Carboxylic acids with diazo compounds

Alkylation of Carboxylic Acids With Diazo Compounds... 

Alkylation of carboxylic acids with diazo compounds... 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

Alkylation of Carboxylic Acids with Diazo Compounds Hydro,acyloxy-de-dlazo-bisubstitution... 

Alcoholysis of trihalides 0-6 Hydrolysis of ortho esters 0-20 Alcoholysis of acyl halides 0-21 Alcoholysis of anhydrides 0-22 Esterification of carboxylic acids 0-23 Transesterification 0-24 Alkylation of carboxylic acid salts 0-25 Cleavage of ethers with anhydrides 0-26 Alkylation of carboxylic acids with diazo compounds... 

Carboxylic acids can be converted to esters with diazo compounds in a reaction essentially the same as 10-15. In contrast to alcohols, carboxylic acids undergo the reaction quite well at room temperature, since the reactivity of the reagent increases with acidity. The reaction is used where high yields are important or where the acid is sensitive to higher temperatures. Because of availability, the diazo compounds most often used are diazomethane (for methyl esters) ... 

Making use of the same reaction principle, disubstituted ketenes 66 have been reacted with aldehydes 80 to form p-lactones 81 [100], with diazo-compounds 82 to form 1,2-diazetidin-3-ones 83 [101] and with nitroso-compounds 84 to form 1,2-oxazetidin-3-ones 85 as precursors of a-hydroxy carboxylic acids (Fig. 42) [102],... 

With less electron-rich pyrroles, hydrochloric acid can be used in the diazotization. The diazo compounds were isolated after neutralization with aqueous ammonia [84H(22)2269]. 3-Diazo-2,5-diphenylpyrrole, although efficiently prepared by diazotization of the 3-aminopyrrole, can also be prepared by oxidation of the 3-nitrosopyrrole with dinitrogen trioxide (60JCS3270). Pyrrole-3-carboxylic acid, with buffered nitrous acid, gave the 3-diazo derivative 295 by displacement of the carboxyl group, together with the 3-diazo-2-carboxylic acid 296, obtained by further hydrolysis (62JCS1638) (Scheme 90). 

Rh(II) carboxylates, especially Rh2(OAc)4> have emerged as the most generally effective catalysts for metal carbene transformations [7-10] and thus interest continues in the design and development of dirhodium(II) complexes that possess chiral51igands. They are structurally well-defined, with D2h symmetry [51] and axial coordination sites at which carbene formation occurs in reactions with diazo compounds. With chiral dirhodium(II) carboxylates the asymmetric center is located relatively far from the carbene center in the metal carbene intermediate. The first of these to be reported with applications to cyclopropanation reactions was developed by Brunner [52], who prepared 13 chiral dirhodium(II) tetrakis(car-boxylate) derivatives (16) from enantiomerically pure carboxylic acids RlR2R3CC OOH with substituents that were varied from H, Me, and Ph to OH, NHAc, and CF3. However, reactions performed between ethyl diazoacetate and styrene yielded cyclopropane products whose enantiopurities were less than 12% ee, a situation analogous to that encountered by Nozaki [2] in the first applications of chiral Schiff base-Cu(II) catalysts. 

Finally, fluorinated carboxylic acids react with epoxides (trimethylaluminum-catalyzed),224 and conveniently with diazo compounds.29,225 227 Cycloaddilion is observed with diazo-methane.228 Reaction of compound 7 with trifluoroacetic acid alone is relatively slow (Freon 113, reflux, 12 h, for completion of reaction) however, catalytic amounts of copper(Il) perchlorate increase the rate of formation of ester 8 (rt, 5 min).229... 

The reactions illustrated in equations (62-64) are each catalyzed by rhodium acetate. Diazo compounds, especially diazoalkanes, can also react by a simple ionic mechanism. The esterification of a carboxylic acid with diazomethane is a familiar example. The ionic pathway is especially likely when the intermediate carbocation would be stabilized. Thus, diazine (158) couples smoothly with phenols, presumably by thermal rearrangement to the corresponding diazo sugar, followed by acid-catalyzed N2 loss... 

Esters can be prepared by acid-catalyzed esterification or by reaction of the acid chloride with the alcohol. In small-scale syntheses, it is often more convenient to prepare the ester by reaction of the carboxylic acid with the appropriate diazo compound. Diazomethane is routinely used for making methyl esters, but more highly substituted esters can be prepared if the corresponding diazo compound is available. Benzhydryl esters, for example, are readily prepared from carboxylic acids by reaction with diphenyldiazomethane ... 

Other applications of NHC-based rhodium catalysts include the cyclization of acetylene carboxylic acids, cyclopropanation of olefins with diazo compounds, or aryl-aryl cross-coupling combined with dynamic kinetic resolution with the help of a lipase or Beckmann rearrangement. Thus, the chemistry of NHC-Rh catalysts is rich and varied, and we expect new catalysts and patterns of reactivity in the years to come. These will provide new tools for synthetic organic chemistry. 

Charette et al. examined a Rh(ll)-carboxylate catalyst with four amino acid derived M-phthaloyl ligands [129]. This catalyst has seen widespread use, for example in the cyclopropanation of alkenes with diazo compounds. Depending on the orientation of these ligands (up or down), four different symmetries are possible. Previous studies were unable to clarify which is the enantioselectively active one (Scheme 15). 

Reagents that provide UV adsorptive derivatives of carboxylic acids are fairly numerous. The preparation of the simple benzyl esters by reacting the carboxylic ion with alkyl halides or diazo compounds has been unsuccessful due to their having unacceptable toxicity. The... 

There are two catalytically active residues in pepsin Asp-32 and Asp-215. Their ionizations are seen in the pH-activity profile, which has an optimum at pH 2 to 3, and which depends upon the acidic form of a group of pKa 4.5 and the basic form of a group of pKa 1.1.160,161 The pKa values have been assigned from the reactions of irreversible inhibitors that are designed to react specifically with ionized or un-ionized carboxyl groups. Diazo compounds—such as A-diazoacetyl-L-phenylalanine methyl ester, which reacts with un-ionized carboxyls—react specifically with Asp-215 up to pH 5 or so (equation 16.28).162-164 Epoxides, which react specifically with ionized carboxyls, modify Asp-32 (equation 16.29). 

Protected 6-amino-hexahydro-l,7-dioxopyrazolo[l,2-4]pyrazole-2-carboxylic acid 274 is available by a thermolytic decomposition of diazo compound 273 via the Wolff rearrangement. The starting compound is simply available by alkylation of racemic 272 with the corresponding bromoacetoacetate and subsequent diazo transfer reaction (Scheme 35) <1996TL4891>. 

Reaction of ethyl 5-amino-3-methylthio-l//-pyrazol-4-carboxylate 267 with sodium nitrite in the presence of hydrochloric acid gives the diazo intermediate 268, which on treatment with active methylenic compounds such as ethyl a-chloroacetate or a-chloroacetylacetone affords the hydrazonyl chlorides 269 and 270, respectively, whose reaction with triethylamine in refluxing ethanol convert them into ethyl 4-hydro-2-methylthiopyrazolo[5,l-c]-[l,2,4]triazole-3,6-dicarboxylate 271 and ethyl 6-acetyl-4-hydro-2-methylthiopyrazolo[5,l-c][l,2,4]triazole-3-carboxy-late 272 (Scheme 23) <2001MI1>. 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

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