Chiral diethyl zinc, aldehydes

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... 

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>. 

Reactions with acid anhydrides (Scheme 110 <2003JA6462>) and acyl chlorides (Scheme 111 <2005S583>) occurred at room temperature in various solvents, and furnish acyl-azocanes in reportedly good to excellent yields (specific yields not given). Compounds of type 267 were studied as inhibitors of the Hepatitis B vims replications. Compound 269 was used as a chiral ligand for the enantioselective addition of diethyl zinc to aromatic aldehydes. 

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/ ... 

Not only polystyrene supports, also other polymer supports were used in the preparation of polymeric amino alcohol ligands for dialkylzinc alkylation. For example, a vinylferrocene derivative with A,N -disubstituted norephedrine was copolymerized with vinylferrocene [60]. This polymeric chiral ligand (53) was used in the ethylation of aldehydes with moderate activity. Brown has reported that chiral oxazaborolidines have catalytic activity in the addition of diethyl zinc to aldehydes [61]. Polymers bearing chiral oxazaborolidines 37 were also active in the reaction and result on moderate enantioselectivity (<58 % ee) [62]. Enantiopure a,a -diphenyl-L-prolinol coupled to a copolymer prepared from 2-hydroxyethylmethacrylate and octadecyl methacrylate... 

Fluorous chiral binaphthol ligands have been used for enantioselective addition of diethyl zinc to aldehydes in a biphasic system [20] (Scheme 3.5). 

In the presence of a chiral catalyst (BINOL), substituted acetylene and diethyl zinc can react with aldehyde to give chiral alkynyl alcohols of up to 99% e.e. ... 

Trost has described very efficient and versatile bimetallic zinc catalyst 10 generated in situ from diethyl zinc and a chiral Ugand derived from proline and p-cresol (Scheme 10) [46], For example, this complex can promote catalytic aldol reactions with high enantiomeric excess. The role of two proximal zinc species is for one of them to form the enolate and for the second one to function as a Lewis acid to activate the aldehyde. 

A number of studies have also been reported using enantiopure Betti base derivatives as chiral ligands in asymmetric reactions. For example, Chan et al. reported that Betti base 33 was a useful ligand for the additional of diethyl zinc to aryl aldehydes, with excellent enantiomeric excesses... 

Pyridines are often used as catalysts or reagents particular notice has been paid recently to how pyridine coordinates to metal centers enabling a wide range of valuable reactions. Chiral pyridine-iridinium complexes, where an N-heterocyclic carbene replaces the phosphinite in Crabtree-type catalysts, have been shown to provide efficient, enantioselective hydrogenation (13AG(1)7422). Chiral-2-pyridylsulfinamides induce excellent enantiose-lecivity in the addition of diethyl zinc to aryl and alkyl aldehydes (13T8422). 

Alkylations Chiral amino alcohol-functionaUzed polystyrene resins [36, 37] were useful catalysts in the enantioselective alkylation of aldehydes with diethyl zinc in continuous-flow columns. Another continuous flow system for the synthesis of enantioenriched diarylmethanols from aldehydes used transmetallation of tti-arylboroxins with diethyl zinc over amino alcohol-functionaUzed polystyrene resin catalyst [38]. 

Chiral bidentate 0,N-ligand (-)-DAIB, (-)-3-exo-(dimethylamino)isobomeol, efficiently catalyzes the alkylation of aldehydes when present in a 1-2 % molar ratio. The ligand coordinates diethyl-zinc in the first step and forms a dimeric complex. An intermediary complex coordinates one mol of aldehyde and decomposes into monomeric species enabling the transfer of ethyl to the carbonyl group. In the last step, chiral alcohol is eliminated, and the ligand returns to the catalytic cycle [9]. 

The formation and control of chiral quaternary centers by multicomponent reactions is undoubtedly a challenging task. The combination of a carbometalation reaction of chiral alkynyl sulfoxide 33, followed by a zinc homologation and an allylation in a four-component process, allowed the preparation of homoallylic alcohols or amines 34 bearing tertiary and quaternary stereocenters in a single step with high yields and diastereoselectivities (Scheme 11.13). The zinc carbenoid used in this reaction can be prepared independently or in situ by the reaction of diethyl zinc and diiodomethane. This carbenoid readily homologates the vinyl copper into the allylic species, which reacted diastereoselectively with aldehydes, to give the expected products. The chiral sulfinyl moiety can be easily removed by treatment with alkyllithi-ums, which allows a further functionalization of the carbon skeleton [35]. 

The alcohol portion of ester 1 was derived from the aldehyde 4, prepared from D-ribose. The absolute configuration of the secondary aUylic alcohol was established by chiral amino alcohol catalyzed addition of diethyl zinc to the unsaturated aldehyde 5. 

Figure 4.10 Chiral poly(BINOL) (l,l -bi-2-naphthol) ligand for asymmetric addition of diethyl zinc to aldehydes.

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