Enantioselective Total Synthesis of (-)-Δ 9 -Tetrahydrocannabinol via N-Heterocyclic Carbene Catalysis

Adam Ametovski, David W. Lupton

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)1212-1215
Number of pages4
JournalOrganic Letters
Volume21
Issue number4
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

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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.",
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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 journalArticleResearchpeer-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

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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.

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