Solid-Supported Nitroso Hetero Diels–Alder Reactions. 2. Arylnitroso Dienophiles: Scope and Limitations

Abstract

Immobilized arylnitroso dienophiles were prepared and used in hetero Diels-Alder (HDA) reactions with a variety of dienes. Polymer-supported arylnitroso species were prepared on several linkers cleavable by different cleavage reagents and used for (i) optimization of reaction conditions for HDA reactions, (ii) evaluation of the reaction outcome with various dienes, (iii) comparison of relative reactivities of dienes, and (iv) assessment of the stability of HDA adducts toward cleavage conditions typically used in solid-phase preparation (TFA). The outcome of the HDA reactions has been evaluated for a set of 19 dienes, and the relative reactivities of dienes that yielded the expected HDA adducts were compared. Cleaved products were submitted to biological assays, and the results are reported.

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

“…The introduction of the nitroso group through the transformation of pendant functional groups includes the oxidation of primary amines [37–41] (Scheme 4) and hydroxamic acids [42–44] (Scheme 5) and the reduction of nitro compounds [45–47]. As oxidants for the amino group transformation, hydrogen peroxide and m -CPBA are the most popular (see examples in Scheme 4).…”

“…The reactivity of dienes has also been studied for the reaction with acyl- [78] and arylnitroso dienophiles [42] that are bound to a solid support. In general, cyclic dienes were more reactive than their acyclic counterparts, and dienes with electron-donating substituents, such as α-terpinene and 2,4-hexadien-1-ol, were more reactive than those with electron-withdrawing substituents such as sorbic acid or ethyl sorbate and their unsubstituted counterparts, 1,3-cyclohexadiene and 2,4-hexadiene.…”

Chemo- and site-selective derivatizations of natural products enabling biological studies

“…Furthermore, Miller and co-workers developed poymer-bound arylnitroso dienophiles for solid-phase chemistry that facilitate the synthesis of natural product-derived libraries for SAR studies. 38–40 …”

Hetero‐Diels‐Alder‐Reaktionen von Nitrosocarbonylverbindungen als nützliches Verfahren in der organischen Synthese

“…In einem von Krchnak et al [80][81][82] beschriebenen Beispiel werden die von den Alkoholen 57 abstammenden festphasengebundenen Hydroxamsäuren 58 auf Wang-Harz verwendet (Schema 10). Die Hydroxamsäuren 58 wurden mithilfe von Tetrabutylammoniumperiodat in Gegenwart von Dienen oxidiert, wobei die Cycloaddukte 59 entstanden.…”