Acyl anions masked equivalents

The realization of the principle of umpolung , in which reactivity at a normally electrophilic site is inverted to that of a nucleophilic species,161 has resulted in the development of numerous masked acyl anion equivalents for carbon-carbon bond formation.162 The use of masked acyl anion equivalents for conjugate additions was made possible by several observations. First, Stork reported that protected cyanohydrins afforded preferential kinetic 1,4-addition with ot, 3-enonesl6b and second, Brown reported that preferential kinetic 1,4-addition of 1,3-dithianes was effected by the use of HMPA.163... 

The use of masked acyl anion equivalents in a synthetic protocol requires additional steps to unmask the carbonyl unit. Sometimes the deprotection procedures are incompatible with sensitive compounds thus, a direct nucleophilic acylation protocol is desirable. While C-nucleophilic carbonyl groups do not... 

See the leading reviews of masked acyl anion equivalents for examples and references (a) Hase, T. A. Koskimies, J. K. Aldrichim. <4cfa1981, 14, 73 ... 

Thus vinylsilanes may be regarded as masked carbonyl groups as exemplified by the two reaction sequences depicted in Equations Si5.22 and Si5.23. Note that in the second example the cuprate is acting as an acyl anion equivalent. 

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. 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

Similar attention has therefore been directed towards the imidoylstannanes, R3SnC(=NR )R" (often called stannylimines), which are formed by reaction of the acylstannanes with amines,71 and which might give lithium reagents which would act as masked acyl anion equivalents. 

Essentially every analog and derivative prepared in the project was ultimately derived from the corresponding 3-chloro-pyri-dazine. With the exception of a few 3-chloropyridazines which originated from a Friedel-Crafts acylation of benzene, the large majority of chloropyridazines were prepared by a sequence based on the addition of the masked acyl anion equivalent of a benzaldehyde to the appropriately substituted acrylate ester. 

Synthesis of the acyclic portion began, as in the previous synthesis, with enantiomerically pure citronellol (25). Protection of the alcohol as the benzyl ether and oxidative cleavage of the olefin to the aldehyde gave 26 (85%). Chain extension via the masked acyl anion equivalent 27, alcohol protection, and concomitant -elimination and isomerization of the allene to die alkyne with butyl lithium gave 28. The resulting protected ketone must now be converted to the P-alcohol required for the completion of the synthesis. Thus hydrolysis to die ketone followed by enantioselective reduction with (—)-N-methylephedrine-... 

The yields in these reactions are not wonderful and most syntheses planned with acyl anion or d1 synthons are realised with one of the reagents we are about to describe rather than with acyl-lithiums. Things may change as understanding of these rather reactive intermediates develops. There are three main types of acyl anion equivalent reagents which can be considered as modified acetals, that is protected aldehydes, masked carbonyl compounds such a nitroalkanes, and substituted vinyl-lithiums. The rest of this chapter will be devoted to these reagents. 

Anibine (108) was synthesized in three steps from a masked acyl anion equivalent, a-(3-pyridyl)-a-(4-morpholino)acetonitrile, and ethyl ( )-4-bromo-3-methoxy-2-butenoate. Acid hydrolysis of the product from this reaction, followed by a thermal, base promoted cyclization gave 108 [307],... 

Masked alkanoyl (acyl) anion An alkanoyl (acyl) anion equivalent. 

Masked acyl anion An acyl anion equivalent. 

Due to the stabilizing effect of two sulfur atoms, 1,3-dithianes are easily lithiated at the a-position on treatment with n-BuLi (see 2-Lithio-l,3-dithiane) The 2-lithio-1,3-dithianes constitute an important class of acyl anion equivalents, permitting electrophilic substitution to occur at the masked carbonyl carbon. Hydrolysis of the 1,3-dithiane functionality into a carbonyl group is effected in the presence of mercury(II) ion (eq 4). ... 

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