Alkylation of resorcinols with monoterpenoid allylic alcohols in aqueous acid: synthesis of new cannabinoid derivatives

Cannabidiol Discovery and Synthesis—a Target‐Oriented Analysis in Drug Production Processes

“…Researchers later formed an allylic carbocation with the limonene framework as a reactive intermediate using isopiperitenol ( 42 ) as a chiral synthon for (−)‐ 2 (Scheme 15). Using (+)‐ cis / trans ‐ 42 and oxalic acid as a catalyst, Cardillo and co‐workers reported the synthesis of (−)‐ 2 in 10 % yield and confirmed the relative stereochemistry by means of NMR spectroscopy [116] . Hanuš and co‐workers, [152, 153] on the other hand, described the stereoselective Friedel–Crafts alkylations of 27 and (−)‐ cis / trans ‐ 42 with Al 2 O 3 ‐supported BF 3 ⋅ OEt 2 as a catalyst, [122] providing the stereoisomers of (+)‐ 2 in 44 % yield.…”

“…Researchers have already used several synthetic strategies to deliver the desired CBD molecule, in both racemic [78,110,111] and enantioselective [112][113][114][115][116][117][118][119] ways (Scheme 8). [112][113][114][115][116][117][118][119] These strategies include, as key steps, reactions such as Friedel-Crafts alkylation, [120][121][122][123] Diels-Alder cycloaddition, [111] anion-ic addition mediated by strongb ases [78] and/oro rganometallic species, [118,124] stereodivergent dual catalysis reactions, [119,125] and biotechnological synthesis. [112] 4.1.…”

“…Using (+ +)-cis/trans-42 and oxalic acid as ac atalyst, Cardillo and coworkers reported the synthesis of (À)-2 in 10 %y ield and confirmed the relative stereochemistry by meanso fN MR spectroscopy. [116] Hanuš and co-workers, [152,153] on the other hand, described the stereoselective Friedel-Crafts alkylations of 27 and (À)-cis/trans-42 with Al 2 O 3 -supported BF 3 •OEt 2 as ac atalyst, [122] providing the stereoisomers of (+ +)-2 in 44 %y ield. Both approaches show the importance of operational variables in the yield and selectivity of the target compound.…”

“…Researchers have already used several synthetic strategies to deliver the desired CBD molecule, in both racemic [78, 110, 111] and enantioselective [112–119] ways (Scheme 8). [112–119] …”

Process Intensification for Obtaining a Cannabidiol Intermediate by Photo-oxygenation of Limonene under Continuous-Flow Conditions

“…To obtain such active compounds, chemical synthesis becomes an important alternative. Different approaches have already been explored to synthesize CBD, using both racemic − and enantio­selective strategies. − One of the most common approaches for the synthesis of (−)-CBD involves the coupling of olivetol and p -mentha-2,8-dien-1-ol ( 1 ) by an acid-catalyzed Friedel–Crafts alkylation. ,,,,− Indeed, this methodology has been also applied in the synthesis of other bioactive cannabinoids, using 1 as a common intermediate (Figure ). ,− …”