Asymmetric reactions Tsuji-Trost reaction, allylic alkylation

The asymmetric alkylation of allylic systems by means of palladium catalysis, the so-called Tsuji-Trost reaction, is one of the most investigated asymmetric catalytic reactions [34,35]. It is therefore no surprise that it has also caused interest in the area of ACTC ligands. 

In 1977, Trost published the first example of an asymmetric variant of the Tsuji-Trost reaction, termed the asymmetric allylic alkylation reaction (AAA). Much of the subsequent development of the AAA reaction can be attributed to the dedicated work of Trost and co-workers.There was a substantial time lag however, in the development of processes where high enantioselectivities were realized in a predictable fashion. This was due, in part, to the fact that chiral, asymmetrically pure ligands must create a chiral environment on the opposite face of the allyl fragment to the metal centre (a stereoelectronic requirement, vide infra)P This obviously represents a significant design challenge in the production of effective ligand systems. 

The protocols for the utilization of ketone-derived silyl enol ethers in Tsuji-Trost reactions were preceded by a report of Morimoto and coworkers on the enantioselective allylation of sUyl ketene acetals 88. Without external activation, they reacted with the allylic substrate 19d in the presence of the palladium complex derived from the amidine ligand 89 to give y,5-unsaturated esters 90 in moderate chemical yield but high enantiomeric excess (Scheme 5.29) [46]. Presumably, the pivalate anion hberated during the oxidative addition functions as an activator of the silyl ketene acetal. The protocol is remarkable in view of the fact that asymmetric allylic alkylations of carboxylic esters are rare. Interestingly, the asymmetric induction originates from a ligand with an uncomplicated structure. The protocol seems however rather restricted with respect to the substitution pattern of allylic component and sUyl ketene acetal. 

The Tsuji-Trost reaction is the palladinum-catalyzed substitution of allylic leaving groups by carbon nucleophiles. The nucleophile can be carbon-, nitrogen-, or oxygen- based compounds such as alcohols, enolates, phenols, and enamines, and the leaving group can be a halide or an acetate. This emerged as a powerful procedure for the formation of C—C, C—O and C—N bonds. The reaction, also known as Trost allylation or allylic alkylation, was named after Jiro Tsuij, who first reported the method in 1965 [42], and Barry Trost, who introduced an asymmetric version in 1973 [43]. 

The use of palladium(II) 7i-allyl complexes in organic chemistry has a rich history. These complexes were the first examples of a C-M bond to be used as an electrophile [1-3]. At the dawn of the era of asymmetric catalysis, the use of chiral phosphines in palladium-catalyzed allylic alkylation reactions provided key early successes in asymmetric C-C bond formation that were an important validation of the usefulness of the field [4]. No researchers were more important to these innovations than Prof. B.M. Trost and Prof. J. Tsuji [5-10]. While most of the early discoveries in this field provided access to tertiary (3°) stereocenters formed on a prochiral electrophile [Eq. (1)] (Scheme 1), our interest focused on making quaternary (4°) stereocenters on prochiral enolates [Eq. (2)]. Recently, we have described decarboxylative asymmetric allylic alkylation reactions involving prochiral enolates that provide access to enantioenriched ot-quatemary carbonyl compounds [11-13]. We found that a range of substrates (e.g., allyl enol carbonates,... 

Allylic alkylation, also known as the Tsuji-Trost reaction, operates via a unique mechanism that exploits the electrophihcity of 7t-allyl Pd complexes. It is a versatile transformation in asymmetric synthesis, and new catalysts are generally tested in this benchmark reaction. The investigation of functionalised NHC ligands containing electronically dissimilar groups has met limited success. Actually, allylic alkylation is one of the rare transformations in which phosphines still outperform NHCs. 

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