Tsuji-Trost protocol

The Tsuji-Trost protocol has been successfiilly employed for the allyUc alkylation of preformed lactone enolates. It has been demonstrated that this Pd-catalysed reaction can be carried out in an enantio- and diastereo-selective manner. The use of additives, such as LiCl, was found to be crucial for reaching high levels of product selectivity. Among the five pathways investigated by DFT methods, the reaction between an (allyl)Pd(BINAP) (2,2 -bis(diphenylphosphino)-1,1 -binaphthyl) complex and a LiCl-lithium enolate adduct was predicted to be the most likely route for C-C bond formation. 

Over the past 30-1- years, cross-coupling protocols utilizing a wide variety of metals and metalloids have been studied. However, we will cover only those that have been applied the most often in organic synthesis. Furthermore, the related Heck (see Heck Reaction) and Tsuji-Trost reactions, which follow different mechanisms (and hence, do not fall under our more narrow definition), are beyond the scope of this entry. 

With ample supplies of 38 provided through this protocol, the Sorensen group could next attempt to attach the atoms needed to prepare 37, the projected intermediate for a second reaction based on 7T-allyl palladium complexes (a Tsuji—Trost reaction) that would hopefully lead to the 19-membered macrocycle 36. In essence, this requirement boiled down to only two key synthetic objectives generating a ketoester moiety from the Weinreb amide, and converting the allylic TES-protected alcohol function at Cl into a methyl carbonate. Neither of these tasks ultimately proved to be overly challenging to carry out, with the first accomplished by treating 38 with excess quantities of the lithium enolate of t-butyl acetate to provide 54, and the second requiring three rela-... 

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. 

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