Organozinc reagents secondary alkyl

Organozinc reagents have been used in conjunction with a-bromovinylboranes in a tandem route to Z-trisubstituted allylic alcohols. After preparation of the vinylborane, reaction with diethylzinc effects migration of a boron substituent with inversion of configuration and exchange of zinc for boron.176 Addition of an aldehyde then gives the allylic alcohol. The reaction is applicable to formaldehyde alkyl and aryl aldehydes and to methyl, primary, and secondary boranes. 

Crucially, this allows organozinc reagents to be prepared from less reactive aryl bromides and secondary or tertiary alkyl bromides. Alternatively, organozinc iodides can be prepared by means of a palladium(0)-catalyzed reaction between alkyl iodides and Et2Zn (Scheme 2.25) [53-56]. 

Aryl and alkyl organozincate reagents, generated in situ by reaction of Grignard reagents and sub-stoichiometric amounts of ZnCl2, cross-couple smoothly in refluxing THF with functionalized aryl and alkenyl as well as primary and secondary alkyl chlorides in the presence of Pd(dppf)Cl2. ... 

The high chemoselectivity of organozinc reagents also allowed the use of the functionalized secondary a-acetoxy alkyl bromide 50 which was converted to 34a (equation 19)36, a product previously obtained by the cyclization of a 5-ethylenic primary iodide bearing the acetoxy group at the allylic position (equation 13). 

The cross-conpling of more hindered secondary and tertiary alkyl hahdes has also been studied. Thus, secondary alkyl halides can be cross-coupled with organozinc reagents in the presence of the so-called pybox hgands (eqnation 9). 

In 2003, Zhou and Fu [239] reported high catalytic activities exerted by nickel-Pybox complexes in the Negishi coupHng of an array of functionalized secondary alkyl bromides and iodides with organozinc reagents at room temperature as presented in Scheme 3.66. Their study opened the door to the possibihty of achieving... 

Secondary alkyl bromides are sufficiently reactive under these conditions, but primary alkyl bromides are usually inert and much better results are obtained by using highly activated Rieke-zinc. Thus, the reduction of zinc chloride with lithium naphthalenide, freshly prepared from finely cut lithium and naphthalene in THF, produces within 1.5 h highly reactive zinc (Rieke-zinc). This form of zinc readily reacts with secondary and tertiary alkyl bromides. Adamantyl bromide (217) was converted into the corresponding organozinc reagent 218. Its reaction with cyclohexenone in the presence of BF3 OEt2 and TMSCl afforded the 1,4-addition product 219 in 54% yield (Scheme 2-87). 

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