General Methodologies Toward cis-Fused Quinone Sesquiterpenoids. Enantiospecific Synthesis of the epi-Ilimaquinone Core Featuring Sc-Catalyzed Ring Expansion.

A stereocontrolled approach to the cis-decalin framework of clerodane diterpenes and biologically active quinone sesquiterpenes is reported. Starting from an inexpensive optically pure tetrahydroindanone, Birch reductive alkylation builds two new contiguous chiral centers-one of which is quaternary and all-carbon-substituted. Also featured is a highly regioselective diazoalkane-carbonyl homologation reaction to prepare the 6,6-bicyclic skeleton. Therein, the utility of Sc(OTf)3 as a mild catalyst for formal 1C insertion in complex settings is demonstrated.

Catalysis of diazoalkane-carbonyl homologation. How new developments in hydrazone oxidation enable the carbon insertion strategy for synthesis.

Diazo compounds continue both to challenge and to fascinate practitioners of chemical synthesis. The most strategically powerful and unique type of reactivity observed with these reagents is a formal insertion of the donor-acceptor carbon into C-C or C-H bonds alpha to carbonyl groups. Although the reaction does not involve discrete carbon-metal bonds, it can be catalyzed by metal-based Lewis acids. This chapter investigates both classical and modern developments in diazoalkyl carbon insertion with a special emphasis on nonstabilized nucleophiles.

Diastereoselective synthesis of complex cis-hexahydroindanes by reductive alkylation.

An efficient and operationally simple approach to complex cis-hexahydroindanes is reported. Upon Birch reduction of unprotected, C4-alkylated tetrahydroindanols and electrophilic trapping of the tetrasubstituted enolate, cis-fused products are formed with a new stereogenic quaternary carbon. The reaction is convergent, completely diastereoselective, and shows a broad scope with regard to the electrophile.

Titration of nonstabilized diazoalkane solutions by fluorine NMR.

A new protocol for titrating nonstabilized diazoalkane solutions by quantitative (19)F NMR is reported. An excess of 2-fluorobenzoic acid dissolved in CDCl(3) is treated with the diazoalkane solution at a low temperature, immediately forming the corresponding 2-fluorobenzoate ester upon warming. A significant difference in the (19)F chemical shift between the ester and acid is seen, allowing facile and accurate integration to determine titer. The procedure is safe, rapid, and indicates the active diazoalkane concentration with high precision.

An enantioselective synthesis of 2-aryl cycloalkanones by Sc-catalyzed carbon insertion.

Current methods for asymmetric α-arylation require blocking groups to prevent reaction at the α'-carbon, basic conditions that promote racemization, or multistep synthesis. This work records the first catalytic enantioselective examples of the diazoalkane-carbonyl homologation reaction. Medium ring 2-aryl ketones are prepared in one step in up to 98:2 er and 99% yield from the unsubstituted lower homologue by Sc-catalyzed aryldiazomethyl insertion with simple bis- and tris(oxazoline) ligands.