Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Catalyzed by Pyrolidine and Piperidine β-Amino Alcohols

The enantioselective alkylation of aryl aldehydes by diethylzinc in the presence of catalytic amounts of several chiral pyrolidine- and piperidine-based amino alcohol ligands, synthesized from the reaction of (R)-2-amino-1-butanol and (S)-2-amino-3-phenylpropan-1-ol with appropriate dibromoalkanes, was studied. The influence of temperature and ligand structure has been investigated. Addition of diethylzinc to aromatic aldehydes under the optimized condition gave the corresponding products in excellent yields with ee values of up to 77%.     

Enantioselective Addition of Phenylacetylene to Aldehydes Catalyzed by Polymer-Supported Sulfonamide

Enantioselective formation of C-C bonds is an area of intense research. Among them, the asymmetric addition of alkynyl reagents to aldehydes is very useful for the synthesis of chiral secondary propargyl alcohols.[1] Recently, many significant homogeneous chiral ligands have been disclosed,[2,3] but very few efficient heterogeneous catalysts have been reported. Herein, we report our research results in the asymmetric addition of phenylacetylene to aldehydes catalyzed by polymer-supported chiral sulfonamide.     

Enantioselective Construction of C−SCF3 Stereocenters via Nickel Catalyzed Asymmetric Negishi Coupling Reaction

The construction of the SCF₃-containing 1,1-diaryl tertiary carbon stereocenters with high enantioselectivities is reported via a nickel-catalyzed asymmetric C−C coupling strategy. This method demonstrates simple operations, mild conditions and excellent functional group tolerance, with newly designed SCF₃-containing synthon, which can be easily obtained from commercially available benzyl bromide and trifluoromethylthio anion in a two-step manner. Further substrate exploration indicated that the reaction system could be extended to diverse perfluoroalkyl sulfide (SC₂F₅, SC₃F₇, SC₄F₉, SCF₂CO₂Et)-substituted 1,1-diaryl compounds with excellent enantioselectivities. The synthetic utility of this transformation was further demonstrated by convenient derivatization to optical SCF₃-containing analogues of bioactive compounds without an apparent decrease in enantioselectivity.     

Organocatalytic Enantioselective Acyloin Rearrangement of α-Hydroxy Acetals to α-Alkoxy Ketones

We report an unprecedented organocatalytic enantioselective acyloin rearrangement of α,α-disubstituted α-hydroxy acetals. In the presence of a catalytic amount of chiral binol-derived N-triflyl phosphoramide, α-hydroxy acetals rearranged to α-alkoxy ketones in good to high yields with high enantioselectivities. Formation of an ion pair between the in situ generated oxocarbenium ion and the chiral phosphoramide anion was proposed to be responsible for the highly efficient transfer of chirality. Conditions for removal of cyclohexyl and cyclopentyl groups from the corresponding α-alkoxy ketones were uncovered underpinning their potential general utility as hydroxy protecting groups. Conversion of the rearranged products to the enantioenriched α-hydroxy ketone, 1,2-diol, β-amino alcohol and 1,4-dioxane was also documented.     

Asymmetric Syntheses XXVI: Catalytic Enantioselective Syntheses of β-Hydroxy Esters via Double Chiral Induction in Asymmetric Reformatsky Reactions

Catalytic asymmetric Reformatsky reactions of benzaldehyde with optically active menthyl bromoacetates in the presence of Zn-Cu couple were performed using 0.25 equiv. of (1R,2S) or (1S,2R)-dimethyl-2-amino-1,2-diphenyl ethanol as chiral ligand to obtain β - hydroxy esters with enantioselectivities up to 60.2%. The obvious double chiral induction effect was observed while chiral ligands matched with optically active substrates.     

Enantioselective Addition of Diethylzinc to Benzaldehyde by Catalysts of Chiral Heterocyclic Ligands

TheenantioselectiveadditionofdiethylzincreagentstoprochiralcarbonylgrouphasbeenachievedprincipallybycatalyticalamountofchiralP-aminoalcoholswhichhaveproventobehighlyeffectivecatalysts'.Ahydroxylgrouphasbeenregardedtobenecessaryforthechiralligandtoformazincalkoxideasthecatalyticspecies'.Wewishtoreporthereinontheethylationofbenzaldehydewithdiethylzincpromotedbyseveralkindsofoxazolidineandthiazolidinederivativeswhichdonotcontainhydroxylgroup.Fourkindschiralheterocyclicligandsweusedarelistedasfoll…     

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by N-Sulfonylated Amino Alcohols

Asymmetric C-C bond forming reactions are of prime importance in modem synthetic organic chemistry. The use of chiral amino alcohol ligands is widespread in this area.[1] Herein, we describe the synthesis of N-sulfonylated amino alcohols 1～4 and enantioselective addition of diethylzinc to aldehydes was carried out employing titanium(Ⅳ) complexes 1～4.     

Addition of Organocuprates to Ketoketenimines. Synthesis of β-enaminoketones

Base-induced ring cleavage of 3-unsubstituted isoxazolium salts followed by reaction of the resulting ketoketenimine with organocuprates affords asymmetric β-enaminoketones in high yields.     

Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to β-nitroacrylates

Michael addition reaction of α-branched aldehydes to β-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, L-phenylalanine, and its lithium salt to give β-formyl-β'-nitroesters having a quaternary carbon centre in good yields (up to 85%) with high enantioselectivity (up to 98% ee). By using benzyl β-nitroacrylates as Michael acceptors, the obtained β-formyl-β'-nitroesters were converted into various 4,4-disubstituted pyrrolidine-3-carboxylic acids including analogues of gabapentin (Neurotin(?)) in one step from the Michael adducts in high yields.     

Catalytic Enantioselective Direct Aldol Addition of Aryl Ketones to α-Fluorinated Ketones

The catalytic enantioselective synthesis of α-fluorinated chiral tertiary alcohols from (hetero)aryl methyl ketones is described. The use of a bifunctional iminophosphorane (BIMP) superbase was found to facilitate direct aldol addition by providing the strong Brønsted basicity required for rapid aryl enolate formation. The new synthetic protocol is easy to perform and tolerates a broad range of functionalities and heterocycles with high enantioselectivity (up to >99:1 e.r.). Multi-gram scalability has been demonstrated along with catalyst recovery and recycling. ¹H NMR studies identified a 1400-fold rate enhancement under BIMP catalysis, compared to the prior state-of-the-art catalytic system. The utility of the aldol products has been highlighted with the synthesis of various enantioenriched building blocks and heterocycles, including 1,3-aminoalcohol, 1,3-diol, oxetane, and isoxazoline derivatives.     

Enantioselective synthesis of β-amino-diacids

An efficient route to orthogonally protected β-amino-diacids is described: chiral derivative 3 was shown to be a precursor of enantiopure substituted β-amino acids. The key step of the procedure is a diastereoselective reduction of β-enaminolactones 5 by NaBH₃CN in CH₂Cl₂. A study concerning the regio- and diastereoselectivity of alkylation of β-enaminolactone 3 is also presented.     

Synthesis of Chiral N-Ferrocenylmethylaminoalcohols and their Application in Enantioselective Addition of Diethylzinc to Aldehydes

Three chiral N-ferrocenylmethylaminoalcohols were synthesized from readily available natural L-valine, leucine and phenylanine, and used as chiral ligands in the enantioselective addition of diethylzinc to aldehydes.     

Using Natural Cinchona Alkaloids to Promote the Enantioselective Addition of Dialkylzinc to N－Diphenylphosphinylimines

Cinchona alkaloids are utilized as chiral ligands to promote the enantioselective addition of dialkylzinc to N-diphenyiphosphinylirnlnes affording enantiomerically enriched N-diphenyiphosphinylamines in up to 91% ee.     

Addition of Organosamarium Reagents toα, β-Unsaturated Esters

Compared to the extensive use of samarium diiodide in organic synthesis', little reportsappeared on the application of samarium metal in organic synthesis. As early as 1971Evans and co-workers had prepared phenylsamarium iodide from iodo-benzene andsamarium metal'. But they found that samarium is not so active as ytterbium. In 1986Fukuzawa also prepared the organosamarium intermediate similar to Grignard reagent'.It was Curran who firstly proved and named the samarium Grignard reaction in 19…     

Enantioselective synthesis of β-hydroxy carboxylic acids: direct conversion of β-oxocarboxylic acids to enantiomerically enriched β-hydroxy carboxylic acids via neighboring group control

β-Oxocarboxylic acids can be reduced to the corresponding β-hydroxy carboxylic acids employing DIP-Cl^™ as a reducing agent. The β-carboxylic substituent exerts a remarkable neighboring group effect on the reduction. The reaction presumably proceeds in an intramolecular fashion through a `rigid' bicyclic transition state assembly, which produces enantioselectivities approaching 99%.     

Catalytic Enantioselective Reactions Part 7. Synthesis of New β-Aminoalcohols Derived from α-D-Glucose as Chiral Catalysts for the Catalytic Enantioselective Addition of Diethylzinc to Aldehydes

A series of new 1, 2-O-isopropylidene-3-O-methyl-6-deoxy-6-N, N-dialkylamino-α-D-glucofuranoses 1 and 1, 2-O-isopropylidene-3, 6-dideoxy-6-N, N-dialkylamino-α-D-glucofuranoses 1′ were prepared from α-D-glucose and their enantiose-lectivities compared as chiral catalysts for the ethylation of benzaldehyde and heptanal with diethylzinc.     

Enantioselective one-pot synthesis of β-sulfonyl ketones and trisubstituted tetrahydrothiophenes via β-elimination/cycloaddition sequence

A mild and efficient enantioselective one-pot synthesis of β-sulfonyl ketones and trisubstituted tetrahydrothiophenes via introducing 1,4-dithiane-2,5-diol to the simple kinetic resolution of β-sulfonyl ketones has been described herein. The one-pot reaction sequence including kinetic resolution and cascade sulfa-Michael/Aldol reaction proceeded successively to afford corresponding sulfonyl ketones and tetrahydrothiophenes with high enantioselectivities (85%–98% ee and 84%–95% ee, respectively).     

Nickel-Catalyzed Enantioselective Decarboxylative Acylation: Rapid,Modular Access to α-Amino Ketones**

A new approach to the enantiocontrolled synthesis of α-amino ketone derivatives is disclosed by employing a decarboxylative acylation strategy. Thus, when an acyl chloride and an α-amido-containing redox-active ester are exposed to a nickel catalyst, chiral ligand, and metal reductant, α-amido ketones are produced in good yield and high ee. The reaction exhibits broad substrate scope, can be easily scaled up, and is applied to dramatically simplify the synthesis of several known structures.     

Highly Efficient InBr3 Catalyzed Michael Addition of Indoles to α, β-Unsaturated Esters

A highly efficient synthetic strategy toward Michael addition of indoles to α,β‐unsaturated esters has been developed using Lewis acid InBr₃ as catalyst. The reactions generated 3‐substituted indoles in high yields with excellent regio‐selectivity in the presence of catalytic amount of InBr₃ under mild reaction conditions. The method is simple, efficient and practical.