A General Photocatalytic Route to Prenylation

Abstract

Prenylation is an essential reaction on which nature relies to modify properties of molecules and build terpenoids, but remains a challenging chemical reaction. Aiming to capitalize on recent advances in photocatalysis to easily and cleanly generate a broad range of carbon based radicals, we have developed a prenyl transfer reagent that is captured by transiently generated radicals. The reagent can be made in bulk, is bench stable, and broadly applicable such that it can be used with existing photocatalytic methods with very few changes to reaction conditions. Ultimately, this provides a true drop‐in solution for prenylation, expanding the scope of substrates that can be readily prenylated.

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis

“… 71 This same catalytic system was utilized in 2020 by Weaver and co-workers for the prenylation of thiophenol using a sulfone reagent, affording the corresponding sulfide in 91% yield. 592 After thiyl radical generation and addition across the olefin moiety as in the above manner, elimination of phenylsulfonyl radical affords the product. Reduction of this radical by EY •– returns the ground-state photocatalyst with phenylsulfinate anion as a byproduct.…”

“…Weaver and co-workers later expanded this methodology to include azole C2-arylation in the presence of electron-rich arenes, 1025 and azole C2-prenylation in the presence of a prenyl sulfone reagent. 592 …”

“…Turnover of the photocatalyst is proposed to result from reduction of a trace amount of molecular oxygen in solution by the reduced photocatalyst ( E 1/2 EY / EY •– = −1.06 V vs SCE in MeCN) . This same catalytic system was utilized in 2020 by Weaver and co-workers for the prenylation of thiophenol using a sulfone reagent, affording the corresponding sulfide in 91% yield . After thiyl radical generation and addition across the olefin moiety as in the above manner, elimination of phenylsulfonyl radical affords the product.…”

“…SV emission quenching experiments were attempted to further study this proposal, but results proved inconclusive due to the weak quenching observed by the azole substrate in the presence or absence of amine or acid additives. Weaver and co-workers later expanded this methodology to include azole C2-arylation in the presence of electron-rich arenes, and azole C2-prenylation in the presence of a prenyl sulfone reagent …”

Defluorodearomatization: A Photocatalytic Birch-Like Reduction That Enables C–C Bond Formation and Provides Access to Unnatural Cannabinoids

“…It could also serve a more abstruse role, such as preventing the formation of light absorbing compounds that could lead to photostarvation (Figure 1). 48 The screening for the identity of the terminal reductants revealed that tributylamine and diisopropylethylamine (Table 2, entries 14−16 and the Supporting Information) were nearly identical, while all the other reductants attempted gave poor yields of or no product. We chose to utilize DIPEA due to its comparatively higher vapor pressure and water solubility, which we anticipated would facilitate product isolation.…”