Cyclohexanone Wacker oxidation

The method involves a regioselective, trans-diastereoselective, and enantioselective three-component coupling, as shown in Scheme 7.26. In this case, the zinc enolate resulting from the 1,4-addition is trapped in a palladium-catalyzed allyla-tion [64] to afford trans-2,3-disubstituted cyclohexanone 96. Subsequent palladium-catalyzed Wacker oxidation [82] yields the methylketone 97, which in the presence of t-BuOK undergoes an aldol cyclization. This catalytic sequence provides the 5,6-(98) and 5,7- (99) annulated structures with ees of 96%. 

These oxidation reactions provide a powerful strategy for the synthesis of cyclohexanone by a combination of Wacker oxidation of ethylene with the present metal-catalyzed oxidation of cyclohexane (Scheme 3.11). 

We are particularly interested in the Wacker oxidation of cyclohexene as the product, cyclohexanone, is a starting material in the synthesis of caprolactam, which is an intermediate in nylon production. Furthermore, we have strong interest in oxidation of acrolein in particular and acryhc compounds in general. Acrolein oxidation leads to a convenient route to 1,3-propanediol, while methyl acrylate oxidation leads to a starting material for adhesives. 

Initial experiments were done in water and resulted in low cyclohexene conversions, low product selectivities, and extensive palladium deactivation by Pd black formation. The low cyclohexanone yield originated from overoxidation of cyclohexanone to 2-cyclohexenone, which undergoes further oxidation to a plethora of by-products. The low cyclohexene conversion can be attributed to the aforementioned low reactivity of the internal double bond as well as the low solubility of cyclohexene in water. Several reaction media have been described in which higher alkenes are oxidized to ketones in organic solvent-based systems. Some typical examples are DMF [4], water mixtures with chlorobenzene, dodecane, sulfolane [5], 3-methylsulfolane andM-methylpyrrolidone [6], or alcohols [7]. These solvent systems indeed lead to increased cyclohexene conversions but still suffer from overoxidation and catalyst deactivation by Pd black formation. Hence, the goal of our research was to find a variation to the Wacker oxidation without over-oxidation of the product and deactivation of the palladium catalyst. 

The cyclopentenone 19 can be prepared by an intramolecular aldol reaction from the diketone 18. This reaction is best achieved with a base such as KOH in MeOH and heat. The diketone 18 can be prepared by Wacker oxidation of the alkene 17. Standard conditions for the Wacker oxidation are 10 mol% PdCla, CuCl, O2, DMF, H2O (see Scheme 5.115). The alkene 17 is prepared by allylation of the enamine of cyclohexanone. See J. Tsuji, I. Shimizu and K. Yamamoto, Tetrahedron Lett. (1976), 2975. 

In 1960, Moiseev and coworkers reported that benzoquinone (BQ) serves as an effective stoichiometric oxidant in the Pd-catalyzed acetoxylation of ethylene (Eq. 2) [19,20]. This result coincided with the independent development of the Wacker process (Eq. 1, Scheme 1) [Ij. Subsequently, BQ was found to be effective in a wide range of Pd-catalyzed oxidation reactions. Eor example, BQ was used to achieve Wacker-type oxidation of terminal alkenes to methyl ketones in aqueous DMF (Eq. 3 [21]), dehydrogenation of cyclohexanone (Eq. 4 [22]), and alcohol oxidation (Eq. 5 [23]). In the final example, 1,4-naphthoquinone (NQ) was used as the stoichiometric oxidant. 

Soeda et al. (358) used Pd-supported heteropoly compounds for a heterogeneous Wacker-type reaction and found that Pd/Cs2 5H0 5PW6Mo6C)4o was active for oxidation of cyclohexene to produce cyclohexanone and cyclohex-enone. The active sites are assumed to be Pd2+ and Pd° for the two products, respectively. Homogeneous Wacker-type reactions are described in Section XI. 

Write balanced equations for (a) the overall oxidation of RCH=CHR in Pd-catalyzed Wacker process (b) a stoichiometric reaction between PdCl and RCH=CHR in water (c) oxidation of cyclohexanone to 8.13 by nitric acid (d) oxidation of 8.13 to adipic acid by nitric acid in the absence of vanadium ions (e) oxidation of 8.13 to adipic acid by nitric acid in the presence of vanadium ions. 

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