Iron acyl complexes aldol reactions

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). 

Aldol reaction of the a-trimethylsilylated enolate 9 with aldehydes provides nearly equal amounts of chromatographically separable ( )- and (Z)-isomers of iron-acyl complexes 11 via silyloxide elimination from the intermedate aldolate 10 (Table 3). This methodology has been the most commonly employed entry to the (Z)-isomer series. 

Table 3. Iron-Acyl Complexes 11 from CarbonyUr/ -acyclopentadienylHl-oxo -ftriinethylsilyllethyl] (triphenylphosphane)iron (8) by the Aldol Reaction with Aldehydes...

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. 

Conducting the aldol reaction at temperatures below —78 "C increases the diastereoselectivity, but at the cost of reduced yields45. Transmetalation of the lithium enolate 2 a by treatment with diethylaluminum chloride generated an enolate species that provided high yields of aldol products, however, the diastereoselectivity was as low as that of the lithium species45. Pre treatment of the lithium enolate 2a with tin(II) chloride, zinc(II) chloride, or boron trifluoridc suppressed the aldol reaction and the starting iron-acyl complex was recovered. 

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. 

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. 

Kinetic resolution of iron acyl complex (Structure 1) via aldol reaction with (+)-camphor 5 (Scheme 4.2) ... 

Several methods have been developed for the preparation of a,3-unsaturated iron acyl complexes, a class of complex which is synthetically valuable because its members may be stereoselectively elaborated at two positions. Methylation of the hydroxy group of an aldol reaction product to give 16 followed by sodium hydride-promoted elimination generates the ( )-unsatu-rated iron acyl complex 17, in many cases exclusively (Scheme 4.9) Since this selectivity is irrespective of the hydroxy group configuration, it is not... 

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 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. 

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... 

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). 

Another useful reaction of these complexes is alkene insertion. This works well with electron-poor alkenes and may be drawn as a Michael addition. One application is in the synthesis of the perfumery compound, CM-jasmone 4.205 (Scheme 4.73). The initial acyl iron complex reacted with methyl vinyl ketone to give a 1,4-diketone 4.204, which underwent a subsequent intramolecular aldol reaction on treatment with a base. 

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. 

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