Tsuji-Wacker oxidation

The lab scale modification - the Wacker-Tsuji Oxidation - is useful for the synthesis of various ketones. 

Rawal and Thadani [160] have taken advantage of alkynes as excellent insertion partners in Pd(II)-catalyzed allylations. Interestingly, the Pd(II) species present in the medium after alkyne insertion into allyl chlorides or bromides can serve for a sequential Wacker-Tsuji oxidation upon introduction of CuCl, oxygen, and water to the reaction medium to give y-halo /-fy-cnones 220 in good yields (Scheme 91). If phenylacetylene is used as an alkyne l-phenyl-pent-2-ene-l,4-dione can be isolated in 77% yield as the result of a subsequent oxidative hydration of the y-halo P,y-enone 220. 

Jiro Tsuji carried out many mechanistic and synthetic studies on the initial Wacker oxidation process.7-" It is now known as the Wacker-Tsuji oxidation for the oxidation of terminal olefin 1 to the corresponding methyl ketone 2 with oxygen in the presence of a catalytic amount of palladium and one equivalent of copper salt.12-" Nowadays, the Wacker-Tsuji oxidation is a standard methodology for transforming the terminal olefin to the corresponding methyl ketone.17 The reaction is so widely used that Tsuji declared that a terminal olefin could be viewed as a masked methyl ketone."... 

The mechanism of the Wacker-Tsuji oxidation has been intensively investigated by both academia and industry and it is now very well elucidated. In the 2002 book Handbook of Orgamopalladium Chemistry for Organic Synthesis, edited by Ei-ichi Negishi, Ptrick M. 

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. 

Not surprisingly, the most prevalent utility of the Wacker-Tsuji oxidation is to convert terminal alkenes to the corresponding methyl ketones. Thus under the standard conditions, terminal alkene 59 was oxidized to methyl ketone 60 in 74% yield.48 In addition, the... 

Wacker-Tsuji oxidation also works for carbohydrates as represented by transformation 61—62.49... 

In 2002, Rawal developed a tandem reaction via multifunction palladium catalysis combining haloallylation and the Wacker-Tsuji oxidation.53 For example, internal alkyne 68 first underwent a bromoallylation to give a 1,4-diene, which was subsequently oxidized to the methyl ketone 69 without addition of the palladium catalyst. 

In Leighton s total synthesis of dolabelide D, the Wacker-Tsuji oxidation diene 70 was achieved chemoselectively to produce methyl ketone 71.54 55 Furthermore, addition of (-)-sparteine as a ligand prevented olefin isomerization and led to selective formation of methyl ketone 71 from the terminal olefin in good yield.56... 

Classic Wacker-Tsuji oxidation was used in the total synthesis of copalol (80— 81)63 and a formal total synthesis of dysidiolide (82— 83).64... 

The Wacker-Tsuji oxidation has been applied in the synthesis of alkaloids as well. In an enantioselective total synthesis of (+)-monomorine 1, alkene 95 was oxidized to ketone 96, which was converted to (+)-monomorine I 97).6S> In addition, the synthesis of ABE tricyclic analogs of methyllycaconitine used a Wacker oxidation-aldol strategy to append the B ring to the AE fragment.7"... 

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