Carboxylate decomposition, reactivity

Although dirhodium(II) carboxamidates are less reactive toward diazo decomposition than are dirhodium carboxylates, and this has limited their uses with diazomalonates and phenyldiazoacetates, the azetidinone-ligated catalysts 11 cause rapid diazo decomposition, and this methodology has been used for the synthesis of the cyclopropane-NMDA receptor antagonist milnacipran (17) and its analogs (Eq. 2) [10,58]. In the case of R=Me the turnover number with Rh2(45-MEAZ)4 was 10,000 with a stereochemical outcome of 95% ee. 

The reaction, formally speaking a [3 + 2] cycloaddition between the aldehyde and a ketocarbene, resembles the dihydrofuran formation from 57 a or similar a-diazoketones and alkenes (see Sect. 2.3.1). For that reaction type, 2-diazo-l,3-dicarbonyl compounds and ethyl diazopyruvate 56 were found to be suited equally well. This similarity pertains also to the reactivity towards carbonyl functions 1,3-dioxole-4-carboxylates are also obtained by copper chelate catalyzed decomposition of 56 in the presence of aliphatic and aromatic aldehydes as well as enolizable ketones 276). No such products were reported for the catalyzed decomposition of ethyl diazoacetate in the presence of the same ketones 271,272). The reasons for the different reactivity of ethoxycarbonylcarbene and a-ketocarbenes (or the respective metal carbenes) have only been speculated upon so far 276). 

On the basis of the obtained results and the literature[17-18], we assume that during the oxidative decomposition of p-coumaric acid 1, three kind of reaction can happen before the opening of the aromatic ring (Scheme 1) cleavage of the very reactive exocyclic double bond to give p-hydroxybenzaldehyde 2, hydroxylation of the aromatic ring to yield 3,4-dihydroxycinnamic acid 3 and oxidation of aldehydes to carboxylic acids such as oxidation of 2 to p-hydroxybenzoic acid 4. Compound 2 can be hydroxylated to yield 3,4- dihydroxybenzaldehyde 6. and Compound 4 can also be hydroxylated to yield 3,4-dihydroxybenzoic acid 5. 

Further work with the same dye (7.43) and carbodiimides (7.44 and 7.45) concentrated on this problem of limited efficiency. Cotton fabric padded with the dye phosphonate solution was aftertreated with the carbodiimide dissolved in various alcoholic solutions to avoid hydrolytic decomposition. Under these conditions cyanamide was much more effective than dicyandiamide. With conventional reactive dyes the efficiency of the dye-fibre reaction is limited by competing hydrolysis of the active dye. Although phosphonated or carboxylated reactive dyes do not hydrolyse, their level of fixation is limited by competing hydrolysis of the carbodiimide activator [46]. 

On Sulphonyl Chlorides and Sulphonamides.—The conversion of benzenesulphonic acid into its chloride and amide shows that derivatives of sulphonic acids, analogous to those of carboxylic acids, can be obtained. The sulpho-chlorides are much less reactive than are the chlorides of the carboxylic acids benzene sulphochloride, for example, can be dis-stilled in steam almost without decomposition. 

The tripeptides in Fig. 6.17 underwent a few breakdown reactions (N-ter-minus elimination, Qm formation, peptide bond hydrolysis), some of which will be considered later in this section. Of relevance here was that, of the two amidated tripeptides, the amide at the C-terminus underwent deamidation predominantly (Fig. 6.17, Reaction a), which, perhaps, explains the somewhat lesser stability compared to the free carboxylic acid forms. While the hexapeptide (6.52, Fig. 6.17) followed a different pattern of decomposition [76b], deamidation was also a predominant hydrolytic reaction at all pH values. Thus, the procedure to extrapolate results from small model peptides to larger medicinal peptides appears to be an uncertain one, since small modifications in structure can cause large differences in reactivity. 

Because of the high nucleophilicity and reactivity of diazoalkanes, catalytic decomposition occurs readily, not only with a wide range of transition metal complexes but also with Brpnsted or Lewis acids. Well-established catalysts for diazodecomposition include zinc halides [638,639], palladium(II) acetate [640-642], rhodium(II) carboxylates [626,643] and copper(I) triflate [636]. Copper(II)... 

The synthesis of the triptycene system illustrates a synthetic use of the important reactive intermediate benzyne (13) which is generated by the thermal decomposition of benzenediazonium-2-carboxylate (see Section 6.5.3, p. 900). The latter is produced when anthranilic acid (11) is treated with an alkyl nitrite in an aprotic solvent, and probably exists mainly as the zwitterionic form (12). 

Benzyne is an important reactive intermediate especially useful for the construction of polycyclic compounds via cycloaddition reactions with various dienes. Several benzyne precursors, including diphenyliodonium-2-carboxylate [ 1 ], have been previously used for the generation of benzyne by thermal decomposition. More recently, several new precursors that generate benzyne quantitatively under very mild conditions have been developed [105 -108]. An efficient benzyne precursor, iodonium triflate 109, can be readily prepared by the reaction of l,2-bis(trimethylsilyl)benzene 108 with [(diacetoxy)iodo]benzene in the presence of trifluoromethanesulfonic acid (Scheme 47) [105]. 

The utilization of perfluorodiacyl peroxides for this purpose has been more widely developed. The rate of decomposition of perfluorodiacyl peroxides in the presence of electron-rich benzene derivatives is enhanced by a significant factor via a process of electron-transfer [66, 280], As can be seen by the contrasting examples below [281], highly reactive arenes are capable of trapping the per-fluoroalkyl carboxyl radical before it decarboxylates to RF, a result which can diminish the synthetic utility of this process. 

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-... 

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