Allylic catalyst loading

Chiral dirhodium(II) carboxamidate catalysts are, by far, the most effective for reactions of allylic diazoacetates [44, 45] and allylic diazoacetamides [46]. Product yields are high, catalyst loading is low (less than 1 mol%), and enan-tioselectivities are exceptional (Scheme 6). The catalysts of choice are the two... 

Few reports describe the cross metathesis of allyl halides [88]. First-generation catalyst 9 does not seem to be sufficiently reactive to promote this reaction in preparatively useful yields and acceptable catalyst loadings, but second-generation catalyst 56d gives good results for allyl chloride. Cross-metathesis... 

Unfortunately, in the case of trifluoroacetimidates COP-Cl (46) still required catalyst loadings, which are not useful for large-scale applications [10 mol% Pd (II)], while long reaction times were necessary for high conversion. Moreover, the scope was limited to substrates bearing a-unbranched alkyl substituents R at the 3-position of the allylic imidate. 

However, modification of the allyl fragment by substitution of one of the terminus positions has provided more active complexes by enabling a more facile activation step [159], This allows the coupling of highly hindered amines with hindered aryl chlorides at room temperature and with low catalyst loadings [160] (Scheme 6.48). 

Very recently, efforts have turned towards the use of [PdCii -CjHjjCKIPr)] 5 for the hydrodechlorination of polychlorinated phenyl substrates [14], In these cases, [PdCri -CjHjjCKIPr)] 5 proved to be less active than the non-allyl containing dimer [Pd( J,-Cl)Cl(IPr)]2 7 for the complete hydrodechlorination of 1,2,4,5-tetrachlo-robenzene to benzene, with conversions of 40% and 95% respectively found at 80°C and 0.02 mol% catalyst loading in the presence of KO Bu/ PrOH. 

Allyl methylcarbonate reacts with norbornene following a ruthenium-catalyzed carbonylative cyclization under carbon monoxide pressure to give cyclopentenone derivatives 12 (Scheme 4).32 Catalyst loading, amine and CO pressure have been optimized to give the cyclopentenone compound in 80% yield and a total control of the stereoselectivity (exo 100%). Aromatic or bidentate amines inhibit the reaction certainly by a too strong interaction with ruthenium. A plausible mechanism is proposed. Stereoselective CM-carboruthenation of norbornene with allyl-ruthenium complex 13 followed by carbon monoxide insertion generates an acylruthenium intermediate 15. Intramolecular carboruthenation and /3-hydride elimination of 16 afford the -olefin 17. Isomerization of the double bond under experimental conditions allows formation of the cyclopentenone derivative 12. 

Ruthenium catalysts have also been used in this context.200,201 In particular, the cationic ruthenium complex, CpRu(CH3CN)3PF6, in conjunction with carboxylic acid ligand 3, has been used to achieve the remarkably chemoselective allylation of a variety of alcohols via dehydrative condensation with allyl alcohol (Equation (50)).202 It is worth noting that this transformation proceeds with 0.05 mol% catalyst loading and does not require the use of excess allyl alcohol. 

As previously discussed, activation of the iridium-phosphoramidite catalyst before addition of the reagents allows less basic nitrogen nucleophiles to be used in iridium-catalyzed allylic substitution reactions [70, 88]. Arylamines, which do not react with allylic carbonates in the presence of the combination of LI and [Ir(COD)Cl]2 as catalyst, form allylic amination products in excellent yields and selectivities when catalyzed by complex la generated in sim (Scheme 15). The scope of the reactions of aromatic amines is broad. Electron-rich and electron-neutral aromatic amines react with allylic carbonates to form allylic amines in high yields and excellent regio- and enantioselectivities as do hindered orlAo-substituted aromatic amines. Electron-poor aromatic amines require higher catalyst loadings, and the products from reactions of these substrates are formed with lower yields and selectivities. 

Similar results were reported by the Barret group by using stoichiometric amounts of an enantiopure 2-(2-pyridinyl)-2-oxazoline [46], hi 1996, Iseki and Kobayashi achieved a catalytic version of the asymmetric allylation [47], They applied proline-based chiral HMPA derivatives for the allylation. The catalyst 21 proved to be the best one regarding catalyst loading down to 1 mol% (Scheme 16) [48],... 

HayasM et al. achieved high catalytic activity by using axially chiral iV-oxide catalyst 27. As compared to other organic catalysts, the reaction proceeded much faster, and high enantioselectivities were obtained with 0.01-0.1 mol% catalyst loading [53-55]. In 2005, Hoveyda and Snapper used a novel proline-based ahphatic A-oxide 28 for an asymmetric allylation (Scheme 19) [56],... 

Rhodium-catalyzed allylic etherification could also be extended to the more challenging tertiary alcohols (Eq. 7). Although preliminary attempts revealed that the alkylation of the allylic carbonate 51 was feasible, the reaction required increased catalyst loading (20 mol%), affording the allylic ether 52 in 67% yield (2° 1°=47 1). 

To the best of our knowledge, the allylation of dithianes has not been previously reported in the literature. A range of dithianes underwent smooth allylation to give the desired thioester products in good yield however, a slightly increased catalyst loading (2-10 mol%) was needed (Table 8). 

A similar approach was taken for the synthesis of 45 by Miyaura. " Shaughnessy and Booth synthesized the water-soluble alkylphosphine 46, and found it to provide very active palladium catalysts for the reaction of aryl bromides or chlorides with boronic acids. The more sterically demanding ligand 47 was shown to promote the reactions of aryl chlorides with better results than 46. Najera and co-workers recently reported on the synthesis of di(2-pyridyl)-methylamine-palladium dichloride complexes 48a and 48b, and their use in the coupling of a variety of electrophiles (aryl bromides or chlorides, allyl chlorides, acetates or carbonates) with alkyl- or arylboronic acids very low catalyst loadings at Palladium-oxime catalysts 8a and 8b) have also been developed. In conjunction with... 

This transformation has been applied to several chiral production processes, the first being the synthesis of a pheromone (Disparlure) intermediate (S) albeit with low turnover numbers and only 91 % ee. Another industrial product is the epoxide of allyl alcohol as developed by PPG-Sipsy, to give a process where catalyst loading was decreased by molecular sieve addition and the safety factors involving peroxide contamination were overcome. These examples are shown in Figure 1.46. 

Pentacarbonyliron can catalyze the isomerization of double bonds under photochemical conditions. Using catalyst loadings as low as 1-5 mol%, this process proceeds smoothly for allyl alcohols, which isomerize to the corresponding saturated carbonyl compounds. 

A nickel hydride complex, NiHCl(diphenylphosphinoethane), catalyses the tandem isomerization-aldolization reaction of allylic alcohols with aldehydes.156 The atom- (g) efficient process proceeds at or below ambient temperature with low catalyst loading, and works well even for bulky aldehydes. Magnesium bromide acts as a co-catalyst, and mechanistic investigations suggest that a free enol is formed, which then adds to the aldehyde in a hydroxyl-carbonyl-ene -type reaction. 

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