Abstract
Enantioselective syntheses of (-)-Δ 8 -tetrahydrocannabinol ((-)-Δ 8 -THC) and (-)-Δ 9 -THC have been achieved in eight and 10 steps, respectively, from a known cinnamic acid. The syntheses take advantage of an enantioselective N-heterocyclic carbene (NHC)-catalyzed (4 + 2) annulation between donor-acceptor cyclobutanes and cinnamoyl fluorides to construct the highly enantioenriched cycloxyl β-lactone shown. Having constructed this A-ring precursor, elaboration to (-)-Δ 8 -THC is achieved through β-lactone alcoholysis followed by oxidation, dual decarboxylation, trimethylation, and cationic cyclization. Finally, the conversion to (-)-Δ 9 -THC is achieved with established chemistry.
| Original language | English |
|---|---|
| Pages (from-to) | 1212-1215 |
| Number of pages | 4 |
| Journal | Organic Letters |
| Volume | 21 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Jan 2019 |
Cite this
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Enantioselective Total Synthesis of (-)-Δ 9 -Tetrahydrocannabinol via N-Heterocyclic Carbene Catalysis. / Ametovski, Adam; Lupton, David W.
In: Organic Letters, Vol. 21, No. 4, 01.01.2019, p. 1212-1215.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Enantioselective Total Synthesis of (-)-Δ 9 -Tetrahydrocannabinol via N-Heterocyclic Carbene Catalysis
AU - Ametovski, Adam
AU - Lupton, David W.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Enantioselective syntheses of (-)-Δ 8 -tetrahydrocannabinol ((-)-Δ 8 -THC) and (-)-Δ 9 -THC have been achieved in eight and 10 steps, respectively, from a known cinnamic acid. The syntheses take advantage of an enantioselective N-heterocyclic carbene (NHC)-catalyzed (4 + 2) annulation between donor-acceptor cyclobutanes and cinnamoyl fluorides to construct the highly enantioenriched cycloxyl β-lactone shown. Having constructed this A-ring precursor, elaboration to (-)-Δ 8 -THC is achieved through β-lactone alcoholysis followed by oxidation, dual decarboxylation, trimethylation, and cationic cyclization. Finally, the conversion to (-)-Δ 9 -THC is achieved with established chemistry.
AB - Enantioselective syntheses of (-)-Δ 8 -tetrahydrocannabinol ((-)-Δ 8 -THC) and (-)-Δ 9 -THC have been achieved in eight and 10 steps, respectively, from a known cinnamic acid. The syntheses take advantage of an enantioselective N-heterocyclic carbene (NHC)-catalyzed (4 + 2) annulation between donor-acceptor cyclobutanes and cinnamoyl fluorides to construct the highly enantioenriched cycloxyl β-lactone shown. Having constructed this A-ring precursor, elaboration to (-)-Δ 8 -THC is achieved through β-lactone alcoholysis followed by oxidation, dual decarboxylation, trimethylation, and cationic cyclization. Finally, the conversion to (-)-Δ 9 -THC is achieved with established chemistry.
UR - http://www.scopus.com/inward/record.url?scp=85061530623&partnerID=8YFLogxK
U2 - 10.1021/acs.orglett.9b00198
DO - 10.1021/acs.orglett.9b00198
M3 - Article
VL - 21
SP - 1212
EP - 1215
JO - Organic Letters
JF - Organic Letters
SN - 1523-7060
IS - 4
ER -