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. 2017 May 1;8(5):4130-4135.
doi: 10.1039/c7sc00161d. Epub 2017 Mar 23.

Total synthesis of aristolactam alkaloids via synergistic C-H bond activation and dehydro-Diels-Alder reactions

Mallu Chenna Reddy  1 , Masilamani Jeganmohan  1   2
Affiliations

Total synthesis of aristolactam alkaloids via synergistic C-H bond activation and dehydro-Diels-Alder reactions

Mallu Chenna Reddy et al. Chem Sci. .

Abstract

A concise total synthesis of aristolactam alkaloids by a synergistic combination of C-H bond activation and dehydro-Diels-Alder reactions is described. To achieve the synthesis two new synthetic methodologies, namely the oxidative cyclization of benzamides with vinyl sulfone leading to 3-methyleneisoindolin-1-ones via a ruthenium-catalyzed C-H bond activation, and a dehydro-Diels-Alder reaction followed by the fluoride ion mediated desulfonylation of 3-methyleneisoindolin-1-ones with benzynes, were developed. The method presented allows the opportunity for the construction of all the rings of aristolactams from easily available starting materials.

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Figures

Scheme 1
Scheme 1. Retrosynthetic analysis.
Scheme 2
Scheme 2. Cyclization of N-substituted benzamides.
Scheme 3
Scheme 3. Scope of substituted benzamides.
Scheme 4
Scheme 4. Scope of alkenes.
Scheme 5
Scheme 5. Dehydro-Diels–Alder reaction with benzynes.
Scheme 6
Scheme 6. Scope of substituted isoindolin-1-ones.
Scheme 7
Scheme 7. Scope of substituted benzynes.
Scheme 8
Scheme 8. Synthesis of N-methyl aristolactam alkaloids.
Scheme 9
Scheme 9. Synthesis of N-H aristolactam alkaloids.
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