Dialkylzincs, addition

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Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

Figure 2-7. The role of [Ti(OPr )4] in dialkylzinc addition reactions. The dioxolane in the rear is deleted for clarity.

BINOL and related compounds have proved to be effective catalysts for a variety of reactions. Zhang et al.106a and Mori and Nakai106b used an (R)-BINOL-Ti(OPr )4 catalyst system in the enantioselective diethylzinc alkylation of aldehydes, and the corresponding secondary alcohols were obtained with high enantioselectivity. This catalytic system works well even for aliphatic aldehydes. Dialkylzinc addition promoted by TifOPr1 in the presence of (R)- or (A)-BINOL can give excellent results under very mild conditions. Both conversion of the aldehyde and the ee of the product can be over 90% in most cases. The results are summarized in Table 2-14. 

Since the discovery of amino alcohol induced dialkylzinc addition to aldehydes, many new ligands have been developed. It has recently been reported that chiral amino thiols and amino disulfides can form complexes or structurally strained derivatives with diethylzinc more favorably than chiral amino alcohols and thus enhance the asymmetric induction. Table 2 15 is a brief summary of such chiral catalysts. 

The reactivity of /V-d i pheny 1 phosphi nyI imines toward dialkylzinc addition in the presence of a stoichiometric or catalytic amount of chiral ligand 165, 166, or 167 has also been meticulously investigated. The reaction in Scheme 3-57 gives good yield with up to 95% ee.106... 

Scheme 7-24. Asymmetric synthesis of the chiral co-side chain via dialkylzinc addition.

There is an equilibrium between the dimer and monomer, and molecular orbital study suggests that the heterochiral dimer is more stable than the homochiral isomer. The existence and behavior of the dimeric species were well confirmed by experiments such as cryoscopic molecular weight and NMR measurement. In the NMR study of a DAIB-catalyzed dialkylzinc addition reaction, noticeable changes were observed in the spectrum of the homochiral dimer on the addition of benzaldehyde, while the spectrum of the heterochiral complex remained the same. This may imply that the heterochiral complex is very stable and does not react, and the homochiral dimer leads to the reaction product. 

Several stereoselective dialkylzinc additions have been reported. The oxazolidine catalyst series (64) gives moderate ee% in the addition of diethylzinc to benzaldehyde. Substituent effects on the mechanism of induction have been explored for a range of... 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

When we entered the field, Tomioka et al. had just introduced the dialkylzinc addition to N-sulfonylimines in the presence of chiral amidophosphine-copper(II) complexes, producing high levels of enantioselectivity (up to 94% ee) [27]. At the... 

Scheme 2.1.3.9 Immobilization of carboxybenzaldehydes 32 on Merrifield resin (31) and synthesis of benzobutyrolactones 34 with dialkylzinc addition using a cyclative-cleavage approach [36].

Aromatic ketones arylations, 10, 140 asymmetric hydrogenation, 10, 50 G—H bond alkylation, 10, 214 dialkylzinc additions, 9, 114-115 Aromatic ligands mercuration, 2, 430 in mercury 7t-complexes, 2, 449 /13-77-Aromatic nitriles, preparation, 6, 265 Aromatic nucleophilic substitution reactions, arene chromium tricarbonyls, 5, 234... 

Scheme 1 Chiral amino alcohol catalyzed asymmetric dialkylzinc addition to aldehydes...

The key point of this scenario is to assume a priori that XY promotes the product of opposite configuration to X. In addition, additive dimers and not monomers are considered as catalytically active species, opposing the commonly accepted mechanism for typical dialkylzinc additions to aldehydes catalyzed by Vamino alcohols [ 18]. 

Only few reports deal with the use of mineral supports for immobilising chiral auxiliaries able to. activate dialkylzinc addition to aldehyde (Scheme 10). 

Scheme 3. Preparation of the 1,3-anti-diol acetal 14 by dialkylzinc addition to 4-acetoxy-1,3-dioxanes 13 according to Rychnovsky et al. TMSOTf = tri-methylsilyltrifluoromethane sulfonate.

In addition to amino alcohols, numerous other ligands such as amines, amino thiols, diols, disulfides, and dis-elenides have been developed and tested. Several have shown a very good enantioselectivity for dialkylzinc additions to a variety of aldehydes. In contrast, the addition of aryl-, vinyl-, and alkynylzinc compounds was not so extensively studied and more work is stiU needed in... 

The dialkylzinc additions catalyzed by N,N-di-n-alkylnorephedrines (most typically DBNE) are not limited to primary organometallic reagents. Diisopropylzinc (with a secondary alkyl substituent) adds to benzaldehyde in the presence of a catalytic amount of DBNE to afford the corresponding alcohol with high ee (entry 4). The reaction of diisopropylzinc in the presence of other types of catalysts may result in the reduction of aldehydes. 

Chiral Lewis acidic catalysts derived from p-amino alcohols constitute a major field of recent development. These reagents have been used for enantioselective reduction of ketones and for dialkylzinc additions to aldehydes. 

A very similar model can be invoked to explain the results of catalytic enantioselective dialkylzinc additions to aldehydes. The catalysts used in these reactions are invariably lithium- or zinc-centered Lewis acids. The transition structure shown in Figure has been put forward by several groups... 

Figure 52 A model for catalytic asymmetric dialkylzinc additions to aldehydes...

Figure 53 Qiiial catalysts for asymmetric dialkylzinc additions to carbonyls...

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