Cycloadditions palladium catalysed

In further examples of sequential cycloaddition - palladium catalysed cyclisations, Grigg and co-workers have demonstrated the formation of polycyclic (3-lactams, e.g. (20) from the imine (19) (Scheme 3) <9stl9053>. 

Fishwick, C.W.G., Grigg, R., Sridharan, V. and Virica, J. (2003) Sequential azomethine imine cycloaddition-palladium catalysed cyclisation processes. Tetrahedron, 59, 4451-68. 

The cycloaddition of alkynes and alkenes to nitrile oxides has been used in the synthesis of functionalised azepine systems <96JHC259>, <96T5739>. The concomitantly formed isoxazole (dihydroisoxazole) ring is cleaved by reduction in the usual way. Other routes to 1-benzazepines include intramolecular amidoalkylation <96SC2241> and intramolecular palladium-catalysed aryl amination and aryl amidation <96T7525>. Spiro-substituted 2-benzazepines have been prepared by phenolic oxidation (Scheme 5) <96JOC5857> and the same method has been applied to the synthesis of dibenzazepines <96CC1481>. 

The 1,3-dipolar cycloaddition of allenes with 1,3-dipoles has been reviewed.56 The scope and limitations of palladium-catalysed intramolecular 3 + 2-cycloaddition of diastereomerically pure methylenecyclopropanes (33) yielding methylenecyclopentenes (34) has been investigated (Scheme 12).57 Chiral 2,5-dialkyl-7-phenyl-7-phosphabicy-... 

The palladium-catalysed intramolecular 3 + 2-cycloaddition of alk-5-enylidene-cyclopropanes produced a variety of bicyclo[3.3.0]octane systems with up to three stereocentres.62 The oxidative addition of cyclopropyl phenyl ketone to Ni(Pcy3) gave nickeladihydropyran, which is a key intermediate in the Ni(0)-catalysed homo-... 

C. W. Holzapfel and T. L. van der Merwe, Palladium-catalysed [3 + 2]-cycloaddition reactions employing sulphonyl-activated unsaturated carbohydrate derivatives, Tetrahedron Lett., 37 (1996) 2303-2306. 

The preparation of amphimedine 7-46 published by Echavarren and Stille [512] is a noteworthy application of 2-aza-1,3-butadienes in natural product synthesis since it is an interesting combination of hetero Diels-Alder methodology with a palladium catalysed cross coupling. Thus, dienophile 7-44 was formed by Stille coupling of the triflate 7-42 with the stannyl aniline 7-43. This qui-none then underwent cycloaddition to the 2-aza-l,3-butadiene 7-45 an acid catalysed hydrolysis of the cycloadduct 7-47 and subsequent N-methylation completed the synthesis of amphimedine 7-46 (Fig. 7-11). 

Palladium-catalysed processes typically utilise only 1-5 mol% of the catalyst and proceed through small concentrations of transient palladium species there is a sequence of steps, each with an organopalladium intermediate, and it is important to become familiar with these basic organopalladium processes in order to rationalise the overall conversion. Concerted, rather than ionic, mechanisms are the rule, so it is misleading to compare them too closely with apparently similar classical organic mechanisms, however curly arrows can be used as a memory aid (in the same way as one may use them for cycloaddition reactions), and this is the way in which palladium-catalysed reactions are explained in the following discussion. (For convenience, an organometallic component can be referred to as the nucleophilic partner and the halide as the electrophilic partner, but this should not necessarily be taken to imply reactivity as defined in classical chemistry. Also, references to the halide should be understood to include all related substrates, such as triflates.)... 

The disylanylstannane 635 adds terminal alkynes regio- and stereoselectively to form (Z)-alkenes 636, which undergo a tetrakis(triphenylphosphine)palladium-catalysed reaction with phenylacetylene to give 1 -sila-4-stannacyclohexa-2,5-dienes 637. 1,4-Dithianes 639 ( = 1) and 1,4-dithiepanes 639 n = 2) are obtained by the azoisobutyronitrile - induced homolytic cycloaddition of alkynes R C=CR (R = Pr, Bu or CMe20H R = H or Pr) to the dithols 63836 7a b. 

The AlCl3-catalysed 3-I-2-cycloaddition of diethyl frans -2,3-disubstituted cyclopropane-1,1-dicarboxylates and aromatic aldehydes produced diethyl 2,5-diaryl-4-benzoyltetrahydrofuran-3,3-dicarboxylates in moderate to good yields and with excellent diastereo-selectivities. The palladium-catalysed 3 -f- 2-cycloaddition of trimethylenemethane with aldehydes produced methylenetetrahydrofurans in good yields and with good enantioselectivities. A novel phosphoramidite ligand possessing a stereogenic phosphorous (29) was used in this transformation. ... 

In 2003, Trost and Frandrick developed a novel type of DYKAT based on the asymmetric palladium-catalysed cycloaddition between isocyanates and vinylaziridines. Performed in the presence of a chiral diphosphine as the ligand, the reaction allowed the access to a broad array of imidazolidin-2-ones with high yields and enantioselectivities of up to 95% ee, as shown in Scheme 2.58. In 2005, the same authors applied this methodology to the total synthesis of (-I- )-pseudodistomin D. ... 

The silyl acetates undergo palladium-catalysed cycloaddition with a range of electron-poor alkenes (Scheme 11.31). The yields are usually good, especially with tri- o-propylphosphite as a ligand. With cyclic alkenes, the cycloaddition occurs, as might be expected, on the less-hindered face. With acyclic alkenes, a stereogenic centre in the allylic position can exert useful stereo-control (Scheme 11.32). In this case the cycloaddition product 11.93 was an intermediate in a synthesis of brefeldin 11.94. ... 

In 1987, Tsuji reported for the first time the racemic palladium-catalysed 1,3-dipolar cycloaddition of vinylcyclopropanes with aryl isocyanates to give the corresponding 5-lactams. ° In 2008, Johnson et al. developed racemic palladium-catalysed cycloadditions of vinylcyclopropanes with aldehydes for the formation of tetrahydrofurans. Inspired by these pioneering results, Kura-hashi and Matsubara have recently developed nickel-catalysed 1,3-dipolar cycloaddition of vinylcyclopropanes with imines to give regioselectively the corresponding substituted pyrrolidine derivatives. As shown in Scheme 1.15,... 

The palladium-catalysed regioselective 3 + 2-cycloaddition of vinylic oxiranes with imines produces the corresponding 1,3-oxazolidines in good to excellent yields. The thermal hetero 1,3-dipolar cycloaddition of trimethylenemethane with IV-sulfonyl- and A-acyl-imines produce o -methylene-y-pyrrolidone acetals which can be hydrolysed to y-amino acids. ... 

Grigg, R Liu, A., Shaw, D Suganthan, S Washington, M.L., Woodall, D.E. and Yoganathan, G. (2000) Palladium-catalysed cascade molecular queuing-cycloaddition, cyclocondensation and Diels-Alder reactions. Tetrahedron Letters, 41,... 

Bamhal RB, Kemmit RDW. [3+3] Cycloadditions of trimethylenemethane to activated aziridines palladium-catalysed synthesis of piperidines. J. Org. Chem. 1989 362 C18-C20. 

The palladium [Pd(Ph3)4]-catalysed 3 + 3-cycloaddition of trimethylenemethane with azomethineimines produced hexahydropyridazine derivatives under mild conditions (40 °C).171 The Lewis acid-catalysed formal oxa-[3 + 3]-cycloaddition of a,f+ unsaturated aldehydes with 6-methyl-4-hydroxy-2-pyrone, 1,3-diketones, and viny-logous silyl esters yielded a variety of pyrones at room temperature.172 Croton-aldehyde has been converted to 6-hydroxy-4-methylcyclohex-l-enecarboxaldehyde by an enantioselective 3 + 3-cycloaddition catalysed by proline. This methodology was used in the synthesis of (—)-isopulegol hydrate, (—)-cubebaol, and (—)-6-hydroxy-4-methylcyclohex-l-ene-1-methanol acetate, an intermediate in the total synthesis of the alkaloid magellanine.173... 

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