Boronic acids imines

Figure 3.17 Emeraldine salt form of PABA (A), self-doped in the presence of fluoride. Proposed cross-link (B), resulting from an interchain dehydration reaction between a boronic acid-imine and a boronic acid moiety, hence maintaining a self-doped state. (Reprinted with permission from Chemistry of Materials, 17, 3803. Copyright (2005) American Chemical Society.)...

Scheme 7.17 Ni-catalyzed coupiing of boronic acids, imines and alkynes.

A structurally related tetrameric macroheterocycle is compound 13 that is prepared in a one-pot synthesis (yield 64%) from salicylaldehyde and (3-aminophenyl)boronic acid in methanol (Fig. 4). Due to its insolubility it has been characterized only by mass spectrometry. If a substitutent is introduced at the imine function (R = Me, Ph), trimeric structures (14 and 15) are... 

Nucleophiles other than hydride can be added to support-bound imines to yield amines. These include C,H-acidic compounds, alkynes, electron-rich heterocycles, organometallic compounds, boronic acids, and ketene acetals (Table 10.9). When basic reaction conditions are used, stoichiometric amounts of the imine must be prepared on the support (Entries 1-3, Table 10.9). Alternatively, if the carbon nucleophile is stable under acidic conditions, imines or iminium salts might be generated in situ, as, for instance, in the Mannich reaction. Few examples have been reported of Mannich reactions on insoluble supports, and most of these have been based on alkynes as C-nucleophiles. 

Jamison has reported the unprecedented nickel-catalyzed assembly of allylic amines 156 from three simple starting materials alkynes, imines, and trialkylbor-anes or boronic acids. The participation of boronic acids in this methodology greatly enhances its synthetic potential, owing to their greater availability (Scheme 8.68) [145]. An asymmetric version of the reaction has also been developed but gave only moderate enantiomeric excesses (33 to 42%). 

The reaction is also referred to as the Boronic Acid Mannich Reaction, since it proceeds via an imine with the organic ligand of the boronic acid acting as the nucleophile, similar to the role of the enolizable ketone component in the original Mannich Reaction. 

The original procedure involved the coupling of aryl bromides with secondary amines. However, since then the scope has been expanded to include substrates such as aryl iodides, chlorides, fluorides, triflates, tosylates, nonaflates, iodonium salts, and even boronic acids. While the reaction has not been extensively utilized with vinyl or alkynyl substrates, it can be performed with various heteroaryl halides. Similarly, numerous types of nitrogen-containing coupling partners, including primary amines, imines, various azoles, lactams, and simple amides, can now be used in this reaction. 

The hydrolysis of salicylaldehyde imines is catalyzed by boric acid, substituted arylboronic acids, and diphenylborinic acid. The effects of different substituted phenyl-boronic acids on the rate of hydrolysis at pH 6.0 has been studied by Rao and Philipp [168]. The second-order rate constants, are higher for phenylboronic... 

Mono-alkyl-fnrans nndergo Mannich substitution under normal conditions," bnt fnran itself reqnires a preformed imininm salt for 2-substitution." iV-Tosyl-imines, generated in situ from iV-snlhnyl-p-tolnenesnlfonamide and aldehydes, bring about tosylaminoalkylation at C-2." The use of furan boronic acids allows Mannich snbstitntions at both a- and P-positions, with primary or secondary amine components." " ... 

Liu studied the activity of cyclopalladated imines in the Suzuki reaction and found them to be extremely active (Fig. 10.13) [129]. He was able to show that reaction of his palladacycle with phenylboronic acid in the presence of K2CO3 and ethanol led to the formation of palladium nanoparticles with a diameter range of 50-60nm (TEM). Upon addition of p-bromoanisole to this solutionp-methoxybi-phenyl was formed quantitatively. Reaction of the same complex with ethanol produced acetaldehyde and also led to the formation of nanoparticles, however, in this case palladium black was soon formed. It thus would appear that aromatic boronic acids are capable of stabUising the palladium nanoparticles. 

Liebeskind reported a copper-catalyzed Chan-Lam C-N crosscoupling methodology for JV-imination of boronic acids by using oxime O-carboxylates 291 as iminating agents and either Cu(I)-thiophene-2-carboxylate (CuTC) or Cu(OAc)2 as the catalyst under nonbasic and nonoxidizing conditions.Subsequently, the A-alkenylated a,3-unsaturated ketoxime 0-pentafluorobenzoates 293, were preeursors in a cascade reaction for the one-pot synthesis of tri-, tetra-, and penta-substituted pyridines 295 in moderate to excellent isolated yields. 

Arylation of a wide range of NH/OH/SH substrates by oxidative cross-coupling with boronic acids in the presence of catalytic cupric acetate and either triethyl-amine or pyridine at room temperature in air. The reaction works for amides, amines, anilines, azides, hydantoins, hydrazines, imides, imines, nitroso, pyrazi-nones, pyridones, purines, pyrimidines, sulfonamides, sulfinates, sulfoximines, ureas, alcohols, phenols, and thiols. It is also the mildest method for NIO-vinylation. The boronic acids can be replaced with siloxanes or starmanes. The mild condition of this reaction is an advantage over Buchwald-Hartwig s Pd-catalyzed cross-coupling. The Chan-Lam C-X bond cross-coupling reaction is complementary to Suzuki-Miyaura s C-C bond cross-coupling reaction. 

Scheme 4.26 Copper-catalyzed N-imination of boronic acids with O-acylketoximes.

Other reactions such as alkane dehydrogenation [159, 160], decarbonylation reactions [161], cyclization of alkynoic acids [162,163], three-component coupling reactions of boronic acids, allenes and imines [164], fluorenone synthesis by sequential reactions of 2-bromobenzaldehydes with arylboronic acids [165], and hydrosilylation reactions [166, 167] using cyclometalation compounds as their catalysts have also been reported. 

Imines of benzaldehyde that have been protected (or activated) with diarylphosphinyl groups, Ph-CH=N-P(=0)Ar2, are enantioselectively arylated by aryl boronic acids, using rhodium(l) liganded with a chiral amldophosphane. The effects of varying the bulk of the aryl substituents on the phosphorus of the substrate are complex ee is not severely impacted (indeed, it is sometimes improved), but reactivity falls, but so also does competing hydrolysis of the imine. 

---