A Versatile Synthesis of β‐Lactam‐Fused Oxacycles through the Palladium‐Catalyzed Chemo‐, Regio‐, and Diastereoselective Cyclization of Allenic Diols. Issue 5 (2nd December 2014)

• Record Type: Journal Article
• Authors: Alcaide, Benito; Almendros, Pedro; Carrascosa, Rocío; Casarrubios, Luis; Soriano, Elena
• Is Part Of: Chemistry. Volume 21:Issue 5(2015)
• Page Start: 2200
• Page End: 2213
• Publication Date: 2014-12-02
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201405181
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <bold>2</bold> with allyl bromide or lithium bromide was effective as 8‐<italic>endo</italic> 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 <bold>4</bold> furnished dioxonines <bold>16</bold> through a totally chemo‐ and regioselective 9‐<italic>endo</italic> oxycyclization. By contrast, the palladium‐catalyzed cyclizative coupling reaction of 2‐azetidinone‐tethered δ, ε‐allendiols <bold>3</bold> with aryl and alkenyl halides exclusively generated six‐membered‐ring compounds <bold>14 a</bold> and <bold>15 a</bold>. These results could be explained through a 6‐<italic>exo</italic> 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.</p> </abstract>