From Heterocycles to Carbacycles: Synthesis of Carbocyclic Nucleoside Analogues from Enals and Hydroxylamines

Abstract

Substituted and stereochemically dense carbacycles can be prepared by sequential dipolar cycloaddition and reductive cleavage from enals and hydroxylamines. The reaction sequence proceeds with high efficiency for a wide variety of enals and hydroxylamines. The reaction is regio- and diastereoselective for the initial formation of a bridged bisisoxazolidine intermediate, which then undergoes quantitative double N–O cleavage to produce carbacycles as single diastereomers.

Nucleoside Analogs: A Review of Its Source and Separation Processes

“…Masayuki Inoue groups [59] have developed a novel method of coupling multiply-hydroxylated aldehydes with α-alkoxyacyl tellurides in order to synthesize various nucleoside antibiotics. Gustavo Moura-Letts groups [60] demonstrated high efficiency in synthesizing nucleoside carbacycles through sequential dipolar cycloaddition and reductive cleavage of enals and hydroxylamines. Guo et al [61] used enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates to prepare chiral carbocyclic nucleoside analogs, including purine, uracil, and thymine derivatives, with high quaternary.…”

Synthesis of Isoxazolidines from Substituted Vinylnitrones and Conjugated Carbonyls via Visible‐Light Photocatalysis

“…Moreover, T2A was further derivatized to carbacycle D1 [17] relying on an all-photocatalytic tandem dipolar cycloaddition sequence. [18] The large scope obtained allowed us to shift the focus towards the study of the visible-light photocatalytic mechanism. It has been established that the in-situ formed N-EDG nitrone is a suitable candidate for photooxidation pathways due to their spin-trapping properties and less demanding oxidative pathways.…”

“…Further validation of the method was obtained by performing a large scale (10 mmol) preparation of T2A (99 % yield, >50 : 1 d.r). Moreover, T2A was further derivatized to carbacycle D1 [17] relying on an all‐photocatalytic tandem dipolar cycloaddition sequence [18] …”

3-Halo-5,6-dihydro-4H-1,2-oxazine N-oxides as synthetic equivalents of unsaturated nitrile oxides in the [3 + 2]-cycloaddition with arynes: synthesis of substituted 3-vinyl-1,2-benzisoxazoles

“…9b,11 This is likely due to selectivity issues in the synthesis of their precursors, unsaturated aldoximes, by the condensation of highly reactive acroleins with hydroxylamines. 12 Since the presence of a double bond in the side chain of benzisoxazoles may open opportunities for subsequent functionalizations, the development of an approach towards 3-vinylbenzisoxazoles looks desirable. 13 Following previous studies on the [4 + 2]-cyclofragmentation of 1,2-oxazine N-oxides to unsaturated oxime derivatives, 14 as well as reactions of 1,2-oxazine N-oxides with arynes, 15 we envisioned 3-halo-substituted 1,2-oxazine N-oxides as viable surrogates of unsaturated nitrile oxides.…”