Highly active chiral phosphoramide-Zn(II) complexes as conjugate acid-base catalysts for enantioselective organozinc addition to ketones

A highly efficient enantioselective organozinc (R2Zn) addition to ketones catalyzed by chiral phosphoramide-Zn(II) complexes (1-10 mol %) has been developed. These complexes serve as conjugate Lewis acid-Lewis base catalysts. Chiral phosphoramides are derived from an inexpensive natural amino acid (i.e., L-valine). From a variety of nonactivated aromatic and aliphatic ketones, the corresponding optically active tertiary alcohols were obtained in high yields with high enantioselectivities (up to 98% ee) under the mild reaction conditions.     

New class of amino-phosphinite chiral catalysts for the highly enantioselective addition of arylzinc reagents to aldehydes

A new class of amino-phosphinite chiral ligands was prepared and applied in zinc-catalyzed addition of aryl boronic acids to aldehydes; the reaction furnished the diarylmethanols in excellent yields and with a high level of enantioselectivity (up to 93% ee).     

Chiral catalysts for the enantioselective addition of organometallic reagents to aldehydes

A mechanistic model for the enantioselective addition of diethylzinc to benzaldehyde with chiral tridentate lithium complexes as catalysts correctly predicts the observed direction of enantioselectivity which occurs at levels of 85–95% ee.     

Modular ligands derived from amino acids for the enantioselective addition of organozinc reagents to aldehydes

A new series of modular chiral ligands that are derived from amino acids were prepared and tested for their ability to catalyze the asymmetric addition of alkylzinc reagents to aromatic and aliphatic aldehydes. The ligands contain a tertiary amine, an amino acid side chain, and a carbamate or amide functional group. One ligand, which was synthesized from Ile, catalyzes the addition of diethylzinc to cyclohexanecarboxaldehyde in 99% ee.     

An amino alcohol ligand for highly enantioselective addition of organozinc reagents to aldehydes: serendipity rules

[reaction: see text] Amino alcohol 4 (or its enantiomer) is prepared in two simple steps. Commercial (1R,2S)-2-amino-1,2-diphenylethanol is dialkylated with bis(2-bromoethyl) ether. Subsequent hydrogenation over 5% Rh on alumina in the presence of morpholine unexpectedly stops at the hexahydro derivative 4. Amino alcohol 4 promotes the enantioselective addition of diethylzinc to aldehydes at room temperature in up to 99% enantiomeric excess.     

Chiral bispyridylamide metal complexes as catalysts for the enantioselective addition of TMSCN to aldehydes

The use of (1R,2R)-N,N′-bis(2-pyridinecarboxyamido)-1,2-diphenylethane metal complexes as catalysts for the enantioselective addition of trimethylsilyl cyanide to aldehydes is described. Enantioselectivities up to 70% ee were obtained with a Ti(IV) catalyst. Complexes with Zr(IV), Sc(III), Yb(III) and Cu(II) afforded less selective catalysts. For the Zr(IV) complex, a rate and selectivity enhancement was observed when adding 0.5 equiv. of water with respect to the catalyst. Studies of the metal complexes involved in the reaction were carried out by means of ¹H NMR spectroscopy. A Zr complex was shown by X-ray crystallography to exhibit distorted octahedral coordination, with the four nitrogen atoms of the doubly deprotonated ligand essentially in one plane.     

Novel thiazolidine derivatives as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes

New chiral thiazolidine derivatives were synthesized conveniently from natural l-cysteine and showed good enantioselectivity (up to 90% ee) in the addition of diethylzinc to aldehydes. The catalytic efficiency of the thiazolidine derivatives is influenced by the different structures of the thiazolidine rings and the bulkiness of R moiety in the ester groups.     

Titanium fluoride complexes as catalysts for the enantioselective addition of Me3Al to aldehydes

We report a Ti(IV) catalyst prepared in situ from TiF₄ for the asymmetric addition of trimethylaluminum to aldehydes. The process we detail herein does not necessitate the use of excess trimethylaluminum or Ti(IV) reagent. Good enantioselectivities are achieved with a variety of aromatic and heteroaromatic aldehydes with the products isolated in high yield.     

Aminohydroxyphosphine ligand for the copper-catalyzed enantioselective conjugate addition of organozinc reagents

An alanine-derived aminohydroxyphosphine ligand was developed for copper-catalyzed asymmetric conjugate addition of organozinc reagents to alpha,beta-unsaturated carbonyl compounds. This new tridentate ligand induces consistently high enantioselectivity in reactions of a variety of acyclic substrates. Theoretical mechanistic analysis suggests that the C-C bond formation takes place through a highly ordered transition state by the coordination of the phosphorus and nitrogen atoms to the copper(III) and zinc(II) atoms, respectively, and of the oxygen anion to both the metal centers.     

Fesulphos-palladium(II) complexes as well-defined catalysts for enantioselective ring opening of meso heterobicyclic alkenes with organozinc reagents

The air-stable and readily available cationic methyl palladium(II) complexes of planar chiral Fesulphos ligands [(Fesulphos)Pd(Me)(PhCN)]+ X- are highly efficient catalysts for the alkylative ring opening of oxa- and azabicyclic alkenes with dialkylzinc reagents, showing broad scope with regards to both the bicyclic substrate and the dialkylzinc reagent. Catalyst loading as low as 0.5 mol % is sufficient to achieve good yields and enantioselectivities ranging 94 --> 99% ee in most cases. {Fesulphos = (1-phosphino-2-sulfenylferrocene); X- = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate or PF6(-)].} The origin of the high asymmetric induction has been rationalized by mechanistic studies combining computational calculations and X-ray structural analysis.     

New homochiral binaphthol-modified organolanthanide reagents for the enantioselective addition to aldehydes

Optically active secondary alcohols were obtained in high chemical yield and optical purity (up to 85% ee) from the lanthanide-mediated enantioselective addition of alkyl nucleophiles to aromatic aldehydes.     

trans-1-Sulfonylamino-2-isoborneolsulfonylaminocyclohexane derivatives: excellent chiral ligands for the catalytic enantioselective addition of organozinc reagents to ketones

The catalytic enantioselective addition of different organozinc reagents (such as alkyl and aryl derivatives or in situ generated aryl, allyl alkenyl, and alkynyl derivatives obtained through different transmetallation processes) to simple ketones has been accomplished by using titanium tetraisopropoxide and chiral ligands derived from substituted trans-1-sulfonylamino-2-isoborneolsulfonylaminocyclohexane, producing the corresponding tertiary alcohols with enantiomeric excesses (ee) up to >99 %. A simple and efficient procedure for the synthesis of the chiral ligands used in these reactions is described.     

Synthesis of new chiral aliphatic amino diselenides and their application as catalysts for the enantioselective addition of diethylzinc to aldehydes

[reaction: see text] A set of chiral aliphatic amino diselenides have been synthesized from readily available starting materials in a straightforward synthetic route via the ring-opening reaction of the parent aziridines. These ligands have been tested as catalysts for the enantioselective addition of diethylzinc to aldehydes. The influence of the alkyl group substituents on the stereoselectivity has been studied, and in the best case, an enantiomeric excess up to 99% could be obtained by using only 0.5 mol % of the chiral diselenide 3a.     

Aziridine sulfides and disulfides as catalysts for the enantioselective addition of diethylzinc to aldehydes

Chiral aziridine sulfides and disulfides were synthesized from readily available and inexpensive R-cysteine by a Mitsunobu reaction; their application in the addition of diethylzinc to aldehydes provides secondary alcohols with up to 99% ee and S-configuration.     

A positional scanning approach to the discovery of dipeptide-based catalysts for the enantioselective addition of vinylzinc reagents to aldehydes

[reaction: see text] A combinatorial library of dipeptide N-acylethylenediamine-based ligands was synthesized by parallel solid-phase methods. These ligands were screened in crude form as catalysts for the asymmetric addition of vinylzinc reagents to aldehydes to give chiral allylic alcohols. Three sites of diversity on the ligands were optimized using a positional scanning approach. The optimized structure from the library, ligand 54, was found to catalyze the formation of 10 different (E)-allylic alcohols with enantioselectivities ranging from 90% to 95% ee. This ligand was effective for both aromatic and alpha-branched aldehydes, and vinylzinc reagents derived from both bulky and straight chain terminal alkynes.     

New β-amino thiols as efficient catalysts for highly enantioselective alkenylzinc addition to aldehydes

A series of new optically active β-amino thiols and thiolacetates prepared from the simple natural amino acid, (S)-(−)-valine, were found to be effective catalysts for the enantioselective addition of alkenylzinc to aldehydes and thereby providing an efficient route for chiral (E)-allylic alcohols with ees of up to >99% in the presence of 7a (1 mol %).     

Chiral pyrrolidine derivatives as catalysts in the enantioselective addition of diethylzinc to aldehydes

A series of pyrrolidine derivatives with β-amino alcohol moieties prepared from (S)-proline were found to catalyze the enantioselective addition of diethylzinc to aldehydes to yield optically active secondary alcohols with high enantioselectivities. A mechanism accounting for the configurational change with the bulkiness of chiral ligands is proposed.     

Phosphinoyl-aziridines as a new class of chiral catalysts for enantioselective Michael addition

A series of new optically pure phosphine oxides containing chiral aziridine subunit were synthesized in good yields and applied as organocatalysts in asymmetric Michael reaction of various aliphatic aldehydes with β-nitrostyrene. The corresponding organocatalysts were synthesized starting from optically pure aziridines in a few simple efficient steps. The appropriate Michael adducts were obtained in most cases in very high chemical yield (up to 97%), excellent enantioselectivity (up to 98% of ee) and diastereoselectivity (up to 95:5 of dr).     

Supported chiral Mo-based complexes as efficient catalysts for enantioselective olefin metathesis

Syntheses and catalytic activities of seven new polymer-supported chiral Mo-based complexes are disclosed. Four of the complexes are polystyrene-based, and three involve polynorbornene supports. Studies concerning the ability of the polymer-bound chiral complexes to promote an assortment of asymmetric ring-closing (ARCM) and ring-opening (AROM) metathesis reactions are detailed. In many instances, levels of reactivity and enantioselectivity are competitive with those of the analogous homogeneous catalysts. The positive effect of lower cross-linking within the polymer backbone on reaction efficiency and asymmetric induction is detailed. The optically enriched products obtained through the use of the supported complexes, after simple filtration and removal of the supported Mo catalysts, contain significantly lower levels of metal impurities as compared to products synthesized with the corresponding homogeneous catalysts.     

3,3'-Diphosphoryl-1,1'-bi-2-naphthol-Zn(II) complexes as conjugate acid-base catalysts for enantioselective dialkylzinc addition to aldehydes

A highly enantioselective dialkylzinc (R(2)(2)Zn) addition to a series of aromatic, aliphatic, and heteroaromatic aldehydes (5) was developed based on conjugate Lewis acid-Lewis base catalysis. Bifunctional BINOL ligands bearing phosphine oxides [P(=O)R(2)] (7), phosphonates [P(=O)(OR)(2)] (8 and 9), or phosphoramides [P(=O)(NR(2))(2)] (10) at the 3,3'-positions were prepared by using a phospho-Fries rearrangement as a key step. The coordination of a NaphO-Zn(II)-R(2) center as a Lewis acid to a carbonyl group in a substrate and the activation of R(2)(2)Zn(II) with a phosphoryl group (P=O) as a Lewis base in the 3,3'-diphosphoryl-BINOL-Zn(II) catalyst could promote carbon-carbon bond formation with high enantioselectivities (up to >99% ee). Mechanistic studies were performed by X-ray analyses of a free ligand (7) and a tetranuclear Zn(II) cluster (21), a 31P NMR experiment on Zn(II) complexes, an absence of nonlinear effect between the ligand (7) and Et-adduct of benzaldehyde, and stoichiometric reactions with some chiral or achiral Zn(II) complexes to propose a transition-state assembly including monomeric active intermediates.