2,3-Dichloro-5,6-dicyano-1,4-benzoquinone-Catalyzed Reactions Employing MnO₂ as a Stoichiometric Oxidant

Abstract

Several oxidative reactions can be effected with MnO 2 in the presence of sub-stoichiometric quantities of DDQ. These transformations include oxidative cyclization, deprotection, and dehydrogenation reactions. The use of MnO 2 as a terminal oxidant for DDQ-mediated reactions is attractive based on economical and environmental factors. DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) is a highly effective oxidant for a number of chemical transformations including protecting group removal, aromatization, acetal formation, and biaryl construction.1 DDQ is moderately expensive, however, with a cost of $526/mol according to the 2009-2010 Aldrich catalog.2 In addition to concerns about cost, DDQ also poses modest toxicity concerns, with an LD 50 of 82 mg/kg,3 and the potential for HCN liberation upon exposure to H 2 O. These issues, coupled with the potential purification difficulties associated with utilizing stoichiometric amounts of an organic oxidant, have led to the search for economical and environmentally benign oxidants that regenerate DDQ from its reduced hydroquinone form (Scheme 1). HNO 3 is a suitable oxidant for this purpose,4 though its strong acidity is often not compatible with functionalized organic compounds and necessitates that the reoxidation be conducted as an independent step. Chandrasekhar and co-workers reported5 that DDQ could be used as a catalytic oxidant with FeCl 3 serving as the stoichiometric oxidant. This system is economically and ecologically attractive, with FeCl 3 costing only $41/mol, and having an LD 50 of 450 mg/kg, though the Lewis acidity of FeCl 3 again makes it incompatible with many functional groups. Sharma and co-workers showed6 that Mn(OAc) 3 is also an effective agent for DDQ regeneration that does not exhibit strong Lewis acidity. However Mn(OAc) 3 •2H 2 O is actually more expensive than DDQ at a price of $647/mol. The cost factor is compounded by the fact that Mn (OAc) In accord with our efforts8 and those of other groups9 to use DDQ as a reagent for oxidative carbon-carbon bond forming reactions and our interest in developing catalytic oxidative transformations,10 we have initiated an effort to identify an inexpensive, non-acidic, and environmentally benign reagent that can be used as a terminal oxidant in the presence of sub-stoichiometric DDQ loadings. Following the observation that the use of FeCl 3 as a terminal oxidant for DDQ-catalyzed carbon-hydrogen bond functionalization reactions induced substrate decomposition, we directed our initial screen for terminal oxidants toward metal oxides that are known to effect phenol oxidations. This search led us to explore PbO 2 11 ($117/mol, LD 50 = 220 mg/kg). Exposing prenyl ether 1 to DDQ (20 mol %) and PbO 2 in CH 3 NO 2 provided tetrahydropyrone 2 in 75% yield after 48 h (Scheme 2). Incorporating 2,6-dichloropyridine made this reaction and subsequent transformations proceed more efficiently because it can act as a non-oxidizable base and because it quenches the acylium ion that forms when the enol acetate gro...

Selective Oxidation of Benzylic and Allylic Alcohols Using Mn(OAc)3/Catalytic 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone

“…It is noteworthy that the loadings of DDQ (20 mol %) and cooxidant (6 mol-equiv) are equal to those reported by Floreancig for quite different transformations. 7 Under these conditions, we obtained consistently reproducible results when Mn(OAc) 3 was used free from excess acetic acid remaining from the preparation of the reagent. 10 …”

“…Recently, Floreancig reported the use of catalytic amounts of DDQ in the presence of excess MnO 2 for other types of oxidative transformations, including cyclizations of ether-containing enol esters to form pyranones, aromatizations, and O -PMB deprotections. 7 Mn(OAc) 3 , which functions as a mild single electron acceptor, 8 has also been used for regeneration of DDQ in the removal of PMB protecting groups. 9 While this previous work did not include the oxidation of alcohols, we wished to determine whether this or a similar protocol would be amenable to our needs.. As a result of investigating this question, we are now pleased to report a new, modified catalytic oxidation procedure that is simple to perform, provides short reaction times, utilizes a readily prepared co-oxidant, and is not only selective for allylic and benzylic alcohols but which also exhibits selectivity for allylic alcohols in the presence of benzylic alcohols.…”

Quinone‐Catalyzed Selective Oxidation of Organic Molecules

“…[28g–o] In connection with this effort, Floreancig and Liu developed conditions for carrying out some of these reactions catalytically (15–20 mol% DDQ) with either excess PbO 2 or MnO 2 (Scheme 9B). [44] …”

2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ)/tert‐Butyl Nitrite/Oxygen: A Versatile Catalytic Oxidation System

“…serving as terminal oxidant. [16] While this manuscript was being prepared, the chemoselective oxidation of alcohols employing catalytic quantities of DDQ as the oxidant and MnA C H T U N G T R E N N U N G (OAc) 3 as the cooxidant was described by Helquist et al [17] There is no doubt that using of a great amount of these inorganic oxidants did cut down the cost but did not change the waste problem which resulted in the serious purification problem and the environmental effluent. Thus, it would be ideal if molecular oxygen can serve as the terminal oxidant in DDQ-mediated reactions.…”