Carbonyl compounds organozinc compound additions

The organozinc compound 2 is less reactive than an organomagnesium compound the addition to an ester carbonyl group is much slower than the addition to an aldehyde or ketone. Nevertheless the addition of 2 to the carbonyl group of unreacted a-halo ester 1 is the most frequently observed side-reaction ... 

The carbonyl substrate 3 to be reacted with the organozinc compound 2 can be an aldehyde or ketone that may contain additional functional groups. With a vinylogous halo ester—i.e. a y-halocrotyl ester—the corresponding y-crotylzinc derivative is formed. 

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). 

One of the important new directions in the study of addition reactions of organozinc compounds to aldehydes is the use of ionic liquids. Usually, application of these compounds in reactions with common organometallic reagents has a serious problem ionic solvents are usually reactive toward them, particularly Grignard and organolithium derivatives. It has been recently reported that carbonyl compounds react with allylzinc bromide formed in situ from allyl bromide and zinc in the ionic liquid 3-butyl-l-methylimidazolium tetrafluoroborate, [bmim][BF4].285 Another important finding is that the more reactive ZnEt2 alkylates aldehydes in a number of ionic liquids at room temperature.286 The best yields (up to 96%) were obtained in A-butylpyridinium tetrafluoroborate, [bpy][BF4] (Scheme 107). 

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... 

The Pd-catalyzed acylation of organozincs was reported in 1983144, and it has since been widely employed as one of the most satisfactory methods of acylation of organometals20. Even in cases where ,/J-unsaturated carbonyl compounds are the products, their subsequent conjugate addition reactions do not appear to be competitive. Among recent examples of its application to the synthesis of natural products, the synthesis of amphidi-nolides Tl, , T4 and T5 by Fiirstner and coworkers213 is particularly noteworthy (Scheme 81). 

The formation of ester-stabilized organozinc reagents and their addition to carbonyl compounds... 

Michael reactions.1 Various organozinc reagents bearing remote ester, nitrile, or a-amino acid groups undergo Michael addition to a,(3-unsaturated carbonyl compounds in the presence of CuCN, (CH3)3SiCl, and HMPA.1... 

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 ... 

Enantioselective Addition of Organozinc Compounds to Carbonyl Compounds Chiral Amplification... 

Several papers are concerned with the threo-erythro stereoselectivity of the reaction of allylic organozinc reagents with carbonyl compounds. The addition (involving allylic rearrangement) of crotylzinc derivatives to various aldehydes occurs stereoselectively, and the relative amount of tAreo-alcohol increases with increasing steric demand of the group R tert-Bu, S4% f-Pr, 707o n-Bt, 46%) and in the sequence of metals Mg < Zn < Cd 3, 7). The temperature or the polarity of the solvent... 

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... 

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). 

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