Iron acyl complexes alkylation

Alkylation of the anion 2 with iodomethane or other haloalkanes provides alkyldicarbonyl(t/5-cyclopentadienyl)iron complexes such as 53,0 (see also Houben-Weyl, Vol. 13/9a, p 209). Migratory insertion of carbon monoxide occurs on treatment with phosphanes or phosphites9 -11 (see also Houben-Weyl, Vol. d3/9a, p257) to provide chiral iron-acyl complexes such as 6. This is the most commonly used preparation of racemic chiral iron-acyl complexes. 

Another route to enantiomcrically pure iron-acyl complexes depends on a resolution of diastereomeric substituted iron-alkyl complexes16,17. Reaction of enantiomerically pure chloromethyl menthyl ether (6) with the anion of 5 provides the menthyloxymethyl complex 7. Photolysis of 7 in the presence of triphenylphosphane induces migratory insertion of carbon monoxide to provide a racemic mixture of the diastereomeric phosphane-substituted menthyloxymethyl complexes (-)-(/ )-8 and ( + )-( )-8 which are resolved by fractional crystallization. Treatment of either diastereomer (—)-(/J)-8 or ( I )-(.V)-8 with gaseous hydrogen chloride (see also Houben-Weyl, Vol 13/9a, p437) affords the enantiomeric chloromethyl complexes (-)-(R)-9 or (+ )-(S)-9 without epimerization of the iron center. 

Subsequent carbonylation of the alkyl-iron complexes with carbon monoxide provides the desired chiral iron-acyl complexes, with essentially complete inversion of configuration at... 

The anion 7 is quite nucleophilic and undergoes exclusive C-alkylation upon reaction with electrophiles including chlorotrimethylsilane °. These reactivity patterns have led to the suggestion that enolates of iron-acyl complexes may be considered to behave similarly to the organic dianion 910- u. 

Most of the work in this area has concerned complexes racemic at iron. Section D.1.3.4.2.5.1.1. details methods for the preparation and resolution of enantiomerically pure iron acyl complexes. The details of alkylation reactions (see Section 1.1.1.3.4.1.3.) and aldol reactions (see Section 1.3.4.2.5.1.2.) of these and other iron acyl enolates are presented later with examples utilizing enantiomerically pure complexes indicated therein. Table 1 illustrates the scope of iron-acyl enolates prepared by deprotonation of complex 10 and its analogs. 

Treatment of the potentially electrophilic Z-xfi-unsaturated iron-acyl complexes, such as 1, with alkyllithium species or lithium amides generates extended enolate species such as 2 products arising from 1,2- or 1,4-addition to the enone functionality are rarely observed. Subsequent reaction of 2 with electrophiles results in regiocontrolled stereoselective alkylation at the a-position to provide j8,y-unsaturated products 3. The origin of this selective y-deproto-nation is suggested to be precoordination of the base to the acyl carbonyl oxygen (see structures A), followed by proton abstraction while the enone moiety exists in the s-cis conformation23536. 

Reaction of Z-a./j-unsaturated iron-acyl complexes with bases under conditions similar to those above results in exclusive 1,4-addition, rather than deprotonation, to form the extended enolate species. However, it has been demonstrated that in the presence of the highly donating solvent hexamethylphosphoramide, y-deprotonation of the -complex 6 occurs. Subsequent reaction with electrophiles provides a-alkylated products such as 736 this procedure, demonstrated only in this case, in principle allows access to the a-alkylatcd products from both Z- and it-isomers of a,/j-unsaturated iron-acyl complexes. The hexamethylphosphoramide presumably coordinates to the base and thus prevents precoordination of the base to the acyl carbonyl oxygen, which has been suggested to direct the regioselective 1,4-addition of nucleophiles to -complexes as shown (see Section 1.1.1.3.4.1.2.). These results are also consistent with preference for the cisoid conformations depicted. 

The range of carbon nucleophiles that have been successfully employed for 1,4-addition to -a,/i-unsaturated iron-acyl complexes is limited to simple alkyl- and aryllithium species. Grignard reagents and the 1,3-propanedioate anion are reported to fail to react with. E-complexes36. The effect of varying the phosphane ligand has been examined little effect upon... 

Methods for the preparation of the requisite -2,/l-unsaturaied iron-acyl complexes are presented in Section D.1.3.4.2.5., but it is noted here that several examples of 1,4-alkylative preparations of a-enolates from in situ generated fi-complexes, such as 9, have been reported in which the alkyllithium base employed acts both as a base to produce the unsaturated species via elimination and subsequently, as a nucleophile to afford alkylation products 10 and 1244. 

Table 6. Alkylation of a-Enolates 2 of Chiral Iron-Acyl Complexes 1 by Carbon Electrophiles...

Electrophiles that have been used for the second alkylation of this tandem Michael addition -alkylation sequence are limited to primary iodoalkanes, (bromomethyl)benzenes and 3-bromo-propenes. Tables 9 and 10 provide details of the alkylations of enolate species prepared by 1,4-additions of -a,/j-unsaturated iron-acyl complexes by anionic carbon nucleophiles and anionic nitrogen nucleophiles, respectively. 

General methods for the preparation of a.jS-unsaturated iron-acyl complexes are deferred to Section D 1.3.4.2.5.1.1. examples of the alkylation of enolates prepared via Michael additions to ii-0 ,/ -unsaturated complexes prepared in situ are included here. Typical reaction conditions for these one-pot processes involve the presence of an excess of alkyllithium or lithium amide which first acts as base to promote elimination of alkoxide from a /f-alkoxy complex to generate the -a,)S-unsaturated complex which then suffers 1,4-nucleophilic addition by another molecule of alkyllithium or lithium amide. The resulting enolate species is then quenched with an electrophile in the usual fashion. The following table details the use of butyllithium and lithium benzylamide for these processes44,46. 

Iron-acyl complex 47 illustrates the diastereoselective a-alkylation of the 3-methyl-l-oxobutyl-substituted enolate 46, prepared by two iterations of the elimination-Michael addition sequence three alkylations are conducted in a single reaction vessel44. 

Rhenium-acyl complexes, such as 1, are isoelectronic with the iron-acyl complexes discussed above and many reactivity patterns are common to the two groups of compounds. Treatment of complex 1 with strong bases, such as butyllithium or lithium diisopropylamide, results in abstraction of a cyclopentadienyl proton which is followed by rapid migration of the acyl ligand to the cyclopentadienyl ring to produce the metal-centered anion 384. Alkylation of 3generates a metal-alkyl species, such as 4. 

Iron acyl complexes are among the most widely studied of the organometallic iron species, especially as applied to organic synthesis. As previonsly mentioned they are prepared to provide access to iron alkyls (via decarbonylation), and because iron acyls can be deprotonated to form enolates much like any carbonyl they have been utilized as chiral auxiliaries in asymmetric synthesis. Also, iron acyls are an important entry point for the preparation of iron carbenes. 

The a-protons of iron acyl complexes are acidic and these can be deprotonated with Lithium diisopropylamide (LDA) or with n-butyllithimn. Thus the corresponding enolates are readily functionalized and undergo reaction with alkyl halides, aldehydes, disulfides, trimethylsilyl chloride, and epoxides to afford the corresponding a-derivatized products. " Early work on racemic complexes revealed that these transformations occur in a highly diastereoselective fashion,... 

Alkylation of iron acyl complexes also provides access to iron carbenes. Thus, the neutral iron acyl complex will react with acid, with alkylating agents, or with trifluoromethanesul-fonic anhydride to afford cationic hydroxy- or aUcoxycarbene complexes (52) and (53) or the cationic vinylidene complex (54, L = CO) (Scheme 20). The vinylidene complex can be used to prepare a more substituted analog of (51) by treatment with a thiol. The enantiomerically pure iron acyl complex (R)-(45a) can be converted to the corresponding enantiopure methoxycarbene complex with Me30Bp4 as well. Finally,... 

In method (b). (1) is again formed the ligand iriphenylphosphine then promotes migratory insertion to give the anionic iron acyl complex (4). Reaction with another alkyl halide gives a complex (5) corresponding to (3) above. 

This iron anion is a good soft nucleophile for alkyl halides and can be used twice over to produce first a monoanion with one alkyl group and then a neutral complex with two alkyl groups and four CO ligands. Each of these complexes has 18 electrons. If extra CO is added by increasing the pressure, CO inserts into one Fe—C bond to form an iron acyl complex. Finally, reductive elimination couples the acyl group to the other alkyl group in a conceptually simple ketone synthesis. It does not matter which Fe—C bond accepts the CO molecule the same unsymmetrical ketone is produced at the end. 

Stereoselective alkylation of an iron acyl complex (Scheme 4.5) ... 

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

Iron(II) alkyl anions fFe(Por)R (R = Me, t-Bu) do not insert CO directly, but do upon one-electron oxidation to Fe(Por)R to give the acyl species Fe(Por)C(0)R, which can in turn be reduced to the iron(II) acyl Fe(Por)C(0)R]. This process competes with homolysis of Fe(Por)R, and the resulting iron(II) porphyrin is stabilized by formation of the carbonyl complex Fe(Por)(CO). Benzyl and phenyl iron(III) complexes do not insert CO, with the former undergoing decomposition and the latter forming a six-coordinate adduct, [Fe(Por)(Ph)(CO) upon reduction to iron(ll). The failure of Fe(Por)Ph to insert CO was attributed to the stronger Fe—C bond in the aryl complexes. The electrochemistry of the iron(lll) acyl complexes Fe(Por)C(0)R was investigated as part of this study, and showed two reversible reductions (to Fe(ll) and Fe(l) acyl complexes, formally) and one irreversible oxidation process."" ... 

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