Dialkylzinc, addition with

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. 

Highly reactive zinc can be prepared by reduction of anhydrous ZnC with potassium/THF or sodium/DME(l 7,29). This zinc has been shown to undergo rapid oxidative additions with alkyl bromides to produce near quantitative yields of the corresponding dialkylzinc. It also underwent oxidative addition with phenyl iodide and bromide. Moreover, the zinc was found to be useful in the Reformatsky reaction. Reactions could be carried out in diethyl ether at room temperature to generate near quantitative yields of the 3-hydroxyester. 

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... 

For a stereoselective dialkylzinc reaction with a phosphinoylimine, see Addition to Organometallics below a resolution via a Schiff base is described under Enolates. 

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].

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

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. 

In 1992, Soai reported the synthesis of enantiomerically enriched amines by the reaction of organozinc reagents with M-diphenylphosphinoylimines [35a, 35b, 35c]. The diphenylphosphinoyl moiety provided the necessary activation of the C=N bond to observe dialkylzinc additions. The reactivity of a series of three N-diphenylphosphinoylimines 22a-c was examined in the presence of Et2Zn and a substoichiometric or a stoichiometric amount of the chiral 3-amino alcohols 18 or 21 (<0.1 g of phosphinoylimine, ca. 0.17 M) (Scheme 13). 

The reduction predominates over addition in the reaction of /(-branched dialkylzinc compounds with alkyl aryl ketones the enantiomeric excess ranges from 2.4-15.2% with ( + )-bis[(S )-2-methylbutyl]zinc (11 f)1 °5. 

This aldehyde had already been converted (26) to methyl nonactate and methyl 8-epinonactate with high selectivity using titanium tetrachloride catalysed addition of dimethyl zinc and lithium dimethylcuprate, respectively. Lygo also found that dialkylzinc addition under different Lewis acid conditions gave different diastereoisomers with high selectivity (Scheme 15). 

In this section, the asymmetric synthesis of the vicinal thio- and selenoalcohols 42 — 45 is described based on the highly enantio- and diastereoselective addition of diethylzinc reagent to racemic a-thio- and selenoaldehydes 41, catalyzed by 20o (( —)-DFPE) and S,R)-2Qo ((+)-DFPE) (Scheme 3-20). Although the enantio-selective addition of dialkylzinc reagents to achiral aldehydes using chiral catalysts has been well investigated [10], there are no known catalytic enantio- and di-asteroselective dialkylzinc additions to aldehydes with chiral centers, except for the alkylation of a-methyl- [58, 59], a-chloro- [59], and j5-alkoxyaldehydes [60]. The reaction of diethylzinc with racemic a-thio- and selenoaldehydes 41 was carried out in the presence of 20o or (S,il)-20o (5 — 50 mol%) in hexane at room temperature for 12 —16h. The results are summarized in Table 3-11. 

The ionic liquids, [BMIMjBr, [BMIM][BF4], [BMIMjlPFe], [BDMIM][BF4], and [BPY][BF4], were examined as the solvent media for dialkylzinc addition to aldehydes giving the corresponding alcohols. The ionic liquid [BPY][BF4] was found to be the solvent of choice, giving the best yields, and was found to be easily recovered and reused [226] (Scheme 5.2-95). It was found that the imidazoUum salts react with diethyl zinc to form a carbene complex of zinc, but the 2-methylimidazolium or pyridinium salts did not react and hence could be recycled. 

Nickel acetoacetonatel2,2 -bipyridyllchiral amine Catalytic asym. 1,4-addition with dialkylzinc compds. 

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