Mechanism and Selectivities in Ru-Catalyzed Anti-Markovnikov Formal Hydroalkylation of 1,3-Dienes and Enynes: A Computational Study

Abstract

The mechanism of the Ru(II)-catalyzed anti-Markovnikov formal hydroalkylation of 1,3-dienes and enynes by hydrazones has been elucidated using density functional theory (DFT) calculations. Our results indicate that the C–C bond formation proceeds through a highly polar outer-sphere transition state (TS) stabilized by the THF solvent, not the ordered inner-sphere TS as originally proposed. The regioselectivity for 1,2-anti-Markovnikov addition is primarily due to the formation of an extensively π-conjugated intermediate after the nucleophilic attack on the 1-position of the diene. The stability of this intermediate means that nucleophilic attack at the 1-position is able to utilize the outer-sphere pathway, while attacks on all other positions of the diene must proceed through more crowded and less-favorable inner-sphere TSs. We show that the electronics of substituents on the hydrazone and the diene have a significant impact on the C–C formation barrier, which rationalizes the limitations on the substrate scope. The preferred coordination sphere around Ru(II) and the rigidity of the reacting substrates lead to a sterically demanding TS geometry, which explains the sensitivity of the reaction to the ligand size.

Publisher

American Chemical Society

Publication Date

8-1-2021

Publication Title

Journal of Organic Chemistry

Department

Chemistry and Biochemistry

Document Type

Article

DOI

10.1021/acs.joc.1c01319

Language

English

Format

text

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