Synthesis and characterization in solution and in the solid State of the palladium aryl bromide complexes [Pd(Ar)Br{(S)-BINAP}]: formation of cyclopalladated complexes and direct observation of a C-N reductive elimination to form heterocycles

Adriano L Monteiro,William M Davis

doi:10.1590/s0103-50532004000100014

Abstract

The complexes resulting from the 1:4 mixture of [Pd2(dba)3] and P(o-tolyl)3 in benzene react with ortho substituted-arylbromides to generate in situ the corresponding bromide dimer [Pd(Ar)(m-Br){P(o-tolyl)3)}] 2. Addition of 2 equiv. of (S)-BINAP gave the corresponding [PdBr(o-RC6H4){(S)-BINAP}] in good yields (57-89%). The crystal structure of [PdBr(o-C6H4CH2 CON(H)Bn){(S)-BINAP}] (1) shows a square planar arrangement around palladium with the aryl ring positioned nearly perpendicular to the square-planar coordination plane. Since these complexes exhibit restricted rotation about the palladium-aryl bond and contain a chiral ligand, they exist as two distinct diastereoisomers discernable by 31P{¹H} NMR. The dynamic behavior of the complexes 1, 13CO-1, and 15N-1 in CDCl3 was studied by 31P{¹H} NMR spectroscopy. 13CO-labeled 1 was also studied by 13C{¹H} NMR. At temperatures below 0 ºC three species were detected on the 31P{¹H} and 13C{¹H} NMR time scale. They were assigned as the two diastereoisomers and the cationic complex [Pd(o-C6H4CH2 CON(H)Bn) {(S)-BINAP}]+Br. Above 40ºC only the two diastereoisomers were detectable. At higher temperatures rotation increased and at 80 ºC a coalescence of the signals was observed by 13C{¹H} NMR. However, no interconversion was observed for 1 in tol-d8 in the -35-120 ºC range on the NMR time scale. In addition, the existence of the interconversion between the two isomers was directly demonstrated by an inversion transfer 31P NMR experiment. The cyclopalladated complexes [Pd(o-C6H4CH2 CONBn)L2] [11 L2= DPPF, 68% yield; 12 L2 = (S)-BINAP, 88 yield] were obtained by treatment of the aryl bromide complexes with NaO-t-Pn. 31P{¹H} NMR spectra of the 15N labeled complexes 11 and 12 clearly showed a Pd-N bond. Decomposition of the palladacycle 12 afforded the heterocycle and the amide reduced product.

Highlights

The palladium-catalyzed amination developed by Buchwald and Hartwig is a powerful tool for producing nitrogen heterocycles, which are one of the most important classes of pharmacologically active compounds.1,2 In particular, Buchwald reported that aryl bromides with pendant secondary amide groups could be cyclized to form tertiary amides.3 P(o-tolyl)3 or P(2-furyl)3 were the ligands used in conjunction with [Pd2(dba)3]
The crystal structure of [PdBr(o-C6H4CH2CON(H)Bn){(S)BINAP}] [1] shows a square planar arrangement around palladium with the aryl ring positioned nearly perpendicular to the square-planar coordination plane. Since these complexes exhibit restricted rotation about the palladium-aryl bond and contain a chiral ligand, they exist as two distinct diastereoisomers discernable by 31P{1H} NMR
Due to the central role of the palladium complex formed from the oxidative addition of aryl bromide to the Pd(0) as well the palladacycle complex in the overall catalytic cycle,8 we have been interested in the factors which influence both the formation and reactivity of these complexes

Summary

Introduction

The palladium-catalyzed amination developed by Buchwald and Hartwig is a powerful tool for producing nitrogen heterocycles, which are one of the most important classes of pharmacologically active compounds. In particular, Buchwald reported that aryl bromides with pendant secondary amide groups could be cyclized to form tertiary amides. P(o-tolyl) or P(2-furyl) were the ligands used in conjunction with [Pd2(dba)3]. P(o-tolyl) or P(2-furyl) were the ligands used in conjunction with [Pd2(dba)3] This methodology allows for easy access to a wide variety of nitrogen heterocycles. These cyclization protocols typically employed high catalyst loadings and often long reaction times were necessary. While this methodology did allow for the formation of five- and sixmembered rings, the preparation of seven-membered rings proceeded in low overall yield. Due to the central role of the palladium complex formed from the oxidative addition of aryl bromide to the Pd(0) as well the palladacycle complex in the overall catalytic cycle, we have been interested in the factors which influence both the formation and reactivity of these complexes. BINAP is an important ligand for the amination of aryl bromides. In this paper are report the synthesis and characterization of a series of [PdBr(o-substitutedAr){(S)-BINAP}] complexes , the reaction of these complexes with base giving the palladacycle complexes,and their reactivity

Results and Discussion

Conclusions

For a review on palladium catalyzed amination see