Table 1. Reaction Conditions Screening of Acid-Catalyzed Cyclization of CBD Using Lewis Acidsa.
| reaction
mixture composition (%)b |
||||||||
|---|---|---|---|---|---|---|---|---|
| entry | acid | solvent | T (°C) | time (h) | Δ9-THC | Δ8-THC | Δ8-iso-THC | Δ4(8)-iso-THC |
| 1 | BF3·OEt2 | CH2Cl2 | –10 | 4 | 44 | 1 | 3 | |
| 2 | BF3·OEt2 | CH2Cl2 | 0 | 6 | 2 | 52 | ||
| 3 | BF3·OEt2 | CH2Cl2 | –78 to −30 | 48 | 10 | 11 | 5 | |
| 4 | BF3·OEt2 | Tol | –10 | 3 | 41 | 2 | 29 | |
| 5 | BF3·OEt2 | Tol | 0 | 6 | 36 | 26 | ||
| 6 | BF3·OEt2 | THF | –10 | 6 | NR | NR | NR | NR |
| 7 | BF3·OEt2 | MeCN | –10 | 6 | 5 | 30 | 5 | |
| 8 | TMSOTf | CH2Cl2 | –10 | 6 | 93 | |||
| 9 | TMSOTf | Tol | –10 | 6 | 12 | 75 | ||
| 10 | In(OTf)3 | CH2Cl2 | –10 | 6 | 52 | 6 | 4 | |
| 11 | In(OTf)3 | CH2Cl2 | 0 to RT | 48 | 72 | |||
| 12 | In(OTf)3 | Tol | –10 | 4 | NR | NR | NR | NR |
| 13 | In(OTf)3 | Tol | 0 | 24 | 98 | |||
| 14 | ZnBr2 | CH2Cl2 | RT | 96 | NR | NR | NR | NR |
| 15 | TiCl4 | CH2Cl2 | –10 | 6 | 34 | 9 | ||
a
RT, room temperature; NR, no reaction.
b
Determined via HPLC and 1H NMR analysis.