Allylmetallation

One of the most gentle methods for the generation of reactive allylmetallic reagents was introduced in 1977 by Hiyama and Nozaki1,2,3,33. By the action of two equivalents of chromi-um(II) chloride on allylic halides in tetrahydrofuran at 0°C in the presence of a carbonyl compound, reductive coupling with the formation of a homoallylic alcohol takes place. 

Scheme 2 Four- versus six-centered processes in allylmetallation.

Allyl chlorides are readily deprotonated a to the halide by strong bases to give allyl carbenoids, which insert into organozirconocene chlorides to afford allyl- or pentadienyl-zirco-nocene chlorides (Scheme 3.23). These allylmetallic species are reactive towards carbonyl compounds, and so an efficient three-component coupling results [50]. 

The impetus for the development of gem-bimetallics was initially to discover alkylidene-transfer reagents akin to Tebbe s reagent [14]. Schwartz prepared bimetallic aluminum—zirconocene derivatives by the hydrometallation of various vinyl metallic compounds [15—17]. Knochel has developed zinc—zirconium gem-bimetallics by hydrozircona-tion of vinylzincs and has used them as alkylidene-transfer reagents [18], More recently, other gem-bimetallics have been developed that exhibit different reactivities of the two carbon—metal bonds. Thus, Normant and Marek have reported the allylmetallation of vinyl metals to afford zinc—magnesium and zinc—lithium gem-bimetallics, which react selectively with various electrophiles such as ClSnBu3, H20, etc. [19, and references cited therein]. However, selective and sequential cleavage of the two carbon—metal bonds... 

Allylmetallic reagents The ally] anions obtained by reductive metallation of ally I phenyl sulfides with lithium l-(dimethy amino)naphthalenide (LDMAN, 10, 244) react with a, 3-enals to give mixtures of 1,2-adducts. The regioselectivity can be controlled by the metal counterion. Thus the allyllithium or the allyltitanium compound obtained from either 1 or 2 reacts with crotonaldehyde at the secondary terminus of the allylic system to give mainly the adduct 3. In contrast the allylcerium compound reacts at the primary terminus to form 4 as the major adduct. 

SCHEME 3. (Alkoxy)allylmetalation of cyclopropene, the four-centered transition states leading to both Qf-adduct and y-adduct are shown. 

It is reasonable to assume, that the counterion prefers to coordinate to the carbon atom with the highest electron density. Hence, according to this crude picture, donor-substituted allylmetallics are to be regarded as 3-metalated hetero-substituted vinyl compounds, acceptor-substituted ones on the other hand as 1-metalated hetero-substituted allyl compounds. 

The allylmetallation of alkynyl metals such as 65a leads to 1,1-dimetallated alkenes such as 94a (equation 44 and Table 10)33. Quenching with electrophiles provides access to stereodefined polysubstituted olefins (see also Section I.E). 

Zinc(II) halide mediated Gaudemar/Normant-type allylmetallation to metal acetylide is also an efficient route. As shown in Scheme 38, the obtained. sp2-gcminated organodizinc reagent reacts with various electrophiles83. 

This Gaudemar/Nonnant type allylmetallation proceeds diastereoselectively when crotylmagnesium bromide is used. As shown in equation 59, the allyl alcohol can be obtained diastereoselectively via the corresponding sp2-geminated organodimetal. 

The same trend is observed for the allylmetallation of 8-heterosubstituted vinyl metals,18 of a metallated pentadiene19 (see Protocol 7) or in the propar-gylmetallation of vinyl metals13 (see Protocol 8). 

The allylmetallation of vinyl metals, y-heterosubstituted with a methoxy-methyl ether as the chelating group, leads to the corresponding gembismetal-lic derivatives,20 but now, warming the reaction mixture to room temperature promotes an internal nucleophilic substitution, leading to a metallated cyclopropane which can react with different electrophiles21 (Equation 7.5 and Protocol 9). 

The allylmetallation of an alkynyl metal leads to a vinylic 1,1-organogem-bismetallic derivative,22 and the stereoselective reaction of this latter with different electrophiles gives a new access to the synthesis of stereodefined poly-substituted olefins, as single stereoisomers23 (Equation 7.6 and Protocol 10). 

Allylmetallation of vinyl lithium derivatives preparation of 4-methyloctene... 

Allylmetallation of vinyl lithium derivatives and alkenylation of the resulting bismetallics preparation of ( )-1-phenyl-3-butyl-1,5-hexadiene... 

Allylmetallation of pentadienyl lithium derivatives preparation of (3/ , 4S )-dimethyl-1,6-heptadiene... 

Allylmetallation of y-heterosubstituted vinyl lithium derivatives and cyclopropanation reaction preparation of 1-(S )-iodo-2-(S M2-propenyl)-3-(R )-propylcyclopropane... 

Allylmetallation of y-heterosubstituted acetylenic lithium derivatives and reaction with different electrophiles preparation of (Z)-2-allyl-3-(terf-butoxy)-1 -chloro-1 -iodohex-1 -ene... 

---