The carbon-nitrogen bond of secondary carboxamides is generally thermodynamically and kinetically unreactive; however, we recently discovered that the trisamidoaluminum(III) dimer Al2(NMe2)6 catalyzes facile transamidation between simple secondary carboxamides and primary amines under moderate conditions. The present report describes kinetic and spectroscopic studies that illuminate the mechanism of this unusual transformation. The catalytic reaction exhibits a bimolecular rate law with a first-order dependence on the Al(III) and amine concentrations. No rate dependence on the carboxamide concentration is observed. Spectroscopic studies (1H and 13C NMR, FTIR) support a catalyst resting state that consists of a mixture of tris-(kappa2-amidate)aluminum(III) complexes. These results, together with the presence of a significant kinetic isotope effect when deuterated amine substrate (RND2) is used, implicate a mechanism in which the amine undergoes preequilibrium coordination to aluminum and proton transfer to a kappa2-amidate ligand to yield an Al(kappa2-amidate)2(kappa1-carboxamide)(NHR) complex, followed by rate-limiting intramolecular delivery of the amido ligand (NHR) to the neutral Al(III)-activated kappa1-carboxamide. Noteworthy in this mechanism is the bifunctional character of Al(III), which is capable of activating both the amine nucleophile and the carboxamide electrophile in the reaction.

Protonolyses of (dfepe)Pt(Me)X (dfepe ) (C 2 F 5 ) 2 PCH 2 CH 2 P(C 2 F 5 ) 2 ; X ) O 2 CCF 3 , OSO 2 H, OSO 2 CF 3 , OSO 2 F) complexes in their respective neat acid solutions cleanly yield (dfepe)-Pt(X) 2 products with rates dependent on relative acid strengths. No (dfepe)Pt(Me)(X) 2 (H) + intermediates were observed by variable-temperature NMR in dichloromethane. The (perfluoroaryl)phosphine analogue (dfppe)Pt(Me) 2 (dfppe ) (C 6 F 5 ) 2 PCH 2 CH 2 P(C 6 F 5 ) 2 ) is much less resistant to protonolysis and rapidly converts to (dfppe)Pt(OTf) 2 in HOTf at 20 °C. Kinetic studies for protonolysis in CF 3 CO 2 H(D) and CF 3 SO 3 H(D) solvents were carried out. Examination of ionic strength and chloride anion effects in trifluoroacetic acid indicate that prior association of anion to (dfepe)Pt(Me)X systems is not kinetically important. k H /k D values were obtained from competitive protonolysis studies (CF 3 CO 2 H, 9 ( 2 (20 °C); H 2 SO 4 , 7 ( 2 (100 °C); CF 3 SO 3 H, 2.7 ( 0.7 (100 °C)). In the case of CF 3 CO 2 H, separate kinetic runs in protio and deuterio acids gave a lower k H /k D value of 3.6(4). The data obtained in these studies do not differentiate between limiting S E 2 and S E (oxidative) protonolysis mechanisms.

A comparative study of new platinum methyl complexes cis-(dfmp) 2 Pt(Me) 2 and trans-(dfmp) 2 Pt(Me)X (dfmp ) (C 2 F 5 ) 2 MeP; X ) O 2 CCF 3 , OTf, OSO 2 F) with previously reported acceptor chelate analogues (dfepe)Pt(Me)X (dfepewhich is inert to both H 2 and CO addition, cis-(dfmp) 2 Pt(Me) 2 reacts readily to form (dfmp) 4 Pt and cis-(dfmp)(CO)-Pt(Me) 2 , respectively. Similarly, whereas (dfepe)Pt(Me) 2 is stable up to 180 °C, thermolysis of cis-(dfmp) 2 Pt(Me) 2 in benzene-d 6 at 80 °C leads to ethane reductive elimination and production of (dfmp) 4 Pt. Dissolving cis-(dfmp) 2 Pt(Me) 2 in neat trifluoroacetic, triflic, or fluorosulfonic acid at ambient temperature cleanly produces the corresponding trans-(dfmp) 2 Pt(Me)(X) complexes. Attempted isolation of trans-(dfmp) 2 Pt(Me)(O 2 CCF 3 ) resulted in dfmp loss and reversible formation of the crystallographically characterized dimer, [(dfmp)Pt(Me)(µ-O 2 CCF 3 )] 2 . Monitoring the thermolysis of trans-(dfmp) 2 Pt(Me)(X) complexes by 31 P NMR in their respective neat acids reveals a kinetic protolytic stability that is dependent on the nature of the trans X ligand: whereas trans-(dfmp) 2 Pt(Me)(O 2 CCF 3 ) is less stable than the corresponding (dfepe)Pt(Me)(O 2 CCF 3 ) complex, trans-(dfmp) 2 Pt(Me)-(OTf) and trans-(dfmp) 2 Pt(Me)(OSO 2 F) are significantly more resistant to protolytic cleavage than the chelating analogues. Thermolysis in CF 3 CO 2 D or DOTf resulted in deuteration of the methyl ligand prior to methane loss, indicating the reversible formation of a methane adduct intermediate.

Cleavage of the C-N bond of carboxamides generally requires harsh conditions. This study reveals that tris(amido)Al(III) catalysts, such as Al2(NMe2)6, promote facile equilibrium-controlled transamidation of tertiary carboxamides with secondary amines. The mechanism of these reactions was investigated by kinetic, spectroscopic, and density functional theory (DFT) computational methods. The catalyst resting state consists of an equilibrium mixture of a tris(amido)Al(III) dimer and a monomeric tris(amido)Al(III)-carboxamide adduct, and the turnover-limiting step involves intramolecular nucleophilic attack of an amido ligand on the coordinated carboxamide or subsequent rearrangement (intramolecular ligand substitution) of the tetrahedral intermediate. Fundamental mechanistic differences between these tertiary transamidation reactions and previously characterized transamidations involving secondary amides and primary amines suggest that tertiary amide/secondary amine systems are particularly promising for future development of metal-catalyzed amide metathesis reactions that proceed via transamidation.

Titanium(IV)-mediated reactions between primary amines and secondary carboxamides exhibit different outcomes, amidine formation versus transamidation, depending on the identity of the TiIV complex used and the reaction conditions employed. The present study probes the origin of this divergent behavior. We find that stoichiometric TiIV, either Cp*TiIV complexes or Ti(NMe2)4, promotes formation of amidine and oxotitanium products. Under catalytic conditions, however, the outcome depends on the identity of the TiIV complex. Competitive amidine formation and transamidation are observed with Cp*TiIV complexes, generally favoring amidine formation. In contrast, the use of catalytic Ti(NMe2)4 (< or =20 mol %) results in highly selective transamidation. The ability of TiIV to avoid irreversible formation of oxotitanium products under the latter conditions has important implications for the use of TiIV in catalytic reactions.