Isoxazoline-carbocyclic aminols for nucleoside synthesis through aza-Diels–Alder reactions

A Straightforward Synthesis of Isoxazoline‐Based Carbocyclic Nucleosides from 1,3‐Cyclohexadiene through Nitrosocarbonyl Chemistry

“…A few examples of cases of cyclopentane-nucleoside derivatives fused with three- [14] and four-membered [15] carbocyclic rings have been reported in the literature, as well as five-membered heterocyclic rings such as pyrazole [16] or isoxazoline systems. [2,17] Nucleosides lacking a methylene group in the side chain belong to the so-called "nor" class and in some cases display reduced cytotoxicity. [18] In pursuit of our studies on the synthetic potential of the nitrosocarbonyl HDA cycloadducts, we detail here the Scheme 1.…”

The Chemoselective Reduction of Isoxazolineγ-Lactams Through Iminium Aza-Diels-Alder Reactions: A Short-Cut Synthesis of Aminols as Valuable Intermediates towards Nucleoside Derivatives

“…The 1,3-dipolar cycloaddition of BNO with 1a was performed by generating the 1,3-dipole with the in situ procedure [37], affording the two regioisomeric cycloadducts 2aA and 2aB in 49% and 43% yields, respectively (Scheme 2) [14]. …”

“…Upon evaporation of the solvent, the residues furnished the desired aminols 11A,B , which were purified by MPLC. Aminols 5A,B were found identical to previously prepared samples [14]. New compounds were fully characterized as follows.…”

“…Recently, we have proposed a novel approach to useful aminols for the synthesis of carbocyclic nucleosides starting from an extremely convenient source, the 2-azanorborn-5-ene 1 (Scheme 1) [14], prepared by Grieco from the cycloaddition of cyclopentadiene with iminium salts generated in situ under Mannich-like conditions, in a mild and “green” aqueous aza-Diels-Alder (ADA) reaction [15–26]. The first iminium salts as dienophiles in DA reactions were used by Böhme et al for the synthesis of piperidinium salts [27] in 1963 but there is no doubt that the appearance of the first paper by Larsen and Grieco in 1985 determined the success in the use of unactivated iminium salts as dienophiles to prepare ADA cycloadducts in very good yields [18].…”

Recent Advances in Nitrile Oxide Cycloadditions. Synthesis of Isoxazolines

“…The reaction gave exclusively the exo adduct as a 1:1 ratio of regioisomers for dicyclopentadiene 49a and >99:1 for dimethyldicyclopentadiene dicarboxylate 49b. A regioisomeric mixture of isoxazolines 50a,b was obtained by Quadrelli et al [44] by reacting N-benzyl-2-azanorborn-5-ene with benzonitrile oxide. The product was further modified to isoxazoline-carbocyclic aminols for the synthesis of nucleosides (Scheme 21).…”