Chiral Cyclobutanones by [2 + 2]‐Cycloaddition of Dichloroketene to Carbohydrate Enol Ethers

Abstract

The title reaction was surprisingly easy to carry out and afforded the product in high yield with a partly unexpected stereochemistry. The cyclobutanones formed by dehalogenation of the initial adduct are promising synthetic precursors in view of their high functionality. The transformation 1 → 2 demonstrates the possibilities of this reaction.

Regio- and Stereoselective Synthesis of C-4′ Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues

“…Numerous syntheses of C-4′ spironucleosides have emerged, providing a broad diversity of not only cyclopropyl and cyclopentyl but also heterocyclic spironucleosides . However, only a few C-4′ spirocyclobutyl nucleosides are known, including our own work on the synthesis of C-4′ spirofused analogues with a 1,3-substituted cyclobutane ring (cf. structure 5 ) .…”

Synthesis and Reactivity of Spirocarbocycles as Scaffolds for Nucleoside Analogues

“…Having access to multigram quantities of building block 15 , the [2 + 2]-cycloaddition reaction of dichloroketene was attempted using standard reaction conditions as performed previously on 4′- exo -methylene substrates of type 6 , that is, the dropwise addition of trichloroacetyl chloride in anhydrous diethyl ether to a mixture of substrate 15 with activated zinc powder. , We were pleased to observe that by using this protocol, cycloadduct 16 was obtained as a single diastereoisomer in an almost quantitative amount (Scheme ). The structure of 16 was elucidated via NOE nuclear magnetic resonance (NMR) analysis, which confirmed that dichloroketene reacts with exo -methylene substrate 15 from the least sterically hindered β-face (Scheme ).…”

From Oxygen to Sulfur and Back: Difluoro-H-phosphinothioates as a Turning Point in the Preparation of Difluorinated Phosphinates: Application to the Synthesis of Modified Dinucleotides

“…The formation of such side products may be explained by a coupling reaction between the carbon-centered radical adduct and the radical generated by the homolytic cleavage of DLP and through an oxidative process on either the starting H-phosphinyl unit or the phosphorus-centered radical, respectively. A similar and somewhat disappointing result was obtained when furanose 14 15 was used (Scheme 2B): the crude mixture of triethylammonium salts 10c and debenzylated side product 10d was acidified (aqueous (aq) KHSO 4 solution) and esterified with a freshly prepared solution of diazomethane in diethyl ether to deliver low isolated yields (14−27%) of the desired phosphinate 15a and debenzylated methyl ester 15b in similar amounts (12−21%). This debenzylation process is presumably the result of a sequential intramolecular 1,5 hydrogen abstraction by the initial radical adduct and an oxidative step.…”