Tsuji-Trost reaction mechanisms

The accepted mechanism of the Tsuji-Trost reaction is as indicated in Scheme 1. The coordinatively unsaturated PdL (n < 4 and possibly n = 2) coordinates the double bond of the allylic system and displaces the... 

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. 

AUylic fluorides react with sodium dimethyl malonate (the Tsuji-Trost reaction) to form initially tight ion pairs [71]. Interestingly, the reaction does not foUow the normal double-inversion mechanism, which has been explained by the competitive reaction of the intermediate ion pair with neutral [PdLjj. 

Palladium-catalyzed allylic substitution reactions, known as Tsuji-Trost reactions, are a well-established method for carbon-carbon bond forming processes [48]. The generally accepted mechanism for this reaction involves the oxidative addition of the allylic substrate to Pd(0) to provide a Jt-allylpalladium complex. The subsequent reaction of the electrophilic 7t-allylpalladium complex with the nucleophile affords the substituted product and Pd(0), which is regenerated to start the catalytic cycle (Scheme 7.26). 

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. 

The basic mechanism of the Tsuji-Trost reaction is as follows All palladium precatalysts are converted to the active palladium(0) catalyst 11 in situ, most commonly by phosphine in phosphine assisted catalytic cycles. Following coordination of the allylic reagent 1 to the palladium(0) catalyst 11, oxidative addition occurs to give Jt-allylpalladium(II) complexes 13/14 (this step is also known as ionization). Complexes 13/14 can interconvert via ligand exchange... 

The formation of diastereomeric product 67 from the substrate E)-65 is plausibly rationalized by a twofold inversion firstly in the formation of the Jt-complex 66 and secondly by an approach of the nucleophilic enolate. In this case, there is no need for a thermodynamically controlled (Z)- to ( )-interconversion, and thus, a net retention in the allylic alkylation results (Scheme 5.22). Analogous stereochemical outcome was observed for the reaction of the lithium enolate of cyclohexanone with the allylic substrates (Z)-60 and ( )-65. The results shown in Schemes 5.21 and 5.22 clearly prove the outer-sphere mechanism for the Tsuji-Trost reaction of ketone lithium enolates [16c]. 

The enantioselectivity associated with quaternary allylation is connected with scenario 5 above (one of the five points associated in the catalytic cycles shown by Schemes 12.10a and b where chirality could be induced), which is where enantioselection of one of two faces of the nucleophile (the enolate ion) occurs. Theoretical studies of the transformation using the PHOX ligand have shown support for an inner sphere mechanism, where nucleophilic attack of the enolate onto the rf-allyl ligand occurs from the Pd-bound enolate and not from an external nucleophile.74 These studies have not been able to definitively determine the step that defines the enantioselectivity of the reaction, and it is not clear how these results would carry over to reactions involving the Trost ligands. At this time, selection of which ligand one should use not only to induce enantioselectivity but also to predict the sense of absolute configuration of any asymmetric Tsuji-Trost allylation is mostly based on empirical results. Work continues on this... 

The Tsuji-Trost allylation of enolates can be viewed as a variant of Pd-catalyzed cross-coupling involving aUylic electrophiles (Sects, ni.2.9 and III.2.10). In recognition of the widely accepted mechanism involving a nucleophilic attack by enolates at the TT-allyl ligand of an allylpalladium derivative on the side opposite to Pd, however, it is discussed separately in Part V together with the Wacker and related reactions, which are... 

The authors then performed a computational study of the reaction mechanism utilizing B3LYP-D3/LACVP. The reaction could be expected to follow the general mechanism shown in Scheme 8.10, which is derived from the mechanism suggested for the classical Tsuji-Trost allylic alkylation [57]. The full ligand and a... 

The reaction of alkenyl epoxides with organometallic species (lithium, magnesium, copper, and boron) affords allylic alcohols, following an Sn and/or Sn mechanism. These processes can accommodate only little organic functionality and exhibit low regio- and/or stereoselectivity. Under smooth conditions, C—C bond formation proceeds by nucleophilic alkylation of vinyl epoxides in the presence of catalytic amounts of zerovalent palladium. Regio- and stereoselectivity can be achieved via the formation of a Tr-allylpal-ladium complex. Trost and Molander and Tsuji and co-workers simultaneously reported the first studies in 1981. Since then, numerous papers have dealt with this subject. Essentially, after chelation and oxidative addition of the palladium onto the vinyl epoxide, the zwitterionic 7r-allylpalladium complex deprotonates the nucleophile, which can in principle attack either carbon 2 (proximal attack) or 4 (distal attack) (Scheme 1). 

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