Asymmetric Diethylzinc Addition

Tanner et al. also used an aziridine carbinol (viz. 54) as chiral ligand in asymmetric addition of diethylzinc to hT-(diphenylphosphinoyl)imines (Scheme 41) [54]. 

E.3. Supported Dendritic Catalysts for the Asymmetric Addition of Diethylzinc... 

Meanwhile, copper salt catalyzed asymmetric conjugate addition of dialkylzincs has been developed. Alexakis and coworkers reported the catalytic addition of diethylzinc to cyclohexenone using copper salt111. Feringa and coworkers developed a marvelous phosphoramidite (49)112. In the presence of 49 and Cu(OTf)2, diethylzinc adds to cyclohexenone in >98% . Recently, asymmetric addition of diphenylzinc using 49 has been reported113. Nowadays, compounds 50114, 51115, 52116, 53117 and 54118 are known as highly enantioselective catalysts. 

In the asymmetric addition of diethylzinc to (V, /V -diphenylphosphinylimine, (lR S)-2-morpholino-l-phenylpropanol with 58% promotes the reaction to afford N,N -diphenylphosphinylamine with 85% (equation 37)122. 

The direct strong steric interaction between substrate substituents and ligand substituents has been demonstrated in asymmetric addition of diethylzinc to aldehydes catalysed by sterically congested ferrocenyl aziridino alcohol derivatives.114 In addi- tion, this non-bonded steric repulsion influenced enantioselectivities significantly, and even led to inversion of the absolute configuration. This fact was further confirmed by theoretical calculations and the design of a new chiral ferrocenyl aziridino alcohol ligand. 

The use of bis(sulfonamide) ligands derived from stilbenediamine in the asymmetric addition of diethylzinc to benzaldehyde has resulted in large changes in product ee over the course of the reaction.106 This effect has been attributed to autoinduction. During the reaction the catalyst evolves by incorporation of the product of the asymmetric addition reaction. 

A library of chiral zinc complexes formed in situ by the combination of achiral and racemic diimines with 3,30-di(3,5-ditrifluoromethylphenyl)-BINOL and diethylzinc have been evaluated in the asymmetric addition of diethylzinc to V-acylimines.126 High enantioselectivities of up to 97% ee and yields of up to 96% have been achieved for a wide range of aromatic imines in dichloromethane at -30 °C. 

Fig. 10.40. Catalytic asymmetric addition of Et2Zn to Ph— C(=0)H. Chiral amplification through a mutual kinetic resolution of the (auxiliary/ZnEt)2 complex which is produced from two molecules of chiral aminoalcohol and diethylzinc each.

The coordination of NHC ligands greatly enhances the copper-catalyzed asymmetric addition of diethylzinc to cyclohexenone [45]. Employing imi-dazolinylidene ligands with chiral centers in the heterocycle, the alkylation of a-enones [46,47] was systematically studied by the groups of Mangeney and Alexakis [10,48-50]. A summary of the results obtained is presented in Table 1. 

Table 1 Catalytic asymmetric addition of diethylzinc to cyclohexenone in the presence of 1-23...

Chiral bis(oxazolines) 51 with an oxalylic acid backbone were used for the Ru-catalyzed enantioselective epoxidation of tran5-stilbene yielding franx-l,2-diphenyloxirane in up to 69% ee [24]. The asymmetric addition of diethylzinc to several aldehydes has been examined with ferrocene-based oxazoline ligand 52 [25], resulting in optical yields from 78-93% ec. The imide 53 derived from Kemp s triacid containing a chiral oxazoline moiety was used for the asymmetric protonation of prochiral enolates [26]. Starting from racemic cyclopentanone- and cyclohexanone derivatives, the enantioenriched isomers were obtained in 77-98 % ee. 

The impact of achiral ligands on the TOP of the catalyst in this system was then examined by following reaction conversions with various catalysts. In the absence of both Ph2-BINOL and diamine ligands, the reaction of diethylzinc with benzaldehyde is very slow, exhibiting about 1% conversion after 8h at 0°C. When Ph2-BINOL was employed in the asymmetric addition to this substrate, the catalyst TOP increased exhibiting 25% conversion after 2 h. To evaluate the TOP of zinc centers bearing diimine derived from ethylene diamine and 2,4,6-trimethylbenzaldehyde (Table 4, entry 5) or the meso diamine (Table 5, entry 7), these ligands were... 

Asymmetric addition of diorganozincs to aldehydes catalyzed by chiral -amino alcohols provides a general method for the preparation of chiral secondary alcohols. Oguni, Noyori, and co-workers found that the aminoalcohol, (2S)-3-exo-(dimethylamino)isobornenol ((2S)-DAIB), acts as a particularly efficient promoter for this asymmetric reaction [9, 10]. Reaction of benzalde-hyde with diethylzinc in the presence of 2 mol% of (2S)-DAIB gives, after aqueous workup, (S)-l-phenylpropanol in high yield with 99% ee as shown in Scheme 8. Detailed mechanistic and theoretical studies of the (2S)-DAIB-pro-moted asymmetric addition have been reported [11]. 

Table 3. Asymmetric addition of diethylzinc to benzaldehydes in tbe presence of diselenide...

Chiral polymer-supported catalysts have been utilized in asymmetric addition of dialkylzinc to aldehydes because of the easy product isolation and workup [26]. In the previous section, a highly enantioselective addition of diethylzinc to aldehydes was described using M-(l-ferrocenylalkyl)-iV-alkylnorephedrines as effective catalysts. We then examined incorporation of the catalyst into polymeric systems. 

The asymmetric addition of diethylzinc to heptanal, a straight-chain aliphatic aldehyde, was catalyzed by compound 20 (Table 3-6). All R,S catalysts 20, except 20s and 20u, afforded (S)-3-nonanol in moderate enantiomeric excess, regardless of the stereochemistry of the asymmetric carbon bearing the hydroxyl group. Cyclo-hexanol derivative 20g, which is less bulky around the carbinol center than catalysts... 

The cinchona alkaloids are particularly valuable ligands in asymmetric addition of diethylzinc to a N-diphenyl phosphinoylimine (228) leading to enantiomerically enriched (R)- and (S)-N-(l-phenylpropyl-diphenylphosphinic amide) (229). Cinchonine and cinchonidine were found to be the pseudo-enantiomeric pair which gave the adduct in highest enantiomeric excess (up to 93% ee) (Scheme 62)." ... 

Cyclopropylcarbinols are prepared from dicyclopropylzinc, and t)ie use of mixed diorganozincs such as MejSiCHjZnEt for the addition has also been explored. Chiral tertiary alcohols are obtained from organozinc addition to ketones in the presence of functionalized isobomeols. (15,2/f)-2-(A -piperidinyl)-l-phenylpropane-l-thiol acetate is a ligand prepared from (+)-norephedrine ° and it catalyzes asymmetric addition of diethylzinc to aldehydes very effectively. 

On the other hand, chiral o-hydroxyarylphosphine oxides such as 52 have been widely applied as catalysts in the asymmetric addition of diethylzinc to a series of aromatic aldehydes [52-54]. 

A large number of chiral a,a -orz/zo-disubstituted diphenyldiselenides with hydroxy and amino functions (e.g., 244 and 245) have been prepared by Wirth and co-workers. They were used as electrophiles for a number of asymmetric addition and cyclization reactions including the total synthesis of the lignan derivatives (-l-)-samin and (-l-)-membrine as well as catalysts in the asymmetric diethylzinc addition to aldehydes. 

During the past two decades the homogeneous and heterogeneous catalytic enan-hoselective addition of organozinc compounds to aldehydes has attracted much attention because of its potential in the preparation of optically active secondary alcohols [69]. Chiral amino alcohols (such as prolinol) and titanium complexes of chiral diols (such as TADDOL and BINOL) have proved to be very effective chiral catalysts for such reactions. The important early examples included Bolm s flexible chiral pyridyl alcohol-cored dendrimers [70], Seebach s chiral TADDOL-cored Frechet-type dendrimers [28], Yoshida s BINOL-cored Frechet-type dendrimers [71] and Pu s structurally rigid and optically active BlNOL-functionalized dendrimers [72]. All of these dendrimers were used successfully in the asymmetric addition of diethylzinc (or allyltributylstannane) to aldehydes. 

The early examples of peripherally functionalized dendrimers, PPl-supported amino alcohol and dendrimer-bound Ti-TADOLates, in the asymmetric addition of diethylzinc to benzaldehyde were reported by the groups of Meijer [96, 97] and Seebach [98], respectively. 

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