Chiral iron acyl complexes

The only main Group III metal, other than boron, that has been utilized in the aldol reaction is aluminum, the enolates of which behave rather capriciously in terms of stereochemistry. The A1—C bond is relatively weak. However, aldol reactions with aluminum enolates derived from chiral acyl-iron complexes proceed with high asymmetric induction. 

Another auxiliary that became well known in enolate chemistry is chiral acyl iron complexes for alkylation, aldol reactions, and conjugate additions indeed, so-called Davies-Liebeskind enolates [60] can be generated either by deprotonation of alkanoyl complexes 124a or conjugate addition of strong nucleophiles like alkyllithium compounds or lithium amides to alkenoyl complexes 127. 

Davies and Liebeskind independently prepared chiral aluminum enolates from enantiomerically homogeneous acyl-iron complexes (137) and recorded the first aluminum-mediated asymmetric aldol reactions. Although the lithium enolate of the chiral iron complex (CHIRAC) provides aldol products with... 

A very different, but similarly effective, auxiliary is the chiral carbonyl(t/5-cyclopentadienyl)(tri-phenylphosphine)iron moiety. When the z./i-unsaturated acyl-iron complex ( -)-(/ )-11 is treated by a modified Simmons Smith reagent, a 91 9 mixture of cyclopropane diastereomers is isolated in good yield73. Precomplexation of the starting iron complex by the Lewis acid zinc(II) chloride seems to be necessary to obtain good selectivity. The chiral iron moiety can then be removed oxidatively by bromine treatment, and the intermediate acyl bromides converted into amides by reaction with (/ )- -phenylethylamine. 

The first explicit discussion of what we have defined as PKR was published using the terminology simultaneous kinetic resolution and predates Vedejs and Chen [6a] by nearly 10 years. The process was described in 1989, within a Ph.D. dissertation of Preston, from Stephen G. Davies laboratory in Oxford [60], a report that escaped our notice until recently. In all probability, this is the first-known attempt to specifically separate enantiomers using a PKR (Scheme 6.38). Preston demonstrated that a mixture of gitosi-enantiomeric chiral enolates 185 and 186 (generated from the corresponding acyl iron complexes and butyllithium) reacts with the racemic a-bromopropionate 184 to give distinct major products 187 and... 

Chiral diene—iron tricarbonyl complexes were acylated using aluminum chloride to give acylated diene—iron complexes with high enantiomeric purity (>96% ee). For example, /ra/ j -piperjdene—iron tricarbonyl reacted with acyl haUdes under Friedel-Crafts conditions to give l-acyl-l,3-pentadiene—iron tricarbonyl complex without any racemization. These complexes can be converted to a variety of enantiomericaHy pure tertiary alcohols (180). 

I.3.4.2.5. Chiral Enolates of Acyl-Metal Complexes J. S. McCallum and L. S. Liebeskind I.3.4.2.5.I. Chiral Iron-Acyl Complexes... 

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. 

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 chiral lithium enolate 2 reacts with symmetrical ketones to produce /(,/i-dialkyl-/l-hydroxy-acyl complexes 3 which serve as precursors to oc,/1-unsaturated iron complexes (see Section 1.3.4.2.5.1.1.). 

Chiral rhenium complexes, such as 1 and 4, are isoelectronic to the a-alkoxy vinyl-iron complexes discussed above and they exhibit analogous chemistry in many respects. Like the iron complexes, they are prepared as the Z-isomer and are readily alkylated by primary iodoalkanes and (bromomethyl)benzene with efficient 1,3-asymmetric induction97. Subsequent, spontaneous loss of halomethane produces the elaborated rhenium-acyl complexes. Two examples of the stereocontrolled preparation of diastereomeric rhenium-acyl complexes via this methodology are illustrated. 

To prepare the enantiomerically pure iron acyl complex (R)-(39), a precursor diastereomeric menthoxyaUcyl complex was resolved and then manipulated (Scheme 14). More recently resolution of the chiral-at-metal acyl complexes themselves was achieved, and this has become the basis for a commercial preparation of the iron acyl developed for use as a chiral auxiliary (see below). Cationic iron complex (43) was treated with potassium L-mentholate to produce diastereomeric esters (44) that were not isolated but were reacted with LiBr/MeLi (Scheme 15). After chromatography and recrystallization the enantiomerically pure ironacyl complex (5 )-(39a) was obtained. It was suggested that only one diastereomeric ester can react (with inversion of configuration at iron, as shown) with the methyl nucleophile the unreactive diastereomer suffers from severe steric congestion about the electrophilic CO ligand. 

Cyclopropanation reactions of nonheteroatom-stabilized carbenes have also been developed. The most versatile are the cationic iron carbenes that cyclopropanate alkenes with high stereospecificity under very mild reaction conditions. The cyclopropanation reagents are available from a number of iron complexes, for example, (9-alkylation of cyclopentadienyl dicarbonyliron alkyl or acyl complexes using Meerwein salts affords cationic Fischer carbenes. Cationic iron carbene intermediates can also be prepared by reaction of CpFe(CO)2 with aldehydes followed by treatment with TMS-chloride. Chiral intermolecular cyclopropanation using a chiral iron carbene having a complexed chromium tricarbonyl unit is observed (Scheme 61). 

Conjugate addition reactions of N-nucleophiles with double stereodifferentiation are known in some cases11-116. While direct reaction of chiral amines with chiral enones11 leads to poor enantiomeric excess of the resulting /l-amino acids, reaction of chiral amines116 with acylated chiral iron complexes gives /J-amino acids with a high enantiomeric excess. 

The Simmons-Smith reaction is an efficient and powerful method for synthesizing cyclopropanes from alkenes [43]. Allylic alcohols are reactive and widely used as substrates, whereas a,j8-unsaturated carbonyl compounds are unreactive. In 1988, Ambler and Davies [44] reported the electrophilic addition of methylene to a,/3-unsaturated acyl ligands attached to the chiral-at-metal iron complex. The reaction of the racemic iron complex 60 with diethylzinc and diiodomethane in the presence of ZnCl2 afforded the c/s-cyclopropane derivatives 61a and 61b in 93 % yield in 24 1 ratio (Sch. 24). 

This complex has several interesting characteristics (i) it is easy to prepare and handle, (ii) it is chiral-at-iron and can be resolved, and (iii) the protons a to the acyl group are acidic and the corresponding metal acyl enolate undergoes a variety of transformations including alkylations, aldol reactions, conjugate addition reactions and Diels-Alder reactions (Scheme 3.6). 

Liebeskind and Davies " ° have independently developed the use of this chiral iron complex for enantioselective organic syntheses, particularly of a variety of optically active molecules. The reasons for this behaviour are that the complex is chiral-at-iron and one face is hindered by the PPha ligand reaction of these acyl-iron enolates occur with very high stereoselectivity (Scheme 3.7). 

Stmcture activity studies with the cyclic hexapeptide siderophores demonstrate that modification of the amino acid sequence in the cyclic peptide does not appreciably influence the ability of the resulting siderophore to transport iron. However, the nature of the hydroxamate acyl substituent has a major influence, the presence of one or more trans anhydromevalonic acid residues severely inhibits the process. Furthermore, the chiral nature of the iron complex has a dominant influence, the cyclic hexapeptide siderophore receptor with a marked preference for the A complex. 

The similar, optically active complex CpFe(CO)(Me)L (in whidi L = a chiral phosphine) forms an acyl complex at low temperatures when conducted in the presence of CO and added BF to accelerate the rate (see below for the effects of Lewis acids on the rate of insertion). Again the reaction proceeds stereospecifically, and the configuration of the product corresponds to that resulting from migration of the methyl group. The photochemical decarbonylation of a similar iron complex was shown by Davison and then by Wojcicki also to proceed predominantly by formal migration of the alkyl group. 

Chiral n complexes of heterocycles with transition metals can serve as effective catalysts for an array of useful organic reactions.The most efficient nucleophilic catalysts previously used had planar structures, e.g., 4-(dimethylamino)pyridine, and therefore required an asymmetric environment in the vicinity of an sp -hybridized nucleophilic atom. In a recent paper, G. C. Fu et al describe a procedure, which they call a second-generation system for kinetic resolution, that employs an iron complex at a mole fraction of 2% as the chiral catalyst, and acetic anhydride as the acylating agent (Figure 9.7.1). The authors attached the 4-(dimethylamino)pyridine moiety to a chiral ferrocene analog. The lower portion of the ferrocene, coordinated to the iron atom is pentaphenylcyclopentadiene, as shown in Figure 9.7.1. 

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