Regioselectivity in the Palladium-Catalyzed Addition of Carbon Nucleophiles to Carbocyclic Derivatives

Abstract

The regioselectivity of Pd-catalyzed malonate additions and arylations to cycloalkenyl esters can be predicted by completing a stereochemical analysis of the Pd-pi-allyl complex. The Pd-catalyzed malonate additions which have the greatest degree of regioselectivity are in which substituents have a steric influence in blocking the incoming nucleophile. Cyclopentenyl substrates displayed lower regioselectivity than the cyclohexyl counterparts presumably due to increased planarity of the system. Arylations using tin and hypervalent silicon reagents were compared.

Understanding the mechanism of Pd-catalyzed allylic substitution of the cyclic difluorinated carbonates

“…Also obvious was that allyl-palladium bonding in trans - trans dimer 8 was almost symmetric: within experimental error, there was not much difference between the Pd1-C2 bond length 2.105 Å (11) and Pd1-C4 bond length 2.118 Å (9), and between the Pd1-C4-C3 bond angle 68.9° (6) and Pd1-C2-C3 bond angle 69.2° (7) ( Table 1 ). Thus, as expected from the proposed model [ 21 ], the symmetrical Pd-π-allyl complex was generated. According to the X-ray structure of the trans - trans dimer 8 , it was clear that C4 position was more shielded than the C2 position, which should guide the attack of nucleophiles from the C2 position.…”

“…The orientation of attack of nucleophiles on the Pd-π-allyl complex could be illustrated via examining the 13 C NMR chemical shifts of three carbon atoms attached to the palladium. According to the model of DeShong et al [ 21 ], it was anticipated that a symmetrical Pd-π-allyl complex should be temporarily generated once the compounds 1 or 4 were treated with palladium catalyst. Thus, α-substitution products should be afforded considering the steric effects.…”

Tetrabutylammonium Difluorotriphenylsilicate

“…15 In a range of reactions, TBAT was shown to give generally superior results to PhSnMe 3 in terms of yields and levels of regiocontrol. 16 In studies of the regio-and enantiocontrol possible in allylic alkylations under palladium catalysis, TBAT was found to have a beneficial effect by promoting the π-σ-π interconversion process in the intermediate organopalladium species. 17,18 Mukaiyama Aldol and Related Processes.…”

Optimisation and Scope of a Palladium-Catalysed Allylic Alkylation Cascade

“…The analysis of Pd-π-allyl intermediates provides a reliable method for predicting and understanding regiochemical outcomes of Pd-AA reactions. 29 In many cases, ionisation of an allylic acetate or benzoate caused by displacement of the leaving group by palladium, provides a "symmetric" η 3 complex, where the metal centre resides "symmetrically" over the π-allyl system (Scheme 1.7). This generally occurs when the Pd-allyl complex rests on the opposite face to any allylic substituents, the η 3 complex is close to symmetrical.…”

“…This arrangement typically favours the 1,4-substituted regioisomer (15) over the 1,2-regioisomer (16), as nucleophilic addition to the least hindered carbon is preferred. 29 Scheme 1.7: Regioselectivity of "symmetric" Pd-π-allyl complexes…”