Aldehydes enantioselective alkylation with

Propargylic esters undergo enantioselective alkylation with aldehydes (R-CHjCHO) to give propargylic alkylated products as a mixture of diastereomers (136), using cooperative catalysis by a copper(I)-BINAP complex and a diarylprolinol TMS ether." ... 

Comito, R. J., Finelli, F. G., MacMillan, D. W. C. (2013). Enantioselective intramolecular aldehyde a-alkylation with simple olefins direct access to homo-ene products. Journal of American Chemical Society, 135, 9538-9361. 

The oxazaborolidines are easily prepared by heating ephedrine with borane dimethyl sulfide or the appropriate boronate ester. The aluminum reagent C is obtained by mixing ephedrine and trimethylaluminum. Borolidinc A is superior to its methyl derivative B and to the aluminum analog C. The diastereomeric borolidine obtained from borane and (S,S)-pseu-doephedrine failed to show any cnantioselectivity25. A variety of aromatic aldehydes can be enantioselectively alkylated in the presence of A, however, with heptanal the enantioselectivity is poor25. 

An attractive alternative to these novel aminoalcohol type modifiers is the use of 1-(1-naphthyl)ethylamine (NEA, Fig. 5) and derivatives thereof as chiral modifiers [45-47]. Trace quantities of (R)- or (S)-l-(l-naphthyl)ethylamine induce up to 82% ee in the hydrogenation of ethyl pyruvate over Pt/alumina. Note that naphthylethylamine is only a precursor of the actual modifier, which is formed in situ by reductive alkylation of NEA with the reactant ethyl pyruvate. This transformation (Fig. 5), which proceeds via imine formation and subsequent reduction of the C=N bond, is highly diastereoselective (d.e. >95%). Reductive alkylation of NEA with different aldehydes or ketones provides easy access to a variety of related modifiers [47]. The enantioselection occurring with the modifiers derived from NEA could be rationalized with the same strategy of molecular modelling as demonstrated for the Pt-cinchona system. 

Woodward and co-workers recently achieved catalytic enantioselective alkylation of aldehydes with (R3Al)2 DABCO complexes or R3A1 (R = Me or Et) in the presence of Ni(acac)2/Feringa s ligand 196 (Equation (81 )).439... 

Alkylation with aldehyde 107 Alkylation, enantioselective 165 Alkylation, intramolecular 134,167 Enantioselective Mannich 151 From alcohol 26,41,86,176 From amide 11, 109,163 Halogenation, enantioselective 158... 

Recently, dendrimers, which are hyperbranched macromolecules, were found to be an appropriate support for polymer catalysts, because chiral sites can be designed at the peripheral region of the dendrimers (Scheme 5). Seebach synthesized chiral dendrimer 14, which has TADDOLs on its periphery and used an efficient chiral ligand in the Ti(IV)-promoted enantioselective alkylation [21]. We developed chiral hyperbranched hydrocarbon chain 15 which has six p-ami-no alcohols [22], It catalyzes the enantioselective addition of diethylzinc to aldehydes. We also reported dendritic chiral catalysts with flexible carbosilane backbones [23]. 

The substrate range - scope and limitations The reaction can be performed efficiently with a broad variety of ketone donors and aldehydes. Enantioselectivity, however, depends on the enolate structure (Scheme 6.11) [60, 61]. In general, eno-lates bearing larger, branched alkyl groups or a phenyl group result in lower enantioselectivity. The best results were obtained with enolates bearing a methyl substituent (product (S)-16, 87% ee) or a siloxymethyl substituent (product (S)-17, 86% ee). 

Enantioselective organocatalytic (with tetrahydro-4//-imidazol-4-one-based catalysts of type 102nHX) 2-alkylation of pyrroles by, -unsaturated aldehydes generates 3-(pyrrol-2-yl) aldehydes 103 (Scheme 46) <2001JA4370, 2002JA1172, 200SJA1S0S1 and references therein>. 

Chiral Ligand of L1A1H4 for the Enantioselective Reduction of Alkyl Phenyl Ketones. Optically active alcohols are important synthetic intermediates. There are two major chemical methods for synthesizing optically active alcohols from carbonyl compounds. One is asymmetric (enantioselective) reduction of ketones. The other is asymmetric (enantioselective) alkylation of aldehydes. Extensive attempts have been reported to modify Lithium Aluminum Hydride with chiral ligands in order to achieve enantioselective reduction of ketones. However, most of the chiral ligands used for the modification of LiAlHq are unidentate or bidentate, such as alcohol, phenol, amino alcohol, or amine derivatives. 

Enantioselective Alkylation. Both antipodes of this chiral amine have been used in the enantioselective alkylation of ketones and aldehydes via their respective chiral, nonracemic lithioe-namines (eq 1). The enantioselectivity in alkylation results from the induced rigidity of the lithioenamine upon chelation with the methoxy group, providing the bias necessary to influence the direction and rate of entry of the electrophile. 

Unlike alkyllithium and Grignard reagents, dialkylzinc does not add to ketones even in the presence of (1). Thus the chemo- and enantioselective alkylation of a keto aldehyde (4-benzoylbenzaldehyde) with Et2Zn using (5)-(l) affords the corresponding optically active hydroxy ketone with 93% ee in 99% yield. ... 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

Catalytic Enantioselective Alkylation of Aldehydes with Dialkylzincs . The chiral M,M-dialkylnorephedrines, analogs of (1), are highly efficient catalysts for the enantioselective addition of dialkylzincs to aliphatic and aromatic aldehydes. Optically active aliphatic and aromatic secondary alcohols with high ee are obtained using N,fV-dialkylnorephedrines (4-6 mol%) as chiral catalyst precursors. When (lS,2/J)-MN-dialkylnorephedrine is used as a chiral catalyst precursor, prochi ral aldehydes are attacked at the si face to afford (S)-alcohols (when the priority order is R >R2)(eq7). 

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