Davies-Liebeskind enolates

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. 

Scheme 4.24 Alkylation reactions of Davies-Liebeskind enolates 125 and 128.

Scheme 4.25 Application of Davies-Liebeskind enolates in a synthesis of (—)-captopril.

Another early solution to the acetate aldol problem came from the so-called Davies-Liebeskind enolates already mentioned in the context of enolate alkylation. As elaborated independently by the groups of Davies [138] and Liebeskind [139], the deprotonation of the chiral acetyl iron complex 124b, transmetallation of the lithium enolate, and addition to aldehydes lead to the predominant formation of diastereomers 279, as proved by a crystal structure analysis. The diastereoselectivity strongly depends on the transmetallation, the best results being obtained with diethylaluminum chloride. With other additives, the topicity is reversed, and the diastereomer 280 is obtained as the major product. The decomplexation of the adducts leads to P-hydroxycarboxylic acids (Scheme 4.64). 

Scheme 4.64 Acetate aldol addition with Iron acetyl complex 124b via Davies-Liebeskind enolates.

The procedure was also extended to the analogous propionyl and benzy-loxyacetyl iron complexes. Although the preparation of enantiomeric iron acetyl complexes (R)- and (S )-124b is Icnown and the reagent became even commercially available under both enantiomeric forms, it was nevertheless used as racemate. It seems that the immolative character of the aldol additions based on Davies-Liebeskind enolates prevented wider application in larger scale [140]. 

Reactions of this pseudooctahedral complex have been studied in particular detail by the Davies group at Oxford and the Liebeskind group in the United States because of its potential use as a chiral auxiliary for control of the absolute stereochemistry of various reactions of the acyl enolate. Both R-( — )-l and S-( + )-1 are now available commercially (Fluka), but at a prohibitive cost ( 125.60 per gram). 

Enolates of iron-acyl complexes have been studied extensively, especially by Davies and Liebeskind and their respective coworkers. The chiral complex [T) -CpFe(PPh3)(CO)COCH2R] is usually used it can be prepared in racemic or optically active form. The enolate usually has the anti conformation with regard to CO and Copper (Z)-enolates give predominantly syn aldols, whereas diethylalumin-... 

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... 

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). 

Davies examined the same reaction.He found that when using an excess of Et2Al adducts of the enolate, the diastereoselectivity ratio became > 100 1. Further, if Cu(I) was used as counter ion the opposite stereochemistry was obtained.Moreover both Davies and Liebsekind used this chiral iron auxiliary in a stereoselective synthesis of S-lactams. " " Liebeskind reported that chiral iron enolate complex condensed with imines in the presence of Et2Al counter ion to give two isomers with a ratio up to 20 1. Oxidation with I2/R3N produced the racemic jS-lacatms (Scheme 3.9)... 

The deprotonation of chiral iron acyl complexes, which can be obtained as enantiomerically pure compounds, leads to the corresponding enolates, as shown by the research groups of Davies and Liebeskind [112-115]. The lithium enolate 67a, however, which originates from propanoate 66a, reacts stereoselectively with aldehydes or ketones only if it has been transmetalated into the corresponding copper or aluminum enolate (Eq. (30)) [116]. 

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