3-Aryl-2,5-Dihydropyrroles via Catalytic Carbonyl-Olefin Metathesis.

Herein, we describe the development of a synthetic strategy towards chiral 3-pyrrolines based on the design principle of iron(III)-catalyzed carbonyl-olefin metathesis. This approach takes advantage of commercially available amino acids as chiral pool reagents and FeCl3 as a Lewis acid catalyst. Our strategy is characterized by its operational simplicity, mild reaction conditions and functional group tolerance. Investigations show that an electron-deficient nitrogen protecting group overcomes limitations arising from competitive binding of the Lewis acid catalyst to unfavorable Lewis basic sites, which ultimately enables catalytic turnover.

Iron(III) Chloride Catalyzed Formation of 3,4-Dihydro-2H-pyrans from α-Alkylated 1,3-Dicarbonyls. Selective Synthesis of α- and ß-Lapachone.

A mild, catalytic method for the synthesis of 3,4-dihydro-2H-pyrans is described. The FeCl3-catalyzed transformation of aryl- and alkyl ß-diketones enables synthetic access to functionalized pyran core structures incorporated in many natural products and biologically active target structures. The method represents a mild alternative to currently available reaction protocols relying on stoichiometric reagents and harsh reaction conditions. This FeCl3-catalyzed transformation has enabled the selective synthesis of α-lapachone in two synthetic transformations and subsequently ß-lapachone in three synthetic transformations, which is currently undergoing clinical trials as a potent anticancer agent.

Rapid access to the heterocyclic core of the calyciphylline A and daphnicyclidin A-type Daphniphyllum alkaloids via tandem cyclization of a neutral aminyl radical.

A streamlined approach to the tertiary amine-containing core of the calyciphylline A and daphnicyclidin A-type Daphniphyllum alkaloids is presented. A known carvone derivative is converted into the core structure in only four synthetic operations, and it is well poised for further elaboration. The key enabling methodology is a radical cyclization cascade beginning with addition of a secondary, neutral aminyl radical to the ß-position of an enone, followed by trapping with a pendant alkyne.