Cyclization palladium catalysed

Intramolecular palladium-catalysed cyclizations can also be applied to N-vinylanilines. Usually the vinyl group carries an EW substituent which serves... 

Ames and Opalko have developed a palladium-catalysed cyclization of compound 24 to afford compound 25 in 56% yield (Scheme 5) <84T1919>. Glover and co-workers published a study involving the synthesis and photolysis of A-halogenobiphenyl-2-sulfonamides (26a or 26b) <86JCS(P2)645>. The photolysis of compound 26a or compound 26b in benzene formed an intermediate A-methylbiphenyl-2-sulfonamidyl radical, which resulted in compound 27a or 27b in 21% or 50% yield, respectively. In this procedure, the reaction only afforded the six-membered ring product 27(Scheme 6). 

Alkylbenzothiazole derivatives have been obtained by palladium-catalysed intramolecular cyclization of A-(o-bromophenyl)thioamides (Scheme 20).42... 

Special dibenzoxazepinones 86, obtained through the general method described in Fig. 16 and containing, as a third additional functionality, a triple bond, have been further cyclized via a palladium-catalysed hydroamination reaction (Fig. 17) [68]. In this way complex polycyclic systems 87 have been assembled in three steps, taking advantage of the three additional functions embedded in the starting component the aryl fluoride, the phenol and the triple bond. 

Efforts have been made to find stereoselective routes which provide disubstituted azetidines. Palladium catalysed cyclization of an enantiomer of allene-substituted amines and amino acids gives the azetidine ester 2 and a tetrahydropyridine in variable yield and ratio, depending on the substituents and conditions <990L717>. The (TRIS)- and (253I )-isomeis of the substituted azetidine-2-carboxylic acids 3 (R = COjH) are obtained in several steps from the corresponding 3 (R = CHjOSiMejBu ) which, in turn, is produced in high yield by photochemical intramolecular cyclization <98HCA1803>. 

Iodophenethylamine derivatives were found to undergo palladium catalysed cyclization to indolines.45 Starting from the appropriate tetrahydro-isoquinoline derivative the reaction was extended by Buchwald to the preparation of tricyclic natural products (3.37.),46... 

Copper was also effective in the creation of carbon-nitrogen bonds. N-(o-halophenyl)-guanidines gave 2-aminobenzimidazoles in the presence of a copper-1,10-phenantroline catalyst system. While the iodo and bromo derivatives in the presence of the copper catalyst gave the cyclized product in 83% and 96% yields respectively, the analogous palladium catalysed transformation showed similar efficiency in both cases, resulting in 88% and 86% yields.52... 

Not only acetylene derivatives do undergo palladium catalysed intarmolecular carbon-nitrogen bond formation with amines. The similar reaction of olefins in a Wacker-type process also leads to ring closure. (0-Aminopentenes bearing a suitable leaving group in the 4-position were converted to pyrroles in a cyclization-isomerisation-elimination sequence (3.65.),82... 

The Heck reaction has now been reviewed448,449. Evidence for the formation of zerova-lent palladium from (AcO Pd and Ph3P via a redox process has been provided450. This explains the origin of Pd(0) required for certain palladium-catalysed reactions in cases where Pd(II) is added to the reaction as the primary form of the Pd-catalyst. Thallium has been found to accelerate the Heck-type cyclization-carbonylation451. 

Trost s synthesis138 of desethylibogamine (233) illustrates the application of a new approach to alkaloid synthesis, in which the two vital cyclization processes involve catalysis by palladium complexes protection of the nitrogen by formation of an amide, so often necessary in conventional syntheses, is here unnecessary. The first of the cyclization processes, (234)—>(235), results in a very neat formation of the isoquinuclidine ring system via a palladium-catalysed SN2 cyclization of the tryptamine derivative (234) (Scheme 24). 

Oxo-/ -carbolines have been also synthesized in 21-31% yield by using arylpalladi-um complexes168. Ten years after the introduction of the method this palladium-catalysed cyclization of cyclic and acyclic Af-(2-iodophenyl)-substituted enaminones was... 

Palladium catalysed cyclization methods for preparing indoles using o-aminophenylacetylenes are discussed (1). 

Hi. Carbon-silicon bonds. Following the earlier reports mentioning the palladium-catalysed addition of organosilylstannanes to alkynes or isonitriles , Mori and coworkers realized tandem transmetallation-cyclization reactions with bifunctional halogeno triflates and Bu3SnSiMe3 18. The reactivity of 18 under palladium catalysis was used for the silylstannylation of alkenes or the synthesis of allylic silanes via a three-component (aryl iodide - - diene - - 18) coupling reaction. Recently, a similar... 

A novel palladium-catalysed carbonylation of iodobenzene has recently been linked to base-induced coupling and cyclization with o-phenylenediamine, to give 2-arylbenzimidazoles without having to use an aryl carboxylic acid (Scheme 3.1.13). Provided that bases with pATa values around 6.6 are used, the yields of 2-arylbcnzimidazoles lie in the range 70-98%. This route is tolerant of a variety of functional groups and complements the classical approaches where the required benzoic acids arc not readily available [85]. 

An attempt to demethylate the psychotomimetic phenylethylamine (8.3) resulted in a cyclized product being isolated [2629]. Another pharmacologically important indole (butotenin) may be synthesized by in situ demethylation of the diether (83) followed by dehydrogenation under alkaline conditions [2696]. Palladium-catalysed coupling of bromoarenes with a stannylethene provides ready access to -ethoxyvinylbenzenes (8.4) which cyclize at room temperature in acid [3929]. 

Palladium-catalysed cyclization of suitable iodo-alkynes (39.1) is improved by the presence of thallium(I) carbonate to give the aminovinylisoquinoline (39.2) otherwise, a poor yield of the vinylisoquinoiine (39.3) is obtained. 

In terms of the yield and reaction rate, the Reformatskii reaction is a rather convenient route to biologically active 3-methylene-substituted 2-oxo-l,2-oxaphosphacyclanes 85, including those having a spiro-structure (Scheme 52) [116, 117]. Metal-catalysed formation of the P-C bond was also successfully used for the synthesis of similar phostones [118]. Thus, 3-methylene-1,2-oxaphosphacycla-nes 85 were formed in reasonable yields by palladium-catalysed intramolecular cyclization in a series of hydrophosphoryl compounds 86 (Scheme 52). 

The synthesis of isosophoramine (26) employs as crucial stages the partial hydrogenation of iV-alkyl salts of ) -acyl (or cyano) pyridines, and acid-catalysed cyclization of the resulting l-alkyl-3-acyl (or cyano)-2-piperideines. Alkylation of nicotinonitrile with 6-bromohexan-2-one ethylene ketal afforded the salt (27), which on palladium-catalysed hydrogenation yielded the piperideine (28). Anhydrous acid-catalysed (TsOH) cyclization of (28) gave the three quinolizidine stereoisomers (29)—(31), which were separated and analysed by n.m.r. spectroscopy and equilibration studies in acid (TsOH-CgH ) and alkaline (KOBu -Bu OH)... 

Rearrangement occurs during the palladium-catalysed cyclization of a-substituted-N-acryloyl-o-bromo-anilines (129), and 4-substituted, e.g. (130), rather than 3-substituted quinolones are obtained (Scheme 53). ... 

Of course, these latter routes do not incorporate the triggering electrophile (e.g. iodine) which lends itself to additional homologation. Beyond the scope of this review are the many palladium-catalysed cyclizations which are formally 5-endo-A % processes and which have been summarized elsewhere <00MI001>. However, the power of these methods both to trigger cyclization and to allow incorporation of an additional substituent post-cyclization in a catalytic manner can be spectacular as illustrated by conversion of the alkyne-diol derivatives 271 into the furans 272 <85T3655>. 

---