Direct Carbocyclizations of Benzoic Acids: Catalyst‐Controlled Synthesis of Cyclic Ketones and the Development of Tandem aHH (acyl Heck–Heck) Reactions

Abstract

The formation of exo-methylene indanones and indenones from simple ortho-allyl benzoic acid derivatives has been developed. Selective formation of the indanone or indenone products in these reactions is controlled by choice of ancillary ligand. This new process has a low environmental footprint as the products are formed in high yields using low catalyst loadings, while the only stoichiometric chemical waste generated from the reactants in the transformation is acetic acid. The conversion of the active cyclization catalyst into the Hermman-Beller palladacycle was exploited in a one-pot tandem acyl Heck-Heck (aHH) reaction, and utilized in the synthesis of donepezil.

Mizoroki–Heck Cyclizations of Amide Derivatives for the Introduction of Quaternary Centers

“…It should be noted that amide derivatives have recently been employed in Pd‐ and Ni‐catalyzed couplings for carbon–heteroatom and carbon–carbon bond formation, although never for the synthesis of quaternary centers . Moreover, precedent for the desired olefin insertion is available from Stambuli's Pd‐catalyzed Mizoroki–Heck cyclization of benzoic anhydrides, albeit without the formation of a quaternary stereocenter, and from Pd‐catalyzed carbonylative Mizoroki–Heck reactions of aryl halides and triflates . Herein, we describe the development and scope of a Ni‐catalyzed Mizoroki–Heck cyclization of amide derivatives .…”

“…Mizoroki-Heck cyclization of benzoic anhydrides,a lbeit without the formation of aq uaternary stereocenter, [9,10] and from Pd-catalyzed carbonylative Mizoroki-Heck reactions of aryl halides and triflates. [11] Herein, we describe the development and scope of aNi-catalyzed Mizoroki-Heck cyclization of amide derivatives.…”

Nickel‐Catalyzed Domino Heck‐Type Reactions Using Methyl Esters as Cross‐Coupling Electrophiles

“…[27] No evidence of the intramolecular Heck enone product is observed, as is often the case in related reactions with acyl electrophiles using Pd catalysis. [28] Ni is known to be relatively reluctant to undergo b-hydride elimination. [17a] This may explain the divergent behavior as well as the need to use 9 as ag ood hydride donor.…”

Iodine(III)-Mediated, Controlled Di- or Monoiodination of Phenols

“…5-Bromo-[2,2′-binaphthalen]-6-ol (59). The following compound was obtained according to the general procedure A, by using 5bromo-[2,2′-binaphthalen]-6-ol as starting material and NH 4 Br.…”

“…Methyl 2-Iodo-4,5-dimethoxybenzoate (44). 59 The following compound was obtained according to a modified general procedure A, by using methyl 3,4-dimethoxybenzoate as starting material and NH 4 I (reaction was in reflux overnight). The crude material was purified by flash column chromatography over silica gel with the system (3% EtOAc/Hexane) to afford the product 44 (59 mg, 36%) as a white solid.…”