Diethylzinc, reactions with carbonyls

A few Pd(0)-catalyzed reactions of aUyUc carbonates cannot be classified under Sects. A-O. Cationic Tj -allylpalladium complexes can be reduced by tin(II) chloride to afford a tin-allyl intermediate provided with nucleophilic reactivity (umpolung), which reacts with carbonyl groups (Scheme 62). Tm(II) chloride has been used by Masuyama and co-workers in Pd(0)-catalyzed reduction of aUylic carbonates,allylic cyclic carbon-ates, and even allylic alcohols,followed by reaction with carbonyl compounds. Related results with cyclic carbonates have been reported by Kang and co-workers Diethylzinc and samarium(II) iodide have been used as the reducing reagent. Protona-tion of the allylsamarium intermediate gives overall reduction of the C—O into C—H bond.f ... 

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). 

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... 

Carbonyl Addition Diethylzinc has been added to benzaldehyde at room temperature in the presence of an ephedra-derived chiral quat (8) to give optically active secondary alcohols, a case in which the chiral catalyst affords a much higher enantioselectivity in the solid state than in solution (47 to 48, Scheme 10.6) [30]. Asymmetric trifluoromethylation of aldehydes and ketones (49 to 50, Scheme 10.6 [31]) is accomplished with trifluoromethyl-trimethylsilane, catalyzed by a quaternary ammonium fluoride (3d). Catalyst 3d was first used by the Shioiri group for catalytic asymmetric aldol reactions from silyl enol ethers 51 or 54 (Scheme 10.6) [32]. Various other 1,2-carbonyl additions [33] and aldol reactions [34] have been reported. 

Asymmetric amplification, 551,700-712 in carbonyl-ene reaction, 551 in diethylzinc addition, 702 Asymmetric autoinduction, 713 Asymmetric aziridination, 317-322 mechanism of, 320 with copper catalysts, 317-321... 

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... 

The Simmons-Smith reaction is an efficient and powerful method for synthesizing cyclopropanes from alkenes [43]. Allylic alcohols are reactive and widely used as substrates, whereas a,j8-unsaturated carbonyl compounds are unreactive. In 1988, Ambler and Davies [44] reported the electrophilic addition of methylene to a,/3-unsaturated acyl ligands attached to the chiral-at-metal iron complex. The reaction of the racemic iron complex 60 with diethylzinc and diiodomethane in the presence of ZnCl2 afforded the c/s-cyclopropane derivatives 61a and 61b in 93 % yield in 24 1 ratio (Sch. 24). 

The non-equivalence of enantiomers through the spontaneous breaking of mirror-symmetry in nature is amplified by asymmetric autocatalytic reaction [34], e.g. Frank s spontaneous asymmetric synthesis [35, 36] (Fig. 7-8). Alberts and Wyn-berg have reported in enantioselective autoinduction that chiral lithium alkoxide products may be involved in the reaction to increase the enantioselectivity (Eq. (7.9)) [37]. The product % ee however does not exceed the level of catalyst % ee. In asymmetric hydrocyanation catalyzed by cyclic dipeptides, the (Si-cyanohydrin product complexes with the cyclic peptide to increase the enantioselectivity in the (S)-cyanohydrin product, the reaction going up to 95.8% ee (Eq. (7.10)) [38]. In the presence of achiral amine, (/ )-l-phenylpropan-l-ol catalyzed carbonyl-addition reaction of diethylzinc has been reported to show lower % ee than that of the catalyst employed [39]. 

Trost and coworkers developed a chiral zinc phenoxide for the asymmetric aldol reaction of acetophenone or hydroxyacetophenone with aldehydes (equations 62 and 63) . This method does not involve the prior activation of the carbonyls to silyl enol ethers as in the Mukaiyama aldol reactions. Shibasaki and coworkers employed titanium phenoxide derived from a phenoxy sugar for the asymmetric cyanosilylation of ketones (equation 64). 2-Hydroxy-2 -amino-l,l -binaphthyl was employed in the asymmetric carbonyl addition of diethylzinc , and a 2 -mercapto derivative in the asymmetric reduction of ketones and carbonyl allylation using allyltin ° . ... 

Using this exchange reaction, some functionalizations of aryl halides were examined. As an example of 1,2-addition to a carbonyl group, the arylzinc prepared from 4-iodobenzoate and diethylzinc in the presence of Bu-P4 base in THF was reacted with benzaldehyde to give the benzhydrol derivative in 78% yield. As for the 1,4-addition reaction, the arylzinc prepared similarly in THF was reacted with chalcone and the 1,4-adduct was obtained in 71% yield under copper-free reaction conditions. Allylation was also carried out in the absence of copper additive, and allylbenzoate was obtained in 98% yield. It has been reported that arylzinc compounds are inert to 1,4-addition and allylation reaction in the absence of additives and conventionally the employment of copper species has been widely used. However, in this case the Bu-P4 base is considered to promote the reactivity of arylzinc compounds toward electrophiles [59] (Scheme 5.38). 

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