Diazo groups have broad and tunable reactivity. Consequently, this feature coupled with other attributes endow diazo compounds with the potential to be valuable reagents for chemical biologists. The presence of diazo groups in natural products underscores their metabolic stability and anticipates their utility in a biological context. Catalytic cycloadditions of stable diazo species with p-bond motifs are powerful tools to access carbocyclic and heterocyclic compounds. The development of these catalytic reactions relies heavily on chemical elaborations of vinyldiazo carbonyl species. Ideally, the diazo species are effective nucleophiles to serve as 2C or 3C building units; their reactions with electrophilic p-bond motifs furnish construction of five- or six-membered rings. In contrast, vinyldiazo carbonyl species can be transformed into electrophilic vinylmetal carbenes that serve as one- or three-carbon building units. So far, reported techniques in literature for the synthesis of such bioactive molecules involves long procedures that give overall low yields.
Despite numerous examples, it is still evident that there does not exist a single example in which a vinyldiazo species can be utilized as a five-atom building units to generate a new large or bicyclic ring. On this account, researchers from the Frontier Research Center for Fundamental and Applied Science of Matters, Department of Chemistry at National Tsing-Hua University in Taiwan: Antony Sekar Kulandai Raj and Professor Rai-Shung Liu; proposed a novel gold-catalyzed bicyclic annulation of 2-alkynyl-1-carbonylbenzenes with vinyldiazo ketones that serve as five-atom building units. Their goal was to utilize the aforementioned reaction to access 4,5-dihydro-benzo[g]indazoles, which form the structural cores of various bioactive molecules. Their work is currently published in the research journal, Angewandte Chemie Internatiional Edition.
According to their mechanistic analysis, the researchers postulated initial [5+4]-cycloadditions between benzopyrilium intermediates and vinyldiazo ketones, followed by 6-π-electrocyclizations to achieve the excellent stereoselectivity. The significance of the said reaction was that it provided easy access to 4,5-dihydro-benzo[g]indazoles, which are commonly found as the structural cores of bioactive molecules.
Remarkably, the outcome was astonishing since the metalcatalyzed [4+2]-cycloadditions of benzopyrilium with alkenes typically formed 1-ketonyl-1,2-dihydronaphthalenes through rapid deprotonation of [4+2]-intermediates In-2. Altogether, the diazo compounds were reported to serve as novel five-atom building units.
In summary, the study described the gold-catalyzed bicyclic annulations of 2- alkynyl-1-carbonylbenzenes with vinyldiazo ketones. The success of the reported high-order cycloadditions was seen to rely on the rigid dienoate conformation of vinyldiazo ketones. In a statement to Advances in Engineering, Professor Rai-Shung Liu, the lead author, highlighted that the synthetic utility of the resulting bicyclic products was manifested by various chemical functionalizations, including a base-promoted deacylation to yield valuable benzoindazole derivatives.
Antony Sekar Kulandai Raj, Rai-Shung Liu. Gold-Catalyzed Bicyclic Annulations of 2-Alkynylbenzaldehydes with Vinyldiazo Carbonyls that Serve as Five-atom Building Units. Angewandte Chemie Internatiional Edition 2019, volume 58, page 10980 –10984.