Tsuji-Trost reaction cyclization reactions

The catalytic version of allylation of nucleophiles via 7r-allylpaUadium intermediates was discovered in 1970 using allylic esters and aUyl phenyl ethers as substrates (Scheme Formation of 7r-allylpaUadium complexes by oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of electrophilic rr-allylpalladium complexes with soft carbon nucleophiles are the basis of the catalytic allylation. After the reaction, Pd(0) is regenerated, which undergoes oxidative addition to the allylic compounds again, making the whole reaction catalytic. The efficient catalytic cycle is ascribed to the characteristic feature that Pd(0) is more stable than Pd(II). Allylation of carbon nucleophiles with allyhc compounds via TT-allylpalladium complexes is called the Tsuji-Trost reaction. The reaction has wide synthetic applications, particularly for cyclization. " ... 

An ingenious extension of the Tsuji-Trost reaction was the cornerstone of Oppolzer s enantioselective synthesis of a heteroyohimbine alkaloid, (-t-j-B-isorauniticine (267) [117]. Substrate 263 was prepared from a commercially available glycinate equivalent by Malkylation, installation of the sultam chiral auxiliary followed by a sultam-directed C-alkylation. As illustrated in Scheme 48, the crucial double cyclization was accomplished by the treatment of 263 with Pd(dba), Bu,P, in the presence of carbon monoxide (1 atm) in acetic acid to give enone 264 and two other stereoisomers in a 67 22 11 ratio. In this case, an allyl carbonate, rather than an allyl acetate, was used as the allyl precursor. Since carbonate is an irreversible leaving group, formation of the n-allylpalladium complex occurs readily. In the presence of Pd(0), the allylic carbonate is converted into a n-allylpalladium complex with concurrent release of CO, and... 

Palladium-catalyzed reactions have been widely investigated and have become an indispensable synthetic tool for constructing carbon-carbon and carbon-heteroatom bonds in organic synthesis. Especially, the Tsuji-Trost reaction and palladium(II)-catalyzed cyclization reaction are representative of palladium-catalyzed reactions. These reactions are based on the electrophilic nature of palladium intermediates, such as n-allylpalladium and (Ti-alkyne)palladium complexes. Recently, it has been revealed that certain palladium intermediates, such as bis-7i-allylpalladium, vinylpalladium, and arylpalladium, act as a nucleophile and react with electron-deficient carbon-heteroatom and carbon-carbon multiple bonds [1]. Palladium-catalyzed nucleophilic reactions are classified into three categories as shown in Scheme 1 (a) nucleophilic and amphiphilic reactions of bis-n-allylpalladium, (b) nucleophilic reactions of allylmetals, which are catalytically generated from n-allylpalladium, with carbon-heteroatom double bonds, and (c) nucleophilic reaction of vinyl- and arylpalladium with carbon-heteroatom multiple bonds. According to this classification, recent developments of palladium-catalyzed nucleophilic reactions are described in this chapter. 

Allylic alcohols can serve as 7t-allyl cation precursors to act as electrophiles in Sn reactions with a tethered O-nucleophile giving rise to the formation of spiroannulated tetrahydrofurans <2000TL3411>. Michael acceptors are also suitable electrophiles for the cyclization to tetrahydrofuran rings <2003T1613>. The Tsuji-Trost allylation has found widespread application in the synthesis of carbo- and heterocyclic compounds. Allylic substitution has been employed in the stereoselective synthesis of 2-vinyl-5-substituted tetrahydrofurans <2001H(54)419>. A formal total synthesis of uvaricin makes twofold use of the Tsuji-Trost reaction in a double cyclization to bis-tetrahydrofurans (Equation 73) <20010L1953>. 

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. 

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