Palladium Claisen rearrangement

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

Moyano A, Rosol M, Moreno RM, Lopez C, Maestro MA (2005) Oxazoline-mediated interannular cyclopalladation of ferrocene chiral palladium(II) catalysts for the enantioselective Azti-Claisen rearrangement. Angew Chem Int Ed 44 1865-1869... 

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. 

The asymmetric aza-Claisen rearrangement of allyl imidates, (86) (87), has been shown to be catalysed by homochiral cationic palladium(II) complexes, and a series of enantiopure cyclopalladated ferrocenyl amines and imines have been... 

In a variation of this method, a dimethylamine adduct can be used in the same way as the methanol adduct described previously [Eq. (20)]. Nickel(II) and palladium(II) complexes with allyl-substituted NHCs are accessible by this route. These compounds cannot be prepared by the cleavage of an electron-rich olefin vide infra) because of an amino Claisen rearrangement of the tetramino-substituted olefin. However, [(NHC)M(CO)4] (M = Cr or Mo) were accessible via cleavage of electron-rich olefins with [M(CO)6] as the precursors but for the very same NHC. ... 

Dehydrobromination of bromotrifluoropropene affords the more expensive trifluoropropyne [237], which was metallated in situ and trapped with an aldehyde in the TIT group s [238]synthesis of 2,6-dideoxy-6,6,6-trifluorosugars (Eq. 77). Allylic alcohols derived from adducts of this type have been transformed into trifluoromethyl lactones via [3,3] -Claisen rearrangements and subsequent iodolactonisation [239]. Relatively weak bases such as hydroxide anion can be used to perform the dehydrobromination and when the alkyne is generated in the presence of nucleophilic species, addition usually follows. Trifluoromethyl enol ethers were prepared (stereoselectively) in this way (Eq. 78) the key intermediate is presumably a transient vinyl carbanion which protonates before defluorination can occur [240]. Palladium(II)-catalysed alkenylation or aryla-tion then proceeds [241]. 

N Claisen rearrangement.3 This Pd(II) salt permits the rearrangement of S- llylthioimidates to N-allylthioamides. Tetrakis(triphcnylphosphine)palladium and various other metal salts are inactive. The rearrangement is inhibited by a substituent til the 2-position of the allyl group. 

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. 

Unfortunately, more heavily substituted hexadienes than those shown in equation (30) do not undergo the rearrangement, presumably because they have very low binding constants with catalytic palladium(II) species. Nevertheless, the Claisen rearrangement of allyl vinyl ethers can only take place provided palladium coordination to the vinyl group is... 

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. ... 

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. 

H. H. Baer and Z. S, Hanna, The preparation of amino sugars and branched-chain sugars by palladium-catalysed allylic substitution of alkyl hex-2-enopyranosides. Can. J. Chem. 59 889 (1981). D. P. Cuiran, An approach to the enantiocontrolled synthesis of pseudomonic acids via a novel mon-Claisen rearrangement. Tetrahedron Lett. 23 4309 (1982). 

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