Deprotonation acyl complexes

Hydroxy-substituted iron-acyl complexes 1, which are derived from aldol reactions of iron-acyl enolates with carbonyl compounds, are readily converted to the corresponding /i-methoxy or /1-acetoxy complexes 2 on deprotonation and reaction of the resulting alkoxide with iodomethane or acetic anhydride (Tabic 1). Further exposure of these materials to base promotes elimination of methoxide or acetate to provide the a,/ -unsaturated complexes (E)-3 and (Z)-3 (Table 2). 

The lithium enolate 2a (M = Li ) prepared from the iron propanoyl complex 1 reacts with symmetrical ketones to produce the diastercomers 3 and 4 with moderate selectivity for diastereomer 3. The yields of the aldol adducts are poor deprotonation of the substrate ketone is reported to be the dominant reaction pathway45. However, transmetalation of the lithium enolate 2a by treatment with one equivalent of copper cyanide at —40 C generates the copper enolate 2b (M = Cu ) which reacts with symmetrical ketones at — 78 °C to selectively produce diastereomer 3 in good yield. Diastereomeric ratios in excess of 92 8 are reported with efficient stereoselection requiring the addition of exactly one equivalent of copper cyanide at the transmetalation step45. Small amounts of triphcnylphosphane, a common trace impurity remaining from the preparation of these iron-acyl complexes, appear to suppress formation of the copper enolate. Thus, the starting iron complex must be carefully purified. 

The a-alkoxy iron-acyl complex 5 may be deprotonated to generate the lithium enolate 6, which undergoes a highly diastereoselective aldol reaction with acetone to generate the adduct 7 as the major product. Deprotonation of acetone by 6 is believed to be a competing reaction 30% of the starting complex 5 is found in the product mixture48 40. 

Although the isolation and reactivity of acyl complexes strongly support the hydride mechanism, the other mechanism cannot be excluded. For example H20, the acid or molecular hydrogen, which can act as a hydride source, can promote the Pd - C splitting of the Pd-alkylcarboalkoxy intermediate in the alkoxy cycle as well. More convincing for the hydride route is the fact that the acid, which does not promote the formation of a Pd-OCH3+ species, has a promoting effect on the catalysis and can activate a Pd(0) complex, otherwise inactive, whilst a base, which not only promotes the formation of this species, but also deprotonates a Pd - H+ species to Pd(0), suppresses the catalysis. 

The resting state of the propanoate catalysts may well be an acyl complex [60,61], while the attack of alcohol at the acylpalladium complex is considered to be the rate-determining step. It is probably more precise to say that fast preequilibria exist between the acyl complex and other complexes en route to it and that the highest barrier is formed by the reaction of alcohol and acylpalladium complex. The precise course of the reaction is still not known presumably deprotonation of the coordinating alcohol and the migratory elimination are concerted processes, accelerated by the steric bulk of the bidentate ligand. Toth and Elsevier showed that the reaction of an acetylpalladium complex and sodium methoxide is very fast and occurs already at low temperature to give methyl acetate and a palladium(I) hydride dimer [46]. 

Enolate Preparation by Deprotonation of Iron-Acyl Complexes a-Deprotonation of Iron-Acyl Complexes... 

Strong bases are required to abstract an a-proton from iron-acyl complexes (see also Houben-Weyl, Volume 13/9a, p 417). Such deprotonations are usually conducted in moderately polar solvents such as tetrahydrofuran. The archetypal complexes 1 and 2 illustrate most of the factors influencing a-proton abstraction. 

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. 

Conditions employed for the generation of extended enolates by y-deprotonation of Z-oc,/ -un-saturated iron-acyl complexes are presented in Table 3. 

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. 

Iron acyl complexes bearing an a,/ -unsaturated acyl ligand possess multiple sites of electrophilic reactivity. Strong bases may be induced to react with the acyl ligand, and in Section 1.1.1.3.4.1.1. the chemoselective y-deprotonation of Z-a,/i-unsaturated acyl ligands to generate enolate species was addressed. The profoundly different reactivity of the unsubstituted complex 1 and E-a,/ -unsaturated acyl complexes, such as 2, is discussed here. 

Iron-acyl enolates, such as 2, prepared by x-deprotonation of the corresponding acyl complexes with lithium amides or alkyllithiums, are nearly always generated as fs-enolates which suffer stereoselective alkylation while existing as the crmt-conformer which places the carbon monoxide oxygen anti to the enolate oxygen (see Section 1.1.1.3.4.1.). These enolates react readily with strong electrophiles, such as primary iodoalkanes, primary alkyl sulfonates, 3-bromopropenes, (bromomethyl)benzenes and 3-bromopropynes, a-halo ethers and a-halo carbonyl compounds (Houben-Weyl, Volume 13/9 a, p 413) (see Table 6 for examples). 

The origin of the third diastereomer produced, complex 12, is of particular mechanistic interest. The configuration at Ca of 12 is opposite to that of the other two products 10 and 11 indicating that the opposite face of the enolate 6 has been approached by the epoxide. Two possible alterations of the geometry of enolate 6 inay be invoked to account for this, adoption of the 5yn- -conformer or adoption of the anti-Z-conformer. Examination of the different structures shown reveals that the observed minor product 12 could arise from a matched reaction pair of the ivn-E-enolate and epoxide (Newman Projection G) or from a mismatched reaction pair of the anti-Z-enolate and epoxide (Newman projection I). The absence of diastereomer 13 strongly suggests that the minor product 12 arises from reaction of the. ryn- -enolate, underscoring the extreme reluctance of iron-acyl complexes to form Z-enolates on deprotonation (see scheme on p 955). 

However, the more hindered, less basic lithium hexamethyldisilazamide reacts slowly with 1 at 0 °C to provide chemoselectively the desired enolate species 5. The a-protons of these rhenium-acyl complexes are believed to have a lower pKa than the cyclopentadienyl protons, but unless treated with hulky, selective hases the cyclopentadienyl protons exhibit greater kinetic acidity due to statistical factors and an earlier, reactant-like transition state since minimal rchybridiza-tion is required at the anionic center after cyclopentadienyl deprotonation. Equilibration of the cyclopentadienyl anion to the thermodynamically more stable enolate species cannot compete with the rapid acyl migration84. 

Hydridotris(3,5-dimethyl-l-pyrazolyl)borate]molybdenum-(i72-acyl) complexes, such as 1, are deprotonated by butyllithium or potassium hydride to generate enolate species, such as 488.8> jjie overa]] structure of these chiral complexes is similar to that of the iron and rhenium complexes discussed earlier the hydridotris(3,5-dimethyl-l-pyrazolyl)borate ligand is iso valent to the cyclopentadienyl ligand, occupying three metal coordination sites. However, several important differences must be taken into account when a detailed examination of the stereochemical outcome of deprotonation-alkylation processes is undertaken. 

Treatment of some iron-acyl complexes with trifluoromethanesul-phonic anhydride (TfzO) affords vinylidene derivatives directly (5 7,38). The reaction is envisaged as a nucleophilic attack on TfzO by the acyl, followed by deprotonation to the vinyl ether complex. A combination of an excellent leaving group (TfO-) with a good electron-releasing substituent on the same carbon atom facilitates the subsequent formation of the vinylidene ... 

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,... 

Terminal and bridging ketenido complexes are prepared by deprotonation of acyl complexes or by insertion of CO into a vinyl-, carbene-or methylene-metal bond. 

Synthesis and Reaction Chemistry of a,p-Unsaturated Acyl Complexes Derived from (2). Two methods for the preparation of optically active ( )- and (Z)-a,p-unsaturated iron acyls from (2) have been reported." One method involves aldol condensation of (2) with aldehydes followed by 0-methylation to produce diastereomeric acyls (18). This mixture (18) is then treated with Sodium Hydride to produce predominantly ( )-a,p-unsaturated acyl complexes (19) (eq 13). Alternatively, (2) can be depro-tonated and treated with Chlorotrimethylsilane to produce the C-silylated complex which is subsequently deprotonated and treated with an aldehyde. This Peterson alkenation produced mixtures... 

The most complex example of this type of consecutive organometallic acylation, subsequent deprotonation, and tetrahydrofuran ring formation was recorded during the synthesis of the right hand portion of X-206 (Scheme 6). The high overall yield obtained in this process is a testament to the method s generality. 

Cyclic cobalt-acyl complexes can be deprotonated, and subsequent reaction of these enolates with aldehydes gives predominantly the anti/threo product (Scheme 63). Rhenium-acyl complexes can be deprotonated in the same manner. These lithium enolates can be alkylated or can react with [M(CO)5(OTf)] (M = Re, Mn) to give the corresponding enolates (Scheme Many transition metal enolates of type (21) or (22) are known, - but only a few have shown normal enolate behavior , e.g. aldol reaction, reaction with alkyl halides, etc. Particularly useful examples have been developed by Molander. In a process analogous to the Reformatsky reaction, an a-bromo ester may be reduced with Smia to provide excellent yields of condensation products (Scheme 65) which are generated through intermediacy of a samarium(III) enolate. ... 

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