Benzylic zinc reagent

Conditions for controlling the regiochemistry of the addition reactions between benzyl zinc reagents and 2,4-dichloroquinoline under palladium-catalyzed conditions were developed <99JOC453>. Similarly, the regiochemistry of the palladium-catalyzed carbonylation of 4,7-dichloroquinoline was evaluated <99TL3719>. 

SCHEME 6. Preparation and uses of functionalized benzylic zinc reagents... 

Ferrocenyl groups are useful tools for stereoselective syntheses. Hayashi and coworkers have discovered a novel class of ferrocenyl catalysts allowing the kinetic resolution of benzylic zinc derivatives, such as 448 . The racemic mixture of the benzylic zinc reagent... 

The principle outlined above can be applied to the synthesis of benzyl zinc reagents via an interesting 1,2-migration/isomerization sequence (equation 16)21. 

The benzyl zinc reagents 38 can be reacted with various electrophiles E-X including aldehydes (or ketones) and acid chlorides, thus providing access to secondary (or tertiary) alcohols and benzylic ketones, respectively. Examples are given in Table 321. 

Normally tosyl cyanide reacts with the functionalized zinc reagents, such as 44, to provide the expected nitrile 45 (0°C to 25 °C, 2 h). However, the benzylic zinc reagent 46 and the corresponding copper-zinc reagent 47 react with tosyl cyanide differently. Whilst the zinc reagent furnishes the SE2 substitution product 48 (functionalization at the ortho position of the phenyl ring), the zinc-copper compound leads to the direct (SE2) substitution product 49 (Scheme 1.14).51... 

Electrochemical preparation of a functionalized benzylic zinc reagent and its coupling with a functionalized aromatic aldehyde preparation of 2-(4-cyanophenyl)-1-(4-methoxyphenyl)ethanol9... 

In efforts to prepare substituted methylthio-2V-heterocycles, researchers at Dupont discovered a new type of Negishi coupling reaction in which benzylic zinc reagents were found to undergo a Pd-catalyzed cross-coupling reaction at the C—S site. 2-(Methylthio) pyrimidine 50 was found to be a particularly reactive substrate for this reaction. Indeed, a 71% isolated yield using 1 mol% Pd( PPh J was obtained with benzyl zinc bromide and 2-(methylthio)pyrimidine in THF. This new cross-coupling method provides a convenient alternative to the use of pyrimidine halides [24]. 

Organozinc chlorides. To avoid generation of dibenzyls during preparation of benzylic zinc reagents from ArCH2Cl in THF, a protocol exploits the beneficial effect of LiCl. Allylzinc chlorides are similarly available, and they add to carbonyl compounds with excellent diastereoselectivity. ... 

Other metals which undergo oxidative addition to benzylic halides are zinc [10] and cadmium [11], Recently, an interesting new synthetic method for benzylic zinc reagent has been reported using triorganozincate [12],... 

Scheme 2-93. Preparation of benzylic zinc reagents starting from the corresponding...

The addition of copper-zinc organometallics to imines is sluggish. However, benzylic zinc halides possess sufficient reactivity and add directly to in situ generated imines. The secondary amine 514 was obtained from the benzylic zinc reagent 515 in 60% yield and 70% de (Scheme 2-148). ... 

Allyl acetates (see also 2.2) are also potent electrophiles in cross-coupling reaction with zinc nucleophiles. However, the regioselectivity of this reaction is quite poor.l In contrast, the reaction of benzyl zinc reagents with alkenyl halides furnish similar structures in good yields (Scheme 5-94). ... 

Scheme 7.10 Importance of the precursor for the preparation of benzylic zinc reagents.

Immobilized zincates such as 177 can be prepared by treating serine-bound 4-iodobenzoate with t-BujZnLi at 0°C. They react readily with aldehydes. Transme-tallation with lithium (2-thienyl)cyanocuprate provides the copper species 178 that undergoes 1,4-additions. Lithium trialkylzincates can be used for the preparation of benzylic zinc reagents using a very elegant approach of Harada. Thus, the treat-... 

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