Acyl enolates

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

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 oxidation of /(-amino-substituted iron acyl complexes which are prepared via condensation reactions of iron-acyl enolates and imines or iminium ions26,5 -47-54 generates /(-lactams 32,33,61. Brief treatment with bromine in dichloromethane at low temperature is the usual procedure. 

In order to overcome the poor electrophilicity ofimines, nitrones arc used as partners for reaction with iron acyl enolates 428. Benzaldehyde phenylnitrone (5) reacts rapidly with the aluminum-based enolate at —78 C to give a crude /J-hydroxyamino iron acyl 6 (68% yield). Treatment with aqueous titanium trichloride in tetrahydrofuran at room temperature causes a selective reduction of the N—O bond and affords the /1-amino iron acyl 7 with inverse configuration compared to the addition ofimines (99% yield d.r. 11 23). 

With a less reactive olefin such as isopropenyl acetate, diazoketone 86 gives only a low yield of cyclopropane 90 a-acyl enol ether 92, resulting from an intramolecular rearrangement of the ketocarbenoid, becomes the favored reaction product. If 91... 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

Acylated product 25 can be obtained by reacting the enolate of 24 with acyl chloride. Interestingly, syn- or anti-26 can be obtained upon treating the acylated enolate 25 with Zn(BH4)2 and KBEt3H, respectively (Scheme 3-11 and... 

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). 

Dimethylbisthiomalonic acid (120), when treated with an acylated enol, produced intermediate 121 thietanediones 122 and 123 then were formed by elimination of thioketone and acetic acid (see Eq. 12). Similarly, cyclobutane-l,l-bisthiolcarboxylic acid gave 123, a previously unknown sulfur analog of malonic anhydride, (Eq. 12). Thermolysis of 120 also results in the formation of the four-membered heterocycles in addition to carbonyl sulfide, hydrogen sulfide, and thiocarbonic acid. ... 

Treatment of lithium enolate species, such as 7, with a variety of metal halide species produces enolates with different reactivities in particular, diethylaluminum(IH) and copper(I) species have been found to profoundly alter stereodifferentiation in reactions of iron acyl enolates (see Section D.1.3.4.2.5.1.). It has not been established whether complex formation or discrete ti ansmetalation occurs usually, a temperature increase from — 78 °C to — 42 °C is required for maximum effect, suggesting that cation exchange is responsible. In some cases, such additives exert an influence at —78 °C13, and this has been attributed to simple Lewis acid-type interactions with the substrate instead of transmetalation of the enolate species. For simplicity, when such additives are allowed to react with enolate species at temperatures of — 42 =C and above prior to the addition of other reagents, the process shall be referred to as transmetalation. 

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. 

Alkylation of Enolates of Chiral Iron-Acyl Enolates by Electrophiles... 

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 molybdenum-acyl enolate 4 has been characterized spectroscopically by NMR and has been reported to exist as a single (observable) isomer88. Extended Hiickel calculations on model complexes suggest that a conformation similar to A is most favorable for enolates such as 488. The deprotonated di-hapto acyl ligand may also be described as a 2-(C,0)-ketene ligand both the ketene and enolate terminology appear in the literature. 

Both enolate species 2a and 2b are readily alkylated by iodomethane to provide the corresponding acyl complexes 3a and 3b, respectively (yield of 3b is not reported)91. No examples of the generation of zirconium-acyl enolates from chiral biscyclopentadienyl zirconium complexes has yet been reported. The reported preparation of the enantiomerically pure complex 4 indicates that chiral zirconium-acyl enolate species may be accessible92. 

The synthesis of chiral cyclobutanone 3 involving asymmetric induction in the a-alkylation of the chiral cyclic transition metal acyl enolate derived from 1 has been reported. The resulting aldol product 2 can be demetalated to the cyclobutanone with 100% ee.24... 

The extent of kinetically controlled formation of the carboxonium ions 31 depends on the nature of R1 and Yy. The possible existence of 31 allows formation of acylated enols 32 (Y = R3CO), which are analogous with w-acylaminostyrene derivatives. As is known, the latter compounds easily undergo an intramolecular acid-catalyzed cyclization to isoquinolines (the Pictet-Gams reaction) (80T1279). 

Enamines are not generally used in aldol condensations, partly because they are not reactive enough, but mainly because they are too much in equilibrium with the carbonyl compound itself and exchange would lead to self-condensation and the wrong cross-couplings. You will see in the next chapter that enamines come into their own when we want to acylate enols with the much more reactive acid chlorides. 

Enol acetates and corresponding derivatives constitute another class of unsaturated compounds that can advantageously be hydrogenated with high enantiomeric excess. This reaction is related to the enantioselective reduction of ketones. Acylated enol carboxy-lates (as an equivalent of a-keto carboxylic acid) can likewise be successfully reduced with rhodium(I) catalysts based on (5,5)-ethyl-DuPHOS (eq 8). Subsequent deprotection of the hydroxyl group or reduction of the carboxylic acid derivatives so obtained deliver chiral a-hydroxy carboxylates and 1,2-diols, respectively. 

Introduction. The toluene-2,a-sultams are recently introduced relatives of the well established 10,2-Camphorsultam chiral auxiliary and have been designed to provide similar high levels of face discrimination in reactions of pendent prochiral functionality. Feamres that distinguish them include high crystallinity and facile NMR and HPLC analysis of derivatives, favorable acylation and aldolization characteristics of derived Al-acyl enolates, and improved cleavage characteristics. 

Under the influence of TiCU, acylation of a ketone via its enol silyl ether can be performed with acyl halides [2,3]- Acyl cyanides can also be used to acylate enol silyl ethers, as illustrated in Eq. (17) [83]. 

A suitable substituted acylated enol may be oxidized similarly in the radical cation of such acylated enols the CO-0 bond cleaves the rate of cleavage is significantly higher in MeCN than in CH2CI2 [94]. 

In acidic media, the electron sink is most often the carbocation produced from protonating the acylating agent, and therefore the sink is very hard. Attack by the Z end (harder end) of the allylic source is very fast. For enols, the Z-acylated kinetic product can be isolated. Since the Z-acylated enol is itself an allylic source (but weaker), it can be forced by more vigorous conditions to equilibrate to the more stable C-acylated product. For enamines, the Z-acylated enamine is a good acylating agent any excess of enamine will attack it and equilibrate it to the more stable C-acylated product. 

Shibata and coworkers extended their enantioselective a-fluorination works [53, 54] to catalytic version using cinchona alkaloids-Selectfluor combination (Scheme 6.33) [61]. Acyl enol esters 110 were employed as substrates in the presence of 112 with Selectfluor and sodium acetate in CH2C12 to afford a-fluoroketones 111 (up to 53% ee). 

In the presence of a stoichiometric amount of SbCls, Friedel-Crafts acylation proceeds with acyl hahdes and acid anhydrides [47], SbCls also promotes the Fries rearrangement of phenyl acetates [48], The electrophilic acylation of fluoro-olefins with acetyl fluoride or benzoyl fluoride is promoted by SbFs in liquid SOy [49], The Friedel-Crafts acylation of benzene and electron-rich arenes is successfully catalyzed by SbCl5-AgClO4 [50], SbCl, Ar.BCl [51], SbCl5-LiClO4 [52], or CaCI, AgSbFg [53] (Scheme 14,19), Acyl chlorides, acid anhydrides, and acyl enolates are used as sources of acyl groups. 

Other derivatives of carboxylic acids and some unusual catalyst systems have found favor. Diarylboryl hexachloroantimonates activate acyl chlorides, carboxylic anhydrides and acyl enolates. A number of metal oxides have been successfully employed. It is worth noting at this point that the chloroacetylium and bromoacetylium ions, which can be prepared in either Freon 113 or sulfur dioxide, are more stable than the acetylium ion and have been shown to give high yields of ketones at low temperatures. ... 

A further antimony derivative, namely, bis-(para-methoxyphenyl) boryl hexachloroantimonate [prepared in situ from antimony pentachlo-ride and bis-(para-methoxyphenyl)boryl chloride] can be utilized (25% mol) in the acylation of anisole and veratrole with acetone acyl enolates in 52%-88% yield. The major advantage of the method resides in the possibility of performing Friedel-Crafts acylation at room temperature in a reaction medium that can be kept almost neutral throughout the reaction, acetone being the only co-product. 

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