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

An unprecedented NH 2 -directed Pd(II)-catalytic carbonylation of quaternary aromatic α-amino esters to yield 6-membered benzolactams has been developed. The reaction shows a strong 10 bias to 6-membered lactams over 5-membered ones. The steric hindrance around the amino group seems to be pivotal for the success of the process.The development of selective methods for the direct conversion of carbon-hydrogen bonds into carbon-heteroatom 15 and carbon-carbon reactions remains a critical challenge in organic chemistry. An interesting approach to address this issue involves the use of aromatic substrates that contain coordinating atoms (or directing groups).1 These ligands bind to the metal center in the first step and a further 20 rearrangement of some atoms allows the C-H bond activation. The factors that influence this well-known cyclometalation reaction are now reasonably well understood. 2The transition-metal-catalyzed carbonylation of arenes involving CO gas is also a significant chemical transformation 25 since it not only extends the carbon chain length but it also introduces a synthetically versatile carbonyl group. Arenes were first carbonylated by Fujiwara in 1980 with Pd(OAc) 2 under 15 atm of CO using the arene substrates as solvent to obtain carboxylic acids.3 However, no control over 30 regioselectivity was observed in the case of substituted arenes. This problem has been overcome by different research groups through the directing group approach.1,4 Thus, Yu et al described very recently the palladium acetate-catalyzed carbonylation of anilides to obtain N-acyl anthranilic acids. In this regard, Orito et al, reported in 2004 the direct carbonylation with CO of aromatic C-H bonds in N-alkyl-ω-arylalkylamines using a Pd(OAc) 2 /Cu(OAc) 2 /air system in toluene solution at 120 ºC, to obtain benzolactams. 4b,5 However, the authors stated that "carbonylation of primary 40 amines, including benzylic amines or phenylethylamines, under the same conditions, produced no benzolactams but produced ureas in good yields". ‡ Thus, a method for catalyzed C-H activation/carbonylation of primary amines under a CO environment has not been established. 45Here we describe the first preparation of benzolactams by palladium acetate-catalyzed aromatic carbonylation of quaternary α-amino α-alkyl esters, by an unprecedented process that uses NH 2 as a directing group. As part of an ongoing research project on bioorganometallic 50 chemistry, 6 we attempted the cyclometallation of imines RCH=NC(Me)(CH 2 Ph)(COOMe) (R = 4-ClC 6 H 4 or 2,6-Cl 2 C 6 H 3 ), derived from quaternary α-amino ester 1a, with Pd(OAc) 2 in toluene or AcOH. Unexpectedly, no imine palladacycle was obtained, but 3a arising from the metallation 55 of the corresponding free amino ester was isolated after subsequent reaction with LiBr (see Scheme 1). When we applied the same conditions to free amino ester 1a, palladacycle 3a was isolated again in 79% yield. We could extend the process to amino esters 1b, 2a, and 2b. These 60 results were unexpected because i...

Tetrahydro-3-benzazepines and tetrahydroisoquinolines are synthesized in one step from allenes and phenylethylamines or benzylamines, respectively. Mechanistically, it is assumed that activation of a C-H bond of an aromatic ring with Pd(II) occurs, directed by the primary amine, leading to the formation of a palladacycle into which an allene then undergoes insertion. The resulting π-allyl intermediate cyclizes to the products by an intramolecular allylic alkylation. The process is particularly useful with 2,3-butadienoates and amines having a quaternary carbon at the α-position.

Preparation of Benzolactams by Pd(II)-Catalyzed Carbonylation of N-UnprotectedArylethylamines. -An unprecedented NH2-directed Pd(II)-catalytic carbonylation of quaternary aromatic α-amino esters produces 6-membered benzolactams. As is shown for substrate (Ie), the process shows a strong bias to 6-membered lactams over 5-membered ones. However, performing the reaction in a stepwise manner affords the 5-membered derivative (IV). The steric hindrance around the amino group seems to be pivotal for the transformation. In some cases, acetylation of the amino group [cf. (XIII)] is observed. -(LOPEZ, B.; RODRIGUEZ, A.; SANTOS, D.; ALBERT, J.; ARIZA, X.; GARCIA*, J.; GRANELL, J.; Chem. Commun. (Cambridge) 47 (2011) 3, 1054-1056, http://dx.doi.org/10.1039/c0cc03478a ; Dep. Quim. Org., Fac. Quim., Univ. Barcelona, E-08028 Barcelona, Spain; Eng.) -M. Paetzel 21-144

Catalytic C-H Activation of Phenylethylamines or Benzylamines and Their Annulation with Allenes. -(RODRIGUEZ, A.; ALBERT, J.; ARIZA*, X.; GARCIA, J.; GRANELL, J.; FARRAS, J.; LA MELA, A.; NICOLAS, E.; J. Org. Chem. 79 (2014) 20, 9578-9585, http://dx.