Arylboronic acids amination

There are several different routes to carboxamides. In most of these reactions, a carboxylic acid is converted to a more reactive intermediate, e.g. the acid chloride, which is then allowed to react with an amine. For practical reasons, it is preferable to form the reactive intermediate in situ. Arylboronic acids with electron-withdrawing groups such as (3,4,5-trifluorophenyl)boronic acid act as highly efficient catalysts in the amidation between carboxylic acids and amines. (3-Nitrophenyl)boronic acid and [3,5-bis(trifluoromethyl)phenyl]boronic acid are also effective eimidation catalysts and commercially available. 

Support-bound benzimidazoles can be N-arylated by treatment with arylboronic acids in the presence of Cu(OAc)2 (Entry 3, Table 15.15). Benzimidazolones, which can be prepared from resin-bound 1,2-diaminobenzenes and di-iV-succinimidyl carbonate (Entry 8, Table 15.14), can also be N-alkylated on insoluble supports (Entry 4, Table 15.15). Benzimidazole-2-thiones, on the other hand, are generally cleanly S-alkylated (Entry 5, Table 15.15). Examples of amination by aromatic nucleophilic substitution at resin-bound halopurines are given in Section 10.1.2. 

Extensive use of Pd-catalyzed reactions was included in the synthesis of 2,6,8-trisubstituted purines (Fig. II).33 The synthesis started by anchoring dichloropurine to Rink resin via N9 linkage. Polymer-bound 2,6-dichloropurine (63) was selectively substituted at C6 via acid-catalyzed SNAr substitutions. In the absence of Pd catalysis, the substitution on C2 could be performed only with strongly nucleophilic amines. To expand the scope of C2 substitution, catalytic amounts of Pd were used. Under these reaction conditions arylboronic acids and amines successfully substituted the chloro atom on C2 to afford C2-C and C2-N bonds. Subsequently, the C8 position was brominated with a bromine-lutidine complex33 (66) to give resin 67. 

Reactions between a representative range of alkyl- and aryl-amines and of aliphatic and aromatic acids showed that the direct formation of amides from primary amines and carboxylic acids without catalyst occurs under relatively low-temperature conditions (Scheme 1). The best result obtained was a 60% yield of N-bcnzyl-4-phenylbutan-amide from benzylamine and 4-phenylbutanoic acid. For all these reactions, an anhydride intermediate was proposed. Boric and boronic acid-based catalysts improved the reaction, especially for the less reactive aromatic acids, and initial results indicated that bifunctional catalysts showed even greater potential. Again, anhydride intermediates were proposed, in these cases mixed anhydrides of carboxylic acids and arylboronic acids, e.g. (I).1... 

This reaction allows aryl carbon-heteroatom bond formation via an oxidative coupling of arylboronic acids, stannanes or siloxanes with N-H or O-H containing compounds in air. Substrates include phenols, amines, anilines, amides, imides, ureas, carbamates, and sulfonamides. The reaction is induced by a stoichiometric amount of copper(II) or a catalytic amount of copper catalyst which is reoxidized by atmospheric oxygen. 

This reaction can be carried out with secondary amines, sterically hindered primary amines, hydrazines or anilines in dichloromethane at room temperature. The range of potential nucleophilic partners includes alkenylboronic acids, and electroneutral as well as electron-rich (hetero-)arylboronic acids. The conversion of electron-poor boronic acids can be effected at elevated temperatures (MW) in suitable solvents. 

Arylboronic acids have been added diastereo- and enantio-selectively to (a) sulflnyl aldimines and (b) phosphinoyl aldimines, using rhodium(I) catalysts.52 These two methods should prove useful in preparing a-branched amines. 

By using this mild and versatile methodology, symmetrical diaryl ethers have been synthesized in a one-pot, two-step procedure starting from arylboronic acids and their partial conversion to the corresponding phenols by oxidation with hydrogen peroxide and a subsequent coupling of the formed phenols with the remaining arylboronic acids upon addition of copper(II) acetate, molecular sieves and triethyl amine (Scheme 7) [22],... 

The cationic rhodium complexes such as [Rh(cod)(MeCN)2]BF4/dppb were the most efficient catalysts for addition of arylboronic acids or Ph4BNa to both aromatic and aliphatic A-sulfonyl imines.993 994 The asymmetric version giving optically active amines was achieved by amidomonophosphine catalysts (Equation (225)).995... 

An impressive range of nucleophiles was successful for arylboronic acids in the presence of Cu(OAc)2 and base, which included amine, anilines, amides, imines, ureas, carbamates, sulfonamides, and aromatic heterocycles (e.g., imidazoles, pyrazoles, triazoles, tetrazoles, benzimidazoles, and indazoles) (Equation (226)) 996 997 1000-1011 For all the reactions investigated with A-nucleophiles, the use of Et3N resulted in yields superior to those obtained with pyridine, but pyridine was the base of choice for the preparation of imidazole derivatives from heteroarenes. For the tetrazole, NMO and DBU were studied as alternative bases. There are mechanistic studies.999,1002-1013... 

A ligandless and base-free Gu-catalyzed protocol for the coupling of arylboronic acids and potassium aryltrifluoro-borates with primary and secondary aliphatic amines and anilines was developed. The process utilized catalytic copper(n) acetate monohydrate or CuCl2 and 4 AMS in dichloromethane at slightly elevated temperatures under an atmosphere of oxygen (Equation (232)).1019-1021... 

The arylation of N-H and 0-H containing compounds, such as amines, amidos, imines, and phenols, with arylboronic acids is promoted by copper(ll) acetate (1 equivalent) and tertiary amine (2-5 equivalents) at room temperature [244-248]. The mild reaction conditions at room temperature permit the synthesis of phenolic amino acids without racemization, methodology that has been applied to an efficient synthesis of (S,S)-isodityrosine from two natural amino acids [248] (Scheme 45). 

The addition of arylboronic acids to imines in an aqueous solvent gave a mixture of amine (Eq. 6) and alcohol (Eq. 4) because the imines were partially hydrolyzed to the aldehyde during the reaction. The use of Ph4BNa in place of phenylboronic acid allowed the catalytic addition to various N-sulfonyl imines in the absence of water (Eq. 6). The representative results are summarized in Table 5. The cationic rhodium complexes such as [Rh(cod)(MeCN)2]BF4 was found to be the most efficient catalyst for both aromatic and aliphatic N-sulfonyl imines whereas no reactions were observed for N-alkyl and N-aryl imine derivatives. 

Antilla, J. C., Buchwald, S. L. Copper-Catalyzed Coupling of Arylboronic Acids and Amines. Org. Lett. 2001,3, 2077-2079. 

B. Copper-mediated Reactions of Arylboronic Acids with Amines. 510... 

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