Scope and Mechanistic Investigations of Pd-Catalyzed Coupling/Cyclization and Cycloisomerization of Allenyl Malonates

Abstract

Pd-catalyzed transformations of allenyl malonates provide convenient access to functionalized carbocycles, but the influence of the ligand, solvent, base, and reaction conditions on the mechanism, regioselectivity, and product outcome of the cyclization is not well understood. Additionally, from the perspective of synthetic utility, access to either fully substituted or enantioenriched cyclopentane building blocks has not yet been achieved. This work describes how targeted changes to the reaction conditions enable predictable control over the mechanism of Pd-catalyzed allene cross-coupling/cyclization and cycloisomerization, irrespective of the allene substitution pattern. Both enantioenriched cyclopropanes and cyclopentenes can be obtained through axisto-center chirality transfer from the allene precursor at room temperature, which is not possible using reported Pd-catalyzed methods that result in racemization of the allene. Finally, the ability to divert the reactivity of the allenyl malonate from cross-coupling/ cyclization to cycloisomerization by a simple switch of the ligand on Pd from a bidentate phosphine to an electron-poor triphenylphosphite is demonstrated.

Role of Noncovalent Interactions in Inducing High Enantioselectivity in an Alcohol Reductive Deoxygenation Reaction Involving a Planar Carbocationic Intermediate

“…Another stride in this direction was reported by Carreira and co-workers concerning an Ir-catalyzed enantioselective reductive deoxygenation of racemic tertiary allenyl alcohol (Scheme ). This transformation is rooted in the early examples of Pd- or Ir-catalyzed nucleophilic substitution reactions on allenyl alcohol derivatives, specifically an early example of Ir-catalyzed allenyl substitution of tertiary allenyl acetate using malonate as the nucleophile by Takeuchi and co-workers …”

Palladium-catalyzed bicyclization of alkynyl aryl iodide with allenyl malonates

“…For example, the Cazes group and Schomaker group reported the palladium-catalyzed coupling-cyclization of (2,3-butadienyl)malonate with organic halides to afford five-membered cyclopentene derivatives. 9 Ma and Oh groups observed that under the catalysis of Pd(PPh 3 ) 4 , the reaction of (2,3-butadienyl)malonate with organic halides formed a three-membered vinylic cyclopropane derivative with high selectivity. 10 The three-component tandem double addition cyclization of (2,3-butadienyl)malonate, organohalides and imines for the synthesis of polysubstituted cis -pyrrolidine derivatives was also achieved by the Ma group.…”