Cyclobutanol Cleavage Research Articles

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C-C Cleavage of Cyclobutanols.

We report a Pd-catalyzed route to heterocycles bearing a tetrasubstituted alkene fragment. Our approach merges the intramolecular carbopalladation of tethered alkynes with an alkylation step produced by the C–C cleavage of cyclobutanol derivatives. An alkenyl-Pd(II) intermediate has been isolated and characterized by X-ray diffraction studies. Interestingly, the nature of the tethering alkynyl chain influences the E/Z stereochemistry of the alkenyl fragment in the functionalized heterocycles.

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

The Ir‐catalyzed conversion of prochiral tert‐cyclobutanols to β‐methyl‐substituted ketones proceeds under comparably mild conditions in toluene (45–110 °C) and is particularly suited for the enantioselective desymmetrization of β‐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 β‐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.

Recent Advances in Ring-Opening Functionalization of Cycloalkanols by C-C σ-Bond Cleavage.

Cycloalkanols prove to be privileged precursors for the synthesis of distally substituted alkyl ketones and polycyclic aromatic hydrocarbons (PAHs) by virtue of cleavage of their cyclic C-C bonds. Direct functionalization of cyclobutanols to build up other chemical bonds (e. g., C-F, C-Cl, C-Br, C-N, C-S, C-Se, C-C, etc.) has been achieved by using the ring-opening strategy. Mechanistically, the C-C cleavage of cyclobutanols can be involved in two pathways: (a) transition-metal catalyzed β-carbon elimination; (b) radical-mediated 'radical clock'-type ring opening. The recent advances of our group for the ring-opening functionalization of tertiary cycloalkanols are described in this account.

Manganese-catalyzed regiospecific sp(3) C-S bond formation through C-C bond cleavage of cyclobutanols.

A manganese-catalyzed regioselective sp(3) C-S bond formation through C-C bond cleavage of cyclobutanols is described. A variety of primary and secondary alkyl thioethers are efficiently prepared under mild reaction conditions. The mechanistic pathways involving radical-mediated tandem C-C bond cleavage and C-S bond formation are proposed.

Phenyliodine diacetate-mediated oxidative cleavage of cyclobutanols leading to γ-hydroxy ketones

Oxidative cleavage of cyclobutanols using PIDA, which leads to efficient entry of γ-hydroxy ketones, is described. When using 2-substituted cyclobutanols, γ-substituted γ-hydroxy ketones are obtained through regioselective C–C bond cleavage.

Oxidative cleavage of tertiary cyclobutanols. A new synthetic approach to 1,4-ketols and 1,4-diketones

The reaction of tertiary cyclobutanols with Jones reagent under mild conditions resulted in the oxidative cleavage of the cyclobutane ring to give, depending on the substitution pattern of the starting alcohol, a 1,4-ketol or a 1,4-diketone.