Photochemistry of cyclobutanones with nitrogen acids. A potential nucleoside synthesis

Abstract

Irradiation of 3-methylene-2,2,4,4-tetramethylcyclobutanone with nitrogen acids such as succinimide, phthalimide, imidazole, 3,s-dimethylpyrazole, purine, and benzimidazole gives 1:l adducts that were identified as cyclic a-aminoacetals structurally related to nucleosides.

Enantiomerically Pure Cyclobutane Derivatives and Their Use in Organic Synthesis

“…Ketone 69 has been used in the synthesis of cyclobutane antivirals such as lubocavir 70 , which is a carbocyclic analogue of the natural product and pharmacologically active oxetanocin. The photochemical ring expansion of cyclobutanones proceeds via a cyclic oxacarbene which can insert into OH and acidic NH groups to give 2-substituted dihydrofurans. , Thus, the photolysis of 69 (R = OBz) in the presence of sugars or substituted purines gives disaccharides and nucleoside analogues, respectively, with stereochemical retention of the ring substituents. It is interesting to note that insertion of the oxacarbene 71 to the sugar 72 is regioselective, with reaction occurring at the primary alcohol function.…”

Photochemical Ring Expansion of α-Alkoxycyclobutanones to 2-Acetoxy-5-alkoxytetrahydrofurans: Nucleophilic Reactions at the 2-Position

“…In addition to its mechanistic interest, the photochemical ring expansion of cyclobutanones has been used to synthesize dioxabicyclic [ n .3.0] ring systems by intramolecular 3 and intermolecular trapping of the oxacarbene by alcohols. Trapping with imides and imidazoles produced cyclic α-amino acetals, while use of purine and pyrimidine bases led to dideoxynucleosides . (In these latter two cases, mixtures of diastereoisomers at the anomeric position were obtained.)…”

Enantioselective Preparation of 2‘,3‘-Dideoxynucleosides and Their Analogues from Ring-Expansion of Cyclobutanones. 2. Synthesis of 2‘,3‘-Dideoxyribosides and (1S,3R)-1- Amino-3-(hydroxymethyl)cyclopentane1

“…We have recently reported a novel approach to the synthesis of a series of 2‘,3‘-dideoxy-3‘- C -(hydroxymethyl)nucleosides and a key intermediate in the synthesis of their carbocyclic analogues by ring-expansion reactions of a chiral cyclobutanone . The key step involved the photochemical isomerization of a cyclobutanone to a transient oxacarbene and the insertion into the NH group of a purine . This reaction proceeded with complete regio- and stereospecificity.…”