Allylation reactions. Tsuji-Trost reaction

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 water soluble vitamin (+)-biotin was synthesized by M. Seki and co-workers from L-cysteine in only 11 steps using inexpensive reagents and mild reaction conditions." The key ring forming step was an intramolecular allylic amination Tsuji-Trost reaction using a nitrogen nucleophile) of a cis allylic carbonate. As expected with a soft nucleophile, the allylation took place with an overall retention of configuration. 

Grigg and coworkers developed bimetallic domino reactions such as the electro-chemically driven Pd/Cr Nozaki-Hiyama-Kishi reaction [69], the Pd/In Barbier-type allylation [70], Heck/Tsuji-Trost reaction/1,3 dipolar cycloaddition [71], the Heck reaction/metathesis [72], and several other processes [73-75]. A first example for an anion capture approach, which was performed on solid phase, is the reaction of 6/1-134 and 6/1-135 in the presence of CO and piperidine to give 6/1-136. Liberation from solid phase was achieved with HF, leading to 6/1-137 (Scheme 6/1.30) [76]. 

The Tsuji-Trost reaction is the palladium-catalyzed allylation of nucleophiles [110-113]. In an application to the formation of an A-glycosidic bond, the reaction of 2,3-unsaturated hexopyranoside 97 and imidazole afforded A-glycopyranoside 99 regiospecifically at the anomeric center with retention of configuration [114], Therefore, the oxidative addition of allylic substrate 97 to Pd(0) forms the rc-allyl complex 98 with inversion of configuration, then nucleophilic attack by imidazole proceeds with a second inversion of configuration to give 99. 

The Tsuji-Trost reaction is the Pd(0)-catalyzed allylation of a nucleophile [48-51]. The NH group in imidazole can take part as a nucleophile in the Tsuji-Trost reaction, whose applications are found in both nucleoside and carbohydrate chemistry. Starting from cyclopentadiene and paraformaldehyde, cyclopentenyl allylic acetate 64 was prepared in diastereomerically-enriched form via a Prins reaction [52], Treating 64 with imidazole under Pd(0) catalysis provided the N-alkylated imidazole 65. 

Extending the aforementioned methodology from imidazole to adenine, the Tsuji-Trost reaction between the sodium salt of adenine and allylic acetate 66 gave 67 as a 82 18 mixture of cis trans isomers. Carbocyclic nucleoside 67 was advantageous over normal nucleosides as a drug candidate because it was not susceptible to degradation in vivo by nucleosidases and phosphorylases [52],... 

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],... 

For further details of this reaction, the reader is referred to Chapter 9. The catalytic allylation with nucleophiles via the formation of Ti-allyl metal intermediates has produced synthetically useful compounds, with the palladium-catalyzed reactions being known as Tsuji-Trost reactions [31]. The reactivity of Ti-allyl-iridium complexes has been widely studied [32] for example, in 1997, Takeuchi idenhfied a [lrCl(cod)]2 catalyst which, when combined with P(OPh)3, promoted the allylic alkylation of allylic esters 74 with sodium diethyl malonate 75 to give branched... 

The Tsuji-Trost reaction, more commonly applied to carbocyclic nucleoside synthesis, has been used in the synthesis of famciclovir 21 (Scheme 5) <2000T4589>. Reaction of 2-amino-6-chloropurine with allylic carbonate 22 in the presence of Pd2DBA3 and bis(diphenylphosphino)ethane (DPPE) gave a 1 1 ratio of 23 to 24 after 1 h (DBA = dibenzylideneacetone). However, a ratio of >95 5 in favor of the thermodynamically favored N-9 isomer 23 was subsequently obtained upon further stirring, highlighting the reversibility of the reaction in this specific instance. 

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... 

The efficient catalytic cycle is ascribed to the characteristic feature that Pd(0) is more stable than Pd(II). Reactions of 7t-allylpalladium complexes with carbon nucleophiles are called Tsuji Trost reactions. In addition to Pd, other transition metal complexes, such as those of Mo [26], Rh [27] and other metals, are used for catalytic allylation. 

The Tsuji-Trost Reaction (or Trost Allylation) is the palladium-catalyzed allylation of nucleophiles such as active methylenes, enolates, amines and phenols with allylic compounds such as allyl acetates and allyl bromides. 

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%. 

Palladium(0)-catalyzed allylation of nucleophiles (the Tsuji-Trost reaction) is a versatile synthetic method that has gained immense popularity in recent years. Rarely applied to ambident nucleophilic aromatic heterocycles before 1991, the Tsuji-Trost reaction has been extensively used in the chemistry of these compounds since 1991. Two factors have played decisive roles in this increased interest in the Pd(0)-catalyzed allylation of such heterocyclic rings one is that, unlike other alkylation procedures, the Pd(0)-catalyzed allylation can sometimes give the product of thermodynamic control when applied to ambident nucleophiles and the second is that the Tsuji-Trost allylation has become one of the standard methods for synthesizing carbanucleosides, which are important antiviral compounds (93MI1, 93MI2). Of course, the double bond of an allylic system can be modified in different directions, thus adding versatility to the Tsuji-Trost reaction. 

We include in Sections I,A and I,B some general features of the Tsuji-Trost reaction with comments on kinetic versus thermodynamic control in allylations and in alkylations in general. Then we review in Sections II, III, and IV all cases known to the authors of the application of the Tsuji-Trost reaction to ambident nucleophilic aromatic heterocycles. This leaves out of the review the allylation of such heterocyclic ambident nucleophiles as 2-piperidone and the like. By aromatic, we mean any heterocycle for which a tautomeric or mesomeric formula can be written that is aromatic in the normal structural sense of having 4n + 2n- electrons cyclically conjugated. 

Palladium(0)-catalyzed allylation of nucleophiles (Tsuji-Trost reaction) has become a powerful synthetic method owing to its versatility, broad... 

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... 

In one of the first papers on the subject, Billups et al. (80SC147) reported that the Pd(0)-catalyzed allylation of indole 96 with allyl acetate gave N-allyl- (97) and 3-allylindole (98) plus the diallylation product 99 (Scheme 21). They also showed that the yV-allyl isomer 97 rearranged under Pd(0) catalysis to the C-3 isomer 98, thus indicating that the formation of 98 was thermodynamically controlled (C > N). The work of Billups also includes the use of allyl alcohol instead of allyl acetate in the Tsuji-Trost reaction. 

The Pd(0)-catalyzed allylation of 96 with acrolein dimethyl acetal gives exclusively compound 104. The 7j3-allylpalladium cationic complex (4, R = OMe) is attacked only at the center bearing the substituent MeO (80SC147), thus emphasizing the importance not only of steric effects in the electrophile but also of the electronic effects in the Tsuji-Trost reaction (92T1695). Indole 96 has been also allylated with epoxide 105 under Pd(0) catalysis by Trost and Molander (81JA5969). The intermediate cationic complex is attacked at the exocyclic position, 106 being formed, as shown in Scheme 22. 

Acemoglu L, Williams JMJ (2002) Synthetic Scope of the Tsuji-Trost Reaction with Allylic Halides, Carboxylates, Ethers, and Related Oxygen Nucleophiles as Starting Compounds. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1689... 

The catalyst is not only active in the Tsuji-Trost reaction (allylic alkylation), but also in the corresponding amination reaction. This was shown by the reaction of (ii)-l,3-diphenylprop-... 

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