Silver-Promoted Radical Ring-Opening/Pyridylation of Cyclobutanols with N-Methoxypyridinium Salts.

The silver-promoted reaction of tertiary cyclobutanols with N-methoxypyridinium salts enables the efficient synthesis of a range of C2-substituted pyridines. The overall process likely occurs by ring-opening (via ß-scission) of the cyclobutoxy radical to generate the corresponding γ-keto alkyl radical that itself adds to the pyridinium salt. A wide range of tertiary cyclobutanols and N-methoxypyridinium salts are compatible with the reaction conditions.

Enantioselective Cleavage of Cyclobutanols Through Ir-Catalyzed C-C Bond Activation: Mechanistic and Synthetic Aspects.

The Ir-catalyzed conversion of prochiral tert-cyclobutanols to ß-methyl-substituted ketones proceeds under comparably mild conditions in toluene (45-110 °C) and is particularly suited for the enantioselective desymmetrization of ß-oxy-substituted substrates to give products with a quaternary chirality center with up to 95 % ee using DTBM-SegPhos as a chiral ligand. Deuteration experiments and kinetic isotope effect measurements revealed major mechanistic differences to related RhI -catalyzed transformations. Supported by DFT calculations we propose the initial formation of an IrIII hydride intermediate, which then undergoes a ß-C elimination (C-C bond activation) prior to reductive C-H elimination. The computational model also allows the prediction of the stereochemical outcome. The Ir-catalyzed cyclobutanol cleavage is broadly applicable but fails for substrates bearing strongly coordinating groups. The method is of particular value for the stereo-controlled synthesis of substituted chromanes related to the tocopherols and other natural products.

Manganese-Catalyzed Oxidative Azidation of Cyclobutanols: Regiospecific Synthesis of Alkyl Azides by C-C Bond Cleavage.

A novel, manganese-catalyzed oxidative azidation of cyclobutanols is described. A wide range of primary, secondary, and tertiary alkyl azides were generated in synthetically useful yields and exclusive regioselectivity. Aside from linear alkyl azides, otherwise elusive medium-sized cyclic azides were also readily prepared. Preliminary mechanistic studies reveal that the reaction likely proceeds by a radical-mediated C-C bond cleavage/C-N3 bond formation pathway.

TFA-Catalyzed [3+2] Spiroannulation of Cyclobutanols: A Route to Spiro[cyclobuta[a]indene-7,1'-cyclobutane] Skeletons.

A straightforward method for the synthesis of spiro[cyclobuta[a]indene-7,1'-cyclobutane] derivatives from cyclobutanols has been developed via one-pot [3+2] spiroannulation. A series of new spiro[cyclobuta[a]indene-7,1'-cyclobutane] derivatives are facilely synthesized in good yields under mild reaction conditions.