Amination of Aryl Tosylates

Much more appealing is the use of inexpensive aryl tosylates, and their use as electrophiles has also been reported. In 1998, Hartwig disclosed details of the amination of aryl tosylates employing DtBPF or JosiPhos as ligands [89]. The scope... 

Buchwald investigated aminations of aryl tosylates in a detailed study [30]. Among a variety of ligands, X-Phos proved to be superior for a variety of coupling partners, while furthermore a catalyhc system generated from Pd(OAc)2, X-Phos and CS2CO3 in a toluene/t-BuOH solvent mixture allowed for the efficient coupling of benzenesulfonates. In addihon to commonly employed amine nucleophiles, amides could be arylated efihciently. 

However, in their study on the amination of aryl tosylates with X-Phos as ligand and CS2CO3 or NaOt-Bu as base, Skjaerbaek and colleagues obtained low yields. 

Until recently, alkylphosphines had been used less often than arylphosphines in crosscoupling chemistry. However, several studies pointed to the potential of such ligands in the palladium-catalyzed amination of aryl halides. Alkylphosphines in combination with palladium catalyst precursors have now been shown to allow milder conditions for the amination of aryl bromides, to improve yields with acyclic secondary amines, to give high turnover numbers, and to induce mild aminations of inexpensive aryl chlorides and tosylates. 

Scheme 13.32 Arylation of prima amines with aryl tosylates at room temperature [93].

However, the Buchwald-Hartwig reaction with NHCs as hgands is not limited to palladium. Nickel has also been successfully employed in this catalytic amination. In situ procedures have been described for the coupling of aryl chlorides [163] and tosylates [164] and, more interestingly, anisoles [165]. The use of well-defined Ni(0) catalysts has also been studied [166] (Scheme 6.49). 

Shi and Xu reported that the chiral amine catalyst 142 also performs quite efficiently in the related addition of N-tosyl aryl imines to methyl vinyl ketone (MVK), to methyl acrylate, and to acrylonitrile (Scheme 6.61) [155]. As shown in Scheme 6.61, enantiomeric excesses > 95% were achieved for several />-N-tosylamino enones 147 obtained by addition of aryl imines (146) to MVK, > 80% for addition to methyl acrylate, and 55% ee (max.) for addition to acrylonitrile (not shown in Scheme 6.61). Reaction times were typically 1-3 days. N-Sulfonylimines derived from aliphatic aldehydes gave rise to complex product mixtures. Under the reaction conditions shown in Scheme 6.61 addition of p-nitrobenzaldehyde to MVK proceeded with only 20% ee. 

Just as deprotonation of NH3 gives the sequence NH3 —> NH2 —> NH2 N3-, alkyl or aryl amines give the NHR- and NR2 species of the last section and finally NR2- which is isoelectronic with O2. There is, however, a difference in that imido ligands can be either linear or bent (see below). In imido compounds the R groups can be H, alkyl, aryl, tosylate, CR2OH, CH2CH=CH2, 1-pyrolylimido, etc. 

Hartwig reported the first amination of an aryl tosylate with an aliphatic amine. Utilizing electron-rich ferrocene-based ligand 20, the coupling with hexylamine shown below proceeded in 83 % isolated yield, Eq. (119) [72]. 

Arylamines.1 A novel method for amination of organometallic reagents involves activation of an O-tosylhydroxylamine by attachment to an auxiliary group that can be recycled. Thus aryl Grignard or lithium reagents react with the O-tosylate oxime of tetraphenylcyclopentadienone (1) to form an imine (2) with elimination of the tosylate anion. The imine is then converted into an ary lamine and the original oxime by treatment with excess hydroxylamine in aqueous pyridine. 

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. 

Intramolecular palladium-catalyzed cyclization reactions have also been used to synthesize pyrazole derivatives. iV-Aryl-iV-(o-bromobenzyl)hydrazines 494 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2//-indazoles 495 (Equation 101) <20000L519>. Palladium-catalyzed intramolecular C-N bond formation of iV-acetamino-2-(2-bromo)arylindolines 496, followed by hydrolysis and air oxidation in the presence of aluminium oxide, allowed the preparation of indolo[l,2-3]indazoles 498 via intermediate 497 (Scheme 58) <2002TL3577>. 3-Substituted pyrazoles have been prepared from the intramolecular cyclization of A -tosyl-iV-(l-aryl/ vinyl-1-propyn-3-yl)hydrazine and then exposme of the reaction mixture of the cyclization to potassium /i //-butoxide <1997SL959>. iV-Aryl-iV -(o-bromobenzyl)hydrazines 499 or [A -aryl-A -(t>-bromobenzyl)hydrazinato-A ]-triphenyl-phosphonium bromides 501 participated in a palladium-catalyzed intramolecular amination reaction to give 1-phenyl-l//-indazoles 500 (Scheme 59) <2001TL2937>. 

FIGURE 8. X-phos, a derivative of ligand 11 in Figure 5, synthesized for amination of unactivated aryl tosylates... 

N Alky] and N aryl imines have received the most attention in the literature, but significant research has also been performed in the area of "activated imines, that is, imines with electron withdrawing substituents at N. In addition to having different reactivity from N alkyl and N aryl imines, these compounds are intrinsically open to further functionalization after hydrogenation. The first of these compounds to be reduced enantioselectively were the N tosyl amines. In contrast to the related reaction with N alkyl and N aryl amines, the asymmetric hydrogenations of N tosyl amines are most often catalyzed by complexes of palladium. 

The few examples indicate that sulfone-stabilized carbanions should react normally with electrophilic animating reagents (Eqs. 145158 and 146465) with the caveat that free a-amino sulfones are unstable.158,465 The (3,y-unsaturated sulfone 74 is animated at the y-position (Eq. 147),250 presumably by an ene reaction. The preparation of a-tosyl azides from nitronates was shown above in Eq. 144. The scope of this reaction does not seem to have been determined. Reaction of the anions of nitrobenzyl aryl sulfones with l-oxa-2-azaspiro[2.5]octane (13a) gives nitrobenzaldehydes by cleavage of the initially formed amination products.466 Similarly, reaction of the lithium salt of benzyl phenyl sulfone with phenyl azide gives benzilydeneaniline and phenyl sulfinate.467 No reports on animations of sulfoxide-stabilized carbanions were found. 

Aryl bezenesulfonates and aryl tosylates (ArOTs) are cheap and easily prepared compared to their triflate counterparts. Buchwald reports that these useful sulfonates can be catalytically animated using L7 (XPhos) as a ligand.42 A variety of base and solvent combinations using f-BuOH was found to be necessary depending upon the nature of the aryl tosylate and amine. In all of the aforementioned examples, a sterically and electronically diverse library of bi-aryl phosphine ligands allowed Buchwald and coworkers to specifically optimize reaction conditions for most ArX/amine combinations. 

Likewise, the oxidative C-H amination of A -aryl-A -tosyl/A -methylsulfonylamidines and N,N -bis(aryl)amidines has been accomplished using iodobenzene as a catalyst to furnish 1,2-disubstituted benzimidazoles in the presence of mCPBA as a terminal oxidant at room temperature (Scheme 4.25) [51]. The reaction is general and the target benzimidazoles can be obtained in moderate to high yields. 

Tosylates are not reactive partners of amination. Even P(t-Bu)3 is not effective. Buchwald reported that amination of tosylates and benzene sulfonates with various amines proceeded smoothly by using biphenyl-based phosphine IV-17 in the presence of CS2CO3 [21a], Bidentate ferrocenyl ligands, Dt-BPF (XI-4), XI-9, and XI-10 are effective not only for aryl chlorides, but also for aryl tosylates 21 to give 22 [22],... 

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