Photochemical [2+2] Cycloaddition of Alkynyl Boronates

Abstract

A photochemical [2+2] cycloaddition of alkynyl boronates and maleimides is reported. The developed protocol provided 35–70% yield of maleimide‐derived cyclobutenyl boronates and demonstrated wide compatibility with various functional groups. The synthetic utility of the prepared building blocks was demonstrated for a range of transformations, including Suzuki cross‐coupling, catalytic or metal‐hydride reduction, oxidation, and cycloaddition reactions. With aryl‐substituted alkynyl boronates, the products of double [2+2] cycloaddition were obtained predominantly. Using the developed protocol, a cyclobutene‐derived analogue of Thalidomide was prepared in one step. Mechanistic studies supported the participation of the triplet‐excited state maleimides and ground state alkynyl boronates in the key step of the process.

Direct Observation of Triplet States in the Isomerization of Alkenylboronates by Energy Transfer Catalysis

“…Thioxanthone (TX) has a venerable history in the vibrant arena of energy transfer catalysis − but despite its popularity, delineating the mechanistic nuances of reactions mediated by this popular organocatalyst is complicated by its nonemissive triplet state. − In contrast to many photoactive metal complexes, − invoking TX room-temperature emission quenching in support of triplet energy transfer is inappropriate, and thus, unifying catalysis data with detailed photophysical investigations would be highly enabling for future reaction design. Of the multitude of photochemical processes mediated by thioxanthone with hydrogen abstraction, electron transfer or energy transfer events being mechanistic key steps, ,− this low molecular weight catalyst has proven to be highly adept in facilitating the geometric E → Z isomerization of a plenum of activated alkenes. − Furthermore, the deracemization of chiral alkenes catalyzed by chiral TX derivatives has also recently been reported . Representative deployments include the isomerization of β-boryl acrylates, − elaborately substituted fumarates, , and photocatalytic cascade reactions to generate well-defined drug discovery vectors. , These transformations are assumed to occur by selective energy transfer from excited state thioxanthone (TX*) to the starting E -isomer: upon excitation, a transient triplet state intermediate is generated that can be processed to either the substrate or product isomers, thereby accumulating the Z -isomer in the reaction mixture (an energy diagram explaining this mechanism for our specific substrate is presented in the Results and Discussion section).…”

[3+2] Cycloaddition of Alkynyl Boronates and in situ Generated Azomethine Ylide

“…Unfortunately, any attempts to introduce alkenyl boronate 3 a and N ‐benzyl maleimide 9 into the photochemical [2+2] cycloaddition under UV irradiation [47] were unfruitful – expected product 10 [48] was not detected at any conditions applied (Scheme 4). Instead, a photoinduced intermolecular hydrogen atom transfer (HAT) process was observed, [49] producing corresponding pyrrole boronate 11 [25] in 89 % yield and N ‐benzyl succinimide as a sole by‐product.…”

Visible-Light-Mediated Catalyst-Free [2+2] Cycloaddition Reaction for Dihydrocyclobuta[b]naphthalene-3,8-diones Synthesis under Mild Conditions

“…In addition, 2,2,6,6-tetramethyl-1-piperidinyloxy (with TEMPO as a radical scavenger) was added in the reaction of Scheme 4C, and only a trace amount of compound 3aa was detected. Based on the control experimental results, DFT-calculated results (see the computational details section) and previous studies of the [2+2] cycloaddition reaction [31], a possible mechanism for this visible-light-photocatalyzed [2+2] cycloaddition reaction was proposed, as shown in Scheme 5. First, the 1a 3,*s was populated by intersystem crossing (ISC) of the singlet excited state 1a * that resulted from visible light irradiation of ground state 1a.…”