Organozinc additions

Nonlinearity was also found for this asymmetric organozinc addition, for example, using 50% ee of chiral modifier 46 resulted in 80% ee of adduct 53. The enanti-oselectivity is also dependent on the reaction concentration >98% ee was obtained at 0.1-0.5 M but only 74% ee at 0.005 M. Kitamura and Noyori s work strongly suggested that heterodimer 72 might be more thermally stable than the homodimer... 

Although the copolymerization of propylene oxide with C02 takes place effectively with organozinc additives or the (tetraphenyl) porphyrin-AlCl system [61], the copolymerization of epichlorohydrin with C02 seldom occurs with these catalysts. Shen et al. [62] showed that a rare earth metal catalyst such as the Nd(2-EP)3/AliBu3 (Al/Nd = 8) system was very effective for the copolymerization of epichlorohydrin with C02 (30-40 atm) at 60 °C (Scheme 16). The content of C02 in the copolymer reached 23-24 mol % when 1,4-dioxane was used as solvent. 

Nowadays, this chemistry includes a wide range of applications. The organozinc compounds employed in the enantioselective addition include dialkylzincs, dialkenylzincs, dialkynylzincs, diarylzincs and the related unsymmetrical diorganozincs. Electrophiles have been expanded to aldehydes, ketones and imines. Asymmetric amplification has been observed in the enantioselective addition of organozincs. Recently, asymmetric autocatalysis, i.e. automultiplication of chiral compounds, has been created in organozinc addition to aldehydes. 

At first glance, the Soai reaction appears to be one of the prominent examples of catalytic asymmetric organozinc additions to carbonyl com-... 

In the reservoir model , which was confirmed by Noyori and coworkers as the prototype case of catalytic asymmetric organozinc additions to carbonyl compounds in the presence of (-)-3-exo-(dimethylamino)isoborncol (DAIB) yielding chiral benzyl alkanols with a higher ee than that of the added DAIB [17,18], there is a reversible equilibration between monomers and dimers. It is assumed that the monomers r and s are the catalysts and that the heterochiral dimers [r s] are of higher thermodynamic stability than their homochiral ([rr] and [s s]) analogues ... 

The research on asymmetric organozinc additions to carbonyl compounds started in 1984 when Oguni and Omi obtained 49% e.e. in the reaction of diethylzinc with benzaldehyde catalyzed by (X)-leucinol. Since then, a huge number of chiral (see Chiral) catalysts, mostly derived from amino alcohols, have been developed and the subject has been extensively reviewed. 63.264 jjjg highly enantioselective (see Electrophile) ligand (—)-3-exo-dimethylaminoisobomeol [(-)-DAIB] developed by Noyori and coworkers in 1986 is still used even if its application is mostly limited to aromatic and heteroaromatic aldehydes (equation 62). As shown by previous studies, chiral (see Chiral) ligands have a dual... 

The development of organozinc addition reactions to imines and imine derivatives has been somewhat limited by both the poor electrophilicity of the azomethine carbon and the low reactivity of organozinc reagents. 

Even the very efficient enantioselective catalysts used in organozinc addition reactions to carbonyl compounds failed to catalyze the corresponding addition reactions to nonactivated imines such as A-silyl-, A-phenyl-, or iV-benzyl-imines. However, enantioselective additions of diaUcylzinc compounds to more activated imines, like iV-acyl- or iV-phosphinoyl-imines, in the presence of catalytic or stoichiometric amounts of chiral (see Chiral) aminoalcohols, have been recently reported. For example, in presence of 1 equiv of (A,A-dibutylnorephedrine) (DBNE) diethylzinc reacts with masked A-acyl imines like A-(amidobenzyl)benzotriazoles, to give chiral A-(l-phenylpropyl)amides with up to 76% e.e. (equation 68). 

Compared to the well-developed organozinc addition to aldehydes, the related addition to ketones has been far less studied. However, the first catalytic addition of diaUcylzinc to ketones has been achieved few years ago using camphorsulfonamide alcohols ligands and Ti(0-(-Pr)4 salt (equation 66). In the same year, it was also discovered that 15 mol % of (-l-)-DAIB catalyze the diphenylzinc addition to ketones to generate chiral (see Chiral) tertiary alcohols with up to 91% e.e. (equation 67). 

Organozinc addition reactions to unsaturated systems lead to an intermediate zinc compound which is in most cases further hydrolyzed to give the corresponding protonated organic compound. This intermediate can also be trapped by reaction with electrophiles (see Electrophile) (E+) such as aldehydes, acyl chlorides, organic halides, silyl halides, and so on. Depending on the nature of the electrophile (see... 

Addition to cyclic iminium salts has been utilized in alkaloid synthesis. A zinc-promoted reductive coupling reaction of iminium salts and alkyl halides has been reported by Shono et al. (Scheme 8). Evidence delineating the mechanistic course (organozinc addition or electron transfer reaction) of the addition has not been established. In contrast to organolithium or Grignard additions, aromatic halogen and alkoxycarbonyl substituents are compatible with this methodology. The intramolecular version of this reaction has been employed for the synthesis of tricyclic amines (53 equation 9). 

Cyclopropylcarbinols are prepared from dicyclopropylzinc, and t)ie use of mixed diorganozincs such as MejSiCHjZnEt for the addition has also been explored. Chiral tertiary alcohols are obtained from organozinc addition to ketones in the presence of functionalized isobomeols. (15,2/f)-2-(A -piperidinyl)-l-phenylpropane-l-thiol acetate is a ligand prepared from (+)-norephedrine ° and it catalyzes asymmetric addition of diethylzinc to aldehydes very effectively. 

Bis(alk-2-enyl)zinc compounds 12, on addition to 3,3-dimethylcyclopropene, yield more than 90% of organozinc addition compounds 13 that can, by acidolysis, be converted into substituted cyclopropanes. Depending on the substitution pattern of the starting material, the reaction can be seen to proceed with allylic inversion. In contrast to addition reactions with unstrained double bonds, the reaction proceeds smoothly at — 20 to — 5 °C. Diethyl ether or tetrahy-drofuran can be employed as solvent and the cA-addition products are formed stereoselectively and in high yield. 

JessopPG, Brown R A, Y amakawa M, Xiao JL, Ikariya T, Kitamura M, T ucker SC, Noyori R. Pressure-dependent enantioselectivity in the organozinc addition to aldehydes in supercritical fluids. J Supercrit Fluids 2002 24 161-172. 

Hydrazone 7 behaves as a bidentate Ugand for zinc species. However, the steric effect of the BINAP moiety on organozinc addition to ArCHO is not sufficient to give good ee of the adducts. ... 

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