Chromium enolate

Chromium enolate chemistry exhibits diverse thermochemical facets. For example, contrast the energetics of enolate addition reactions to benzaldehyde and to benzaldehyde JT-bonded to Cr(CO)3 and of the enolate addition reactions to acetophenone and to acetophenone 71-bonded to Cr(CO)3. Thermochemical analysis is still unreported, although the reactions are synthetically usefuP . It is clear that the organic ligands are electronically coupled to the metallic center—PhCHO Cr(CO)3 is red, PhCH(OEt)2 Cr(CO)3 is yellow but benzaldehyde and its diethyl acetal are both colorless. It is well established that acetophenone, and presumably other acylated benzenes such as benzaldehyde, binds Cr(CO)3 rather more weakly than does toluene, and presumably other alkylated benzenes such as the aforementioned benzaldehyde acetal. The enthalpy of hydrolysis of the metallated acetal remains unknown other than it is therefore smaller than that of the unmetallated species . ... 

Consider the reaction of bis(l-bromocyclopropyl) ketone with [Cr(CO)4NO] to form the bicyclic 2-metalafuran derivative 36, which may be considered as a chromium enolate in two contexts. The first one relates to the endocyclic 2-chromafuran. The second one relates to the O—C=C—CH2—O substructure of the bicyclic system. We may also ask questions about the relative aromaticity of chromafuran and furan by thermochemical criteria where we note that delocalization is suggested for both species by stractural criteria. 

The aldol-type reaction of a-bromo ketones with aldehydes, mediated by CrCh, has been studied by Dubois and coworkers. The reaction is carried out by addition of (241 equation 80) to a solution of (242) and CrCh in THF. The reaction proceeds with high levels of syn selectivity with bulky bromo ketones (241), independent of the substrate aldehyde used (Table 11, entries 1-6). However, the reaction is stereorandom with bromoacetophenone (entry 7) and selectively anti with 2-bromocyclohexanone (entry 8). No explanation of the stereoselectivity has been advanced, but the reaction is believed not to proceed via a simple chromium enolate since no condensation reaction is obtained by addition of (242) to a solution of (241) and CrCh. Moreover, Nozaki and coworkershave demonstrated that chro-mium(II) chloride treatment of 1-bromocyclododecanone followed by treatment with either methyl iodide or TMS-Cl produces only cyclododecanone. 

Acyclic a,a-disubstituted tin enolates 6 inevitably form as cis/trans-mixtures. Nevertheless, application of the chromium alkylation protocol with the modified salen complex 7 provides fair enantioselectivity with various alkylating agents R CH2X hke allyl bromide, benzyl bromide, allyl iodide, and ethyl iodoacetate, as outlined in Scheme 5.5. A plausible explanation is based on the assumption of a rapid cis/trans-isomerization of the tin enolates 6 through the C-bound tautomer and the postulate that one of the enolate diastereomers reacts distinctly faster than the other. The role of the additive BugSnOMe, which has a beneficial effect on the enantioselectivity, might be to catalyze the cis/trans-isomerization of the enolate. Several models have been proposed for the mechanisms of the enantioselective enolate alkylation like transmetallation of tin into a chromium enolate, formation of a stannate by iodine transfer from chromium to tin, as well as activation of the alkyl halide by chromium [5]. 

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

Oxidation of ecgonine (2) by means of chromium trioxide was found to afford a keto acid (3). This was formulated as shown based on the fact that the compound undergoes ready themnal decarboxylation to tropinone (4)The latter had been obtained earlier from degradative studies in connection with the structural determination of atropine (5) and its structure established independently. Confirmation for the structure came from the finding that carbonation of the enolate of tropinone does in fact lead back to ecgonine. Reduction, esterification with methanol followed by benzoylation then affords cocaine. 

S)-Tricarbonyl(2-methoxyacetophenone)chromium is a starting material which provides remarkable substrate-induced stereoselectivity. Thus, its conversion into a boron enolate and subsequent addition to aldehydes delivers the chromium complexes 7 and 8 with diastereomeric ratios of 92 8 to 95 559. 

In a rather different approach optically active chromium complexes of 2,3-dihydro-1 H-in-denone are used as chiral enolate precursors. These chiral complexes react with 3-buten-2-one in benzene using l,5-diazabicyclo[4.3.0]non-5-ene as the base. The diastereomeric ratio of the product is the same irrespectively of whether the exo- or the Noisomer of the chromium... 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

Seven-membered carbocycles are also available from the reaction of alkenylcarbene complexes of chromium and lithium enolates derived from methyl vinyl ketones [79b] (Scheme 65). In this case, the reaction is initiated by the 1,2-addition of the enolate to the carbene complex. Cyclisation induced by a [1,2]-migration of the pentacarbonylchromium group and subsequent elimination of the metal fragment followed by hydrolysis leads to the final cyclo-heptenone derivatives (Scheme 65). 

For cyclopropanation of enol ethers with in situ-generated acyloxycarbene complexes of chromium and in the absence of CO, see reference [10a]... 

Not all carbon nucleophiles will add to arene chromium tricarbonyl complexes. For example, alkyllithium reagents and simple ketone enolates do not give adducts.325... 

The synthesis of the C(17)-C(24) segment also began with a diastereoselective boron enolate aldol addition. The adduct was protected and converted to an aldehyde in sequence H. The terminal diene unit was installed using a y-silylallyl chromium reagent, which generates a (3-hydroxysilane. Peterson elimination using KH then gave the Z-diene. 

We had two possible routes in which alcohol 72 could be used (Scheme 8.19). Route A would involve rearrangement of tertiary alcohol 72 to enone 76. Deprotonation at C5 and generation of the enolate followed by exposure to an oxaziridine or other oxygen electrophile equivalents might directly afford the hydrated furan C-ring of phomactin A (see 82) via hydroxy enone 81. We had also hoped to make use of a chromium-mediated oxidative rearrangement of tertiary allylic alcohols. Unfortunately, treatment of 72 to PCC produced only unidentified baseline materials, thereby quickly eliminating this route. 

Cyclopropanation of l,3-dienes. a,0-Unsaturated carbenes can undergo [4 + 2]cycloaddition with 1,3-dienes (12, 134), but they can also transfer the carbene ligand to an isolated double bond to form cyclopropanes. Exclusive cyclopropanation of a 1,3-diene is observed in the reaction of the a,(3-unsaturated chromium carbene 1 with the diene 2, which results in a frans-divinylcyclopropane (3) and a seven-membered silyl enol ether (4), which can be formed from 3 by a Cope rearrangement. However, the tungsten carbene corresponding to 1 undergoes exclusive [4 + 2]cycIoaddition with the diene 2. 

---