Amines with aryl boronic acids

Watanabe reports a new method for the direct conversion of o-choroacetaldehyde N,N-disubstituted hydrazones into 1-aminoindole derivatives 93 by palladium-catalyzed intramolecular ring closure of 92 in the presence of P Bu3 or the bisferrocenyl ligand 94 <00AG(E)2501>. When X = Cl, this cyclizative process can be coupled with other Pd-catalyzed processes with nucleophilic reagents (e.g., amines, azoles, aryl boronic acids) so as to furnish indole derivatives with substituents on the carbocyclic ring. 

Copper-promoted C-heteroatom bond-coupling reactions of N-H, O-H, and S-H containing substrates with aryl-boronic acids were found to proceed at room temperature in the presence of Cu(OAc)2 and an amine base.996-998 The reactions have been reviewed.3,999... 

The Pd-catalysed, mild C-H ort/zo-arylation and intramolecular amination oriented by a phosphinamide group have been reported by Han and co-workers. Mixtures of mono- and di-arylated phosphinamide derivatives (745) and (746), have been obtained in the reaction of (743) with aryl boronic acids (744) (Scheme 208). The phosphinamide group has been also found to be an effective orienting group for direct C-H amination of diaryl substituted phosphinamides (746) (Scheme 209). ... 

FIGURE 21. Numerous macrocycles based on salicylideneamino alcohols, arising from (a and b) aliphatic and (c and d) aromatic amines, interacting with aryl boronic acids have been identified, (e) Analogous semianhydride bridged structures have also been observed. 

Cu(II)-mediated N-arylation of amines and azoles with aryl boronic acids has been reviewed recently [59]. Pfizer chemists have demonstrated that N-arylpyr-roles can be prepared from aryl boronic adds and dectron-defident pyrroles via Cu(OAc)2 mediated coupling reaction at room temperature in air [60]. These reaction conditions are compatible with a variety of functional groups on boronic adds, but are sensitive to steric hindrance. The method could be successfully applied for the synthesis of compound 93 bearing a 4-cyanoaryl group which is a pivotal intermediate in the synthesis of MMP inhibitor AG3433 (Scheme 3.40). 

Acyl aryl boron species also react with amines to yield amides with mixed results. Eor example, catecholborane was used to generate lactams successfully (46). Aryl boronic acids with electron-withdrawing groups, such as 3,4,5-trifluorobenzene-boronic acid and 3,5-bis-(trifluoromethyl)benzeneboronic acid, can act efficiently as an amidation catalyst when added to a mixture of acid and amine (47). 

In 2000, Guy reported the stoichiometric coupling of alkane thiols and arylboronic acids, which was initially thought to be mediated by Cu(ll) [71]. Liebeskind proposed that the reaction was more likely catalyzed by Cu(l), generated by oxidation of the alkane thiols into dialkyl disulfides. Based on this hypothesis, Liebeskind predicted that disulfides and disulfide equivalents should be effective reagents for thioether formation [34]. This process would constitute a modification of the Chan-Evans-Lam, which involves the coupling of arylboronic acids and amines or alcohols in the presence of tertiary amine bases, generating aryl amines and ethers, respectively. Indeed, the coupling of diphenyl disulfide with phenyl boronic acid would yield diphenyl sulfide. 

These catalytic methods all rely on the use of Ugands or a base. A ligand-less, base-free method was subsequently developed to effect high-yielding crosscouplings of anilines and a wide range of aliphatic amines with various aryl boronic acids (Scheme 4.14) [50]. Relative to the myristic acid-based method, this protocol was shown to be superior for aliphatic amines, but inferior in the hans-formation of aniline derivatives. 

Reactions of Aryl Boronic Acids with Amines and Aicohols (Chan-Evans-Lam Couplings)... 

With Rhodium In 2010, the groups of Ellman and Bergman [47] reported the Rh(III)-catalyzed aryla-tion of Boc-Imines (see Chapter 6, for imine arylation) via C-H bond functionalization (Figure 4.22). This in fact was a very interesting method for the synthesis of chiral amines, being complementary to the variety of aryl boronic acid methods that are currently known [48]. 

Boronic esters will also react under appropriate circumstances. Petasis used bis(isopropyl) (2B)-bromoethenylboronic ester in a reaction with glyoicyUc acid and aminodiphenylmethane [34]. Scobie and co-workers have reported the coupbng of pinacolyl aryl and alkenylboronic esters with secondary amines (38). The reaction gave good yields with alkenylboronic esters (70-82%), but worked poorly with aryl-boronic esters (0-12%). In contrast to the above results, the reaction did not proceed with primary amines under the same conditions. 

Scheme 15.20 C-N/C-O bond-forming reactions of aryl boronic acids with amines, amides or phenols.

In Ullman-type coupling, aryl boronic acids are much more efficient coupling partners with amines and phenols as compared with aryl halides. They successfully couple at room temperature in the presence of a copper acetate/triethylamine (or pyridine) catalyst system and the corresponding arylated products were provided in high yields (Scheme 15.20). Similarly, aryl boronic acids are successfully coupled with structurally and electronically diverse substrates such as amides and sulfonamides to afford the corresponding IV-arylated products. 

OxidativeN-Arylation. Cu(OAc)2 has been shown to facilitate synthetically useful oxidative formation of carbon-nitrogen bonds. The amination of various boronic acids, pioneered by Lam et al. has been employed as a mild alternative to aromatic amination of aryl halides. Various aryl and vinylboronic compounds were aminated in presence of a base and either a stoichiometric or a catalytic amount of Cu(OAc)2 in latter case with air as the oxidant and myristic acid as a co-catalyst (eq 22). Dichloromethane or toluene were the solvents of choice. The influence of various oxidants and co-oxidants on the reaction process was also examined. ... 

Other organometaloids also undergo similar reactions. Analogous Cu(OAc)2 mediated reaction of aryltins, arylsiloxanes, arylbismuth compounds, and arylleads with various amines lead to arylated products in good yields. An interesting modification of amine or amide arylation by aryl boronic acids mediated... 

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