Chelation‐Driven Rearrangement of Primary Alkyl Aminopalladation Products to Stable Trisubstituted Alkyl–Palladium Complexes

Abstract

The formation of highly substituted carbon centers using catalysis has been aw idely sought after goal, but complexes of highly substituted carbon atoms with transition metals are rare,and the factors that affect the relative stability of complexes with differentially substituted carbon atoms are poorly understood. In this study,aset of equilibrating alkylpalladium complexes were subtly tuned to form either ap rimary or trisubstituted alkylc omplex as the more thermodynamically favored state,d epending on either the substrate or reaction conditions.A nX -ray crystal structure of the trisubstituted alkyl-palladium complex is presented and compared with the corresponding primary alkylc omplex. The mechanism for rearrangement and the factors that drive the change in stability are discussed.Alkyl-metal complexes are key intermediates in aw ide variety of important organic reactions.[1] Among the more challenging goals of organic synthesis is the formation of highly substituted carbon centers,a nd metal-catalyzed reactions have the potential to be powerful tools in the realization of this goal.[2] However,s uch reactions are still quite challenging because of the scarcity of highly substituted alkyl-metal complexes.U nderstanding the factors that control the structure and stability of alkyl-metal intermediates is critical to expanding the scope of these metal-catalyzed processes.Ther elative stability of primary,s econdary,a nd tertiary alkyl-metal complexes is generally expected to follow the trend for organolithium compounds, [3] in which the highly polarized CÀLi bond results in alarge negative-charge density at the carbon atom. Increasing the substitution of the carbon atom with electron-donating alkyl groups increases the negative charge at the carbon center,a nd thus destabilizes tertiary alkyllithium compounds relative to primary alkyllithium compounds.T his model works well for many alkylmetal complexes,b ut the analysis is more complicated for transition metals such as palladium. Information on the relative stability of alkyl-palladium complexes is sparse, contradictory,a nd without clear general trends.Tw oexperimental studies of the relative stability of alkylpalladium complexes have been reported. Reger et al. [4] studied Pd complexes bearing dithiocarbamate ligands,i n which the small size of the ligands presumably minimizes any steric effects on stability.Inthis study,the stability of the alkyl complexes followed the traditional order:p rimary > secondary @ tertiary.However,alkyl groups bearing electron-withdrawing groups,such as CF 3 or CN,overrode this preference to put those groups next to the PdÀCb ond. More recently, Brookhart and co-workers [5] studied the isomerization of alkyl-palladium complexes with ad iimine ligand. Here,t he relative stability of the alkyl complexes was highly dependent on the structure of the fourth ligand. When no ligand or acetonitrile was bound in cis position to the alkyl ligand, [6] the secondary alkyl complex was more stable,b ut when bulkier ligands were pre...

Palladium(II)‐Catalyzed Aminotrifluoromethoxylation of Alkenes: Mechanistic Insight into the Effect of N‐Protecting Groups

“…To gain insights into the effects of the palladium catalysts and the amino protecting groups, the reactions using stoichiometric amounts of the palladium catalysts were conducted and monitored at –25 o C (Figure ). As reported by Michael and coworkers, the palladacycle intermediate 4 could be converted into the five‐membered palladacycle 5 via β‐hydride elimination and reinsertion, which was indeed observed in the reactions of the substrates 1b and 1c using Pd(OTFA) 2 ; in addition, the isomerization of the palladacycle 4b to 5b (Figure A) was much faster than that of 4c to 5c (Figure B). However, in the presence of Pd(CH 3 CN) 4 (OTf) 2 , the aminocyclization proceeded much faster than that using Pd(OTFA) 2 , and a similar trend towards the isomerization from 4 to 5 was also observed.…”