Organozinc addition reaction

The development of organozinc addition reactions to imines and imine derivatives has been somewhat limited by both the poor electrophilicity of the azomethine carbon and the low reactivity of organozinc reagents. 

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). 

Organozinc addition reactions to unsaturated systems lead to an intermediate zinc compound which is in most cases further hydrolyzed to give the corresponding protonated organic compound. This intermediate can also be trapped by reaction with electrophiles (see Electrophile) (E+) such as aldehydes, acyl chlorides, organic halides, silyl halides, and so on. Depending on the nature of the electrophile (see... 

The synthesis of 2.217 initiated with the preparation of chiral vinyl iodide 2337 and the dithiane 2.343 for the organozinc addition reaction. To this end, epoxide opening reaction of commercially available (5)-glycidol (5)-2.249 with treatment... 

Scheme 2.75 Asymmetric organozinc addition reaction, "reaction time after addition of aldehyde 2.338. combined yield of 2.353 and 2.353. "the diastereomeric ratio was determined by integration of the H NMR of the mixture, dropwise addition of aldehyde, "slow addition of dienal by syringe pump.

Determination of the absolute stereochemistry of the newly generated C(15) stereocenter of 2.353 was achieved by Mosher ester analysis of the major dia-stereomer following the procedure reported by Kakisawa and co-workers (Scheme 2.76) [225]. The Mosher esters of the organozinc addition reaction product were prepared as shown in Scheme 2.76. Analysis of the (S)- and (R)-MTPA esters prepared from 2.353 obviously indicated that the C(15) alcohol was of the desired configuration (/ ), which was consistent with the results via reagent controlled asymmetric organozinc addition reaction. 

Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents... 

Henry reactions 317-20 hydrosilylations 333 organozinc reagents, addition to ketones 156-80 PrMgCl to cyclohexenone with crown thioether ligands 100-1 see also specific ZnEt2 and ZnR2 addition reactions... 

Nonlinearity was also found for this asymmetric organozinc addition, for example, using 50% ee of chiral modifier 46 resulted in 80% ee of adduct 53. The enanti-oselectivity is also dependent on the reaction concentration >98% ee was obtained at 0.1-0.5 M but only 74% ee at 0.005 M. Kitamura and Noyori s work strongly suggested that heterodimer 72 might be more thermally stable than the homodimer... 

Because of the separation of this chapter into fundamental synthetic and structural aspects of organozinc compounds and the applications of these compounds in organic synthesis, many topics are treated twice, but with decidedly different emphases. By way of example, the important organozinc alkoxides are covered first in the inorganometallic section, where the emphasis is on their syntheses, structures, and applications other than in organic synthesis. Later, in Section 2.06.16.2, the uses of such compounds as chiral catalysts in asymmetric addition reactions are discussed. 

Addition of Organozinc Reagents to Aldehydes, Ketones, and a-Ketoesters 2.06.16.2.1 Chiral ligands used in addition reactions of diorganozincs with aldehydes... 

One of the important new directions in the study of addition reactions of organozinc compounds to aldehydes is the use of ionic liquids. Usually, application of these compounds in reactions with common organometallic reagents has a serious problem ionic solvents are usually reactive toward them, particularly Grignard and organolithium derivatives. It has been recently reported that carbonyl compounds react with allylzinc bromide formed in situ from allyl bromide and zinc in the ionic liquid 3-butyl-l-methylimidazolium tetrafluoroborate, [bmim][BF4].285 Another important finding is that the more reactive ZnEt2 alkylates aldehydes in a number of ionic liquids at room temperature.286 The best yields (up to 96%) were obtained in A-butylpyridinium tetrafluoroborate, [bpy][BF4] (Scheme 107). 

Overall, green solvents appear to be a valuable alternative to conventional solvents in addition reactions of diverse organozinc reagents to aldehydes. 

Feringa and co-workers described the tandem addition-aldol cyclization protocol leading to the formation of 6,6-, 6,7-, and 6,8-annulated bicyclic systems (Scheme 68).39 Using Cu(n)-29 as catalyst and functionalized organozinc reagents as nucleophiles, the conjugate addition reaction followed by aldol cyclization can offer highly enantioselec-tive annulation products (up to 98% ee). This method can be used in the synthesis of carbocyclic compounds, such as steroids, terpenes, and other natural products. 

Feringa, B. L. Naasz, R. Imbos, R. Arnold, L. A. Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents. In Modem Organocopper Chemistry Krause, N. Ed. Wiley-VCH GmbH Weinheim, 2002 Chapter 7, pp 224—258. 

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