Tsuji regioselectivity

For internal olefins, the Wacker oxidation is sometimes surprisingly regioselective. By using aqueous dioxane or THF, oxidation of P,y-unsaturated esters can be achieved selectively to generate y-keto-esters (Eq. 3.18).86 Under appropriate conditions, Wacker oxidation can be used very efficiently in transforming an olefin to a carbonyl compound. Thus, olefins become masked ketones. An example is its application in the synthesis of (+)-19-nortestosterone (3.11) carried out by Tsuji (Scheme 3.5).87... 

Pd(0)-catalyzed allylations of 4(5)-nitroimidazole, 2-methyl-4(5)-nitroimidazole, 4(5)-bromoimidazole and 4(5)-methoxyimidazole resulted in complicated mixtures, which did not necessarily reflect the tautomeric ratios of the starting material [7], For example, poor regioselectivity for the products (70 and 71) was observed in the Tsuji-Trost reaction of 4(5)-bromoimidazole with cinnamyl carbonate. However, the same reaction with 4(5)-nitroimidazole and 2-methyl-4(5)-nitroimidazole led predominantly to the l-allylation products. In addition, removal of the 77-imidazole allyl groups can be selectively effected under mild conditions by Pd-catalyzed ic-allyl chemistry [55],... 

Shimizu and Tsuji [4] reported the first highly regioselective synthesis of 1,2-di-substituted allylic amines through capture of a Jt-allylpalladium complex by pyrrolidine (Scheme 16.2). This methodology has since been extended to a wide range of amines and allenes [5]. 

The exterior surface of the mesoporous support was first deactivated by treatment with PhaSiCk under non-diffusive conditions. The inner walls of the materials were then functionalised with 3- (5)-l-[(/ )-r,2-bisdiphenyl-phosphino)ferrocenyl]ethyl-A/,Ar-dimethylethylenediamino propylsilane chains. The mesoporous chiral catalyst obtained on reaction of with PdCl2, revealed higher regioselectivity (50%) and enantioselectivity (99%) in the Trost-Tsuji reaction than the same catalytic site bound on non porous high-area silica (values in brackets on Fig. 1). 

S. Y. Tosaki, R. Tsuji, T. Ohshima, M. Shibasaki, Dynamic ligand exchange of the lanthanide complex leading to structural and functional transformation One-pot sequential catalytic asymmetric epoxidation-regioselective epoxide-opening process, J. Am. Chem. Soc. 127 (2005) 2147. 

Tsuji and coworkers have developed diisobutylaluminum phenoxide-pyridine as an effective aldol condensation catalyst and applied it to the macrocyclization of 2,15-hexadecanedione (equation 132). Addition of the diketone at high dilution to a solution of the catalyst in hexane provides a mixture of cis and trans isomers of the and A enones. Catalytic hydrogenation of the mixture affords ( )-muscone. The authors explain the regioselectivity of the process by assuming that the aluminum phenoxide functions as a Lewis acid, coordinating to the carbonyl group. Pyridine functions as a base to remove a proton from the less hindered methyl group. 

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. 

In 1987, Tsuji reported for the first time the racemic palladium-catalysed 1,3-dipolar cycloaddition of vinylcyclopropanes with aryl isocyanates to give the corresponding 5-lactams. ° In 2008, Johnson et al. developed racemic palladium-catalysed cycloadditions of vinylcyclopropanes with aldehydes for the formation of tetrahydrofurans. Inspired by these pioneering results, Kura-hashi and Matsubara have recently developed nickel-catalysed 1,3-dipolar cycloaddition of vinylcyclopropanes with imines to give regioselectively the corresponding substituted pyrrolidine derivatives. As shown in Scheme 1.15,... 

Transition metal-catalyzed allylic substitution reactions with carbon nucleophiles are among the most important carbon-carbon bond formation methods in modem organic synthesis, because of their broad substrate scope under mild reaction conditions. In addition, they are applicable to enantioselective reactions, as well as exhibiting versatility towards the alkene functionality adjacent to the chiral centre for stereoselective derivatization. Tsuji-Trost allylic substitution, involving a (Ti-allyl) metal intermediate, has provided a particular advance in this regard [34, 35]. Most recently, Sawamura et al. [36, 37] have improved the regioselectivity of this reaction with unsymmetrically substituted allylic esters, and thus opened a new approach to sertraline. 

Scheme 3 Tsuji s regioselective allylic alkylation reactions...

Scheme 5-6. Regioselectivity issues in the Tsuji-Trost reaction. ...

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