Functionalization with various electrophilic reagents

Cumulenic anions, C=C=C and C=C=C=C, without strongly electron-withdrawing substituents are much stronger bases than acetylides, CsC- and are therefore also stronger nucleophiles. In view of the poor stability of the cumulenic anions at normal temperatures this is a fortunate circumstance the usual functionalization reactions such as alkylation, trimethylsilylation and carboxylation in most cases proceed at a sufficient rate at low temperatures, provided that the 

The anions derived from allenic sulfides, RCH=C=C-SR , which are stable in liquid 

The enormous difference in basicity between the two anionic centers in the 

If two equivalents of the reagents are used, disubstitution to ECeC-CH(E)R occurs in most cases, but interestingly the reaction of LiCeCCH(Li)R with an excess of COj gives mainly the allenic dicarboxylic acids. These are probably the result of a rapid isomerization of the primary dilithium salt of the acetylenic diacid during the work-up or during the reaction of the dilithio compound with COj  

The reaction of cumulenic anions with electrophiles in principle may give two products  

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The imidazo[l,5-a]pyridine ring system has been successfully functionalized with various electrophilic reagents, metalated, and reduced in one case. No nucleophilic displacements of leaving groups have been reported on appropriate derivatives. 

A large number of experimental procedures show how polar organometallic intermediates of the broad spectrum of organic compounds can be generated and how these can be functionalized with various electrophilic reagents. All procedures (on the 0.05-0.10 molar scale) have bee preparatively checked in the laboratory of the authors. The reaction conditions recommended reflect reactivities of starting compounds and intermediates directly. This may save the user a considerable amount of time. 

Analogous for other pyridines with a 2-methyl group. Functionalization with various electrophilic reagents. 

Reactions of zinc-copper reagents bearing acidic hydrogen and sulfur functionalities with various electrophiles, including nitroalkenes, have been reported, as shown in Eq. 4.86108 and Eq. 4.87,109 respectively. 

The pyrrolidinylmethylzinc reagents derived from the carbocyclization of zinc enolates were further functionalized with various electrophiles such as iodine or allyl bromide. In this last case, three carbon-carbon bonds, and one ring were formed in a single operation. 

Corey and Chaykovsky had discovered that dimethyl sulfoxide is converted to methyl-sulfmyl carbanion upon treatment with sodium hydride " and that this conjugate base of DMSO reacts with various electrophiles This finding has opened up various reactions with a-sulfinyl carbanions derived from sulfoxides, since the sulfinyl function can be removed either by thermolysis or by subjecting the compound to reductive desulfurization. Thus a-sulfinyl carbanions have become versatile synthetically useful reagents. 

The terminal carhanionic sites of "living" polymers can be reacted with various electrophilic compounds of yield (o)-functional polymers. Esters, nitriles, acid chlorides, anhydrides, lactones, epoxides, benzyl or allyl halogenides have been used for their high reactivity with metal organic sites, to yield appropriate functions.2 Carbon dioxide is also an efficient reagent to yield terminal carboxylic functions. 

Diels-Alder reactions of a,fi-unsaturatedN,N-dimethylhydrazones.1 These readily available hydrazones can function as 1-amino-l-aza-l,3-dienes in Diels-Alder reactions. Thus, 1 undergoes regioselective cycloaddition with various electrophilic dienophiles to give tetrahydropyridines such as 2 and 3. Unfortunately, removal of the dimethylamino group with zinc and acetic acid (or other reagents) also effects reduction of the double bond. The initial adduct from cycloaddition of 1 with naphthoquinone is unstable and undergoes spontaneous elimination of the elements of dimethylamine to give the aromatic adduct 4. 

Acyliron complexes have found many applications in organic synthesis [40]. Usually they are prepared by acylation of [CpFe(CO)2] with acyl chlorides or mixed anhydrides (Scheme 1.13). This procedure affords alkyl, aryl and a,P-unsaturated acyliron complexes. Alternatively, acyliron complexes can be obtained by treatment of [Fe(C5Me5)(CO)4]+ with organolithium reagents, a,P-Unsaturated acyliron complexes can be obtained by reaction of the same reagent with 2-alkyn-l-ols. Deprotonation of acyliron complexes with butyllithium generates the corresponding enolates, which can be functionalized by reaction with various electrophiles [40]. 

It can be observed that in several cases the addition reaction proceeds with excellent diastereomeric excesses. Although the reaction temperature, the solvent and the nature of the counter anion are different from case to case, nevertheless the data reported in the table can be used to have preliminary indications about the ability of the various electrophilic reagents to transfer the chirality to the newly generated stereocenters. The information gained from these experiments, however, must be used with caution since the stereoselectivity is also a function of the alkene employed and examples are known in which a reagent which gives unsatisfactory results with styrene can, in contrast, be efficient with other alkenes. This is clearly evident from the data reported in Table 2 in which the diastereomeric excesses measured for the reactions of the electrophilic reagents derived from the diselenides 24 and 26 with various alkenes are reported. In both cases the results obtained with other alkenes are much better than those observed with styrene. 

Substituted dialkylzinc reagents.h Reagents of this type can be obtained by reaction of functional alkyl iodides with HsJzZn. These zinc reagents react with various electrophiles in the presence of CuCN 2LiCl. 

Allenyl-lithium reagents, generated by metallation of allenic hydrocarbons or from haloallenes by halogen-metal exchange, react with various electrophiles with retention of the allenic structure to give functionalized allenes. High yields of allenylsilanes and sulphides, allenic acids and dialkylamides, and fi-allenic alcohols are available by this method. However, additions to ketones are less satisfactory since propargylic alcohols are formed in some cases. 

The addition of LiCI also strongly enhances the rate of zinc insertion into alkyl halides, making possible a very simple and versatile preparation of functionalized alkylzinc reagents of type 247, which can be in situ trapped with various electrophiles or subjected to cross-coupling reactions (Scheme 2-98). ... 

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