Photochemical [2 + 2] Cycloaddition of Alkenyl Boronic Derivatives: An Entry into 3-Azabicyclo[3.2.0]heptane Scaffold

Abstract

The synthesis of 3-azabicyclo[3.2.0]heptyl boropinacolates and trifluoroborates via the [2 + 2] photocycloaddition of the corresponding alkenyl boronic derivatives and maleimides or maleic anhydride is described. Optimization of the reaction conditions (i.e., wavelength, concentration of the reagents, photosensitizer) was carried out, and the scope and limitations of the method were studied. Alkenyl boronic acid pinacolates were found to be more suitable for the [2 + 2] cycloaddition, providing better reaction outcomes compared to the trifluoroborates. The utility of this approach was shown by the preparation of bi-and trifunctional building blocks (21 examples), which could be easily synthesized on up to 60 g scale. These cycloadducts provide a convenient entry into the 3-azabicyclo[3.2.0]heptane scaffold through the C−C coupling or oxidative deborylation reactions.

A Catalyst and Base Free Approach to Polycyclic Aromatic Compounds via Intramolecular [2+2] and retro‐[2+2] Cycloadditions

“…According to the above experimental results and previous relevant literature reports, [11,[13][14][15][16] a plausible mechanism was proposed for the formation of 3 a and butyl p-toluenesulfinate 4 (Scheme 8). First, the reaction between dialdehyde 1 a and ptolylsulfonylhydrazine 2 produced bis-(N-tosylhydrazone)s 14, which underwent a thermo-induced intramolecular [2 + 2] cycloaddition [13] to afford 1,2-diazetidine A, [14] followed by a retro-[2 + 2] cycloaddition [15] via a stepwise cleavage of one CÀ N bond to form a biradical transition state B followed by fragmentation to afford 3 a and 5. [16] The decomposition of 1,4ditosyltetraaz-2-ene 5 along with the liberation of nitrogen [17] was expected to form the N-centered sulfonamidyl radical C, [18] which could dimerize to form 1,2-bis(p-tolylsulfonyl)hydrazine 13.…”

Emerging Building Blocks for Medicinal Chemistry: Recent Synthetic Advances

“…[465] Intermolecular photochemical [2 + 2] cycloaddition of maleimides was another efficient approach to 3-azabicyclo[3.2.0] heptanes allowing not only for the preparation of 3,6disubstituted derivatives, but also tricyclic systems of type 102 that can be considered as extended M/P/P analogs (Scheme 59). [466][467][468] One more retrosynthetic disconnection of the 3-azabicyclo [3.2.0]heptane core relied on the [3 + 2] cycloaddition of cyclobutene derivatives and azomethine ylides, used for the construction of 1,3-disubstituted derivatives (Scheme 60). [459] A copper-catalyzed asymmetric version of this transformation leading to polysubstituted 3-azabicyclo[3.2.0]heptanes was also reported.…”

A Photochemical Microfluidic Reactor for Photosensitized [2+2] Cycloadditions

“…To test the suitability of our developed system as a photochemical reactor we applied it to the [2+2] cycloaddition of N-methylmaleimide and diversely functionalized alkenes and alkynes. While similar reactions have been explored, 9,11,12 they require expensive iridium-based photocatalysts or high-energy UV light, typically 250 nm in wavelength. 13,14 As an alternative, we sought to identify a readily available photosensitizer (PS) which was both cheap and enabled the use of lower energy light, reducing operational risks of carrying out the transformation.…”