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Synthesis of 1,4-Diazacycles by Hydrogen Borrowing

Anju Nalikezhathu, Adriane Tam, Valeriy Cherepakhin, Van K. Do and Travis J. Williams*

*Donald P. and Katherine B. Loker Hydrocarbon Institute and Department of Chemistry, University of Southern California, Los Angeles, California 90089-1661, United States, Email:

A. Nalikezhathu, A. Tam, V. Cherepakhin, V. K. Do. T. J. Williams, Org. Lett., 2023, 25, 1754-1759.

DOI: 10.1021/acs.orglett.3c00468

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A (pyridyl)phosphine-ligated ruthenium(II) catalyzes a diol-diamine coupling to provide piperazines and diazepanes. The conditions tolerate different amines and alcohols that are relevant to key medicinal platforms.

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General Procedure

In the drybox, a 1-dram vial was charged with diamine (x equiv), diol (y equiv), and catalyst. The vial was capped, taken out of the glovebox, and heated to 110 C. The solution turned to a dark brown color. After the given time, the reaction mixture was allowed to cool to room temperature followed by a dichloromethane/water work up. Products were isolated either by a gravity column or flash column.

Catalyst Evolution in Ruthenium-Catalyzed Coupling of Amines and Alcohols

V. Cherepakhin, T. J. Williams, ACS Catal., 2020, 10, 56-65.

Key Words

piperazines, N-heterocycles

ID: J54-Y2023