NH₂ As a Directing Group: From the Cyclopalladation of Amino Esters to the Preparation of Benzolactams by Palladium(II)-Catalyzed Carbonylation of N-Unprotected Arylethylamines

Abstract

shows a strong bias to 6-membered lactams over the 5-membered analogues, which can be explained by a greater reactivity of the six-membered palladacycles.3

Cyclopalladation and Reactivity of Amino Esters through CH Bond Activation: Experimental, Kinetic, and Density Functional Theory Mechanistic Studies

“…It is clear that the preparation of complexes 3 from 1 i⋅ HCl– 1 l⋅ HCl is favored with respect to 1 a⋅ HCl, because better yields were obtained under the same experimental conditions, even in shorter reaction times in some instances. Table 1 also reflects the difference between the reactivity of 1 i⋅ HCl and 1 k⋅ HCl and that reported for their free amino esters 1 i and 1 k 13a. b Once again, orthopalladated compounds 3 were obtained with better yields starting from the hydrochloride salts.…”

“…b Once again, orthopalladated compounds 3 were obtained with better yields starting from the hydrochloride salts. Interestingly, whereas the reaction of 1 k⋅ HCl with Pd(OAc) 2 under the standard conditions regioselectively afforded 3 k , which contains the palladium incorporated at the ortho position of the Ph ring, thus forming a five‐membered metallacycle, the reaction of 1 k with Pd(OAc) 2 in toluene at 80 °C for 22 h produced a mixture of isomers derived from the Pd II incorporation to both Ph and Bn rings (75 and 15 %, respectively) 13a. b Clearly, the method reported here gives a better yield of the orthopalladated compound, with the regioselectivity also being improved.…”

“…However, catalytic reactions are still limited to a few examples,13 and the functionalization of α‐aminophosphonic esters is still unknown. Despite recent reports,13a problems in the CH bond activation step have been associated with these lack of results. Aiming to develop more efficient functionalization processes based on CH bond activation, we report here a comprehensive study of the influence of the substituents on the CH bond activation step in phenylglycine‐based amino acids and amino phosphonic esters.…”

Neutral and ionic platinum compounds containing a cyclometallated chiral primary amine: synthesis, antitumor activity, DNA interaction and topoisomerase I–cathepsin B inhibition

“…30 The success of the synthesis under mild conditions has been related to the presence of both a naphthyl substituent and a methyl group at the α-position of the amine in agreement with the fact that the cyclometallation of amines is promoted by steric encumbrance, as established for palladium analogues. 33 The lability of the dimethylsulfoxide ligands allows for the synthesis of neutral compound [PtCl{(R)-NH 2 CH(CH 3 )C 10 H 6 }(PPh 3 )] (2-R) upon reaction with PPh 3 , while ionic compound [Pt{(R)-NH 2 CH(CH 3 )C 10 H 6 }-{Ph 2 PCH 2 CH 2 PPh 2 }]Cl (5-R) containing a chelating diphosphine is obtained upon reaction with 1,2-bis(diphenylphosphine)ethane. 33 The lability of the dimethylsulfoxide ligands allows for the synthesis of neutral compound [PtCl{(R)-NH 2 CH(CH 3 )C 10 H 6 }(PPh 3 )] (2-R) upon reaction with PPh 3 , while ionic compound [Pt{(R)-NH 2 CH(CH 3 )C 10 H 6 }-{Ph 2 PCH 2 CH 2 PPh 2 }]Cl (5-R) containing a chelating diphosphine is obtained upon reaction with 1,2-bis(diphenylphosphine)ethane.…”

Transition Metal-Catalyzed Carbonylative CH Bond Functionalization of Arenes and C(sp3)H Bond of Alkanes

“…A tentative mechanism for this carbonylation is proposed in Scheme 16. Electrophilic palladation of the C2H bond of N-methyl aniline 18 by Pd(OAc) 2 [24] The steric hindrance around the amino group is pivotal for the success of the process. The stoichiometric cyclometallation of a variety of amino esters was studied to evaluate the influence of different variables (size of the metallacycle, aromatic ring substituents, and steric bulk) in the process, and a complete kinetico-mechanistic study of the cyclopalladation process was carried out.…”