Enantioselectivity asymmetric allylation

The enantioselective asymmetric allylation of imines has been a synthetic challenge, the initial solutions of which required stoichiometric amounts of chiral allylbor on [87], allylsilane [88], allylzinc [89], or allylindium reagents [90]. Itsuno showed that a chiral B allyloxazaborolidine derived from norephedrine could add to the N trimethylsilyl imine prepared from benzaldehyde in high yield and enantiomeric excess (Scheme 1.22) [91]. Brown later reported that B allyldiisopinocamphenylbor ane is also very effective for the allylation of the same electrophiles, but the addition of a molar amount of water is necessary to obtain high yields [92]. The diastereo and... 

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... 

Helquist et al. [129] have reported molecular mechanics calculations to predict the suitability of a number of chiral-substituted phenanthrolines and their corresponding palladium-complexes for use in asymmetric nucleophilic substitutions of allylic acetates. Good correlation was obtained with experimental results, the highest levels of asymmetric induction being predicted and obtained with a readily available 2-(2-bornyl)-phenanthroline ligand (90 in Scheme 50). Kocovsky et al. [130] prepared a series of chiral bipyridines, also derived from monoterpene (namely pinocarvone or myrtenal). They synthesized and characterized corresponding Mo complexes, which were found to be moderately enantioselective in allylic substitution (up to 22%). 

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

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... 

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... 

The aforementioned polymer-supported bis-pyridyl ligand has also been applied in microwave-assisted asymmetric allylic alkylation [140], a key step in the enantio-selective synthesis of (R)-baclofen (Scheme 7.118), as reported by Moberg and coworkers. The ( (-enantiomer is a useful agonist of the GABAb (y-aminobutyric acid) receptor, and the racemic form is used as a muscle relaxant (antispasmodic). Under microwave heating, the enantioselectivity could be improved to 89% when using toluene as solvent (see also Scheme 6.52) [140],... 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

This procedure describes the preparation and use of an effective chiral catalyst for the asymmetric allylation of aldehydes. A previous synthesis of optically pure 1-(phenylmethoxy)-4-penten 2-ol requires seven steps from D-mannitol.4 This procedure has been employed successfully with other aldehydes,5 and also with methallyltributylstannane5 (see Table). Catalysts prepared from (R)- or (S)-BINOL and Ti(0-i-Pr)4 at 2 1 stoichiometry have also proven useful in these reactions.The olefinic products may be regarded as latent aldol products between aldehydes and the enolate of actetaldehyde or acetone. In all cases examined thus far, enantioselectivity... 

When nitroalkenes were used as Michael acceptors, high yields and enantioselectivities of the desired Michael addition products were also obtained (Scheme 5.22). In these reactions, a well-defined chiral Ru amido complex (Figure 5.9) was an efficient catalyst. The mild reaction conditions and high reactivities and stereoselectivities allowed a large-scale reaction in the presence 1 mol% Ru catalyst. By using a chiral Pd(II) catalyst, an asymmetric allylic arylation was reported by Mikami and coworkers to give the cross-couphng product via the activation of both allylic C H and aryl C H bonds in moderate enantioselectivity (Scheme 5.23). ... 

Asymmetric allylic oxidation and benzylic oxidation (Kharasch-PSosnovsky reaction) are important synthetic strategies for constructing chiral C—O bonds via C—H bond activation.In the mid-1990s, the asymmetric Kharasch-Sosnovsky reaction was first studied by using chiral C2-symmetric bis(oxazoline)s. " Later various chiral ligands, based mainly on oxazoline derivatives and proline derivatives, were used in such asymmetric oxidation. Although many efforts have been made to improve the enantioselective Kharasch-Sosnovsky oxidation reaction, most cases suffered from low to moderate enantioselectivities or low reactivities. 

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],... 

Leighton has combined this concept of strained silacycles [62-66] with the asymmetric allylation chemistry in a series of pubhcations [60, 67-70], Leighton s aUyhc silacyclopentane 29 [67] (Scheme 20) works equally for allylation of aromatic and ahphatic aldehydes in the absence of additional Lewis bases (promoter activator) or Lewis acids with high yield and enantioselectivity. The mechanism of... 

Next to P(0) or N(0) Lewis bases, there are very rare cases where enantiopure sulfoxides are used in combination with silanes. Kobayashi and coworkers reported a highly diastereoselective and enantioselective allylation of hydrazones with chiral sulfoxide 32 (Scheme 23) [76], Massa [77,78] and Bamess [79] reported the asymmetric allylation of aldehydes with enantiopure sulfoxides, respectively, with moderate selectivity. 

Last year, a short enantioselective total synthesis of herbarumin III (42) in 11% overall yield was published the approach applied uses Keck s asymmetric allylation and Sharpless epoxidation to build the key fragment. Esterification with 5-hexenoic acid and a RCM was used to yield 42. Finally, another asymmetric synthesis of herbarumin III (42) was carried out using (R)-cyclohexylidene glyceraldehyde as the chiral template. The key steps of the synthesis were the enantioselective preparation of the... 

As described in the previous section, when acyclic and symmetric allylic esters such as l,3-diphenyl-2-propenyl acetate and l,3-dialkyl-2-propenyl esters are used as substrates, high to excellent enantioselective allylic alkylation is performed by using a variety of chiral ligands. In contrast, the number of successful examples of the asymmetric allylic alkylation of acyclic and unsymmetric allylic esters is relatively limited. 

In 2001, Takahashi and his co-workers developed the first asymmetric ruthenium-catalyzed allylic alkylation of allylic carbonates with sodium malonates which gave the corresponding alkylated compounds with an excellent enantioselectivity (Equation (Sy)). Use of planar-chiral cyclopentadienylruthenium complexes 143 with an anchor phosphine moiety is essential to promote this asymmetric allylic alkylation efficiently. The substituents at the 4-position of the cyclopentadienyl ring play a crucial role in controlling the stereochemistry. A kinetic resolution of racemic allylic carbonates has been achieved in the same reaction system (up to 99% ee). ... 

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