Amines, arylation with arylboronic acids

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. 

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). 

Zhu X, Zhang Q, Su W. Solvent-free A-arylation of amines with arylboronic acids under ball milling conditions. RSC Adv 2014 4 22775-8. 

It is used for making NHCs for metal catalysed a-arylation of acychc ketones, e.g. propiophenones, and amination of haloarenes [Matsubara et al. J Org Chem 72 5069 2007], It has been sirlfonated for making sulfonated anilines, and consequently sulfonated NHCs, which provide water soluble Pd-NHCs used for Suzuki coupling of arylhalides with arylboronic acids in aqueous medium [Fleckenstein et al. Chem Commun 2870 2007],... 

During the same year, nano-Cu20 was employed to facilitate the N-arylation of azoles and amines with arylboronic acids (Scheme 4.34). Several Af-aryl azole derivatives could be efficiently assembled at room temperature under base-free conditions (Sreedhar et al., 2008). 

Kantam, M. L., Venkanna, G. T., Sridhar, C., Sreedhar, B., and Choudary, B. M. 2006. An efficient base-free N-arylation of imidazoles and amines with arylboronic acids using copper-exchanged fluorapatite. /. Org. Chem. 71(25) 9522-9524. 

The coupling of anilines with arylboronic acids has been described in a process catalysed by palladium acetate without the need for ligands, bases, or salts. The mechanism shown in Scheme 17, where S represents solvent, involves in situ formation of the dia-zonium salt from the aniline, and formation of an arylpalladium alkoxo complex which allows the transmetallation step with arylboronic acids. It has been shown that a free amine may be used as a DG in a palladium-catalysed reaction promoted by soluble silver salts. The latter aid the formation of intermediates, (136), which may undergo cyclopalladation followed by transmetallation with an arylboronic acid and reductive elimination. Related work has shown thatbiaryl-2-amines may react with aryl iodides in the presence of palladium acetate and silver acetate to give mono- or di-arylated species such as (137). 

The copper-catalyzed coupling of l//-pyrazolo[3,4-fc]pyridin-3-amines with arylboronic acids affords N-arylated products in good to excellent yields (Scheme 3.101) [103]. The chemistry was insensitive to the electronic composition of the arylboronic acid, and an array of electron-donating and electron-withdrawing groups were well tolerated. One of the most attractive aspects of this chemistry was the ability to carry out the arylation reaction under air at room temperature. 

We reported [82] the W-arylation of imidazoles and amines with arylboronic acids with copper-exchanged fluorapatite (Cu-FAP) in methanol at room temperature. The products W-arylimidazoles and W-arylamines were isolated in good to excellent yields. A variety of arylboronic acids were converted to the corresponding W-arylimidazoles and A-arylamines, demonstrating the versatility of the reaction. 

Later we reported [84] the (V-aiylation of imidazoles, imides, amines, amides, and sulfonamides with arylboronic acids using a recyclable Cu(0Ac)2 H20/[bmim] [BF4] system in the absence of a base or additive to afford the corresponding (V-arylated products in good to excellent yields. 

AU these authors proposed that the mechanism bears some similarity to the copper-mediated arylation of amines from triarylbismuth compounds, described by Barton et al. [273]. Thus, the reaction would proceed via the formation of a cupric acetate complex with the nucleophile followed by a transmetallatimi with arylboronic acid playing the role of the triarylbismuth, before affording the N-arylated compound by reductive elimination. This last step would be facilitated by prior oxidation by dioxygene of a copper II intermediate to a copper IB intermediate [266-270, 274]. Some authors reported that the addition of molecular... 

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. 

Lam and coworkers292 and Antilla and Buchwald297 expanded the scope of this type of catalytic coupling to encompass reactions of amines. Lam reported the coupling of aliphatic and aromatic amines, as well as heterocycles with N—H bonds with a combination of Cu(OAc)2 (10 mol%) and co-oxidants like pyridine A-oxide (PNO) or TEMPO in air. No single set of conditions led to coupling of all substrates. Concurrently, Buchwald reported reactions at room temperature catalyzed by Cu(OAc)2 (5-10 mol%) and myristic acid with stoichiometric amounts of 2,6-lutidine as base. Substituted anilines, as well as primary and secondary amines, reacted with a series of arylboronic acids. Excellent yields of arylated products were obtained for reactions of anilines, but only moderate yields were obtained for reactions of aliphatic amines. Yudin and coworkers employed this protocol to prepare A-aryl aziridines (equation 72)298. 

In contrast to the apparent need to conduct the copper-catalyzed reactions of arylboronic acids and amines in the presence of oxygen, the A-arylation of imidazoles was reported with 5 mol% of [Cu(OH)tmeda]2Cl2 in a mixture of NMP and water under a nitrogen atmosphere (equation 74)302. 

Arylations. Copper(II) acetate catalyzes the reaction of arylboronic acids with phenols and amines (including imidazole and amides) to provide diaryl ethers (e.g., for synthesis of thyroxine) and arylamines, respectively. The reactions are quite erratic, although some preparatively useful cases have been found. 

The transition metal catalyzed asymmetric addition of aryl organometallic reagents to aldehydes, ketones, and imines has provided efficient access to chiral aryl alcohols or aryl amines [89]. Arylboronic acids are less toxic, stable toward air and moisture, and tolerant towards a variety of functional groups, and are ideal reagents for the addition to aldehydes. However, when Sakai et al. [90] attempted the enantioselective Rh-catalyzed addition of phenylboronic acid to naphthaldehyde, only 41% ee was obtained. Chiral spiro phosphite complex (S)-18c was found to be an efficient catalyst for asymmetric addition reactions of arylboronic acids to aldehydes, providing diarylmethanols in excellent yields (88-98%) with up to 87% ee (Scheme 30) [20c]. 

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