Development of the reaction system has led to various catalytic systems to address selectivity of the reaction, as well as introduction of intermolecular and intramolecular oxidations with non-water nucleophiles.
Regioselectivity Markovnikov addition The oxidation of terminal olefins generally provide the
Markovnikov ketone product. In rare cases where substrate favors the aldehyde (discussed below), different ligands can be used to enforce Markovnikov regioselectivity.
Sparteine (Figure 2, A) favors nucleopalladation at the terminal carbon to minimize steric interaction between the palladium complex and substrate.
Quinox (Figure 2, B) favors ketone formation when the substrate contains a directing group. When such substrate bind to Pd(Quinox)(OOtBu), this complex is coordinately saturated which prevents the binding of the directing group, and results in formation of the Markovnikov product. The efficiency of this ligand is also attributed to its electronic property, where anionic TBHP prefers to bind
trans to the oxazoline and olefin coordinate
trans to the quinoline.
Anti-Markovnikov addition The anti-Markovnikov addition selectivity to aldehyde can be achieved through exploiting inherent
stereoelectronics of the substrate. Placement of directing group at homo-allylic (i.e. Figure 3, A) and
allylic position (i.e. Figure 3, B) to the terminal olefin favors the anti-Markovnikov aldehyde product, which suggests that in the catalytic cycle the directing group
chelates to the palladium complex such that water attacks at the anti-Markovnikov carbon to generate the more thermodynamically stable palladacycle. Anti-Markovnikov selectivity is also observed in styrenyl substrates (i.e. Figure 3, C), presumably via η4-palladium-styrene complex after water attacks anti-Markovnikov. More examples of substrate-controlled, anti-Markovnikov Tsuji-Wacker Oxidation of olefins are given in reviews by Namboothiri, Feringa, Grubbs and co-workers paved way for anti-Markovnikov oxidation of
stereoelectronically unbiased terminal olefins, through the use of palladium-nitrite system (Figure 2, D). In his system, the terminal olefin was oxidized to the aldehyde with high selectivity through a catalyst-control pathway. The mechanism is under investigation, however evidence
Scope Oxygen nucleophiles The intermolecular oxidations of olefins with alcohols as
nucleophile typically generate
ketals, where as the palladium-catalyzed oxidations of olefins with carboxylic acids as nucleophile generates
vinylic or allylic
carboxylates. In case of
diols, their reactions with alkenes typically generate ketals, whereas reactions of olefins bearing electron-withdrawing groups tend to form
acetals. Palladium-catalyzed intermolecular oxidations of
dienes with carboxylic acids and alcohols as donors give
1,4-addition products. In the case of cyclohexadiene (Figure 4, A), Backvall found that
stereochemical outcome of product was found to depend on concentration of LiCl. This reaction proceeds by first generating the Pd(OAc)(benzoquinone)(allyl) complex, through anti-nucleopalladation of diene with acetate as nucleophile. The absence of LiCl induces an
inner sphere reductive elimination to afford the trans-acetate stereochemistry to give the trans-1,4-adduct. The presence of LiCl displaces acetate with chloride due to its higher binding affinity, which forces an outer sphere acetate attack anti to the palladium, and affords the cis-acetate stereochemistry to give the cis-1,4-adduct. Intramolecular oxidative cyclization: 2-(2-cyclohexenyl)phenol cyclizes to corresponding dihydro-benzofuran (Figure 4, B); 1-cyclohexadiene-acetic acid in presence of acetic acid cyclizes to corresponding lactone-acetate 1,4 adduct (Figure 4, C), with
cis and
trans selectivity controlled by LiCl presence.
Nitrogen nucleophiles The oxidative
aminations of olefins are generally conducted with
amides or
imides;
amines are thought to be
protonated by the acidic medium or to bind the metal center too tightly to allow for the
catalytic chemistry to occur. B) == Notes ==