Rocío Carrascosa

Metal‐Catalyzed Cycloetherification Reactions of β,γ‐ and γ,δ‐Allendiols: Chemo‐, Regio‐, and Stereocontrol in the Synthesis of Oxacycles

Versatile routes that lead to a variety of functionalized enantiopure tetrahydrofurans, dihydropyrans, and tetrahydrooxepines are based on chemo-, regio-, and stereocontrolled metal-catalyzed oxycyclization reactions of β,γ- and γ,δ-allendiols, which were readily prepared from (R)-2,3-O-isopropylideneglyceraldehyde. The application of Pd(II), Pt(II), Au(III), or La(III) salts as the catalysts gives controlled access to differently sized oxacycles in enantiopure form. Usually, chemoselective cyclization reactions occurred exclusively by attack of the secondary hydroxy group (except for the oxybromination of phenyl β,γ-allenic diols 3b and 3d) to an allenic carbon atom. Regio- and stereocontrol issues are mainly influenced by the nature of the metal catalysts and substituents.

Chemo- and regioselective palladium-catalyzed oxycyclization reactions of allendiols: preparation of five-, six-, and eight-membered cycles.

Positive discrimination: Chemo- and regioselective palladium-catalyzed cycloetherification of allendiols, namely beta,gamma- and gamma,delta-allendiols, may occur by judicious choice of palladium-catalyzed conditions owing to their potential ability to discriminate between both nucleophilic sites (see scheme).

PdII-Catalyzed Domino Heterocyclization/Cross-Coupling of α-Allenols and α-Allenic Esters: Efficient Preparation of Functionalized Buta-1,3-dienyl Dihydrofurans

A mild, palladium(II)-catalyzed reaction of alpha-allenols with alpha-allenic esters in a heterocyclization/cross-coupling sequence, applicable to a wide range of substitution patterns, has been developed for the preparation of 2,3,4-trifunctionalized 2,5-dihydrofurans. Our studies indicate high levels of chemo- and regiocontrol. The possibility of using optically active substrates as well as substrates of increased steric demand, such as tertiary alpha-allenols, makes this novel sequence of heterocyclization/cross-coupling an attractive method in organic synthesis. The current mechanistic hypothesis invokes a regiocontrolled palladium(II)-mediated intramolecular oxypalladation of the free allenol component, that then undergoes a cross-coupling reaction with the allenic ester partner, followed by a trans-beta-deacyloxypalladation with concomitant regeneration of the Pd(II) species.

A Versatile Synthesis of β-Lactam-Fused Oxacycles through the Palladium-Catalyzed Chemo-, Regio-, and Diastereoselective Cyclization of Allenic Diols

Chemo-, regio- and stereocontrolled palladium-catalyzed preparations of enantiopure morpholines, oxocines, and dioxonines have been developed starting from 2-azetidinone-tethered γ,δ-, δ,ε-, and ε,ζ-allendiols. The palladium-catalyzed cyclizative coupling reaction of γ,δ-allendiols 2 with allyl bromide or lithium bromide was effective as 8-endo cyclization by attack of the primary hydroxy group to the terminal allene carbon to afford enantiopure functionalized oxocines; whereas the palladium-catalyzed cyclizative coupling reaction of 2-azetidinone-tethered ε,ζ-allendiols 4 furnished dioxonines 16 through a totally chemo- and regioselective 9-endo oxycyclization. By contrast, the palladium-catalyzed cyclizative coupling reaction of 2-azetidinone-tethered δ,ε-allendiols 3 with aryl and alkenyl halides exclusively generated six-membered-ring compounds 14 a and 15 a. These results could be explained through a 6-exo cyclization by chemo- and regiospecific attack of the secondary hydroxy group to the internal allene carbon. Chemo- and regiocontrol issues are mainly influenced by the length of the tether rather than by the nature of the metal catalysts and substituents. This reactivity can be rationalized by means of density functional theory calculations.