As acyl anion equivalents

Protected cyanohydrins may be employed as acyl anion equivalents in 1,4-additions in the presence of HMPA129. For instance cyanohydrins prepared from arylaldehydes add in a 1,4-fashion under thermodynamic control (THF or THF/HMPA) to cyclohexenone, isophorone and decalone systems in the latter case c/.s-octahydro-2(l/f)-naphthalenones are exclusively obtained 130-131. 

Stork first demonstrated the utility of protected cyanohydrins as acyl anion equivalents in 1971 [2]. The acetal-protected cyanohydrin 8 was transformed into the corresponding anion with LDA in THF/HMPA, which was then alkylated with a range of alkyl halides, including secondary bromides (Scheme 2). A mild acidic hydrolysis yielded a cyanohydrin, which provided the ketone after treatment with base. The Stork cyanohydrin alkylation and its variants have become important methods in natural product synthesis [3,4]. 

Acylzirconocene chlorides 78, which are easily available through the hydrozirco-nation of alkenes or alkynes with Cp2Zr(H)Cl and subsequent CO insertion, can be used as acyl anion equivalents Cu(I)-catalyzed reactions with propargyl compounds 77 afford allenyl ketones 79 (Scheme 3.40) [86]. The use of an excess of 77 (2 equiv. to 78) is important for the selective preparation of 79, which prevents an undesirable side reaction of the allenic products 79 with 78. 

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). 

The widespread use of compounds derived from the 1,3-dithiane carbanion or its homologues as acyl anion equivalents (for applications see Section 4.2.1.1) followed the pioneering works of Corey and Seebach on nucleophilic acylation (for reviews, see [43] and [44]). 

Diethyl-3,5-octadiene 174 Dithiane oxides alkylation of 84 carbanions of 84 Dithianes alkylation of 76,79 as acyl anion equivalents 75 carbanions of 76,79 cleavage of 14-18.76,79 desulfurization of 78 oxidation of 23... 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

C-C BOND-FORMING REACTIONS 4.2.1 Use of sulfides, dithioacetals and orthotrithioesters 4.2.1.1 1,3-Dithianes as acyl anion equivalents... 

Ligands functioning as acyl anion equivalents also proceed efficiently in the conjugate addition to enones, producing the -substituted product in high yield (equation 54).1,3 Removal of the protecting group results in the free keto unit, and provides an alternative to the direct acylation (vide supra).37,38... 

Several aromatic and heterocyclic acyl trimethylsilanes have been used as acyl anion equivalents by treatment with fluoride ion (Scheme 81, path a)23 133 154b160191192. Provided that the acyl substituent is electron-withdrawing, and that there are no aryl substituents on the silicon atom, acyl anions can be trapped by various electrophiles in moderate to good yields indeed, acyl anions and pentacoordinate silicon anionic species have both been detected in gas-phase reactions of acyl silanes with fluoride ion193. 

A sequence in which a carbonyl group has been masked as a sulfur derivative, alkylated with an electrophile, and then revealed again is a nucleophilic acylation. These nucleophilic equivalents of carbonyl compounds are known as acyl anion equivalents. In the retrosynthetic terms of Chapter 50 they are d1 reagents corresponding to the acyl anion synthon. 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves9 and by the addition of hydrogen cyanide to silyl enol ethers.10 Sllylated cyanohydrins have proved to be quite useful 1n a variety of synthetic transformations, including the regiospecific protection of p-quinones,11 as Intermediates in an efficient synthesis of a-aminomethyl alcohols,6 and for the preparation of ketone cyanohydrins themselves.1 The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as acyl anion equivalents, providing general syntheses of ketones13 and acyloins.1 ... 

C862-864. This vinyllithium reagent reacted with different electrophiles in good yields except for alkylating reagents (44-94%). However, this reagent has not been used as acyl anion equivalent. 

Vinyllithiums bearing an alkyl or arylsulfanyl (663) and selanyl (664) group at the a-position can be used as acyl anion equivalents. The reaction of these intermediates... 

In this section, the preparation and reactivity of ce-lithiated dienyl and trienyl ethers as well as dienyl thioethers as acyl anion equivalents will be considered749-751. 

The anions of hindered hydrazones allow the introduction of electrophiles at the a-position, thus functioning as acyl anion equivalents after isomerization back to a hydrazone and hydrolysis.For example, the r-butylhydrazone of acetaldehyde gives phenylacetone following the sequence of reactions shown in equation 44. 

Ketone synthesis. Phosphonates of this type serve as acyl anion equivalents. Thus lithiation followed by alkylation gives 2, which can be hydrolyzed to ketones 3 by base. However, the alkylation must be conducted at -78- 20° to prevent a Brook-Wittig rearrangement to 4. 

Z4.8 a-HETEROSUBSTITUTED PHOSPHONATE CARBANIONS AS ACYL ANION EQUIVALENTS... 

Bis(seleno)alhfl metals as acyl anion equivalents... 

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