Additions of Organozinc Reagents

Seheme 7.26 Asymmetric diethylzinc addition to benzaldehyde using ammonium-tagged ligand 34. 

The same concept was studied with biphenyl diols and TADDOL-based ligands. Indeed, the group of Kumadaki and Ando prepared several families of axially dissymmetric chiral ligands bearing perfluoro allg l groups and also TADDOLs functionalised with fluorinated chains (Table 7.3). 

The addition of diethylzinc to benzaldehyde was performed in the presence of 5 mol% of ligand 37 and 97% enantiomeric excess was recorded (entry 1). The scope of the reaction was extended to methylation of aromatic and aliphatic aldehydes using dimethylzinc as nucleophile and 20 mol% of diol 37 (entries 2-6). Secondary alcohols were isolated with good yields and 

Fig ure 7.5 TADDOL ligand immobilised on porous silica material. 

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

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

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... 

Addition of Organozinc Reagents to Aldehydes, Ketones, and a-Ketoesters 383... 

Addition of Organozinc Reagents to Aldehydes, Ketones, and a-Ketoesters 2.06.16.2.1 Chiral ligands used in addition reactions of diorganozincs with aldehydes... 

Catalytic properties of external chiral additives such as (2S,3/ )-4-dimethyl-amino-l,2-diphenyl-3- methyl-2-butoxide (A 16) (574, 575) and 2-magnesium-3-zinc salts of dialkyl (f ,f )-tartrate (A17) were employed in the highly stereoselective addition of organozinc reagents to derivatives of 3,4-dihydro-isoquinoline-A-oxide (Scheme 2.147) (576). 

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... 

For enantioselective copper catalyzed addition of organozinc reagents to imines, see [97-116]. Enantioselective Ni-catalyzed alkyne, imine, triethylborane 3-component coupling has been reported, but modest selectivities (51-89% ee) are observed. For this method, vinylation is accompanied by ethyl transfer [149]... 

Nucleophilic addition of organozinc reagents generated from a-haloesters to carbonyls. 

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