Copper-catalyzed aerobic oxidation

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

II. First Generation Copper-Catalyzed Aerobic Oxidation Protocol... 

Copper-Catalyzed Aerobic Oxidation of Alcohols Using DBAD-H2... 

Lin L, Juanjuan M, Liuyan J, Yimyang W (2008) Molecular sieve promoted copper catalyzed aerobic oxidation of alcohols to corresponding aldehydes or ketones. J Mol Catal A Chem 291 1 ... 

Copper-Catalyzed Aerobic Oxidation oe Alcohols under Fluorous Biphasic Conditions (97,98)... 

Fig. 31. Selective copper-catalyzed aerobic oxidation of primary alcohols 9,103).

Stahl et al. reported a continuous homogeneous copper-catalyzed aerobic oxidation method for primary alcohols [32]. A modified tube reactor was used (Figure 23.3). A dilute oxygen source (9% O2 in Nj) was controlled by a mass flow controller and mixed with the substrate and catalyst solution, respectively, by... 

In this domino process, benzylamine was reacted with 2-halobenzamides through UUman-type coupling to yield the N-arylated intermediate 144 (Scheme 9.26). Then, a copper-catalyzed aerobic oxidation of 144 afforded the intermediate 145, which underwent an intramolecular nucleophilic addition of the amide to provide 146. Under the used reaction conditions, the intermediate 146 was oxidized to provide the desired products 147 in excellent yield. This protocol was also utilized by Fu et al. [80] by employing easily available a-amino adds instead of benzylamines to synthesize similar analogs. Very recently, the same method was applied for the synthesis of pyrimido[4,5-b]carbazoles by Nagarajan et al. [81]. 

Wendlandt, A. E., Suess, A. M., and Stahl, S. S. 2011. Copper-catalyzed aerobic oxidative C-H functionalizations Trends and mechanistic insights. Angew. Chem. Int. Ed. 50(47) 11062-11087. 

Table 5.10 Copper-catalyzed aerobic oxidation of alcohols to the corresponding aldehyde or ketone...

Most recently, Waldmann and co-workers disclosed a cascade transformation to allow the highly diastereo- and enantioselective synthesis of structurally complex 5,5,5-tricyclic products with eight stereocenters, which initiated by copper-catalyzed aerobic oxidation of cyclopentadiene to cyclopentadienone followed by catalytic asynunetric double 1,3-dipolar cycloaddition with azomethine ylides (Scheme 18) [33]. 

In 2008, the Stahl group published the first copper-catalyzed aerobic oxidative amidation of terminal alkynes [200]. An extensive screening of various copper sources, Br0nsted bases, and solvents led to the optimal conditions shown in Scheme 4.51. 

Synthesis of 2-Hetarylquinazolin-4(3 -ones. The title compound has been employed in an efficient method for the synthesis of 2-hetarylquinazolin-4(3/f)-ones via a copper-catalyzed aerobic oxidative amination protocol (eq 16). ... 

McCann SD, Stahl SS. Copper-catalyzed aerobic oxidations of organic molecules pathways for two-electron oxidation with a four-electron oxidant and a one-electron redox-active catalyst. Aa Chem Res. 2015 48 1756-1766. 

Tao C, Liu F, Zhu Y, Liu W, Cao Z (2013) Copper-catalyzed aerobic oxidative synthesis of aryl nitriles from benzylic alcohols and aqueous ammonia. Org Biomol Chem 11(20) 3349-3354... 

Tang C, Jiao N (2014) Copper-catalyzed aerobic oxidative C-C bond cleavage for C-N bond formation from ketones to artrides. Angew Chem hrt Ed 53(25) 6528-6532... 

Gu L, Jin C (2015) Copper-catalyzed aerobic oxidative cleavage of C-C bonds in epoxides leading to aryl nitriles and aryl aldehydes. Chem Commun 51 6572-6575... 

An efficient Cu(OTf)2-catalyzed 2,4,6-trisubstituted pyridine derivatives synthesis via C-N bond cleavage of aromatic methylamines and C(sp )-H bond activated of ketones was developed by Jiang s group (Scheme 8.80). A wide range of 2,4,6-trisubstituted pyridines could be obtained up to 95% yield at 100 °C under CU/O2 under this catalytic system with neat conditions. This process should be initiated by copper-catalyzed aerobic oxidative cleavage of C-N bond of aromatic methylamines [150]. 

Zhang G, Han X, Luan Y, Wang Y, Wen X, Ding C. 1-Proline an efficient N, O-bidentate hgand for copper-catalyzed aerobic oxidation of primary and secondary benzybc alcohols at room temperature. Chem Commun. 2013 49 7908-7910. 

It is only very recently that rhodium-based catalytic systems have been described in efficient oxidative olefination reactions. Inspired by the work of Satoh and Miura on rhodium/copper-catalyzed aerobic oxidative coupling of benzoic acids with internal allqmes or acrylates (Scheme 9.11), Glorius and co-workers described, in 2012, a rhodium-catalyzed directing group assisted olefination of 2-aryloxazolines under air. This method, which necessitated rhodium, silver and copper metal sources, afforded the desired olefin-oxazoline products in moderate-to-good yields (Scheme 9.12). 

Tab. 4.13 Copper-catalyzed aerobic oxidation of alcohols under fluorous biphasic conditions ...

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