Addition Of Dialkylzincs Research Articles

Dendritic Catalysis in Asymmetric Synthesis

In this review, we have focused our attention on the application of dendrimers as asymmetric catalyst in organic synthesis, which appeared in the literature. Dendrimers have been identified as a promising candidate for catalysis application. The combination of high surface area and high solubility makes dendrimers as useful nanoscale catalysts. The main advantage of the dendritic catalysts is they can be separated from the reaction mixture by simple solvent precipitation and reused for several times with similar catalytic activity. Importance of catalytically active substances like metal salts or organic molecule like pyrrolidinylmethanol thatare attached either to the core or to the periphery of the dendrimers have been highlighted and their applications in important organic reactions such as Baylishillman, Mannich-type, Diels-Alder, Wittig reaction, Michael addition, addition of dialkylzinc to aldehyde, asymmetric epoxide ring opening, asymmetric hydrogenation and asymmetric epoxidation are also presented. Use of dendrimer based salts and chiral compounds in asymmetric syntheses are discussed and the advantages and disadvantages of those catalysts are brought out in this review. Keywords: Dendritic catalyses, Asymmetric syntheses, Organic transformations, Chiral catalysts, residues, boundchiral ligands, Dendrimers, catalysts, pyrrolidinylmethanol, ethylvinyl ketone

Diastereoselective chelation-controlled additions to β-silyloxy aldehydes.

A general diastereoselective method for the addition of dialkylzincs and (E)-di- and (E)-trisubstituted vinylzinc reagents to β-silyloxy aldehydes is presented. This method employs alkyl zinc triflate and nonaflate Lewis acids and affords chelation-controlled products (6:1 to > 20:1 dr).

Synthetic approach toward cis-disubstituted γ- and δ-lactones through enantioselective dialkylzinc addition to aldehydes: application to the synthesis of optically active flavors and fragrances

A versatile and straightforward approach to optically active cis-4,5-disubstituted γ- and δ-lactones by catalytic enantioselective addition of dialkyzincs to cinnamic aldehydes and RCM ring closure has been reported. The synthetic importance of the enantioselective dialkylzinc alkylation of aldehydes has been thus widened. Such an approach has then been employed for the enantioselective synthesis of naturally occurring γ-lactone flavors like (S)-5-ethyl-butanolide (6a) and (4S,5S)-cis-whisky lactone (6b) and extended to the preparation of δ-lactones like (5S,6S)-5-methyl-6-ethylpentanolide (9a), precursor of the pheromone serricornin.

ヒドロキシ-アミド置換アゾリウム塩存在下、非環状エノンへのジアルキル亜鉛の銅触媒不斉共役付加反応

ヒドロキシ-アミド置換アゾリウム塩存在下、非環状エノンへのジアルキル亜鉛の銅触媒不斉共役付加反応

Re‐Evaluating the Nucleophilicity of Zinc Enolates in Alkylation Reactions

AbstractThe use of toluene allows for allylic and benzylic alkylation of zinc enolates, derived from an asymmetric copper‐catalyzed conjugate addition of dialkylzinc, using a range of valuable electrophiles. The one‐pot procedure avoids the use of additional transition‐metal catalysts and does not require highly activated electrophiles.

Paracyclophanes in Action: Asymmetric Catalytic Dialkylzinc Addition to Imines Using [2.2]Paracyclophane‐based N,O‐Ligands as Catalysts

AbstractThe asymmetric addition of dibutylzinc to imines is achieved by employing [2.2]paracyclophane‐based ketimine ligands with good to excellent enantioselectivities. A comparison to other organozinc reagent is made.

Enantioselective conjugate addition of dialkylzincs to α,β-unsaturated enones catalyzed by Ni(acac)2 and (+)-(1S,2R)-7,7-dimethyl-1-morpholinoisonorborneol

A mixture of chiral ligand 4 [(+)-MINBOL] and Ni(acac)2 (12.5 and 0.5mol% respectively) is able to successfully catalyze the enantioselective conjugate 1,4-addition of dialkylzinc to α,β-unsaturated enones in propionitrile to give the corresponding chiral Michael adducts in good yields and with high enantioselectivities (up to 93% ee).

Synthesis of novel chiral bidentatephosphite ligands derived from the pyranoside backbone of monosaccharides and their application in the Cu-catalyzed conjugate addition of dialkylzinc to enones

A series of novel bidentatephosphite ligands, derived from methyl 3,6-anhydro-α- d-glucopyranoside and chlorophosphoric acid diaryl ester, were easily synthesized. These ligands were successfully employed in the Cu-catalyzed asymmetric conjugate 1,4-addition of the organozinc reagents diethylzinc and/or dimethylzinc to enones. The stereochemically matched combination of glucopyranoside and ( R)-H 8-binaphthyl in ligand 2,4-bis{[( R)-1,1′-H 8-binaphthyl-2,2′-diyl] phosphite}-methyl 3,6-anhydro-α- d-glucopyranoside was essential to afford 85% ee for 3-ethylcyclohexanone with an ( S)-configuration in THF, using Cu(OTf) 2 as a catalytic precursor. When the reaction was carried out at lower temperatures, changing from −10 to −80 °C, a marginal influence of the temperature on the enantioselectivity of the reaction was observed. The presence of the methyl substituent at the 1-position of the glucopyranoside skeleton had a negative effect on the enantioselectivity in the 1,4-addition of ZnEt 2 to acyclic enones.

ChemInform Abstract: Highly Diastereoselective Chelation‐Controlled Additions to α‐Silyloxy Ketones.

AbstractIn the presence of an alkyl zinc halide Lewis acid, the addition of dialkylzincs and (E)‐di‐, (E)‐tri‐, and (Z)‐disubstituted vinylzinc reagents to α‐silyloxy ketones proceeds chelation‐controlled to give syn‐diol products with diastereoselectivities of < 95%.

Highly diastereoselective chelation-controlled additions to α-silyloxy ketones.

The polar Felkin-Anh, Cornforth-Evans, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected α-hydroxy ketones proceeds via a nonchelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature, and few methods for chelation-controlled additions of organometallic reagents to silyl-protected α-hydroxy ketones have been introduced. Herein, we present a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri-, and (Z)-disubstituted vinylzinc reagents to α-silyloxy ketones using alkyl zinc halide Lewis acids, RZnX, to give chelation-controlled products (dr ≥18:1). The compatibility of organozinc reagents with other functional groups makes this method potentially very useful in complex molecule synthesis.

Radical Zinc-Atom Transfer Based Multicomponent Approaches to 3-Alkylidene-Substituted Tetrahydrofurans

A domino 1,4-addition/alkyne carbozincation sequence basedon a radical zinc-atom transfer process is disclosed. Two efficientmulticomponent approaches to 3-alkylidenetetrahydrofurans from β-(propargyloxy)enoatesbearing pendant alkynes (including ynamides) have been established:one involving the direct addition of dialkylzincs, and the secondinvolving the dimethylzinc-mediated addition of alkyl iodides. Bothsequences utilize the stereoselective formation of intermediatealkylidenezincs well suited for in situ functionalizationwith electrophiles. 1 Introduction 2 1,4-Addition/Cyclization of Dialkylzincs on β-(Propargyl-oxy)enoates 2.1 β-(Propargyloxy)enoates with a Pendant TerminalAlkyne 2.2 β-(Propargyloxy)enoates with a Pendant Substituted Alkyne 2.3 β-(Propargyloxy)enoates with a Pendant Ynamide 3 1,4-Addition/Cyclization of Alkylzinc Halides on β-(Propargyloxy)enoates 4 Dialkylzinc-Mediated 1,4-Addition/Cyclization ofAlkyl Iodides on β-(Propargyloxy)enoates 5 Conclusion; Current and Future Work

Synthesis of sterically constrained tricyclic pyrrolidinyl alcohol ligands for the enantioselective ethylation of aryl aldehydes: assessment of the influence of ring strain and N-alkyl chain length on asymmetric induction

A series of chiral sterically constrained tricyclic pyrrolidinyl alcohol ligands were synthesized from the appropriate amino acids, and a comparative study of the activity and selectivity of the ligands for the enantioselective ethylation of aromatic aldehydes was carried out. The results obtained were compared with those previously reported for related monocyclic analogues; it was found that the bicyclo[2.2.2]octane backbone fused to pyrrolidine and the groups attached to the carbinol centre, as well as the chain length of the β-amino alcohol, had a marked effect on the enantioselectivity. The enantioselective addition of dialkylzincs to aryl aldehydes in the presence of ligands with diethyl substituents on the carbinol carbon afforded ( R)- sec-alcohols in up to 99% enantiomeric excess (ee).

Enantioselective Conjugate Addition Nitro-Mannich Reactions: Solvent Controlled Synthesis of Acyclicanti- andsyn-β-Nitroamines with Three Contiguous Stereocenters

We report an enantioselective conjugate addition nitro-Mannich reaction protocol which combines dialkylzinc, aromatic nitro alkene and imine to form two C-C bonds and three contiguous stereocenters in one reaction vessel. Absolute stereochemistry was controlled from the initial 1,4-addition of dialkylzinc to aromatic nitroalkenes by known copper-chiral ligand catalysts. The choice of solvent dictated the formation of either the syn,anti or syn,syn diastereoisomers, two of the four possible diastereoisomers. The syn,syn isomer is a rare example of a syn-selective nitro-Mannich reaction. The diastereoselectivity is dependent upon the presence or not of Zn(O(2)CCF(3))(2) in the reaction mixture and empirical transition state models are proposed to account for the observed stereochemical course of the two reaction conditions. The extent of enantioselectivity and structural diversity of the process is limited by current methodology for the catalytic asymmetric addition of dialkylzincs to nitrostyrenes. The synthetically versatile products are the most complex β-nitro amines prepared using the nitro-Mannich reaction and are formed in high yield and enantioselectivity.

ChemInform Abstract: Reversal of Stereoselectivity in the Cu‐Catalyzed Conjugate Addition Reaction of Dialkylzinc to Cyclic Enone in the Presence of a Chiral Azolium Compound.

AbstractThe addition of dialkylzinc to cyclic enones can give the (R)‐ and/or (S)‐enantiomers using the same chiral ligand AZO but different Cu salts.

Asymmetric Arylation ofN-Tosyl Ketimines

The authors disclose an application of the rhodium diene catalyst to the addition of aryl nucleophiles to N-tosyl ketimines. These ­substrates comprise a relatively challenging class of electrophiles for asymmetric organometallic ­additions, and as a result, only a few examples of allylboronate and dialkylzinc additions are known. The resulting products are chiral amines containing a quaternary stereocenter.

Highly Enantioselective Addition of Dialkylzinc to Trifluoroacetophenones, Catalyzed by 1,2-Diamines. Synthesis of Key Fragments of Inhibitors of the Enzyme 11β-HSD1 and Kinetic Analysis of the Process

Chiral diamines derived from (R,R)- or (S,S)-1,2-diphenylethylenediamine and (S)- or (R)-2,2′-bis(bromomethyl)-1,1′-binaphthalene perform very well as catalysts in the enantioselective addition of ZnEt2 and ZnMe2 to trifluoroacetophenones, avoiding reduction products, in contrast to the poor results with amino alcohols. Excellent yields (up to 99%) and high enantioselectivity (up to 92%) are achieved with the best ligands. A kinetic study at low temperature (−37 °C) shows that the reduction reaction rate on ligandless ZnEt2 is negligible (2 orders of magnitude slower) compared to the rate of addition reaction on [ZnR2(N−N)]. Using this new procedure, reported fragments of inhibitors of enzyme 11β-HSD1 that are active against obesity and type 2 diabetes mellitus, as well as new unreported modified fragments of these bioactive molecules, were produced efficiently and enantioselectively.

ChemInform Abstract: Copper‐Catalyzed Asymmetric 1,4‐Conjugate Addition of Dialkylzinc to Enones.

AbstractA new bifunctional copper catalytic system containing no phosphorus atom at the BINOL‐derived ligand is shown to form a Lewis acid—Lewis base centre in the 1,4‐conjugate addition reaction of dialkyl zinc to enones, thus inducing enantioselectivities of up to 84% e.e.

Control of Enantioselectivity with Flexible Biaryl Axes: Terpene‐Based Alkylzinc Catalysts in Enantioselective Dialkylzinc Additions

New enantiopure pyridyl alcohols are efficiently accessible through few synthetic steps from commercially available terpenes, that is, (+)-fenchone, (-)-menthone and (-)-verbenone as well as 2,6-diphenylpyridine. These chelating pyridyl alcohols exhibit flexible pyridyl-phenylene axes, which give rise to P and M conformers. Alkylzincation of the hydroxy groups eliminates equilibria of the conformers and generates alkylzinc complexes with adjusted biaryl axes, as it is demonstrated by NMR studies. These alkylzinc catalysts perform well in the addition of dimethylzinc or diethylzinc to benzaldehyde with yields up to 99% and ee's up to 95%. The adjusted pyridylphenylene conformations in the ligands now control enantioselectivities of the catalysts, which were also analysed by computations at the DFT level.

ChemInform Abstract: Enantioselective Addition of Dialkylzincs to Aldehydes Using Heterogeneous Chiral Catalysts Immobilized on Alumina and Silica Gel.

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ChemInform Abstract: Asymmetric Synthesis Using Chiral Piperazines. Part 3. Enantioselective Addition of Dialkylzincs to Aryl Aldehydes Catalyzed by Chiral Piperazines.

ChemInform Abstract: Asymmetric Synthesis Using Chiral Piperazines. Part 3. Enantioselective Addition of Dialkylzincs to Aryl Aldehydes Catalyzed by Chiral Piperazines.