Intramolecular Tsuji-Trost reaction

As an alternative to this electrophilic activation/heterocyclization, Pd(0)-catalyzed intramolecular Tsuji—Trost reactions have been reported for the synthesis of THPs. For instance, in the presence of a Pd(0) complex and Trost s ligand [(R,R)-diphenylphosphino benzoic acid (DPPBA)]... 

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... 

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. 

Palladium Catalysts Palladium catalysts are effective and powerful for C—H bond functionalization. Carbene precursors and directing groups are commonly used strategies. Generally, sp3 C—H bond activation is more difficult than sp2 C—H bond activation due to instability of potential alkylpalladium intermediates. By choosing specific substrates, such as these with allylic C—H bonds, palladium catalytic systems have been successful. Both intramolecular and intermolecular allylic alkylation have been developed (Scheme 11.3) [18]. This methodology has presented another alternative way to achieve the traditional Tsuji-Trost reactions. 

Tsuji-Trost reaction is used to prepare the requisite secondary aminoalkyne for intramolecular hydroamination. Finally, olefin isomerization results in the preparation of functionalized 1,2,5-pyrroles [327]. 

More recently, in 2003, Sorensen demonstrated an impressive, scalable synthesis of cytotoxic natural product (+)-FRl 82877 34, which employed an intramolecular Tsuji-Trost allylation reaction to prepare the 19-membered macrocycle 33. Exposure of allylic carbonate 32 to 10 mol% palladium catalyst under high dilution formed the key bond in good yield and complete diastereoselectivity. This key intermediate was subsequently converted to (+)-FRl 82877 34 via an intramolecular Diels-Alder reaction. 

While the reaction of aliphatic alcohols can be problematic, there are several examples reported in the synthesis of complex molecular targets. For example, the use of Tsuji-Trost reaction in the synthesis of cis-2,5-disubstituted tetrahydrofiirans was reported by Williams and co-workers. They used a soft oxygen nucleophile in an intramolecular reaction to prepare the C7-C22 core of amphidinolide K 45. It was found the addition of MesSnCl was necessary to both suppress acyl migration and ensure the oxygen was strongly nucleophilic. 

In 2006 Fukuyama published a total synthesis of racemic morphine starting from isovanillin and a cyclohexene-epoxide [16, 17]. The key features in their synthesis are (1) a construction of the ether linkage between A and C rings by Tsuji-Trost coupling, (2) an intramolecular Heck reaction to construct A-C-E tricyclic system, and (3) an intramolecular Mannich-type reaction of a ketone with an aminal to provide the pentacyclic structure of morphine in a one-step reaction by double cyclization. 

Intramolecular Reaction of Ally Halides Tsuji-Trost-Type Reaction... 

The comparison of intramolecular carbopalladation reactions of allenes and alkenes outlined in Schemes 9-5 and 9-6 illustrates that not every transition metal catalyzed ring closure necessarily involves a template effect. Others, however, clearly benefit from it. A prototype example is the palladium catalyzed cycloisomerization of alkenyl epoxides carrying distal pre-nucleophiles [38, 39], representing one variant of the famous Tsuji-Trost allylation [40]. 

In 2006, Fukuyama presented an approach to codeine and morphine based on a Tsuji-Trost coupling and intramolecular Heck reaction as key steps [49, 61]. The synthesis was carried out in the racemic manifold however, by devising an alternative stereoselective route to epoxide 41, access to either the natural or the enantiomeric form of morphine could be achieved. 

Furthermore, following an analogous methodology, combining the Morita-Baylis-Hillman reaction and the Trost-Tsuji reaction, Krische and co-workers have obtained allyl-substituted cyclopentenones 94 [84], Reaction was initiated by Michael addition of tributyl phosphine to an enone moiety 92, generating a latent enolate 93 which reacts intramolecularly with a jr-allylPd complex as the electrophile partner. A final -elimination step of trib-utylphosphine, favored by the presence of the methoxide ion, delivered the substituted cyclopentenones 94 (Scheme 36). 

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