Benzophenone imine amination reactions

Aryl triflates are also good substrates for the benzophenone imine coupling reaction. For example. Singer and Buchwald prepared the desired amino-BlNOL precursor in 87% yield after acidic hydrolysis the amination itself proceeded in 90% NMR yield when DPEphos (19) was used as the supporting ligand, Eq.(132) [107]. 

N-Alkyl benzophenone imines. Amines generally react very slowly with aromatic ketones to form imines. However, if titanium tetrachloride is used as catalyst, the reaction of benzophenones proceeds at room temperature in benzene with yields of 75-98%.3... 

The scope aromatic C-N bond formation extends beyond simple amine substrates. For example, selected imines, sulfoximines, hydrazines, lactams, azoles, and carbamates give useful products from intermolecular aromatic C-N bond formation. Intramolecular formation of aryl amides has been reported. In addition, allylamine undergoes arylation, providing a readily cleaved amine alternative to the ammonia surrogates benzylamine, t-butylcarbamate, or benzophenone imine. Although it is an amine substrate, the reaction of this reagent is included here because of its special purpose. 

Benzophenone inline or allylamine can be used as ammonia equivalents in the CN coupling reactions of halopyr-idines <1996JOC7240,1998TL1313>. Primary S-aminopyrimidines can also be prepared using benzophenone imine as the amine source, as demonstrated by the synthesis of 970 from 968 via 969 <20060PD70>. Aromatic amines also efficiently aminate S-bromopyrimidine (Scheme 115) <2005OL3965>. 

Arylation reactions of aromatic ketimines were developed, and in many cases the products of the reaction were isolated after subsequent hydrolysis. Therefore, these arylations constitute an indirect method for the preparation of arylated aromatic ketones, the direct functionalizations of which are often more difficult. Thus, direct arylation of imine 42 with sodium tetraphenylborate catalyzed by [RhCl(cod)]2 afforded a mixture of mono- and diarylated benzophenone imines (44 and 45) (Scheme 9.16) [53]. The formation of the corresponding amine 46 clearly indicated that 42 also acted as a hydride acceptor in this transformation. Most likely, the reaction occurs via initial coordination by the benzophenone imine to a phenylrho-dium intermediate followed by orfho-rhodation to afford the five-membered rhoda-cyde intermediate 47 (Scheme 9.16). Subsequent reductive elimination generates the monophenylated product 44 and a rhodium hydride, which then reduces imine 42 in the presence of ammonium chloride as proton donor to regenerate the catalytically active speties. 

Enanliopure tetrahydrobenzo-l,4-diazepin-3-(3//)-one 42 was obtained by intramolecular amination of the aryl iodide 41 using BINAP as a ligand without racemization [36], The chiral imidazole 47 was prepared by successive Pd-catalyzed amination of the chiral amine 43 with 1,2-dibromobenzene to give 44, which was iminated with benzophenone imine (45). Then deprotection gave 46, and acid-catalyzed ring closure yielded 47 [37], The reactions have been applied to the synthesis of various chiral imidazolium salts as precursors of chiral carbene ligands [38]. Amination of aryl bromides proceeds very rapidly by temperature-controlled microwave heating [39]. 

One strategy to prepare protected anilines is the reaction of diallylamine with aryl halides using the catalysts best suited for reactions of secondary amines. " The formation of N-aryl benzophenone imines by Pd-catalyzed C—N bond formation is a second strategy that allows for straightforward deprotection to the parent aniline. Benzophenone imine is commercially available. 

Because of the problems encountered with the protected benzaldehyde imines undergoing Cannizzaro reactions during functionalization with polymeric organolithium compounds, the corresponding benzophenone imines were investigated (eqn [20]). It was envisioned that this would be a useful primary amine functionalization agent because it does not contain enolizable a-hydrogens nor a proton on the imine carbon that could participate in Cannizzaro-type, hydride-transfer reactions. 

A different type of photoreaction in ILs has been studied by Jones and co-workers the photoreduction of benzophenones by primary amines. Prior work by Cohen demonstrated that photolysis of benzophe-none in benzene in the presence of sec-butylamine afforded benzopinacol (and an imine). This reaction proceeds through a radical pair formed by hydrogen-atom abstraction by the triplet excited state ben-zophenone from the amine. In the much more polar environment of an IL, the radical pair may instead undergo single electron transfer to form an iminium cation and a hydroxyl-substituted carbanion. Proton transfer from the cation to the anion will yield benzhydrol and an imine. 

Photoreduction of benzophenone by primary and secondary amines leads to the formation of benzpinacol and imines [145]. Quantum yields greater than unity for reduction of benzophenone indicated that the a-aminoalkyl radical could further reduce the ground state of benzophenone. Bhattacharyya and Das confirmed this in a laser-flash photolysis study of the benzophenone-triethylamine system, which showed that ketyl radical anion formation occurs by a fast and a slow process wherein the slow process corresponds to the reaction of a-aminoalkyl radical in the ground state of benzophenone [148]. Direct evidence for similar secondary reduction of benzil [149] and naphthalimides [150] by the a-aminoalkyl radical have also been reported. The secondary dark reaction of a-aminoalkyl radicals in photo-induced electron-transfer reactions with a variety of quinones, dyes, and metal complexes has been studied by Whitten and coworkers [151]. 

Primary amines. Copper(I)-catalyzed Grignard reaction with the reagent gives (V-substituted imines. Acid hydrolysis releases the primary amines and the bis(trifluoromethyl)benzophenone. 

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