Tsuji-Trost reaction allylic derivatives

The formation of chromane derivatives has also been realised in the palladium catalyzed intramolecular nucleophilic substitution of allyl carbonates (Tsuji-Trost reaction). In most cases the reaction is accompanied by the formation of a new centre of chirality. Using Trost s chiral ligand the ring closure was carried out in an enantioselective manner. The asymmetric allylation of the phenol derivative shown in 4.20. was achieved both in good yield and with excellent selectivity.23... 

The palladium catalyzed intramolecular nucleophilic substitution of allyl alcohol derivatives (Tsuji-Trost reaction) has successfully been extended to the closure of a seven membered ring. The coupling of the allyl alcohol unit and the enamide was the key step in the preparation of the natural product claviciptic acid (5.14.),14... 

Tsuji-Trost reaction (Scheme 11.12). xy -Disubstituted allyl derivatives can react with retention of the alkene geometry although y-monosubstituted allyl derivatives undergo geometrical scrambling typically to the extent of 10-15%. 

Leaving groups in the Tsuji-Trost reaction include acetates, halides, ethers, carbonates, sulfones, carbamates, epoxides, and phosphates. Reviews (a) Tsuji, J. In Handbook of Organopalladium Chemistry for Organic Synthesis, Negishi, E. deMeijere, A., Eds. Wiley-lnterscience New York, 2002 Vol II, Palladium-Catalyzed Nucleophile Substitution Involving Allyl Palladium, Propargyl-palladium and Related Derivatives, pp. 1669-1687. (b) Frost C. G. Howarth, J. Williams, J. M. J. Tetrahedron Asymmetry 1992, 3, 1089-1122. 

The allylation of active methylene compounds with allyl alcohols or their derivatives, called the Tsuji-Trost reaction, is a widely used process in academia as well as in industry. Ranu et al. have reported that the reaction of active methylene compounds with allyl acetate catalyzed by palladium(O) nanoparticles (Scheme 5.22) led to mono-allylation in water, whereas the reaction in THF provided the bis-allylated product. This is a remarkable example of controlling the direction of a reaction by water. 

Two crucial requirements for any catalytic reactions are (i) that the overall catalytic processes be thermodynamically favorable (i.e., AAG<0) and (ii) that all steps in a given catalytic cycle be kinetically accessible (i.e., of reasonably low activation energies). Moreover, so long as these two requirements are met, one or more of the microsteps in a catalytic cycle can be thermodynamically unfavorable. This is an obvious principle that nonetheless is frequently misunderstood. For example, the stoichiometric oxidative addition reaction of allyl acetate with Pd(0) complexes does not normally give the desired allylpalladium derivative in significant yields, and it may well be thermodynamically unfavorable. And yet, the Tsuji-Trost reaction of allyl acetate with malonates is normally facile. It is very important not to rule out any potentially feasible catalytic processes simply because some microsteps are or appear to be thermodynamically unfavorable. 

One distinguishes palladium(0)- and palladium(ll)-catalysed reactions. The most common palladium(O) transformations are the Mizoroki-Heck and the cross-coupling transformations such as the Suzuki-Miyaura, the Stille and the Sonogashira reactions, which allow the arylation or alkenylation of C=C double bonds, boronic acid derivates, stan-nanes and alkynes respectively [2]. Another important palladium(O) transformation is the nucleophilic substitution of usually allylic acetates or carbonates known as the Tsuji-Trost reaction [3]. The most versatile palladium(ll)-catalysed transformation is the Wacker oxidation, which is industrially used for the synthesis of acetaldehyde from ethylene [4]. It should be noted that many of these palladium-catalysed transformations can also be performed in an enantioselective way [5]. 

The advent of the catalytic Tsuji-Trost reaction in the early 1970s " (Sects. V.2.1.1 and V.2.1.2) has significantly expanded the scope of enolate allylation and related reactions. Noteworthy among others is that the range of allylic electrophiles was vastly expanded from allylic halides, such as chlorides and bromides, to a much wider range of derivatives including not only halides but also O, S, N, and other heteroatom-containing derivatives. Curiously, however, the scope of the Tsuji-Trost reaction had essentially been limited to the Pd-catalyzed allylation of extra-stabilized enolates, such as those derived from malonate and acetoacetate esters, until around 1980. 

Contrary to earlier notions that the Pd-catalyzed a-allylation of carbonyl compounds would be limited to those carbonyl compounds that are extrastabilized (the Tsuji-Trost reaction), the use of Zn, B in the forms of BRjK or Li + 2 BR3, where R = Et, and so on, Si, and Sn has been shown to permit the use of those enolates of ordinary ketones, aldehyde esters, and so on, where the pATj of the carbonyl compounds may be 20. In some cases, however, even lithium enolates can provide satisfactory results. Since most of the enolates mentioned above are derived via alkali metal enolates containing Li, Na, or K, these parent enolates should be tested before converting or modilying them with reagents containing other metals. 

In the Tsuji-Trost reaction, an allylic acetate first oxidatively adds to the Pd(0) catalyst to give a Tr-allyl complex, which undergoes nucleophilic attack by the carbanion derived from the deprotonated active methylene compound allyl alcohols and aldehydes can be coupled by a related procedure. 

The first diastereoselective and enantioselective allylic alkylation of cyclohexanone (through the magnesium enolate 18a) with diphenylallyl acetate 19a was reported in 2000 by Braun and coworkers [16a]. (7J)-BINAP (23) served as the optimum chiral ligand, and the alkene 20 was obtained as an almost pure diastereomer with an enantiomeric excess of 99% ee. The relative configuration was proven by the crystal structure analysis the absolute configuration was assigned unambiguously by chemical correlation. A first diastereoselective and enantioselective Tsuji-Trost reaction of a lithium enolate derived from... 

Ester enolates, much more sensitive and capricious than ketone and amide enolates, seemed to be unsuitable for palladium-catalyzed allylic alkylations. Thus, Hegedus and coworkers [24] reported on low yields and predominant side reactions in the allylation of the lithium enolate of methyl cyclohexanecarboxylate. It seems that so far the only reliable and efficient version of a Tsuji-Trost reaction with ester enolates is based on the chelated zinc enolates 41 derived from N-protected glycinates 40 - a procedure that was developed by Kazmaier s group. 

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. 

One classic application of the Tsuji-Trost reaction in natural products synthesis is found in the synthesis of strychnine by Overman and co-workers in 1993. Reaction of acetoacetate derivative 138 with enantiopure allylic carbonate 137 in the presence of Pd2(dba)3, PPh3, and NaH in THF yielded the cw-adduct 139 in 91%. It is worth noting that the selective displacement of carbonate group occurs with retention of the configuration and proceeds via the reactive 7i-allyl intermediate (see. Scheme 13.38). Derivative 139 could then be elaborated in a number of steps, to complete the total synthesis of strychnine. 

Negishi, E.-i. Palladium-catalyzed cross-coupling involving 3-hetero-substituted compounds. Palladium-catalyzed a-substitution reactions of enolates and related derivatives other than the Tsuji-Trost allylation reaction. Handbook of Organopalladium Chemistry for Organic Synthesis 2002, 1, 693-719. 

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... 

III.2.14.1 Palladium-Catalyzed of-Substitution Reactions of Enolates and Related Derivatives Other than the Tsuji-Trost Allylation Reaction... 

In this section, attention is focused on the Pd-catalyzed a-substitution reactions of enolates and related derivatives represented by Method I in Scheme 1, other than Tsuji-Trost allylation and propargylation. Additionally, its charge-affinity inverted version represented by Method II in Scheme 1 is also discussed. In general, it is advisable to consider simultaneously various other alternatives including those shown in Scheme 1, especially Method III. Indeed, Method III discussed in the following section provides the currently most... 

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... 

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