Addition Of Dialkylzincs Research Articles

Highly Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Isoindolinyl Alcohol as a Chiral Ligand.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An Easy and Convenient Synthesis of Optically Active β‐Amino Alcohols and 1,2‐Diamines. Applications in Enantioselective Deprotonation of Cyclohexene Oxide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric, Catalytic Synthesis of α‐Chiral Amines Using a Novel Bis(phosphine) Monoxide Chiral Ligand.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Mechanism of Asymmetric Dialkylzinc Addition to Aldehydes Catalyzed by Titanium(IV) Complexes of N-Sulfonylated β-Amino Alcohols

A series of dimeric complexes [TiL*X2]2 (H2L* = (1R,2S)-2-(4-methylbenzenesulfonylamino)-1,3-diphenyl-1-propanol (5); X = O-i-Pr (4), NMe2 (6), or O-t-Bu (7)) were prepared, and the asymmetric Et2Zn additions to benzaldehyde catalyzed by the complex 4, 6, or 7 with the addition of excess Ti(O-i-Pr)4 give excellent enantioselectivities up to 96.3% ee. The 1H NMR study shows that the catalytic systems of these complexes involve a common active intermediate. The reaction of 4 with 2 molar equiv of Ti(O-i-Pr)4 afforded another dimeric complex, 9, with the structure (i-PrO)2TiL*Ti(O-i-Pr)4. Complex 9 is demonstrated to provide a suitable environment, achieving an enantioselectivity of 95.6% ee. Complex 9 in solution is shown as a mixture of complexes 4, 9, and Ti(O-i-Pr)4, and the equilibrium among these three complexes is solvent and temperature dependent. The reaction of complex 4 or 9 with MeTi(O-i-Pr)3 furnished the complex (i-PrO)2TiL*Ti(O-i-Pr)3Me (10), which reacted stoichiometrically with benzaldehyde to afford the complex (i-PrO)2TiL*Ti(O-i-Pr)3(OCHMePh) (11), which dissociates to give a mixture of the complexes 4, 11, and Ti(O-i-Pr)4. A complete scope of the mechanism is clearly deduced from stepwise reactions starting from complex 4 to 9, 10, 11 and then back to 4. This is an example of a mechanism with all intermediates confirmed structurally or spectroscopically except complex 12, which proceeds directly to complex 11. This mechanism is also suggested to apply for the reactions catalyzed by the titanium complexes of BINOLs and diols. One of the roles of excess Ti(O-i-Pr)4 is to facilitate removal of the product from the metal center. However, more importantly, the two major roles of Ti(O-i-Pr)4 are to exchange an alkyl group with the dialkylzinc reagent and to regenerate complex 9 from complex 11 for next cycles of reactions.

不斉触媒および反応場の設計に基づく高エナンチオ選択的不斉合成反応の研究

Highly enantioselective asymmetric syntheses, i.e., enantioselective addition of alkylmetal reagents to aldehydes and imines, enantioselective conjugate addition of dialkylzincs to enones, and asymmetric autocatalysis have been developed by designing asymmetric catalysts (or chiral ligands) and chiral environment of the reactions. Automultiplication of chiral compounds by asymmetric autocatalysis was discovered where a chiral product acts as a chiral catalyst for its own production. Asymmetric autocatalysis with>99.5% ee in a yield of > 99% was attained using pyrimidyl alkanol as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. The asymmetric autocatalysis exhibits significant positive non-linear effect on ee. Asymmetric autocatalyst with very low (ca. 0.00005%) ee enhances its ee significantly up to > 99.5% ee during the consecutive asymmetric autocatalysis without the assistance of any other chiral auxiliary. Moreover, amino acids and [6] helicene with very low ee which are produced by asymmetric photolysis and photosynthesis using circularly polarized light serve as chiral initiators of asymmetric autocatalysis, and pyrimidyl alkanol with high ee is obtained. Inorganic chiral crystals such as quartz and sodium chlorate, [2.2] paracyclophanes, allenes, chiral cobalt complexes due to the topology of coordination, chiral primary alcohols due to the deuterium substitution also work as chiral initiators. Asymmetric autocatalysis is capable to discriminate efficiently the chirality of various chiral compounds. Moreover, the reactions of pyrimidinecarbaldehyde with diisopropylzinc without adding chiral substance exhibit the formation of enantioenriched S or R pyrimidyl alkanols with approximate stochastic distribution, which indicates the reaction is a spontaneous absolute asymmetric synthesis. These results correlate for the first time the proposed origins of chirality of organic compounds with the chirality of organic compounds with very high ee.

Organometallic reactions in ionic liquids. Alkylation of aldehydes with diethylzinc

The ionic liquids, [bmim][Br] (2a), [bmim][BF4] (2b), [bmim][PF6] (2c), [bdmim][BF4] (8) and [bpy][BF4] (9), were examined as the solvent media for dialkylzinc addition to aldehydes giving the corresponding alcohols. The ionic liquid [bpy][BF4] was found to be the solvent of choice, giving the best yields, easily recovered and reused.

Novel Concepts in Directed Biaryl Synthesis. Part 107. Synthesis of Enantiopure Axially Chiral C3‐Symmetric Tripodal Ligands and Their Application as Catalysts in the Asymmetric Addition of Dialkylzinc to Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Enantioselective 1,4‐Conjugate Addition of Dialkylzinc to α,β‐Unsaturated Lactone Catalyzed by Diphosphite—Copper Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An Easy and Convenient Synthesis of Optically Active β-Amino Alcohols and 1,2-Diamines. Applications in Enantioselective Deprotonation of Cyclohexene Oxide

Optically active β-dialkylamino alcohols and 1,2-diamines are not only a common structural component in a vast group of naturally occurring and synthetic molecules, but also can be widely used as versatile chiral building blocks and chiral catalysts or ligands in a variety of asymmetric synthesis, such as enantioselective dialkylzinc addition to aldehydes, enantioselective conjugated addition and enantioselective deprotonation of meso ketones and epoxides. Accordingly, many synthetic methods including aminolysis of chiral epoxides, optical resolution of their racemic mixtures and reduction of non-racemic O-acetyl mandelamides, reduction of chiral α-amino carboxamides, asymmetric reduction of α-amino ketones and aminolysis of aziridinium salts for those compounds have been reported. However, aminolysis of chiral epoxides is commonly accompanied by the formation of undesired regioisomers. The resolution method of racemic mixture suffers from providing intrinsic limitation where the maximum yield of one enantiomer from the starting material is only 50%. In the case of reduction of α-amino carboxamides, unnatural α-amino acids are not economical viable to use them as starting materials since they are expensive, but also racemization can occur in the reaction of some N-protected amino acids with dialkylamines to give α-amino carboxamides. For example, O’Brien et al. reported significant levels of racemization when N-protected phenylglycine was reacted with pyrrolidine in the presence of coupling reagent to form the corresponding α-amino carboxamide. Recently, we reported the synthesis of nearly enantiopure β-adrenergic agonists and β-hydroxy nitriles from optically active 1,2diol monotosylates 1 obtained from CBS-oxazaborolidinecatalyzed borane reduction of α-sulfonyloxyketones. We wish to report here an easy and simple method for the synthesis of nearly enantiopure β-dialkylamino alcohols 2 and 1,2-diamines 4-10 starting from 1 and their applications in enantioselective deprotonation of cyclohexene oxide using chiral lithium amides. The monotosylates 1 were directly reacted with 3 equiv. of N,N'-dialkylamines under solvent-free conditions at 40-50 C for 2-96 h to give 2 in 80-93% yield (Scheme 1). The optical purities and absolute configurations of 2 were determined by HPLC analysis using chiral columns and/or by comparing optical rotation values of the known compounds. As shown in Table 1, all the products 2 obtained have very high optical purities approaching 100% ee. To obtain chiral diamines 4-10, the reaction was carried out by treatment of 2.0 equiv. of methanesulfonyl chloride with each of the selected amino alcohols, such as 2e, 2h, 2j, and

Highly Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Isoindolinyl Alcohol as a Chiral Ligand

Enantioselective alkylation of carbonyl compounds is a challenged domain of asymmetric C-C bond formation. Particularly, asymmetric addition of diethylzinc to aldehydes is one of the important synthetic methods for the preparation of optically active secondary alcohols, and numerious efforts have been made to find effective chiral ligands. To date, most of the successful results were obtained by using sterically constrained β-amino alcohols such as N,Ndialkylated norephedrine derivatives. Extensive studies by Soai on the effect of ligand structure on enantioselectivity indicated that the chain length of the N-alkyl substituent is very imporant. Thus, the catalyst with N-alkyl substituents of a chain length of four carbons, 1 (DBNE), gave the best results in dialkylzinc addition to various aliphatic (87-93% ee) and aromatic (90-95% ee) aldehydes. It has been recently reported that some azacyclo β-amino alcohols (2 and 3) are among the most efficient chiral ligand in catalytic asymmetric reaction. Employment of conformationally rigid rings such as pyrrolidine and piperidine would provide beneficial on controlling precisely the stereochemical sense in asymmetric catalysis. Here we wish to report a new-type of amino alcohol (4) bearing isoindolinyl moiety as a face blocker and its catalytic efficiency in asymmetric addition of diethylzinc to various aldehydes. The isoindolinyl moiety may possess similar steric and electronic properties with substituted groups at nitrogen of the DBNE, but conformationally more rigid. Hence, compare to DBNE or pyrrolidine ligand 2, it may block effectively the approach of the attacking species to one of the enantiotopic faces of aldehydes. The (1S,2R)-1-phenyl-2-(2-isoindolinyl)-1-propanol[(1S,2R)4] was easily prepared in 95% yield by the reaction of (1S,2R)-norephedrine with α,α'-dibromoxylene in ethanol in the presence of potassium carbonate (Scheme 1). In order to examine the catalytic ability of the ligand 4, the enantioselective addition of diethylzinc to aldehydes was Figure 1. β-Aminoalcohols for diethylzinc addition.

Asymmetric, catalytic synthesis of alpha-chiral amines using a novel bis(phosphine) monoxide chiral ligand.

We have shown that Me-DuPHOS monoxide (BozPHOS) is a very effective ligand in the copper-catalyzed addition of dialkylzinc to N-phosphinoylimines providing access to alpha-chiral amines. The new ligand is particularly effective for the addition of the lesser reactive dimethylzinc. The major advantages of this process are high yields, broad substrate scope, and high enantioselectivities with low catalyst loading (3 mol %).

Highly enantioselective 1,4-conjugate addition of dialkylzinc to α,β-unsaturated lactone catalyzed by diphosphite–copper complexes

The 1,4-addition of diethylzinc and dimethylzinc to 5,6-hydro-2 H-pyran-2-one using new chiral diphosphite–copper catalysts gave products in up to 98% ee.

Synthesis of enantiopure axially chiral C3-symmetric tripodal ligands and their application as catalysts in the asymmetric addition of dialkylzinc to aldehydes.

The enantioselective synthesis of a novel-type C(3)-symmetric tripodal ligand that is composed of a central mesitylene-derived core and three functionalized, axially chiral biaryl subunits is described. The triol (M,M,M)-3 is a suitable catalyst for the enantioselective addition of dialkylzinc to various aromatic aldehydes with asymmetric inductions of up to 98% ee.

The design of chiral dendritic catalysts and ligands bearing chiral sites at the periphery for the highly enantioselective addition of dialkylzincs to aldehydes and N-diphenylphosphinylimines

Chiral dendrimers bearing β-amino alcohols on their hyperbranched chain-ends serve as highly enantioselective catalysts and ligands in the enantioselective addition of dialkylzincs to aldehydes with up to 93% ee, and in the enantioselective addition of dialkylzincs to N-diphenylphosphinylimines with up to 94% ee, respectively. To cite this article: K. Soai and I. Sato, C. R. Geoscience 6 (2003).

Highly Enantioselective Addition of Dialkylzinc Reagents to Ketones Promoted by Titanium Tetraisopropoxide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Dialkylzinc Additions with a Chiral Osmaimidazolidine Ligand from Asymmetric Diamination of Olefins.

AbstractFor Abstract see ChemInform Abstract in Full Text.

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

AbstractCinchona alkaloids are utilized as chiral ligands to promote the enantioselective addition of dialkylzinc to N‐diphenylphosphinylimines affording enantiomerically enriched N‐diphenylphosphinylamines in up to 91% ee.

Catalytic Enantioselective Addition of Dialkylzinc to N‐Diphenylphosphinoylimines. A Practical Synthesis of α‐Chiral Amines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Evaluation of chiral oxazolines for the highly enantioselective diethylzinc addition to N-(diphenylphosphinoyl) imines.

On the basis of the principle that the incorporation of the structurally rigid and conformationally restricted skeleton in beta-amino alcohols is beneficial to the enantioselective diethylzinc addition to imines, a series of chiral oxazolines, which had been designed and conveniently prepared from commercially available (1S,2S)-2-amino-1-phenylpropane-1,3-diol, were applied in the diethylzinc addition to diphenylphosphinoyl imines to give high yields of 68-84% and excellent ee values of 90-95%. The configuration of the product was controlled by the chirality of the carbon bonded to the hydroxyl group in the oxazoline. Oxazolines bearing a para- or meta-substituted phenyl group generally offered higher enantioselectivity than those containing an ortho-substituted phenyl. The X-ray structures of 4f and 4j, in combination with the proposed transition state, preliminarily explained why oxazolines with a para- or meta-substituent on the phenyl group gave higher enantioselectivities than those bearing an ortho-substituent. This successful example using chiral oxazolines to promote the titled reaction implies that a large family of chiral compounds containing an oxazoline ring moiety have the potential to be developed for promoting the highly enantioselective dialkylzinc addition to N-(diphenylphosphinoyl) imines.

Dialkylzinc additions with a chiral osmaimidazolidine ligand from asymmetric diamination of olefins

A new chiral ligand was prepared in a convenient two-step procedure starting from an asymmetric diamination reaction. Subsequent treatment of the resulting osmaimidazolidine with a phenyl Grignard reagent and titanium tetra( iso-propoxide) furnished a complex that catalyses asymmetric dialkylzinc additions to aromatic aldehydes.