Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi (HeteroBioLab), Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, Via della Lastruccia 3/13, I-50019 Sesto Fiorentino, Italy.
Molecules. 2010 Mar 12;15(3):1722-45. doi: 10.3390/molecules15031722.
Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal SNAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives.
尽管缺电子的吡啶嗪在分子间杂 Hetero Diels-Alder (HDA) 反应中声誉不佳，但 4,5-二氰基吡啶嗪 (DCP) 在具有不同亲二烯体的逆电子需求 HDA 过程中作为杂环氮二烯显示出惊人的反应性。使用烯烃、炔烃和烯胺作为 2p 电子对应物，分别得到二氰基环己-1,3-二烯和取代的邻苯二甲腈，而使用合适的双亲二烯体提供了通过周环三步同双 Domino 过程一锅合成多环碳和杂笼体系的一般策略。杂环亲二烯体的 HDA 反应允许直接苯并环化：特别是吡咯和吲哚衍生物转化为二氰基吲哚和 -咔唑。此外，还证明了 DCP 作为 C-4 碳上非常活泼的杂环亲电试剂的前所未有的反应性：通过改变实验条件，通过作为碳亲核试剂的吡咯和吲哚体系的反应，通过正式的 SNAr2 过程获得氰基吡咯基和氰基吲哚基吡啶嗪，其中 DCP 的 CN 基团作为离去基团。因此，仔细控制反应条件可以利用这两种途径合成不同类别的杂环衍生物。
