Anti-Markovnikov Wacker oxidation

Figure 23.14 Schematic setup for the synthesis of phenyiacetaidehydes from styrenes through an aerobic anti-Markovnikov Wacker oxidation.

The impressive activity achieved by Teles catalyst was improved some years later by the use of CO as an additive [92]. In this study, Hayashi and Tanaka reported a TOF of 15600h 1, at least two orders of magnitude higher than [as-PtCl2(tppts)2], for the hydration of alkynes, providing an alternative synthetic route to the Wacker oxidation. Although several solvents were tested, the best results were obtained with aqueous methanol, and sulfuric acid or HTfO as acidic promoters. Unlike Utimoto s observation, in this case terminal propargylic alcohols partially (17-20%) delivered anti-Markovnikov product, in addition to the Markovnikov species. Some years before, Wakatsuki et al. had already reported the anti-Markovnikov hydration of terminal alkynes catalyzed by ruthenium(II) [93]. 

It was observed that the substitution of a methyl group on the terminal carbon of styrene or adamantane [Eq. (9.185)] switches the regioselectivity from Markovnikov to anti-Markovnikov in the Wacker oxidation 1310... 

Numerous variations and improvements exist for the Wacker-Tsuji oxidation. Herein, only two major categories are discussed anti-Markovnikov products and the Wacker-type oxidation. 

Reversal of the regioselectivity has been observed for the Wacker-Tsuji oxidation of alkene systems. Mechanistically, the regiochemistry of the Wacker-Tsuji oxidation stems from the Markovnikov addition (which takes place for the vast majority of the cases) versus the anti-Markovnikov regioselectivity although methyl-ketone 2 is often the major product and aldehyde 7 is the minor product. However, abnormal regiochemistry has been observed where aldehyde 7 is the major or even sole product in the Wacker-Tsuji oxidation. 

Pellissier and colleagues reported that terminal olefin 18 underwent a Wacker oxidation to give methylketone 19 as the major product in 85% yield and aldehyde 20 as the minor product in 7% yield.23,24 However, when the configuration of the neighboring lactone was switched like in substrate 21, the yield for the anti-Markovnikov addition product 23 was 35%. The authors proposed the assistance of the neighboring oxygen contributed to the regiochemistry. 

For the stereoselective synthesis of C-glycosides, deoxygenation of hemiketals, obtained from Wacker oxidation of sngar-derived olefin alcohols, was envisaged as an easy and efficient protocol. In our earlier study on the synthesis of 4-epiethisolide, attempted PdCV mediated conversion of the terminal olefin (1), obtained from sugar chiron into a methyl ketone (2) resulted in the exclnsive formation of an anti-Markovnikov product (3), which happened to be the first report in the literature (Scheme 22.1). 

SCHEME 2.113 An anti-Markovnikov selective Wacker-type oxidation [169]. 

Need a practical version of the Wacker oxidation of alkenes with anti-Markovnikov selectivity... 

Alteration of regioselectivity of the Wacker oxidation of styrenes (90) in favour of the corresponding aldehydes (92) rather than methylketones has been achieved simply using t-BuOH rather than water. The reaction presumably proceeds via the vinyl ether (91), resulting from the anti-Markovnikov attack of the bulky nucleophile at the sterically less hindered terminal carbon. A similar reversion was observed for other terminal olefins (styrenes, allyl ethers, and 1,5-dienes) when the oxidation was carried out in the presence of pinacol, another bulky nucleophile, which produced acetals of the corresponding aldehydes. Similar effects of bulky alcohols have been reported previously. ... 

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