Diethyl-zinc additions

The use of the zinc complex of the BINOL ligand 946 in the hDA reaction between Danishefsky s diene 947 and aldehydes proceeds in excellent yield and enantioselectivity to afford dihydropyran-4-ones 948 (Equation 370, Table 45) <2002OL4349>. An asymmetric diethyl zinc addition can occur in tandem with the cycloaddition reaction between Danishefsky s diene 947 and isophthalaldehyde using a related catalyst 949 (Equation 371) <20030L1091, 2005T9465>. 

The use of inorganic supramolecular compounds in catalysis has also been successful in recent years. Hupp etal. incorporated a Mn(IIl)-porphyrm (see Porphyrin) epoxidation catalyst inside a molecular square, a system that shows enhanced catalyst stabihty and substrate selectivity as compared to the free catalyst. In another example, chiral metaUocyclophanes were constructed from Pt(PEt3)2 units and enantiopme atropoisomeric t,t -binapthyl-6,6 -bis-(acetylenes) and used in enantioselective diethyl zinc addition to aldehydes to afford chiral secondary alcohols. The first organometaUic triangle based on Pt(II) and alkyne-di-substituted-binaphfhyl system was reported and found to effect asymmetric catalysis reactions of aldehydes to alcohols with excellent conversion rates and enantiomeric excess/ ... 

The post-synthetic methodology has also been used to incorporate catalytic centres. The incorporation of chiral l,l -bi-2-naphthols (BINOLs) into CMPs has been used to perform catalytic reactions using the alcohol groups to bind to catalytically active centres such as phosphoric acids for asymmetric transfer hydrogenations or titanium for diethyl-zinc additions. Other metal-containing functionalities have also been incorporated into CMP networks. The coordination of metals to pyridine or phenylpyridine via Sonogashira reactions has also been reported for catal5Aic transformations such as reductive amination or aza-Henry reactions, a-atylations and oxyaminations. ... 

Reaction of an alkyl (usually trimethyl) of Group-IIIb element (Al, Ga, In) with a hydride of a Group-Vb element (P, As, Sb) at 600-800°C and 1 atm. [4i][42] p. doping obtained from addition of diethyl zinc or bis(cyclopentadienyl) magnesium. 

Kragl and Dreisbach (1996) have carried out the enantioselective addition of diethyl zinc to benzaldehyde in a continuous asymmetric membrane reactor using a homogeneous soluble catalyst, described in their paper. Here a,a-diphenyl-L-proline was used as a chiral ligand, coupled to a copolymer made from 2-hydroxy ethyl methacrylate and octadecyl methacrylate, which had a sufficiently high molecular weight to allow separation by ultra-filtration (U/F). The solvent-stable polyaramide U/F Hoechst Nadir UF PA20 retained more than 99.8% of the catalyst. The ee was 80 %, compared to 98 % for a noncoupled catalyst. 

The latter effect has been demonstrated by Meijer et al., who attached chiral aminoalcohols to the peripheral NH2-groups of polypropylene imine) dendrimers of different generations [100]. In the enantioselective addition of diethyl-zinc to benzaldehyde (mediated by these aminoalcohol appendages) both the yields and the enantioselectivities decreased with increasing size of the dendrimer (Fig. 28). The catalyst obtained from the 5th-generation dendrimer carrying 64 aminoalcohol groups at its periphery showed almost no preference for one enantiomer over the other. This behavior coincides with the absence of measurable optical rotation as mentioned in Sect. 3 above. The loss of activity and selectivity was ascribed to multiple interactions on the surface which were... 

The quaternary ammonium salt 48 derived from (+)-ephedrine was utilized for the enantioselective addition of diethyl zinc to aldehydes.1421 The chiral ammonium fluorides 7 (R=4-CF3 or 2,4-(CF3)2, X=F) were also useful for the enantioselective trifluoro-methylation of aldehydes and ketones with moderate enantioselectivity,1431 shown in Scheme 17... 

Acyclic Enones as Substrates Compared to cyclic enones, acyclic enones are generally more challenging substrates for the copper-catalyzed asymmetric 1,4-addition reactions. Several ligands have been reported that can achieve high ee when p-aryl acyclic enones are used as substrates in the 1,4-addition of diethyl-zinc (Figure 3.5). ° ... 

Examples, like the application of enantiopure ioiuc hquids in the copper catalyzed enantioselective 1,4-addition of diethyl zinc to enones giving up to 76% ee, will not be presented [178], since here the chiral ionic liquid, CIL, acts as a ligand for a metal catalyzed reaction. 

The use of other metal cations such as those derived from zinc, lithium, or aluminium proved less effective (136). Treatment of allyl alcohol with diethyl zinc in the presence of a catalytic amount of diisopropyl (/ ,/ )-(+ )-tartrate (DIPT) in 1,4-dioxane, however, afforded the corresponding (5/f)-2-isoxazolines with excellent selectivity er >92 8) (178). Addition of dioxane was necessary in order to avoid precipitation of the complex of zinc salts containing the DIPT moiety. Without this solvent, lower stereoselectivity was found, probably due to the precipitation mentioned above, which prevents the favorable catalytic cycle proposed (Scheme 6.32) (178). 

The chiral ligand 4 is used in the asymmetric addition of diethyl zinc to aldehydes to give sec-alcohols in high yield having 5-absolute configuration <99TA1673>. 

Compared with asymmetric ethylation, reports on asymmetric phenylation are limited. We disclosed the enantioselective phenylation using diphenylzinc prepared in situ from phenyl Grignard reagent and zinc chloride. This method needs a stoichiometric amount of chiral amino alcohol DBNE 18 but good ee of 82% was achieved [32], A catalytic phenylation was examined using planar chiral compound 1 based on ferrocene, and chiral diaryl carbinols of moderate ee were provided from diphenylzinc and 4-chlorobenzaldehyde (Scheme 10) [33]. A catalytic and highly enantioselective phenylation was realized by binaphthyl-based chiral catalyst 23. In this reaction, the addition of 2 equivalents of diethyl-zinc against catalyst increases the yield and ee [34]. Recently, chiral amino alcohol DPMPM 9 was also reported to be an efficient catalyst for asymmetric phenylation [35]. 

Diethyl zinc undergoes enantioselective addition to 2-pyridinecarbaldeyde in 91% ee in the presence of 0.5 mol% optically pure diselenide 68 in toluene at room temperature <2003OL2635> (Equation 48). The reaction is postulated to proceed by in situ formation of a chiral zinc selenolate formed by nucleophilic attack of Et2Zn on diselenide 68. 

Scheme 8. Amplification index I (top) and ratio of product ee to expected ee for a system with no NLE (bottom) versus enantiomeric excess of auxiliary (eeaux) in the (-)-DAIB catalyzed addition of diethyl zinc to benzaldehyde.

According to Jenkins diethylzinc has no effect on molar mass [157]. In contrast to the negative result published by Jenkins there are reports from two other sources on the successful use of diethyl zinc [180-182,466,467]. These differences are either due to different catalyst systems or are due to differences in the addition order of catalyst components. Strong evidence in favor of molar mass control by diethyl zinc was provided by Lynch who used NdV/MgR2-based catalyst systems [466,467]. In combination with NdV/DIBAH/EASC the use of ZnEt2 also resulted in a reduction of molar mass [ 180-182]. A careful study revealed that the formal number of polymer chains (pexp) formed per Nd atom increases with increasing nznEt2/ Ndv-ratios (Table 24). 

The asymmetric addition of diethyl zinc to aryl aldehydes in flow has evoked much academic interest. Supported amino alcohol 6 (Scheme 4.52) was placed in a jacketed column cooled to 0 °C and pretreated with the aldehyde. A 1 1.4 aldehyde diethyl zinc solution was then flowed through the column and collected, and after a simple aqueous workup, the desired product was obtained. In one example, 5 mmol of 6 was used to produce 90 mmol of product in 90% yield and 94% ee, and in a second example 0.7 mmol of 6 produced 58 mmol of product with 92% ee [170]. 

However, an encouraging result was obtained very recently for the 1,4-conjugate addition of dialkyl zinc to a variety of Michael acceptors catalyzed by copper. Alexakis, Roland and coworkers have investigated the addition of diethyl zinc to cycloheptenone and observed an enantiomeric excess of 93% (95% yield) in the presence of Cu(OAc)2 and the silver carbene derivative of imidazolium 1 (Scheme 3) [10]. Silver carbene complexes are efficient transfer agents to copper(II) and therefore the potentially harmful use of a base to generate the catalytic species is avoided. 

Alkylidenemalonate 59 was a substrate in the Taddol-based phosphoramidite 61-mediated addition of diethyl zinc to afford the ethyl adduct 60 in 73% ee [39]. The unsaturated imine 62 was a substrate in an amidephosphine 64 copper-catalyzed ethylation to afford 63 in moderate ee after hydrolysis (Scheme 7) [40]. 

An unusual syn addition to epoxides occurs when 1,3-diene monoepoxides are treated with organozinc reagents. Thus, the cyclic vinyl epoxide 72 was converted to the cis-ethyl-cyclohexenol 75 with diethyl zinc in methylene chloride and trifluoroacetic acid. The syn addition is believed to derive from an initial coordination of the oxiranyl oxygen to the organozinc compound, which then delivers the alkyl group to the same face. This transfer is facilitated by a relaxation of the sp3 hybridization brought about by the Lewis acidic zinc center and the allylic character of the incipient carbocation <020L905>. 

Triaryl telluronium compounds can be prepared by the quick addition of a solution of tellurium tetrachloride (1 mol) in diethyl ether to an excess of the Grignard reagents (5 mol) (Vol. IX, p. 1080). Trialkyl telluronium compounds do not seem to be accessible in this manner6. In contract, tellurium tetrachloride and diethyl zinc produced triethyl telluronium chloride (Vol. IX, p. 1080). 

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