Diethylzinc reduction with

Acetals of a,j8-unsaturated aldehydes with 3-0-alkylated derivatives of 1,2-0-isopropylidene- -D-fructopyranose and l,2-0-isopropylidene-/l-D-psicopyranose, which are readily available from D-fructose, were cyclopropanated with diethylzinc/diiodomethane with good stereoselectivity. The acetals were hydrolyzed and the aldehydes reduced to give cyclopropyl-substituted alcohols e.g. cyclopropanation of 103 to give 104 and hydrolysis and reduction to R,2R)-2-phenylcyclopropylmethanol (105). Extensive studies were carried out, with both exo- and endo-acQta structures, to determine the effects of the structure of the acetals on the enantioselec-tivity. Among various isomeric compounds, the asymmetric cyclopropanation reaction provided good enantioselectivity (consistent attack on the same face) with high chemical yields especially with en sfo-acetals of l,2-0-isopropylidene-3-0-(4-phenylbenzyl)-iS-D-fructopyranose. 

The triethylborane procedure provides exceptional o t/-diastereoselectivities when 2-substituted dienes are employed and thus provides a highly effective strategy for the homoallylation of carbonyls (Scheme 3-55). The use of diethylzinc as reductant with Ni(acac)2 also provides homoallylation products, and complementary scope with organoboranes and organozincs was illustrated. 

In addition to the preceding methods that involve functionalization of an enone or enoate p-carbon with an alkyl or aryl functionality, methods for the nickel-catalyzed reductive aldol functionalization of enoates have also been developed (Scheme 3-81). Using triethylborane as the terminal reductant with Ni(cod)2 as catalyst, reductive aldol reactions proceed to give syn aldol adducts. An unusual role of phenyl iodide as a promoter for the process was found in this study. Intramolecular reductive aldol additions utilizing Ni(acac)2 as catalyst and diethylzinc as the terminal reduetant were also described. ... 

Although the previous protocol suggests it is not necessary to deprotonate the sulfonamide prior to exposure to the zinc carbenoid, a experimentally simpler procedure can be envisioned wherein the alcohol and promoter are deprotonated in a single flask (Fig. 3.15). In protocol IV, the alcohol and promoter are combined in flask A and are treated with diethylzinc, thus forming the zinc alkoxide and zinc sulfonamide. In sub-protocol IVa, this solution is transferred to flask C which contains the zinc carbenoid. Sub-protocol IVb represents the reversed addition order. Sub-protocol IVa is not only found to be the superior protocol in this sub-set, it is found to out-perform all of the previous protocols Despite the persistence of the induction period, a large rate enhancement over the uncatalyzed process is observed. This considerable rate enhancement also translates to a reduction in the overall reaction time when compared to sub-protocols la and Ilia. Selectivity rises... 

In general, an ethyl(monoalkoxy)zinc is formed with amino alcohols6. Therefore, in the presence of an equimolar amount of chiral amino alcohol, a slow reduction of benzaldehyde to benzyl alcohol is observed rather than alkylation1. Alkylation only occurs with a ratio of diethylzinc to amino alcohol greater than equimolar. Consequently, a two-zinc species is postulated to be the actual catalyst1, n. 

Ni(COD)2 alone catalyzes intramolecular alkylative cyclization of an alkynal with diethylzinc, while Ni(COD)2/PBu3 catalyzes reductive cyclization with the same zinc reagent (Scheme 87). 

N-Methylation of 3 and reduction of the crystalline oxazolidinone 4 with lithium aluminum hydride was found to give a superior yield of DAIB (5) and a more easily purified product than exhaustive methylation of 2 with methyl iodide and reduction of the quaternary methiodide with Super-Hydride. Recently, a modified version of DAIB, 3-exo-morpholinoisoborneol MIB), was prepared by Nugent that is crystalline and that is reported to give alcohols in high enantiomeric excess from the reaction of diethylzinc with aldehydes. ... 

They have also developed a catalytic version of the reaction in which the chiral ligand DIPT was used in 20 mol% (379-381). In spite of the reduction of the amount of the chiral ligand, enantioselectivities of up to 93% ee were obtained in this work. The addition of a small amount of 1,4-dioxane proved to be crucial for the enantioselectivity of the reaction. A proposal for the reaction mechanism is outlined in Scheme 12.88. Allyl alcohol, hydroximoyl chloride 274 and diethylzinc react to form 276, which is mixed with the ligand and an additional amount of... 

On use as homogeneous catalysts in the asymmetric reductive alkylation of benzaldehyde with diethylzinc to form secondary alcohols, the corresponding dendritic titanium-TADDOL complexes having either chiral or achiral dendrons gave enantiomeric excesses (ee) of up to 98.5 1.5 at a conversion of 98.7% (for the catalyst with GO dendrons). With larger dendrons the reduction of the ee to 94.5 5.5 (G4) remained within reasonable limits, while the drop in conversion to 46.8% (G4) proved to be drastic. In comparison, the unsubstituted Ti-TAD-DOL complex gave an ee of 99 1 with complete conversion. This negative den-... 

See also reduction of imines with diethylzinc under Addition of Organometallics above, and ionic hydrogenation of Iminium Species below. 

Cyanopyridines undergo titanium-mediated reductive cyclopropanation to give pyridylcyclopropylamines in good yield <20030L753>. Both 2- and 3-cyanopyridine react with the titanium species 81 formed from diethylzinc and methyltriisopropyloxytitanium in the presence of lithium isopropoxide to give the cyclopropylamine product in 80% and 82% yield, respectively (Equation 55). 

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). 

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 ° . ... 

Homoallylation. Carbonyl compounds afford 4-aIkenols from a Ni-catalyzed condensation with 1,3-dienes that is promoted by diaUcylzinc (as alternative to the previously reported triethylborane). With diethylzinc there is an overall reductive alkylation but dimethylzinc also donates a methyl group to the product. ... 

Although mechanistically different, functionalized alkenylsilanes are prepared stereoselectively by the reaction of 1-alkynes with iodotrimethylsilane (123) and diethylzinc. At hrst oxidative addition of 123 to Pd(0) generates 125. Then insertion of 1-octyne to 125 affords the alkenylpalladium 126. Transmetallation with Et2Zn gives 127 and reductive elimination provides the alkenylsilane 124. The reaction can be regarded as a Heck-type reaction of alkyne with MesSi-I, followed by Negishi coupling [37]. 

Reduction of the ester fimction of polymer 169 or treament with a dimagnesium bromide reagent led to the two immobilized aminoalcohols 174 and 175 (Scheme 77). Chiral polymer 174 proved to be not efficient for the diethylzinc addition to benzaldehyde (11% yield and no ee) and with chiral polymeric ligand 175, for the same reaction, the yield was excellent but the enantioselectivity was low (40%) [131]. 

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