Alkylation asymmetric allylic

Nemoto and Hamada [50] has described the development of a new class of chiral phosphorus ligand - aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs - and their application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation was initially examined in detail using diaminophosphine oxides 77, resulting in the highly enantioselective construction of quaternary stereocenters. With the use of the Pd-DIAPHOX catalyst system, asymmetric allylic alkylation, asymmetric allylic amination, and enantioselective construction of quaternary carbons were achieved with high ee (up to 97-99% in many cases) (Scheme 24). 

Keywords Allylic alkylation Asymmetric catalysis Decarboxylation Enolate a-alkylation Palladium catalysis PHOX ligands Quaternary stereocenters... 

Pd-catalyzed asymmetric allylic alkylation is a typical catalytic carbon-carbon bond forming reaction [ 126 -128]. The Pd-complex of the ligand (R)-3b bearing methyl, 2-biphenyl and cyclohexyl groups as the three substituents attached to the P-chirogenic phosphorus atom was found to be in situ an efficient catalyst in the asymmetric allylic alkylation of l-acetoxy-l,3-diphenylprop-2-en (4) with malonate derivatives in the presence of AT,0-bis(trimethylsilyl)acetamide (BSA) and potassium acetate, affording enantioselectivity up to 96% and quantitative... 

Scheme 30. Example of Pd-catalyzed asymmetric allylic alkylation...

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

Fig. 2.22 Combination of chiral imidazolidin-2-ylidenes and biphenyl linkers in the chiral catalysts or catalyst precursors for the asymmetric allylic alkylations...

Scheme 1. Asymmetric allylic alkylation of rac-3-acetoxy-l,3-diphenyl-l-propene (rac-I) with dimethyl malonate catalysed by Pd/1 colloidal system. (Reprinted from Reference [44], 2004, with permission from American Chemical Society.)...

In 1999, Ikeda et al. reported a new type of sulfur-oxazoline ligands with an axis-fixed or -unfixed biphenyl backbone prepared in good yields by coupling reactions of methoxybenzene derivatives substituted with a chiral oxazoline and a sulfur-containing Grignard reagent. These ligands were subsequently evaluated for the test palladium-catalysed asymmetric allylic alkylation... 

The catalytic enantioselective addition of vinylmetals to activated alkenes is a potentially versatile but undeveloped class of transformations. Compared to processes with arylmetals and, particularly alkylmetals, processes with the corresponding vinylic reagents are of higher synthetic utility but remain scarce, and the relatively few reported examples are Rh-catalysed conjugate additions. In this context, Hoveyda et al. reported very recently an efficient method for catalytic asymmetric allylic alkylations with vinylaluminum reagents that were prepared and used in Thus, stereoselective reactions... 

Moreover, a few chiral ferrocenylsulfur-imine ligands were investigated in the palladium-catalysed asymmetric allylic alkylation of 1,3-diphenylpropenyl acetate and cyclohexenyl acetate with dimethyl maionate (Scheme... 

Trost and co-workers have explored asymmetric transition metal-catalyzed allylic alkylations. Details on this subject have been well reviewed by Trost and others.90 With the use of asymmetric palladium-catalyzed desymmetrization of meso-2-ene-l,4-diols, cw-l,4-dibenzoy-loxy-2-cyclopentene can be converted to the enantiometrically pure cA-4-tert-butoxycar-bamoyl-l-methoxycarbonyl-2-cyclopentene.91 The product is a useful and general building block for synthesis of carbocyclic analogs of nucleosides as presented in Scheme 5.12. 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

Some attempts to obtain a polymer-supported catalyst for chiral asymmetric allylic alkylation have been reported with some success in respect of catalyst recycling on activity, but with unsatisfactory results concerning enantioselectivity.188,189... 

They demonstrated that the C2-symmetric bis-benzothiazine (R,R)- 91 was an effective ligand in the asymmetric allylic alkylation reaction. The best result in this case was the reaction of 198 and 199 in the presence of BSA, Pd2(dba)3 and (/ ,/ )-197, which gave the product (S)-200 in 75% yield and 86% ee. More experimental data revealed that solvent effects are very important in this reaction (Scheme 57). Relatively nonpolar solvents resulted in good yields and enantiomeric excesses while reaction in CH3CN and CH2CI2 gave only racemic products in moderate yields (Table 8). 

The asymmetric allylic alkylation (AAA) reaction has been adapted for use with pyrrole nucleophiles <06JACS6054>. For example, treatment of pyrrole 55 and cyclopentene 56 with a palladium catalyst in the presence of a chiral additive gave pyrrole 57 in up to 92% ee. The latter was elaborated into piperazinone-pyrrole natural product, agelastatin A 94. 

A few intriguing developments in the area of tetrahydro-P-carboline synthetic methodology include the report of a catalytic asymmetric Pictet-Spengler reaction <06JACS1086> and an enantioselective Pd-catalyzed intramolecular allylic alkylation of indoles <06JACS1424>. A one-step synthesis of 1-substituted-P-carbolines from L-tryptophan has appeared that bypassed the tetrahydro intermediate <06T10900>. 

Copper-catalyzed Asymmetric Allylic Alkylations with Alkylzinc Reagents 403... 

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