Iron-catalyzed Oxidative Ring-opening Functionalization Of Unstrained Cyclic Tertiary Alcohols

The functionalization of C-C bonds has been a great challenge in synthetic chemistry owing to their kinetic inert and thermodynamic stability.Tertiary cycloalkanols are stable and easy to prepare,and have been proven to be privileged precursors for regiospecific synthesis of distally functionalized ketones by cleavage of the strained cyclic C-C bonds.In the past few decades,C-C bond activation has relied on strained cyclopropanol and cyclobutanol having thermodynamic driving forces to construct various chemical bonds,such as C-X,C-N,C-S,C-C,etc.However,C-C bond activation of unstrained cycloalkanols(especially 5-6 membered ring)has not been fully explored to a large extent.Although some progress has been made in the functionalization of C-C bonds of unstrained cycloalkanols,there are still many problems that need to be solved urgently,such as the use of precious metals,the requirement of prefunctional substrates,difficulty in complex molecule conversion,and the laborious and tedious procedures.This paper mainly includes three parts:(1)An iron-catalyzed oxidation of unstrained tertiary cycloalkanols for ring-opening alkylation of quinone compounds was developed;(2)An iron-catalyzed oxidation of unstrained tertiary cycloalkanols for ring-opening alkenylation was developed;(3)An iron-catalyzed oxidation of unstrained tertiary cycloalkanols for ring-opening cyanation was developed.The main contents are shown as follows:1.A new method of iron-catalyzed oxidation of unstrained tertiary cycloalkanols for ring- opening alkylation of quinone compounds has been developed.Using 1-phenyl cyclohexanol and 1,4-naphthoquinone as template substrates,catalyst,oxidant,solvent and temperature were all optimized.The optimal reaction conditions were obtained:acetonitrile and water as the solvent,ferrous phthalocyanine as the catalyst,K₂S₂O₈ as the oxidant and the reaction temperature of 80?.Under optimal conditions,the scope of tertiary cycloalkanols and quinone substrates were tested,respectively.It was found that the method had good functional group compatibility and can modify active and complex molecules.Preliminary investigation of the reaction mechanism proved that the reaction proceeded in a free radical pathway.2.A new method of iron-catalyzed oxidation of unstrained tertiary cycloalkanols for ring-opening alkenylation has been developed.The catalyst,oxidant,solvent and temperature were optimized by using 1-phenylcyclohexanol and trans-nitrostyrene as template substrates.The optimal conditions were as follows:acetonitrile and water as the solvent,ferrous chloride as the catalyst,K₂S₂O₈ as the oxidant and the reaction temperature of 90?.Under the optimal conditions,the scope of tertiary cycloalkanols and trans-nitrostyrene compounds was examined,respectively.Aromatic substrates with different substitution patterns and electronic properties,were employed without significant differences in reactivity.We also conducted a preliminary investigation on the mechanism of the reaction and proved that the reaction was involved in a free radical process.3.A new method for iron-catalyzed oxidation of unstrained tertiary cycloalkanols for ring-opening cyanidation has been developed.The catalyst,oxidant,solvent and temperature were optimized with 1-phenylcyclohexanol and 4-toluenesulfonyl cyanide as template substrates.The optimal conditions were obtained as follows:acetonitrile and water as the solvent,iron acetylacetone as the catalyst,H₂O₂ as the oxidant and the reaction temperature of 90?.When the substrates were tested under optimal conditions,most of the target products were obtained in 60%-80%yields with good selectivity.In addition,we also made a preliminary investigation into the mechanism of the reaction and proved a free radical process in the transformation.