Alkylzinc reagents

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

Mote teceal invesligations have shown tlial tliis reaction operates even under catalytic crrnditions f3-IO mol96 of copperfit) salt), witli alkylzinc reagents as tlie stoicliiometric otganometaliic source fSclieme 6.42) [89]. 

Alkynes react with indium reagents such as (allyl)3ln2l3 to form dienes (allyl substituted alkenes from the alkyne). Allyltin reagents add to alkynes in a similar manner in the presence of ZrCU Alkylzinc reagents add to alkynes to give substituted alkenes in the presence of a palladium catalyst. ... 

The preparation and the use of several C2-symmetric disulfonamides derived from 1,2-amino alcohols in the Ti-catalysed enantioselective addition of di-alkylzinc reagents to aldehydes was described by Yus et al., in 2002. The best... 

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

This must reflect activation of the carbonyl group by magnesium ion, since ketones are less reactive to pure dialkylzinc reagents and tend to react by reduction rather than addition.141 The addition of alkylzinc reagents is also promoted by trimethylsilyl chloride, which leads to isolation of silyl ethers of the alcohol products.142... 

Aryl zinc reagents are considerably more reactive than alkylzinc reagents in these catalyzed additions to aldehydes.151 Within the same computational framework, phenyl transfer is found to have about a lOkcal/mol advantage over ethyl transfer.152 This is attributed to participation of the tt orbital of the phenyl ring and to the greater electronegativity of the phenyl ring, which enhances the Lewis acid character of the catalytic zinc. 

Lewis acid-catalyzed additions can be carried out in the presence of other chiral ligands that induce enantioselectivity.156 Titanium TADDOL induces enantioselectivity in alkylzinc additions to aldehydes. A variety of aromatic, alkyl, and a, (3-unsaturated aldehydes give good results with primary alkylzinc reagents.157... 

Lewis acids catalyze the reaction of alkylzinc reagents with acyl chlorides.160 The reaction is also catalyzed by transition metals, as is discussed in Chapter 8. 

Catalytic amounts of chiral amino alcohols both catalyze the reactions of alkylzinc reagents with aldehydes and induce a high degree of enantioselec-tivity. Two examples are given below. Formulate a mechanism for this catalysis. Suggest transition structures consistent with the observed enantioselectivity. 

Configurational integrity of secondary alkylzinc reagents had been demonstrated by Knochel although the preparation of the zinc reagent was not practical (Scheme 8.8) [13],... 

Copper-catalyzed Asymmetric Allylic Alkylations with Alkylzinc Reagents 403... 

A unique nickel-catalyzed alkylative monofunctionalization of cyclic anhydrides using dialkylzinc and diphenylzinc provided 7- or f3-keto acids (Scheme 124).323 This reaction also required the use of Ni(cod)2 or Ni(acac)2 and a bidentate ligand. As it was observed by Knochel in the reactions of dialkylzinc with alkyl iodides (vide infra), addition of an electron-deficient alkene,324 for example, 4-fluoromethylstyrene, accelerated the rate of the reaction and increased the yield of the desired products. The alkylzinc reagents BuZnBr and Et02CCH2CH2ZnBr also reacted with anhydrides, although the yields were lower. 

Kataoka et al. showed that vanadium(m) or (rv) chloride, upon reaction with 1 equiv. of an alkylzinc reagent, generates an alkylvanadium species in situ which reacts with aldehydes or ketones at 0 °C to give the corresponding secondary or... 

Zr-Catalyzed Enantioselective Imine Alkylations with Alkylzinc Reagents... 

Scheme 6.16. Zr-catalyzed enantioselective addition of alkylzinc reagents to imines utilizes peptidic ligands and can be used to prepare a variety of aromatic amines in high optical purity.

Scheme 6.17. With the peptidic amine ligand 54, a variety of alkylzinc reagents can be added to imines in a highly enantioselective and efficient manner in the presence of Zr(OiPr)4 HO/Pr.

As is also illustrated in Scheme 6.23, the optically enriched amino nitriles can be converted to the corresponding a-amino esters through a four-step sequence (74—> 75). Unlike the aforementioned imine alkylations with alkylzinc reagents, methylation of the phenolic OH is required, since the corresponding o-methoxy aniline is less reactive and affords significantly lower enantioselectivities similar observations are made when aniline is used. 

More recent investigations have shown that this reaction operates even under catalytic conditions (3-10 mol% of copper(II) salt), with alkylzinc reagents as the stoichiometric organometallic source (Scheme 6.42) [89]. 

More recently, we have discovered that Pd-JOSIPHOS complexes effectively desymmetrize a variety of succinic anhydrides in excellent yield and enantio-selectivity [Eq. (10.54)]. The reaction proceeds at ambient temperature in some cases and can deliver aryl and alkylzinc reagents with equal facility. For reasons that are unclear, the latter protocol requires a styrenic additive for high enantioselectivity ... 

High degrees of enantioselectivity have been observed when alkylzinc reagents react with aldehydes in the presence of chiral ligands.120 Among several compounds that have been used as ligands are exo - (dime th y I a m i no )no rb o rn c o I (A)121 122 123 124 and diphenyl(l-methyl-pyrrolin-2-yl)methanol (B) as well as ephedrine derivatives C and D. 

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