Organozinc additions, asymmetric

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... 

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. 

As mutual face selectivity between an alkenylmetal and a substituted ally lie organozinc reagent, combined with the alkenylmetal-induced diastereoselection, enabled the creation of two stereocenters, turning the sp3 dimetallated carbon into an additional asymmetric carbon has also been examined. 

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... 

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. 

Similarly, in other enantioselective additions of organozinc compounds asymmetric autocatalyses were also demonstrated, [17] though they always gave a product with a much lower ee value than that of the catalyst used. Only at the end of 1995 was an important breakthrough achieved [3,4] when Soai et al. showed that the presence of 20 mol% of the pyrimidyl alcohol (S)-9a... 

Table 7.3 Asymmetric organozinc addition to aldehydes using ligands 34, 38 and 39.

With aldehyde 2338 in hand, we attempted to stereoselectively install the C(15) secondary carbinol by the asynometric organozinc addition (Scheme 2.75) [223, 224]. We envisioned that the asymmetric addition of a highly functionalized... 

Scheme 2.75 Asymmetric organozinc addition reaction, "reaction time after addition of aldehyde 2.338. combined yield of 2.353 and 2.353. "the diastereomeric ratio was determined by integration of the H NMR of the mixture, dropwise addition of aldehyde, "slow addition of dienal by syringe pump.

Determination of the absolute stereochemistry of the newly generated C(15) stereocenter of 2.353 was achieved by Mosher ester analysis of the major dia-stereomer following the procedure reported by Kakisawa and co-workers (Scheme 2.76) [225]. The Mosher esters of the organozinc addition reaction product were prepared as shown in Scheme 2.76. Analysis of the (S)- and (R)-MTPA esters prepared from 2.353 obviously indicated that the C(15) alcohol was of the desired configuration (/ ), which was consistent with the results via reagent controlled asymmetric organozinc addition reaction. 

Design of chiral catalysis and asymmetric autocatalysis for diphenyl-(l-methyl-pyrrolidin-2-yl) methanol-catalyzed enantioselective additions of organozinc reagents 97YGK994. 

Scheme 2.30 Copper-catalysed asymmetric conjugate addition of organozincs to enones...

In 1998, two other examples of chiral ligands that enabled the asymmetric addition of organozinc reagents to ketones were reported by two groups independently. Thus, Dosa and Fu employed the nonsulfur-containing Noyori s DAIB " ligand in the asymmetric addition of ZnPh2 to ketones with... 

Because of the separation of this chapter into fundamental synthetic and structural aspects of organozinc compounds and the applications of these compounds in organic synthesis, many topics are treated twice, but with decidedly different emphases. By way of example, the important organozinc alkoxides are covered first in the inorganometallic section, where the emphasis is on their syntheses, structures, and applications other than in organic synthesis. Later, in Section 2.06.16.2, the uses of such compounds as chiral catalysts in asymmetric addition reactions are discussed. 

Perhaps the most investigated reaction of organozinc compounds is their addition to the carbonyl group of aldehydes. A broad range of simple and functionalized diorganozincs and a great variety of aldehydes have been studied in this transformation. The reaction furnishes chiral secondary alcohols, which are essential building blocks in the synthesis of natural products and other important compounds. Recent studies of this transformation have been devoted to its asymmetric catalytic versions (Scheme 103). 

Nucleophilic addition of metal alkyls to carbonyl compounds in the presence of a chiral catalyst has been one of the most extensively explored reactions in asymmetric synthesis. Various chiral amino alcohols as well as diamines with C2 symmetry have been developed as excellent chiral ligands in the enantiose-lective catalytic alkylation of aldehydes with organozincs. Although dialkylzinc compounds are inert to ordinary carbonyl substrates, certain additives can be used to enhance their reactivity. Particularly noteworthy is the finding by Oguni and Omi103 that a small amount of (S)-leucinol catalyzes the reaction of diethylzinc to form (R)-l-phenyl-1 -propanol in 49% ee. This is a case where the... 

TADDOL 104 and 126 afford 95-99% ee in the asymmetric addition of organozinc reagents to a variety of aldehydes. The best enantioselectivities are observed when a mixture of the chiral titanium TADDOL compound 127 and excess [Ti(OPr1)4] are employed (Scheme 2-49). The mechanism of the alkylzinc addition involves acceleration of the asymmetric catalytic process by the... 

Various catalytic or stoichiometric asymmetric syntheses and resolutions offer excellent approaches to the chiral co-side chain. Among these methods, kinetic resolution by Sharpless epoxidation,14 amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde,15 lithium acetylide addition to an alkanal,16 reduction of the corresponding prochiral ketones,17 and BINAL-H reduction18 are all worth mentioning. 

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