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. 2024 Jun 5;4(5):534-544.
doi: 10.1021/acsorginorgau.4c00032. eCollection 2024 Oct 2.

Direct Organocatalytic Chemoselective Synthesis of Pharmaceutically Active 1,2,3-Triazoles and 4,5'-Bitriazoles

Badaraita Gorachand  1 , Gundam Surendra Reddy  1 , Dhevalapally B Ramachary  1
Affiliations

Direct Organocatalytic Chemoselective Synthesis of Pharmaceutically Active 1,2,3-Triazoles and 4,5'-Bitriazoles

Badaraita Gorachand et al. ACS Org Inorg Au. .

Abstract

Carbonyl-containing 1,4,5-trisubstituted- and 1,4-disubstituted-1,2,3-triazoles are well-known for their wide range of applications in pharmaceutical and medicinal chemistry, but their high-yielding metal-free synthesis has always remained challenging, as no comprehensive protocol has been outlined to date. Owing to their structural and medicinal importance, herein, we synthesized various carbonyl-containing 1,4,5-trisubstituted- and 1,4-disubstituted-1,2,3-triazoles and unsymmetrical 4,5'-bitriazoles with high yields and chemo-/regioselectivity from the library of 2,4-diketoesters and azides in a sequential one-pot manner through the combination of organocatalytic enolization, in situ [3 + 2]-cycloaddition, and hydrolysis reactions. The commercial availability of the starting materials/catalysts, diverse substrate scope, performance in a one-pot manner, chemo-/regioselectivity of organo-click reaction, quick synthesis of unsymmetrical 4,5'-bitriazoles, a large number of synthetic applications, and numerous medicinal applications of carbonyl-containing 1,2,3-triazoles are the key attractions of this metal-free organo-click work.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Previous Organocatalytic Azide-Carbonyl [3 + 2]-Cycloaddition Reactions
(a), (b), and (c) reproduced with permission from refs (, , , and 50), respectively. Copyright 2008, 2011, 2014, and 2014 John Wiley & Sons, Inc.
Figure 1
Figure 1
Biologically active carbonyl-containing 1,2,3-triazoles.
Scheme 2
Scheme 2. Reaction Design for the Chemoselective Organocatalytic Azide-Carbonyl [3 + 2]-Cycloaddition (OrgACC) Reaction
Figure 2
Figure 2
Selective one-pot synthesis of chiral 4,5′-bitriazoles 7.
Scheme 3
Scheme 3. Gram-Scale Synthesis of the OrgAKC Product 4aa
Scheme 4
Scheme 4. Gram-Scale Synthesis of the OrgAKC Product 4ea
Scheme 5
Scheme 5. Synthesis of Carbonyl-Containing 1,4-Disubstituted-1,2,3-triazoles 6
Scheme 6
Scheme 6. Reduction of Ketone and Ester Groups of 1,2,3-Triazoles 4aa/6aa
Scheme 7
Scheme 7. Synthesis of Biologically Active 1,2,3-Triazoles 11aa (D) and 12nu (A)
Scheme 8
Scheme 8. Synthesis of Benzodiazipene-Containing 1,2,3-Triazole 14aa
Scheme 9
Scheme 9. Reaction Mechanism for the TMG-Catalyzed Enolate-Mediated Chemoselective [3 + 2]-Cycloaddition
See this image and copyright information in PMC

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