Aminoacetoxylation

The first example of intermolecular Pd-catalysed aminoacetoxylation of alkenes, such as (52), with phthalimide as the nitrogen source and PhI(OAc)2 as the stoichiometric oxidant and source of acetate has been reported. The reaction is highly regio- and diastereo-selective mechanistic studies revealed that the reaction proceeds... 

Liu G, Stahl SS (2006) Highly regioselective Pd-catalyzed intermolecular aminoacetoxylation of alkenes and evidence for cis-aminopalladation and SN2 C-O bond formation. J Am Chem Soc 128 7179-7181... 

A very interesting Pd"aminoacetoxylation reaction of alkenes was recently developed jointly by the Sorensen and Lee groups [60]. In a representative example, treatment of 75 with Pd(OAc)2 and PhI(OAc)2 provides oxazohdinone 76 in 65% yield with >20 1 dr (Eq. (1.33)). This transformation is heheved to proceed via a Pd"/Pd catalytic cycle that is initiated by antLatninopaUadation of the alkene to afford 77. The intermediate Pd complex is then oxidized by PhI(OAc)2 to alkyl Pd intermediate 78, which undergoes C—O bond-forming reductive elimination to afford 76. 

In recent years a series of aminoacetoxylation reactions have been reported, which all appear to follow the same concept (Scheme 4.7). These approaches were initiated within an investigation on direct aminoacetoxylation of alkenes by Sorensen [29]. This protocol provides a convenient approach to various pyrrolidines, piperazines, lactams, oxazolidin-2-ones and oxazinan-2-ones containing a... 

Phl(02CfBu)2 Phl(02CfBu)2 Scheme 4.8 Additional NaOAc Na02CfBu aminoacetoxylation N NHCOjfBu OjCfBu reactions employing iodosobenzene diacetate as... 

The overall process of this transformation was the subject of a detailed study [32]. It revealed that the reaction is reminiscent of the stereochemical pathways outlined above for aminoacetoxylation reactions, hence consisting of a syn-aminopalladation with an anti-C—N bond formation as the second step. The first step was found to be rate-determining, while the final one was suggested to involve a palladium(IV) catalyst state. 

For example, a (Z)-configured cinnamyl derivative 126 underwent clean aminoacetoxylation to 127 with complete preservation of stereo information, while the... 

An important study by Stahl and liu on intermolecular aminoacetoxylation of aUyl ethers revealed that this type of transformation could be carried out intermolecularly with complete regio- and stereoselectivity. The reaction was developed for terminal alkenes 176, and 13 examples of allyl ethers were presented with products 177 obtained in yields from 30 to 84% [119]. It suffers from the requirement of a twofold excess of alkene, but the demonstration of a first example of this type of reaction is a striking accomplishment (Scheme 16.47). 

The authors also used this transformation to investigate the overall stereochemical course, and in particular the pathway of oxidative intermolecular aminopalladation. Within this detailed mechanism, they arrived at the conclusion of an overall sequence of syn-aminopalladation and anti-C-O bond formation to explain the observed product stereochemistry for aminoacetoxylation of an internal alkene. This final result matches with the observed stereochemistry from related intramolecular cases [87]. 

It is also important to note that the obtained regioselectivity of this aminoacetoxylation reaction is opposite to the one observed in the seminal Sharpless asymmetric aminohydroxylation reaction (Sharpless AA reaction) [120]. Although processes of palladium(IV) catalysis currently cannot induce enantioselectivity, future development should render this unique reactivity complementary to existing enantioselective transformations. 

Pd(PhCN)2Cl2-catalyzed cyclic aminoacetoxylation of Al-tosyl pent-4-enamide with PhI(OAc)2 afforded 5-acetoxymethyl-l-tosylp)rrolidin-2-one, while the same reaction of allyl tosylcar-bamate or but-3-enyl tosylcarbamate formed 4-acetoxymethyl-3-tosyl-oxazolidin-2-one or4-acetoxymethyl-3-tosyl 1,3-oxazinan-2-one, respectively (eq 86). 4... 

They also realized the Cu(OAC)2-catalyzed aminoacetoxylation of N-alkenylamidines using PhI(OAc)2 as an oxygen source for synthesis of 4-acetoxymethyl-4,5-dihydroimidazoles [84] (Scheme 8.46). The aliphatic C-H bonds of Af-alkylamidines also could be activated to various dihydroimidazoles and tetrahydropyrimidines with Cu(0Ac)2/Phl(0Ac)2/K3P04 catalytic system [85] (Scheme 8.46). 

In recent years, a number of novel palladium-catalyzed diaslereoselective alkene difunctionalization reactions, such as aminohalogenation [34], aminoacetoxylation [35], aminofluorination [36], and diamination [37], have been studied intensively by the combination of other reactions with an amino- or oxopaUadation reaction. In some of these transformations, a Pd(IV) species is believed to be the key intermediate (Scheme 6.21). 

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