binaphthol (1) or from 3,3 -di-t-butyl-5,5 -dimethoxybiphenyl-2,2 -diol (m) [10] (Scheme 2.1.5.1, Method A). Alternatively, the anion 1 can be reacted with an excess (in order to avoid multiple substitution) of phosphorous trichloride to obtain the corresponding phosphorous dichloridite 2, which can be isolated (Scheme 2.1.5.1, Method B). In a second step, 2 is converted into 4 by reaction with the desired diol in the presence of triethylamine. 

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