Synlett 2019; 30(18): 2027-2034
DOI: 10.1055/s-0037-1611912
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© Georg Thieme Verlag Stuttgart · New York

Ruthenium-Catalyzed Direct Cross-Coupling of Secondary Alcohols to β-Disubstituted Ketones

Subramanian Thiyagarajan
,
School of Chemical Sciences, National Institute of Science Education and Research (NISER), HBNI, Bhubaneswar-752050, India   Email: gunanathan@niser.ac.in
› Author Affiliations
We thank SERB New Delhi (EMR/2016/002517), DAE, and NISER for financial support.
Further Information

Publication History

Received: 17 June 2019

Accepted after revision: 01 August 2019

Publication Date:
13 August 2019 (online)


Abstract

The β-disubstituted ketone functionality is prevalent in biologically active compounds and in pharmaceuticals. A ruthenium-catalyzed direct synthesis of β-disubstituted ketones by cross-coupling of two different secondary alcohols is reported. This new protocol was applied to the synthesis of variety of β-disubstituted ketones from various cyclic, acyclic, symmetrical, and unsymmetrical secondary alcohols. An amine–amide metal–ligand cooperation in a Ru catalyst facilitates the activation and formation of covalent bonds in selective sequences to provide the products. Kinetic and deuterium-labeling experiments suggested that aliphatic alcohols oxidize faster than benzylic secondary alcohols. A plausible mechanism is proposed on the basis of mechanistic and kinetic studies. Water and H2 are the only byproducts from this selective cross-coupling of secondary alcohols.

1 Introduction

2 Catalytic Self- or Cross-Coupling of Alcohols and Selectivity Challenges

3 Recent Developments in the Synthesis of β-Disubstituted Ketones

4 Scope of Ruthenium-Catalyzed Cross-Couplings of Secondary Alcohols

5 Mechanistic Studies and Proposed Mechanism

6 Conclusion

 
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