Multigram Scale Synthesis of Piperarborenines C-E

Abstract

We report the multigram scale synthesis of heterodimeric β-truxinic imides piperarborenines C-E using a catechol-tethered diastereoselective intramolecular [2 + 2] photocycloaddition. Key innovations lie in the use of catechol as a practical auxiliary for the synthesis of homo- and heterodimeric β-truxinates and the use of a UV-LED flow photoreactor in the [2 + 2] step. This approach is highly scalable, requiring a single column purification, no photocatalysts, and no cryogenic conditions.

Triple-Dearomative Photocycloaddition: A Strategy to Construct Caged Molecular Frameworks

“…In order to increase light penetration and further improve conversion on a larger scale, we employed a flow photoreactor setup I, which vastly improved the reaction efficiency and delivered the caged product 6 in 95% conversion within 3 h on a 75 mg reaction-scale (Table , entry 2), which compares to a 67% conversion using batch conditions over 70 h on a 50 mg reaction scale (Table , entry 1). Further optimization using a 365 nm LED light source with a lower loading of furan (7:1 MeCN/furan) using the flow photoreactor setup II (Figure ) developed by Beeler and co-workers , led to a 92% conversion of 3 to 6 in 2.5 h residence time on a 100 mg reaction-scale (Table , entry 6).…”

Access to Symmetrical and Unsymmetrical Cyclobutanes via Template-Directed [2+2]-Photodimerization Reactions of Cinnamic Acids

“…3.6 Å) 32 so as to ensure that Schmidt's distance criterion (<4.2 Å) is satisfied, template 5 also enables the attachment of two different cinnamic acids selectively and sequentially (Scheme 2c). We should note that, Beeler and co-workers recently described the use of catechol as a covalent tether in the photochemical heterodimerization reactions of cinnamic acids in solution, and showed the application of this method to the syntheses of the natural products piperarborenines C-E. 35 Herein, we report a full account of our studies on the selective and controlled homodimerization and heterodimerization reactions of cinnamic acids via the use of 1,8-DHN (5) as a covalent template, and extension of its scope to the selective photodimerization of heteroaromatic substrates (Scheme 2c).…”

Accessing Cyclobutane Polymers: Overcoming Synthetic Challenges via Efficient Continuous Flow [2 + 2] Photopolymerization

“…For covalently tethered cinnamic esters, the linker defines the absolute configuration of the cyclobutane products, resulting in high diastereoselectivity. 27 Generally, intramolecular syn head-tohead cycloadditions afford the β-truxinate isomers, 1,28 while intermolecular anti head-to-head cycloadditions yield δtruxinate isomers. 24 Additionally, these reactions require an appropriate triplet-sensitizer to initiate photopolymerization.…”

“…Additionally, in contrast to traditional batch photoreactors which are often plagued by scalability issues, continuous flow is a viable alternative for efficient, large-scale photopolymerizations. Continuous flow strategies have been previously employed for [2 + 2] photocycloadditions of small molecules ,, and as postpolymerization ring-closing mechanisms of polymer reactive end-groups; however, this report describes the first continuous flow [2 + 2] polymerization. We constructed an in-house flow photoreactor comprised of 1/8-in.…”