Gold(i)-catalyzed 6-endo-dig azide-yne cyclization: efficient access to 2H-1,3-oxazines
Geoffroy Hervé Lonca1, Ciputra Tejo2, Hui Ling Chan2
1Département de Chimie, UMR 7652 and 7653 CNRS, Ecole Polytechnique, 91128 Palaiseau, France.
Chemical Communications (Cambridge, England)
|December 20, 2016
Summary
Gold catalysis enables a rare 6-endo-dig azide-yne cyclization, yielding 2H-1,3-oxazines from α-propargyloxy-β-haloalkylazides. Electronic and resonance effects of alkyne substituents control this novel reaction pathway.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Azide-yne cyclization is a key reaction in organic synthesis.
- Gold catalysis has emerged as a powerful tool for activating alkynes.
- The 6-endo-dig cyclization mode is less common in gold-catalyzed azide-yne reactions.
Purpose of the Study:
- To develop a novel gold-catalyzed denitrogenative 6-endo-dig azide-yne cyclization.
- To synthesize 2H-1,3-oxazines using this new methodology.
- To investigate the factors controlling this cyclization pathway.
Main Methods:
- Utilized gold catalysis for the cyclization reaction.
- Employed α-propargyloxy-β-haloalkylazides as substrates.
- Analyzed the influence of alkyne substituents on reaction outcomes.
Main Results:
- Successfully achieved denitrogenative 6-endo-dig azide-yne cyclization.
- Synthesized various 2H-1,3-oxazine derivatives.
- Demonstrated that electronic and resonance effects of alkyne substituents facilitate and control the cyclization.
Conclusions:
- Established a new synthetic route to 2H-1,3-oxazines via gold-catalyzed 6-endo-dig azide-yne cyclization.
- Highlighted the importance of substituent effects in directing rare cyclization modes.
- Explored further molecular transformations of the synthesized oxazines.
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