Acyl Anion Chemistry

Transfer of the acyl group from the acylzirconocene chloride to aluminum (transmetala-tion) by treatment with aluminum chloride has been reported to give an acylaluminum species in situ, and the possibility of the acylaluminum acting as an acyl anion donor has been suggested (Scheme 5.5) [7]. However, the acyl anion chemistry through this trans-metalation procedure appears to be limited since only protonolysis to the aldehyde proceeds in good yield, which could be achieved by direct hydrolysis of the acylzirconocene chloride. 

The acyl anion chemistry of acylzirconocene chlorides has also been applied to the stereoselective preparation of ( )-a,(3-unsaturated selenoesters and telluroesters (Scheme 5.35) [38]. Although no carbon—carbon bond was formed, this reaction reflects the synthetic interest in ( )-a,(3-unsaturated selenoesters and telluroesters, which are well-known precursors of acyl radicals and acyl anions, respectively. 

Even acyl groups may be transferred from Zr to Al, as in equation (48) this generates an acylalumin-um or acyl anion equivalent (45). Its acyl anion chemistry appears limited, however only protonolysis to the aldehyde was achieved in good yield, and that could have been done directly with the acylzirco-nium precursor. ... 

In a series of publications beginning in 1973, Hermann Stetter and coworkers reported that activated olefins could intercept the putative acylanion intermediate of the benzoin reaction. Typical catalysts for the benzoin reaction, sodium cyanide and thiazolylidine carbenes, were found to perform well in this new reaction. Stetter also established that the success of the reaction is due to the reversible nature of the benzoin condensation relative to the irreversible formation of 1,4-dicarbonyl products. As a consequence, benzoins or aldehydes can be used interchangeably as reactants. The reaction has proven to be a highly efficient method for the synthesis of 1,4-dicarbonyl compounds and 4-oxonitriles. A resurgence of interest in acyl anion chemistry has resulted in many new discoveries, including alternative acyl donors, as well as catalysts capable of highly enantioselective intra- and intermolecular Stetter reactions. ... 

Although many carbonyl derivatives act as acyl cation equivalents, R(C=0)" in synthetic chemistry, the inherent polarity of the carbonyl group makes it much more difficult to find compounds that will act as equivalents of acyl anions, R(C=0) . Since the 1960s, major progress has been made in this area, and there are now a wide variety of compound types that can react in this way. As in so many areas of organic chemistry, heterocyclic compounds take pride of place and form the basis of many of the most useful methods. In recent years there has been particular interest in developing chiral acyl anion equivalents that will show high... 

An example where the presence of a counterion makes a difference between the gas phase and solution phase pathways involves the intriguing carbanion produced on deprotonation of 1,3-dithiane at C-2. In solution, this species, almost invariably produced by reaction of the dithiane with butyllithium, is widely used as an acyl anion equivalent in synthetic chemistry. Its importance for the present work is that this is a configurationally stable lithiated species in solution the carbanion stays sp -hybridized, and the lithium prefers the equatorial position, even to the extent of driving a terr-butyl group on the same acidic C-2 carbanion to the axial position in the lithiocarbon species. The carbanion is thought to be stabilized primarily by orbital overlap with the C-S antibonding orbitals, as opposed to more conventional polar and 7t-resonance stabilization. ... 

The most important use of 1,3-dithianes (792) stems from their ability to function as acyl anion equivalents (794 Scheme 184). Metallation of this heterocycle followed by alkylation of the anion and cleavage of the dithiane group produces a carbonyl compound. Since such aspects of dithiane chemistry have been extensively documented (69S17 75JOC231), only a few of the more current applications of these heterocycles are highlighted. We again note here that the application of heterocycles to the synthesis of carbonyl compounds has been the sole subject of an extensive review (77H(6)73l). 

Nitro compounds can be alkylated and are good at conjugate addition (chapter 21) so the products of these reactions can be used to make aldehydes, ketones and amines. A simple synthesis of octanal5 shows that these methods can work very well indeed. Alkylation of nitromethane with bromoheptane gives the nitro-compound 11. Formation of the anion 12 and oxidation with KMnC>4 gives octanal in 89% yield. This chemistry gives us the disconnection to an alkyl halide and a carbonyl anion. The anion 12 is an acyl anion equivalent and we shall need these in the next chapter. 

Acyl anion and acyl radical chemistry 1.92.3.6 Miscellaneous... 

Hie anions of 68 and 79 are then useful acyl anion equivalents, but in natural product syntheses they are far less popular than reagents containing two sulphur atoms54, particularly dithians55. The chemistry of dithians, e. g. 86 and 87 has been well explored and they have been used in the synthesis of many natural products . The synthesis56 of the Douglas-Fir tussock moth sex pheromone 88 is an example of the way a dithian 86 acts as an acyl anion equivalent in ketone syntheses. 

Acyl anions require special chemistry because they have umpolung of reactivity specific enols have normal reactivity but the problem of regioselectivity must be solved. The carbonyl compound must enolise under the reaction conditions only on the required side and, as carbonyl compounds are also electrophilic, it must not condense with itself under these conditions. 

More recently, Yamamoto and coworkers [36] have developed a new acyl anion equivalent based upon the ethoxyethyl-protected a-hydroxymalonodini-trile derivative shown in Scheme 13 and have applied it in the area of N-sulfonyl imine chemistry. Thus, the carbanion derived from the dinitrile was added to imine 60 to afford adduct 61 which was rather unstable. However, N-alkylation of 61 with chloromethyl methyl ether yielded the stable product 62. Removal of... 

Lithium salts of t-butylhydrazones of aldehydes have been shown to be useful acyl anion equiv-alents. Treatment of an aldehyde r-butylhydrazone with an alkyllithium reagent or LDA gives the am-bident nucleophile (95), which reacts with both aldehydes and ketones to give carbon-substituted products as shown in equation (35). The condensation works best with nonenolizable carbonyl derivatives. Extension of this chemistry to the reaction of (95) with a,3-unsaturated carbonyl compounds met with mixed success. While good yields of Michael products were seen in the addition of (95) to methyl crotonate, other a,p-unsaturated electrophiles such as methyl acrylate, acrylonitrile and methyl P,p-di-methylacrylate gave negligible yields of carbon-substituted products. 

Most of the chemistry associated with this series of heterocycles is a consequence of the acetal moiety. For example, all three saturated systems undergo acetal hydrolysis, the dioxanes being the most acid-sensitive. The chemistry of 1,3-dithianes and 1,3-oxathianes is further dominated by the acidity of the C-2 protons, leading to the use of the derived carbanions as acyl anion equivalents, particularly in the case of 1,3-dithiane derivatives. Oxidation at sulfur is also a common process. 

The conjugate addition chemistry of a number of formyl- and acyl- anion equivalents has been studied these include the... 

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