CBD hydroxyquinone photo-isomerises to a highly reactive intermediate.

The legalisation of hemp has led to wide commercial availability of cannabidiol (CBD)-containing products. Here we show that the CBD-hydroxyquinone (HU-331), a readily formed oxidation product and common impurity in CBD isolates, undergoes a previously unknown photo-isomerisation to produce a highly reactive intermediate in solution. Studies supported by calculations indicate that this intermediate rapidly reacts with oxygen to form a multitude of cannabinoid products. The purple colour observed in light-aged CBD-containing solutions is largely due to the anions of these by-products and is not significantly due to the HU-331 anion. Our findings suggest that these uncharacterized cannabinoid derivatives can be present in CBD-containing e-liquids and solutions that have been stored under ambient light conditions, calling for quality control processes that manage HU-331 contamination.

Sulfur(iv) reagents for the SuFEx-based synthesis of substituted sulfamate esters.

Sulfur(vi) fluoride exchange chemistry has been reported to be effective at synthesizing valuable sulfur(vi) functionalities through sequential nucleophilic additions, yet oxygen-based nucleophiles are limited in this approach to phenolic derivatives. Herein, we report a new sulfur(iv) fluoride exchange strategy to access synthetically challenging substituted sulfamate esters from alkyl alcohols and amines. We also report the development of a non-gaseous, sulfur(iv) fluoride exchange reagent, N-methylimidazolium sulfinyl fluoride hexafluorophosphate (MISF). By leveraging the reactivity of the sulfur(iv) center of this novel reagent, the sequential addition of alcohols and amines to MISF followed by oxidation afforded the desired substituted sulfamates in 40-83% yields after two steps. This new strategy expands the scope of SuFEx chemistry by increasing the accessibility of underdeveloped -S(O)F intermediates for future explorations.

Facile synthesis of sulfonyl fluorides from sulfonic acids.

Herein, we demonstrate two complementary strategies for the syntheses of sulfonyl fluorides using sulfonic acids and their salts. One strategy involves the conversion of sulfonic acid sodium salts to sulfonyl fluorides using thionyl fluoride in 90-99% yields in one hour. Lessons learned from the mechanism of this reaction also have enabled a complementary deoxyfluorination of sulfonic acids using Xtalfluor-E® - a bench stable solid - allowing for the conversion of both aryl and alkyl sulfonic acids and salts to sulfonyl fluorides in 41-94% yields. Notably, using Xtalfluor-E® enabled milder conditions and the use of both sulfonic acids and their sodium salts.

Rapid and column-free syntheses of acyl fluorides and peptides using ex situ generated thionyl fluoride.

Thionyl fluoride (SOF2) was first isolated in 1896, but there have been less than 10 subsequent reports of its use as a reagent for organic synthesis. This is partly due to a lack of facile, lab-scale methods for its generation. Herein we report a novel protocol for the ex situ generation of SOF2 and subsequent demonstration of its ability to access both aliphatic and aromatic acyl fluorides in 55-98% isolated yields under mild conditions and short reaction times. We further demonstrate its aptitude in amino acid couplings, with a one-pot, column-free strategy that affords the corresponding dipeptides in 65-97% isolated yields with minimal to no epimerization. The broad scope allows for a wide range of protecting groups and both natural and unnatural amino acids. Finally, we demonstrated that this new method can be used in sequential liquid phase peptide synthesis (LPPS) to afford tri-, tetra-, penta-, and decapeptides in 14-88% yields without the need for column chromatography. We also demonstrated that this new method is amenable to solid phase peptide synthesis (SPPS), affording di- and pentapeptides in 80-98% yields.