Endo-Effect-Driven Regioselectivity in the Cyclopalladation of (S)-2-tert-Butyl-4-phenyl-2-oxazoline

Abstract

Direct cyclopalladation of (S)-2-tert-butyl-4-phenyl-2-oxazoline using palladium acetate in acetic acid or acetonitrile provided a mixture of two isomeric compounds, the endo μ-AcO dimeric complex with a C(sp3)−Pd bond and the corresponding exo derivative with a C(sp2)−Pd bond, with the former being the major product. The μ-AcO dimeric complexes were converted to the corresponding μ-Cl analogues 3 and 4 by treatment with LiCl in acetone; the latter compounds were transformed to the corresponding PPh3 adducts 5 and 6. The NMR data suggested the puckered structure of the endo palladacycle in complexes 3 and 5, the twisted λ(S) conformation of the oxazoline ring in 3, 4, and 6, and the δ(S) conformation of the heterocycle in complex 5. The X-ray crystal structure of 5 confirmed the δ(S) conformation of the oxazoline ring in the solid state and the twisted conformation of the palladacycle and revealed a P-propeller chiral configuration of the PPh3 ligand. A series of ab initio quantum chemical calculations were performed on two model compounds generated by replacing the PPh3 ligands with NH3 in complexes 5 and 6. The structures and energies of the two model exo and endo isomers were calculated at the RHF, BLYP, and MP2 levels of theory with a 6-31G* basis for the light atoms and LANL2DZ ECP for the palladium and were found to be comparable. Single point coupled cluster calculations, with single double excitations (CCSD), corroborated the results.

Solvent-free cyclopalladation on silica gel

“…It is well known that, in general, activation of aromatic (sp 2 )C-H bonds proceeds more easily than that of aliphatic (sp 3 )C-H bonds [29]. On the other hand, exclusive or predominant formation of endo palladacycles over exo isomers in solutions has been well documented for imines and oxazolines [30][31][32][33][34]. It was found that oxazoline 1j reacted with Pd(OAc) 2 on SiO 2 followed by treatment with LiCl to form exclusively endo-2j in 64% yield with no traces of the exo isomer (Scheme 8).…”

A new imine ligand avoiding imine–enamine rearrangement and cyclometallation: Synthesis and coordination of Me3C6H2CH2NCHtBu

“…Because of the tert-butyl substituent in 1, there is no hydrogen atom available for an imine-enamine rearrangement. However, formation of a dinuclear palladacycle has been reported from a similar imine by proton abstraction from a methyl substituent of the tert-butyl groups with palladium acetate and lithium chloride, but the cyclopalladation does not occur in the reaction with palladium chloride [8]. Accordingly, we synthesized the new complex trans-[PdCl 2 (2,4,6-Me 3 C 6 H 2 CH 2 N@CH t Bu) 2 ] (2) by reacting the ligand 1 with [PdCl 2 (C 6 H 5 CN) 2 ] in dichloromethane [9].…”

Synthesis of Pd(II) coordination complexes of (S)-4-isobutyl-2-methyl-2-oxazoline and (S)-2-(2,2-dimethylpropyl)-4-isopropyl-2-oxazoline

“…The structures of the complexes were supported by 1 H, 13 C, DEPT, COSY and HSQC NMR spectra. Coordination of the Pd atom with the N atom of the heterocycle was supported by the wavelength shift of the C@N absorption band in the IR spectra [5,7] of the complexes [m 1666 cm À1 for PdCl 2 (1) 2 and 1643 cm À1 for PdCl 2 (2) 2 ] compared to that of the corresponding ligands (m 1677 cm À1 for 1 and 1666 cm À1 for 2). According to 1 H and 13 C NMR spectra of PdCl 2 (1) 2 prepared by the reaction of ligand 1 with Pd(OAc) 2 in MeCN (1:1 ratio, 66°C, 6 h) followed by reaction with LiCl in acetone, the coordination complex was a mixture of two isomers in a ratio of ca.…”

“…A variety of monooxazoline-derived five-membered exo-and endo -palladacycles with a central chirality have been described; they contain either the (sp 3 )C-Pd or (sp 2 )C-Pd bond [5]. C-Chiral oxazoline-based six-membered exo-and endo-palladacycles with a (sp 2 )C-Pd bond have also been reported (A-C, Chart 1) [6,7].…”

“…It is noteworthy that although cyclopalladation resulting in the (sp 2 )C-Pd bond formation is more common, palladacycles with the (sp 3 )C-Pd bond are not rare [11]. Moreover, in some cases [e.g., F (R 1 = H, R 2 = Ph) and H, Chart 2], the (sp 3 )C-Pd bond formation is favored over the aromatic C-H bond activation [5]. Usually, aliphatic C-H bond activation takes place in the benzylic [8,12] or tert-butyl [13] fragments, although other examples also exist [14] (Chart 2).…”