Synthesis of Nitrogen Heterocycles via Photochemical Ring Opening of Pyridazine N-Oxides

Abstract

A photochemical method for the direct synthesis of 1H-pyrazoles from pyridazine N-oxides was developed. This chemistry features a regioselective approach to nonsymmetrically substituted pyridazine N-oxides. Herein, we highlight the first strategic use of photoinduced ring-opening reactions of 1,2-diazine N-oxides for the preparative synthesis of nitrogen heterocycles.

Detection and Identification of Reaction Intermediates in the Photorearrangement of Pyridazine N-Oxide: Discrepancies between Experiment and Theory

“… An attempt to resolve the growth of 15 by nanosecond laser flash photolysis failed; obviously, the formation of 15 was complete within the duration of the laser pulse. The rearrangement of derivatives of 5 to intermediary diazo compounds has recently been employed in a new heterocycle synthesis …”

A Photoinduced Cascade for the Synthesis of 1H‐Indole‐2‐Acetamide Derivatives

“…In contrast, when the photochemistry was repeated in the absence of Rh 2 (esp) 2 the major product was pyrazole 4 a, which, consistent with our earlier work, arises from the non-catalyzed thermal rearrangement of transient diazo species A (entry 2). [12] We also found that a minimum catalyst loading of 1 mol% was needed to suppress formation of 4 a (entry 3).…”

“…Our early work in this area established that electron-rich pyridazine N-oxides (1, X=H) selectively isomerize to Z-diazoalkenes A when exposed to UV light. [12] A recent follow up study focused on diverting transient species A to 2-aminofurans (2) via the corresponding metallocarbenoid intermediate. [13] This goal was accomplished using Rh 2 (esp) 2 as a catalyst.…”

Pyridazine N-Oxides as Precursors to 2-Aminofurans: Scope and Limitations in Complexity Building Cascade Reactions

“…With assembly of scaffold 1 as our goal, we considered that the requisite 2-aminofurans might be prepared from pyridazine N -oxides 2 using photochemistry . As shown in Scheme , we previously reported that exposure of 3-aryl-6-aminopyridazine N -oxides (e.g., 2a ) to UV light generates ( Z )-diazoalkenes A , which isomerize to pyrazoles (e.g., 3a ) at 65 °C . Notably, incorporation of an electron-donating amine substituent to C 6 of the pyridazine nucleus was found to be critical for suppressing photodeoxygenation of 2 .…”

“…At the outset, we realized that successful implementation of the strategy outlined in Scheme required a catalyst capable of intercepting A faster than it could isomerize to pyrazole 3 . Along these lines, experiments to identify an effective catalyst focused on substrates 2a (X = H) and 2b (X = NH 2 ), which were prepared on gram-scale via a modification of our reported two-step synthesis . As outlined in Table , photolysis ( h ν = 350 nm) of 2a at 35 °C in THF (0.3 M) for 2 h afforded pyrazole 3a in 93% yield in the absence of a catalyst (entry 1) .…”