Ruthenium-Catalyzed Oxidation of Secondary Alcohols Assisted by a Simple Alkene

Abstract

The oxidation of alcohols to carbonyl compounds has been recognized as a fundamental organic transformation in synthetic organic chemistry. Besides conventional routes, many elegant transition metal-catalyzed methods assisted by co-oxidants are known and used for such transformations. As part of our ongoing studies on ruthenium catalysis, it has recently been found that carbonyl compounds are coupled with alcohols in several routes. The coupling of ketones 1 with primary alcohols 2 preferentially afforded coupled ketones 4 (Scheme 1, route a) or coupled secondary alcohols 5 (Scheme 1, route b) according to the molar ratio of 2 to 1. In addition, secondary alcohols 3 was also found to be coupled with 2 to give 5 (Scheme 1, route c). Among them, in connection with this report, the addition of sacrificial hydrogen acceptor (1-dodecene) in the case shown in route c of Scheme 1 was essential for the dramatic enhancement of reaction rate. This could be due to the acceleration of initial oxidations of both starting alcohols by transfer hydrogenation from alcohols to 1-dodecene. Under these circumstances, this report describes a rutheniumcatalyzed oxidation of secondary alcohols in the presence of 1-dodecene. The results of several attempted oxidations of 1-(2naphthyl)ethanol (3a) to 2'-acetonaphthone (4a) under several conditions are listed in Table 1. Treatment of 3a in the presence of a catalytic amount of RuCl2(PPh3)3 (2 mol%) along with KOH in dioxane at 100 C afforded 4a in 15% isolated yield with 35% conversion of 3a (run 1). However, when 1-dodecene was further added, the oxidation rate was remarkably enhanced and 4a was formed in 77% yield with 85% conversion of 3a (run 2). As has been noted in our recent report, the fate of 1-dodecene seems to be partially converted into dodecane by accepting hydrogen. It is known that the carbon-carbon double bond of α,βunsaturated carbonyl compound works as a hydrogen acceptor for the ruthenium-catalyzed oxidation of secondary alcohols to ketones. Lower reaction temperature (80 C) resulted in a slightly lower yield of 4a (run 3). Performing the reaction under K2CO3/toluene in place of KOH/dioxane produced 4a in only 41% yield with incomplete conversion (43%) (run 4). Similar treatment of 3a in the presence of RhCl(PPh3)3 under the employed conditions resulted in lower yield of 4a (60%) when compared to the use of RuCl2(PPh3)3 catalyst (run 5). Given the controlled reaction conditions, various secondary alcohols 3 were employed to investigate the reaction scope. The results are summarized in Table 2. Aryl(methyl) carbinols (3b-3e) were oxidized into the corresponding ketones (4b-4e) in the range of 21-79% yields. The ketone yield was considerably affected by the electronic nature of the substituent on the aromatic ring of aryl(methyl) cabinols. With 3c and 3d having electron-donating substituent on the Scheme 1 Table 1. Oxidation of 3a into 4a under several conditionsa