Transition carboxylic acid derivatives

Phenylthio)nitroalkenes are also excellent intermediates for the synthesis of other heterocyclic ring systems. For example, tetrahydropyran carboxylic acid derivatives are formed by the intramolecular addition of oxygen nucleophile to l-(phenylthio)nitroalkene predominantly as the m-isomer (9.1 1) (see Eq. 4.40). The reaction may proceed via the chair-like transition state with two pseudo-equatorial substituents.50... 

The terphenyl carboxylic acid derivatives have also been employed as supporting ligands in transition metal chemistry. For example, several binu-clear rhodium(II) terphenyl carboxylates (Fig. 20) have been reported.95 These were synthesized using the alternative route described in Eq. (8).96... 

A series of reagents have been developed which are prepared in situ from a geminal dihalide or a dithioacetal [635,730] and a transition metal complex. Titanium-based reagents of this type olefinate a broad range of carbonyl compounds, including carboxylic acid derivatives (Table 3.12), and are a practical alternative to the use of isolated carbene complexes. 

GatCAB amidotransferase.This natural product mimics the charged 3 -terminus of aa-tRNA and has been used as a tool for the study of protein biosynthesis. The parent compound 22 is a very weak inhibitor of AdT. The amino acid chain is related to tyrosine and differs from the glutamic and aspartic side chains transformed in the kinase or the transamidase steps. Replacement of the methoxyphenyl moiety of puromycin by carboxylic acid derivatives (23-26) improved the ability to inhibit this AdT. Stable analogues of the transition state in the last step of the transamidation process (27-29) where the carbonyl to be attacked by NH3 is replaced by tetrahedral sulfur or phosphorus atom with a methyl group mimicking ammonia exhibited the highest activity. 

In summary, therefore, the detailed mechanism of the hydrolysis of carboxylic anhydrides is still in doubt and we must hope for further experimental evidence to clarify the position. As for the hydrolysis of the other carboxylic acid derivatives dealt with in this chapter, none of the mechanistic criteria, that have been used to interpret the kinetic data, gives an unambiguous interpretation, resulting in a situation where details of mechanism are open to argument. This is particularly the case for solvolysis reactions where uncertainty as to the structure and effect of the solvent preclude a firm assignment of transition state structures. This is not to say that the mechanisms are not... 

The hydrocarboxylation reaction of alkenes and alkynes is one which utilizes carbon monoxide to produce carboxylic acid derivatives. The source of hydrogen is a protic solvent (equation 35) dihydrogen is not usually added to the reaction. There are a number of variations to this reaction, since the solvent can be water, alcohols, amines, acids, etc. The catalysts can be Group VIII-X transition metals, but cobalt, rhodium, nickel, palladium and platinum have found the most use. 

Another important reaction typically proceeding in transition metal complexes is the insertion reaction. Carbon monoxide readily undergoes this process. Therefore, the insertion reaction is extremely important in organoiron chemistry for carbonylation of alkyl groups to aldehydes, ketones (compare Scheme 1.2) or carboxylic acid derivatives. Industrially important catalytic processes based on insertion reactions are hydroformylation and alkene polymerization. 

Straight-chain alkyl carboxylic acids derived from petroleum that also have a terminal cyclohexyl or cyclopentyl group are known as naphthenic acids. They form complexes, presumably polymeric, with many transition metals, and these compounds are freely soluble in petroleum. Copper naphthenates are used as fungicides, aluminum naphthenate was used as a gelling agent in napalm, and cobalt naphthenates are used in paints. 

The carbonylation of allylic compounds by transition metal complexes is a versatile method for synthesizing unsaturated carboxylic acid derivatives (Eq. 11.22) [64]. Usually, palladium complexes are used for the carbonylation of allylic compounds [65], whereas ruthenium complexes show characteristic catalytic activity in allylic carbonylation reactions. Cinnamyl methyl carbonate reacts with CO in the presence of a Ru3(CO)i2/l,10-phenanthroline catalyst in dimethylformamide (DMF) to give methyl 4-phenyl-3-butenoate in excellent yield (Eq. 11.23) [66]. The regioselectivity is the same as in the palladium complex-catalyzed reaction. However, when ( )-2-butenyl methyl carbonate is used as a substrate, methyl ( )-2-methyl-2-butenoate is the major product, with the more sterically hindered carbon atom of the allylic group being carbo-nylated (Eq. 11.24). This regioselectivity is characteristic of the ruthenium catalyst [66]. 

Several reviews compile general aspects of the applications of transition metal catalyzed hydrocyanation of alkenes and alkynes1-6. This method is synthetically interesting since, starting from nonactivated alkenes. access is achieved not only to nitriles, but also to carboxylic acid derivatives, amines and isocyanates. Of industrial importance is the double addition of hydrogen cyanide to butadienes yielding adipodinitrile7,8. 

It is generally true that restrictions on conformational mobility minimize the number of competing transition states and simplify analysis of the factors that affect selectivity. Chelation of a metal by a heteroatom often provides such restriction and also often places the stereocenter of a chiral auxiliary in close proximity to the a-carbon of an enolate. This proximity often results in very high levels of asymmetric induction. A number of auxiliaries have been developed for the asymmetric alkylation of carboxylic acid derivatives using chelate-enforced intraannular asymmetric induction. The first practical method for asymmetric alkylation of carboxylic acid derivitives utilized oxazolines and was developed by the Meyers group in the 1970 s (Scheme 3.16a), whose efforts established the importance and potential for chelation-induced rigidity in asymmetric induction (reviews [77-79]). In 1980, Sonnet [80] and Evans [81,82] independently reported that the dianions of prolinol amides afford more highly selective asymmetric alkylations (Scheme 3.16b). 

The majority of catalytic antibodies [18,19] so far known have been designed to catalyse the hydrolysis of carboxylic acid derivatives, and have been raised against phosphonate baptens 2, which models the structure of the tetrahedral transition states involved (1). 

Catalytic and highly enantioselective fluorination of acyl chlorides was reported by Lectka et al. where O-benzoyl quinidine (O-Bz-QD), is combined with a transition metal-based cocatalyst, (l,3-dppp)NiCl2 or trans-(PPh3)2PdCl2, to generate chiral ketene enolates from acyl chlorides, which are fluorinated with NFSI to produce ot-fluorinated carboxylic acid derivatives. These derivatives are then in situ reacted with different nucleophiles such as methanol, water or variety of amines affording a-fluoro esters, acids... 

The metallocarbene intermediates are most often formed from thermal, photolytic, or metal-catalyzed deconposition of diazocarbonyl compounds, with concomitant loss of dinitrogen. Under transition metal catalysis, the initially formed species is a metallocarbene rather than a free carbene, and this is usually desirable due to the moderated reactivity (and, hence, fewer undesired side reactions) of the metal-complexed carbene. The two most common methods for introduction of the diazo group are acylation of diazoalkanes with suitably activated carboxylic acid derivatives and diazo transfer reactions in the case of more acidic active methylene substrates fScheme 16.12T... 

In the industrial importance of carbonylation in afiphatic carboxylic acid derivatives production, we are going to take the hydrocarbonxylation of aUcene as an example to discuss the activity differences of the catalysts. Effective catalysts for the hydrocarboxylation are the transition metals Ni, Co, Fe, Rh, Ru, Pd, Pt, and Ir. Under reaction conditions, the corresponding metal carbonyls or hydridocarbonyls are formed from various catalyst precursors which can be metal salts (halides preferred), complex salts, oxides, or, in some special cases, even fine metal... 

Ketenes are especially reactive in [2 + 2] cycloadditions, and an important reason is that they offer a low degree of steric interactions in the transition state. Another reason is the electrophilic character of the ketene LUMO. The best yields are obtained in reactions in which the ketene has an electronegative substituent, such as halogen. Simple ketenes are not very stable and usually must be generated in situ. The most common method for generating ketenes for synthesis is by dehydrohalogenation of acyl chorides. This is usually done with an amine such as triethylamine. Other activated carboxylic acid derivatives, such as acyloxypyridinium ions, have also been used as ketene precursors ... 

As a rule, alkenes do not react with 78-80 unless there is another reagent present—specifically, a transition metal. This reaction will not be discussed further. In sharp contrast, peroxycarboxylic acids such as 81 react directly with alkenes. Peroxycarboxylic acids 81 are named by adding the term peroxy to the name of the carboxylic acid (see Chapter 5, Section 5.9.3 and Chapter 16, Section 16.4). Using the common names, the peroxy analog of formic acid is peroxyformic acid (82), and others include peroxyacetic acid (83), peroxytrifiuo-roacetic acid (84), peroxybenzoic acid (85), and me a-chloroperoxybenzoic acid (abbreviated mCPBA, 86). Peroxycarboxylic acid 85 is a derivative of the aromatic carboxylic acid benzoic acid (PhCOOH), and the carboxylic acid precursor to 86 is clearly another aromatic carboxylic acid. (The nomenclature and structural features of benzoic acid and other aromatic carboxylic acid derivatives will be discussed in detail in Chapter 21, Section 21.2.) The salient feature of peroxyacids 82-86 is the presence of the electrophihc oxygen atom mentioned previously, which will react with an alkene. 

The catalytic hydrocarbonylation and hydrocarboxylation of olefins, alkynes, and other TT-bonded compounds are reactions of important industrial potential.Various transition metal complexes, such as palladium, rhodium, ruthenium, or nickel complexes, have widely been used in combination with phosphines and other types of ligands as catalysts in most carbonylation reactions. The reactions of alkenes, alkynes, and other related substrates with carbon monoxide in the presence of group VIII metals and a source of proton affords various carboxylic acids or carboxylic acid derivatives.f f f f f While many metals have successfully been employed as catalysts in these reactions, they often lead to mixtures of products under drastic experimental conditions.f i f f f In the last twenty years, palladium complexes are the most frequently and successfully used catalysts for regio-, stereo-, and enantioselective hydrocarbonylation and hydrocarboxylation reactions.f ... 

In conjugate reduction of enones with other transition metals such as chromium, the rates of reduction were shown to be dependent on the conformation of the substrate, with faster reactions being observed with the cisoid forms as compared with the transoid onesJ However, with the Pd/Si/Zn system, the rigid transoid enone of cyclohexenone and the flexible enone of acetylcyclohexene are both reduced in comparable rates. This indicates that palladium interacts exclusively with the olefinic part of the enone without significant participation of the carbonyl. Interestingly, this method is highly selective for unsaturated ketones and aldehydes, as the reduction of corresponding o,jS-unsaturated carboxylic acid derivatives, such as esters, amides, and nitriles, is very slow under the conditions used. Thus, ben-zylideneacetone is selectively and cleanly reduced in the presence of methyl cinnamate, dnnamonitrile, or dnnamamide.t" ... 

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