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. 2020 May 19;10(32):19003-19007.
doi: 10.1039/d0ra03400b. eCollection 2020 May 14.

Cascade annulation reaction (CAR): highly diastereoselective synthesis of pyranopyrazole scaffolds

Manickam Bakthadoss  1 , Manickam Surendar  1
Affiliations

Cascade annulation reaction (CAR): highly diastereoselective synthesis of pyranopyrazole scaffolds

Manickam Bakthadoss et al. RSC Adv. .

Abstract

An unprecedented domino protocol for the novel synthesis of highly diverse and functionalized tetrahydro pyranopyrazole scaffolds using chalcone epoxide has been reported for the first time. This synthetic protocol generates three consecutive stereogenic centres in a highly diastereoselective manner with the formation of vicinal diol and a quaternary carbon centre. A wide range of substrates were utilized for the scope of this methodology and provided very good yields of pyranopyrazoles. The pyranopyrazoles were also transformed into densely functionalized tetrasubstituted olefins.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Some representative examples of bioactive pyranopyrazole scaffolds.
Scheme 1
Scheme 1. Reported methods and present approach for the synthesis of pyranopyrazole scaffolds.
Scheme 2
Scheme 2. Synthesis of optically active pyranopyrazole scaffold from chiral chalcone epoxide.
Fig. 2
Fig. 2. Possible transition state models for the racemic chalcone epoxide with C-nucleophile.
Fig. 3
Fig. 3. Favoured (3a) and disfavoured (3ab) conformations.
Scheme 3
Scheme 3. Functional group transformation of 3a.
Scheme 4
Scheme 4. The proposed reaction pathway for the preparation of racemic tetrahydropyranopyrazoles.
Scheme 5
Scheme 5. Proposed mechanism for the formation of densely functionalized tetrasubstituted olefins.
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