Linearly fused polycyclic piperidines represent common substructures in natural products and biologically active small molecules. We have devised a Pd-catalyzed annulation strategy to these compounds that converts readily available 2-tetralones and indanones into these scaffolds with the potential for control of both enantio- and diastereoselectivity. Importantly, these compounds can be chemoselectively functionalized, providing an efficient and robust methodology to these important nitrogen-containing molecules. We report a stereoselective Pd-catalyzed annulation strategy to linearly fused polycyclic piperidines from readily available substrates. These products can be chemoselectively functionalized to generate analogs that represent common substructures in bioactive compounds. image

A manganese-catalyzed electrochemical deconstructive chlorination of cycloalkanols has been developed. This electrochemical method provides access to alkoxy radicals from alcohols and exhibits a broad substrate scope, with various cyclopropanols and cyclobutanols converted into synthetically useful β- and γ-chlorinated ketones (40 examples). Furthermore, the combination of recirculating flow electrochemistry and continuous inline purification was employed to access products on gram scale.

A general iron-catalyzed methylation has been developed using methanol as a C1 building block. This borrowing hydrogen approach employs a Knolker-type (cyclopentadienone)iron carbonyl complex as catalyst (2 mol %) and exhibits a broad reaction scope. A variety of ketones, indoles, oxindoles, amines, and sulfonamides undergo mono- or dimethylation in excellent isolated yields (>60 examples, 79% average yield).

Pd catalysis provides a convenient method for the generation of zwitterionic intermediates that offer significant opportunities for the synthesis of functionalized heterocycles. The combination of electrophilic π-allyl Pd fragments and C-, N- and O-centered nucleophiles allows these intermediates to react with readily available substrates to furnish a range of high value products with control of chemo-, regio- and stereo-selectivity.

A readily available cyclic carbamate 1 functions as a general precursor to a range of functionalized piperidine products via a new Pd-catalyzed annulation strategy. An asymmetric catalytic variant provides a rapid and efficient means to access these heterocycles with high to excellent levels of enantiocontrol. Finally, these richly functionalized compounds are amenable to further chemoselective elaboration.

Pd Catalysis A readily available cyclic carbamate functions as a general precursor to a range of functionalized piperidine products using a new Pd-catalyzed annulation strategy. An asymmetric catalytic variant provides a rapid and efficient means to access these heterocycles with high to excellent levels of enantiocontrol. In addition, these richly functionalized compounds are amenable to further chemoselective elaboration. For more information, see the Communication by J. P. A. Harrity et al. on page 13000 ff.