A mechanistically distinctive copper-catalyzed radical
annulation
to valuable 2-(trifluoromethyl)pyrazolo[1,5-a]pyridines
and their benzo analogues has been described for the first time. Notably,
the newly developed complementary process allows the synthesis of
4- or 6-substituted target molecular entities as a single product,
which was previously challenging to access by existing methods. The
utility of this process is further demonstrated by the facile construction
of four different ring systems, a gram-scale synthesis, and the late-stage
functionalization of bioactive molecules.
Diazoacetates are widely used to synthesize highly valuable indoles. Previous research has focused on using metal carbene reactivity or the innate nucleophilicity of the diazoacetates to create indoles through a traditional two-electron pathway. However, these strategies are constrained by the need for transition metals, oxidants, or substrate prefunctionalization. To overcome the limitations, we report herein an open-shell strategy that utilizes the radical reactivity of diazoacetates to synthesize indoles for the first time, especially for more valuable [a]-annulated indoles. Notably, this visible-light-driven transformation is enabled by a single organophotocatalyst, proceeding without metals ot additives. Preliminary mechanistic studies and density functional theory calculations disclose a relay visible-light photoredox catalytic process that probably involves several discrete photoredox catalytic cycles in a single operation with one organophotocatalyst.
Given the importance of both the CF 3 group and the alkyne moiety in synthetic/medicinal chemistry, we report here the first example of efficient synthesis of 2-pyrazolines with a CF 3 -and alkyne-substituted quaternary carbon center. This methodology has the advantages of high functional group compatibility, the avoidance of base and open-flask conditions, easily available and easy to handle reagent, and broad substrate scope. Notably, this protocol allows for the late-stage functionalization of biologically active molecules and the gram-scale synthesis.P yrazoline derivatives constitute an important class of nitrogen heterocyclic compounds in biological, medicinal, and synthetic chemistry. 1 The incorporation of a trifluoromethyl group (CF 3 ) into pyrazolines is often an effective way to enhance the metabolic stability and lipophilicity. 2 The 2pyrazolines with a quaternary CF 3 -substituted carbon contiguous to the NH moiety are particularly attractive synthetic targets because of their remarkable biological activities and their unique structural features. 3 Representative examples of such molecules are depicted in Figure 1. 1a,4 However, currently available synthetic routes to this class of compounds are not only rare but also suffer from an extremely narrow substrate scope and limited functional group compatibility (Scheme 1). The groups of Huisgen and Reissig reported the 1,3-dipolar cycloaddition reactions of electron-deficient olefins with diazo
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