Enantioselective Friedel-Crafts alkylations of alpha,beta-unsaturated 2-acyl imidazoles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes

An enantioselective Friedel-Crafts alkylation with alpha,beta-unsaturated 2-acyl imidazoles and electron-rich aromatic nucleophiles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes has been accomplished. These alpha,beta-unsaturated 2-acyl imidazoles are effective electrophiles for the Friedel-Crafts reaction. The resulting adduct 2-acyl imidazole is easily converted to amides, esters, carboxylic acids, ketones, and aldehydes by methylation and subsequent displacement of the imidazole residue.     

Enantioselective Friedel-Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes

The enantioselective Friedel-Crafts addition of a variety of indoles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes (Sc(III)-pybox) was accomplished utilizing a series of beta-substituted alpha,beta-unsaturated phosphonates and alpha,beta-unsaturated 2-acyl imidazoles. The acyl phosphonate products were efficiently transformed into esters and amides, whereas the acyl imidazole adducts were converted to a broader spectrum of functionalities such as esters, amides, carboxylic acids, ketones, and aldehydes. The sense of stereoinduction and level of enantioselectivity were found to be functions of the size of the substrate employed, the substitution on the ligand, and the catalyst loading. Molecular modeling of the catalyst with the bound substrates was performed based on the crystal structures of the catalyst complexes and the sense of stereoinduction observed in the addition reaction. Nonlinear effects over a range of catalyst concentrations implicate a mononuclear complex as the active catalyst.     

Enantioselective indole Friedel--Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes

A highly enantioselective Friedel-Crafts alkylation of electron-rich aromatic nucleophiles catalyzed by scandium(III) triflate-pyridyl(bis)oxazoline complexes has been accomplished. The reaction involves alpha,beta-unsaturated acyl phosphonates as electrophiles and primarily substituted indoles as nucleophiles. The reactive acyl phosphonate product is converted to the corresponding ester or amide in good overall yield by adding an alcohol or amine directly to the reaction mixture.     

Catalytic enantioselective pyrrole alkylations of alpha,beta-unsaturated 2-acyl imidazoles

[reaction: see text] Enantioselective additions of pyrroles to alpha,beta-unsaturated 2-acyl imidazoles catalyzed by the bis(oxazolinyl)pyridine-scandium(III) triflate complex (1) have been accomplished. The alpha,beta-unsaturated 2-acyl imidazoles were synthesized in high yields through Wittig olefination. A short, enantioselective synthesis of the alkaloid (+)-heliotridane has been accomplished utilizing this methodology and a 2-acyl imidazole cleavage and cyclization. This methodology was then extended to the one-pot asymmetric synthesis of 2-substituted indoles.     

Chiral DBFOX/Ph complex catalyzed enantioselective nitrone cycloadditions to alpha,beta-unsaturated aldehydes

1,3-Dipolar cycloadditions of nitrones with alpha-alkyl- and alpha-arylacroleins are catalyzed with the DBFOX/Ph complexes of nickel(II) and magnesium(II) salts to produce the sterically controlled isoxazolidine-5-carbaldehydes, while the reactions with alpha-bromoacrolein are effectively catalyzed with the zinc(II) complexes to produce the electronically controlled isoxazolidine-4-carbaldehydes. Enantioselectivities up to 99.5% ee have been observed in the reactions performed at room temperature. [reaction: see text]     

Enantioselective oxidation of olefins catalyzed by chiral copper bis(oxazolinyl)pyridine complexes: a reassessment

Copper complexes of chiral tridentate pybox ligands synthesized using a modified procedure have been studied as catalysts for the enantioselective allylic oxidation of olefins. A variety of olefins have been used in this reaction. Using 5 mol% of a Cu(II) complex of the tridentate pybox ligand, phenylhydrazine, and tert-butyl perbenzoate as oxidant in acetone, optically active allylic benzoates were obtained up to 94% ee in few hours. It was also observed that the use of molecular sieves in the reaction did not alter the enantioselectivity. Temperature was found to be very crucial in rate of the enantioselective allylic oxidation of olefins. Using EPR spectra, it has been shown that the Cu(II) species is reduced to Cu(I) by phenylhydrazine and phenylhydrazone, but the reduction with the former is faster in comparison to the latter. It was concluded that the rate enhancement was not specific to the presence of phenylhydrazine or phenylhydrazone, but both were equally responsible provided acetone was used as a solvent.     

Enantioselective addition of allyltin reagents to amino aldehydes catalyzed with bis(oxazolinyl)phenylrhodium(III) aqua complexes

Bis(oxazolinyl)phenylrhodium(III) aqua complexes, (Phebox)RhX?(H?O) [X = Cl, Br], were found to be efficient Lewis acid catalysts for the enantioselective addition of allyl- and methallyltributyltin reagents to amino aldehydes. The reactions proceed smoothly in the presence of 5-10 mol % of (Phebox)RhX?(H?O) complex at ambient temperature to give the corresponding amino alcohols with modest to good enantioselectivity (up to 94% ee).     

Highly enantioselective nitrone cycloadditions with 2-alkenoyl pyridine N-oxides catalyzed by Cu(II)-BOX complexes

Enantioselective nitrone cycloadditions with 2-alkenoyl pyridine N-oxides as dipolarophiles have been reported. The reaction is catalyzed by Cu(II)-BOX complexes to give the expected isoxazolidine products with high diastereo- and enantioselectivity.     

Enantioselective Michael additions to alpha,beta-unsaturated imides catalyzed by a Salen-Al complex

(Salen)aluminum complex 1b is an efficient catalyst for the conjugate addition of di- and trisubstituted nitriles to a wide range of acyclic alkyl- and aryl-substituted alpha,beta-unsaturated imides. This new methodology provides access to multifunctional compounds that previously have not been readily accessible in enantioenriched form. Synthetic applications of these products include the preparation of enantiomerically enriched piperidines, as exemplified by an expedient asymmetric catalytic synthesis of (-)-paroxetine.     

Asymmetric Henry reaction catalyzed by oxazolinyl Cu(II) complexes

A novel family of oxazolinyl copper(II) catalysts have been developed and used as Lewis acid catalysts in the asymmetric Henry reaction of various aldehydes with nitromethane. The corresponding nitroalcohol products were obtained in moderate yields (40–80%) and with moderate enantioselectivity (10–40% ee).     

Enantioselective pinacol coupling of aryl aldehydes catalyzed by chiral Salan-Mo(IV) complexes

Reported herein is the asymmetric pinacol coupling of aromatic aldehydes with chiral Salan-Mo(VI) dioxo complex as an effective precatalyst. Chiral diols were obtained with high diastereoselectivity and enantioselectivity up to 92/8 and 95%, respectively. The possible mechanism of the pinacol coupling reaction with the catalytic system was investigated. The X-ray crystal structure of the precatalyst Mo(L3)O2 was determined and the oxidation state of the intermediate C was confirmed as +4 with X-ray photoelectron spectroscopy study. The proposed mechanism speculated the stereochemical outcome of the reaction, and a working model for the radical coupling of E was proposed, which explained the absolute configuration of the favored (S,S)-enantiomer of the dl isomer.     

Enantioselective Friedel-Crafts reaction of acylpyrroles with glyoxylates catalyzed by BINOL-Ti(IV) complexes

We report the first efficient enantioselective Friedel-Crafts hydroxyalkylation of pyrroles having one electron-withdrawing group at the α, β or N-positions with alkyl glyoxylates catalyzed by readily available chiral BINOL-Ti(IV) complexes (1-5 mol %). The reaction regioselectively led to the desired pyrrole-hydroxyacetic acid derivatives with good yields (70-96%) and enantiomeric excesses up to 96%, and is applicable in multigram scale with low loading of the catalyst (1 mol %).     

Enantioselective and diastereoselective Mukaiyama-Michael reactions catalyzed by bis(oxazoline) copper(II) complexes.

The scope of highly enantioselective and diastereoselective Michael additions of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these additions are useful synthons that contain termini capable of differentiation under mild conditions. Michael acceptor pi-facial selectivity is consistent with two-point binding of the imide substrate and can be viewed as an extension of substrate enantioselection in the corresponding Diels-Alder reactions. A model analogous to the one employed to describe the hetero Diels-Alder reaction is proposed to account for the observed relation between enolsilane geometry and product absolute diastereocontrol. Insights into modes of catalyst inactivation are given, including spectroscopic evidence for inhibition of the catalyst by a dihydropyran intermediate that evolves during the course of the reaction. A procedure is disclosed in which an alcohol additive is used to hydrolyze the inhibiting dihydropyran and afford the desilylated Michael adduct in significantly shortened reaction time.     

Highly efficient Suzuki-Miyaura coupling reactions catalyzed by bis(oxazolinyl)phenyl-Pd(II) complex

Bis(oxazolinyl)phenyl-palladium(II)(Phebox-Pd) complexes were found to be efficient catalysts for Suzuki-Miyaura coupling reactions of aryl boronic acids and their derivatives with aryl halides to give the corresponding biaryl products in high yield along with moderate enantioslectivities in the case of axially chiral induction. The catalytic activity was attained more than 900,000 of TON and 45,000 of TOF. The catalyst can be recovered quantitatively and could be reused for Suzuki-Miyaura reactions.     

Enantioselective cyanosilylation of aldehydes catalyzed by novel camphor derived Schiff bases-titanium(IV) complexes

Five tridentate Schiff bases have been prepared from (1R,2S,3R,4S)-3-amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol and salicylaldehydes. X-ray structure investigation revealed differences in their molecular conformation, and their titanium(IV) complexes have been studied with NMR techniques. Among them the complex with the Schiff base obtained from 2-hydroxy-3-isopropylbenzaldehyde, is the most selective catalyst for the cyanosilylation of aliphatic, alicyclic, aromatic, and heteroaromatic aldehydes. The highest enantioselectivity, >99%, was achieved for the addition of trimethylsilyl cyanide to cinnamaldehyde.     

Enantioselective intramolecular alkene hydroaminations catalyzed by yttrium complexes of axially chiral bis(thiolate) ligands

[structure: see text] A yttrium(III) complex derived from proligand 7c has been shown to be a superior catalyst for enantioselective intramolecular alkene hydroaminations that provide cyclic amines with ee's ranging from 69% to 89%.