Palladium 11 -catalyzed Claisen Rearrangement

Palladium-Catalyzed Claisen Rearrangement General Procedure135 ... 

Al-Allyl-2(l//)-pyridones 41 are obtained by a palladium(II)-catalyzed Claisen rearrangement of 2-(allyloxy)pyridines 40 <96TL(37)2829>. 

Cyclic 1,2-diketones, such as3-methylcyclopentane-l,2-dione, act as oxygen nucleophiles in palladium(0)-catalyzed reactions with a range of cyclic and acyclic allylic esters. The products of these reactions were subjected to a lanthanide-catalyzed Claisen rearrangement to access the C-alkylated products. 

Konno, T., Daitoh, T., Ishihara, T. and Yamanaka, H. (2001) A novel and expedient synthesis of optically active fluoroalkylated amino acids via palladium-catalyzed allylic rearrangement and Ireland-Claisen rearrangement. Tetrahedron Asymmetry, 12, 2743-2748. 

Late transition-metal-catalyzed asymmetric Claisen rearrangement takes place in a different mode from that of Lewis-acid-catalyzed Claisen rearrangement Late transition metal catalysis is based on affinity for the Claisen diene system. Among late transition metals, palladium complexes are the most useful and effective for the Claisen rearrangement. 

Gamer AL, Koide K (2008) Oxidation state-specific fluorescent method for palladium(II) and platinum(IV) based on the catalyzed aromatic Claisen rearrangement. J Am Chem Soc 130 16472-16473... 

This series of rearrangements includes the dithia-Claisen rearrangement mentioned above (Section IV.E.l) as well as the palladium-catalyzed [3,3]-sigmatropic isomeriza-tions of allyl methyl N-aryldithiocarbonimidates 627 (refluxing dioxane, 20 h, 62-90%) (equation 275)376 and a Pd11-catalyzed tandem [2,3]-sigmatropic shift, followed by 1,3-dipolar cycloaddition which takes place at equilibrium between O-allyl ethers of oximes 628 and the corresponding N-allyl nitrones 629 (equation 276)377. 

A 1,3-diene moiety has been introduced to the 5-position of 6-hydroxyquinoline by palladium-catalyzed addition of allene <2001T7965>. It is thought that the reaction proceeds by initial 0-alkylation followed by Claisen rearrangement to give the C-alkylated product (Equation 8). 

In accessing chiral allyl vinyl ethers for Claisen rearrangement reactions, Nelson et al. employed the iridium-mediated isomerization strategy. Thus, the requisite enantioenriched diallyl ether substrate 28 was synthesized via a highly enantioselective diethylzinc-aldehyde addition protocol10 (Scheme 1.1k). The enantioselective addition of Et2Zn to cinnamaldehyde catalyzed by (—)-3-exo-morpholinoisobomeol (MIB 26)11 provided an intermediate zinc alkoxide (27). Treatment of 27 with acetic acid followed by 0-allylation in the presence of palladium acetate delivered the 28 in 73% yield and 93% ee. Isomerization of 28 with a catalytic amount of the iridium complex afforded the allyl vinyl ether... 

Two key intermediates in the production of vitamin A are citral and the so-called C5 aldehyde. In the modem routes to these intermediates, developed by BASF and Hoffmann-La Roche, catalytic technologies are used (see Fig. 2.29 and 2.30). Thus, in the synthesis of citral, the key intermediate is 2-methyl-l-butene-4-ol, formed by acid-catalyzed condensation of isobutene with formaldehyde. Air oxidation of this alcohol over a silver catalyst at 500°C (the same catalyst as is used for the oxidation of methanol to formaldehyde) affords the corresponding aldehyde. Isomerization of 2-methyl-l-butene-4-ol over a palladium-on-charcoal catalyst affords 2-methyl-2-butene-4-ol. The latter is then reacted with the aldehyde from the oxidation step to form an enol ether. Thermal Claisen rearrangement of the enol ether gives citral (see Fig. 2.29). 

The 10-hydroxy group can facilitate the alkylation of C-9 via a Claisen rearrangement, as in the case of 7-ethyl-lO-hydroxy-CPT [29], or nitration in the same position, possibly followed by removal of the OH and reduction of the nitro group by palladium-catalyzed deoxygenation to give 9-aminoCPT (7)[30], another drug candidate (Scheme 16.5). 

The Cope- and Claisen rearrangements are also catalyzed by square-planar transition metal complexes. Palladium complexes have been responsible for spectacular increases in the rates of Cope rearrangements by factors of up to 10 . Certain other sigmatropic rearrangements are also catalyzed by transition metal complexes. 

Potentially, the Claisen rearrangement is of greater synthetic utility merely because it is not coirfined to hydrocarbon substrates. However, no palladium-catalyzed thio-Claisen rearrangements have been observed, possibly owing to sulfijr poisoning the catalysts. Nevertheless, thioimidates have been rearranged in the presence of catalytic quantities of [PdCl2(PhCN)2]. 

The palladium(0)-catalyzed asymmetric O-allylation of phenols has been described using five-, six- and seven-membered ring allylic carbonates and acyclic allylic carbonates (eq 9). The products from these reactions were subjected to a Claisen rearrangement to provide C-alkylated phenols. A study of various ligands for the reaction of phenol with 2-cyclohexenyl-l-methyl carbonate clearly showed that the Trost ligand is superior. ... 

Palladium(II) salts catalyze the rearrangement of 1-allyloxy-l-siloxycyclopropanes to provide a mixture of hexenoic acids. The rearrangement proceeds via a double-bond isomerization followed by a ring opening of cyclopropane rather than homo-Claisen rearrangement. 

A related tetrakis(triphenylphosphino)palladium catalyzed aza-Claisen rearrangement is described in ref 134. For another example of 1.4-asymmetric induction in aza-Claisen rearrangements see ref 122. 

The stereochemistry of the Claisen rearrangement is generally predicted on the basis of conformational analysis in chairlike transition states (J) leading to the (E) substrate 49 and to the syn product. However, in this Pd(II)-catalyzed reaction, the (E) substrate 49 gave anti-50. This anomalous stereoselectivity is explained by six-membered ring boat transition states (K) via bidentate coordination to the palladium catalyst (Scheme 36). 

Linton and Kozlowski have installed quaternary centers at oxindole C3 in enantioselective fashion via the Pd-catalyzed rearrangement of 2-allyloxy indoles (Scheme 2) [16]. For example, indole 7 underwent an enantioselective Meerwein-Eschenmoser-Claisen rearrangement in the presence of Pd(SbF6)2 and the chiral phosphinooxazoline ligand 8 to afford oxindole 9 in 89% yield and 89% ee. A two-point coordination of the chiral palladium catalyst to the C3 carbonyl and C2 oxygen (6-membered coordination system) has been proposed to rationalize the enantioselectivity of the transformation. Modest to good enantioselectivities were also observed for a series of bisphosphine chiral ligands. 

Unfortunately, under these conditions the aUyUc amino add was obtained not via Claisen rearrangement, but an intermolecular palladium-catalyzed allyUc alkylation. For ejample, in reactions of crotyl esters two regioisomers are obtained. This fact, as well as the nearly complete lack of diastereoselectivity in the newly generated amino add of 25 synlanti 2 1) is a dear indication for an intermolecular process and the appearance of Tt-allylpaUadium intermediates. 

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