Masked anions alkylation

The formation of a-naphthols of type 189 from 1-alkyl-substituted salts 30, on heating with dimethylamine hydrochloride in ethanol, occurs by another mechanism and will be explained in Section III,C,4,b,i. The interaction of l-aryl-3-carboxy-substituted salts 62 with secondary amines in benzene is initiated probably as in the reaction of these salts with primary amines, and the attack by the secondary amine on position 3 is the primary step of this reaction. However, since protonation of the intermediate anion 190, a masked acyl anion, becomes difficult, an interaction of this anion with the carbonyl group of the benzophenone fragment occurs (86KGS125). The enamines 191 thus formed are usually hydrolyzed on purification, yielding five-membered cyclic acyloins 192. 

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. 

RCHO to a ketone RCOR (for other methods, see 10-71, 16-82, and 18-9). In this procedure the normal mode of reaction of a carbonyl carbon is reversed. The C atom of an aldehyde molecule is normally electrophilic and is attacked by nucleophiles (Chapter 16), but by conversion to the protected cyanohydrin this carbon atom has been induced to perform as a nucleophile. The German word Umpolung is used to describe this kind of reversal (another example is found in 10-71). Since the ion 166 serves as a substitute for the unavailable R— C=0 anion, it is often called a masked R( C=0) ion. This method fads for formaldehyde (R = H), but other masked formaldehydes have proved successful. In an interesting variation of nitrile alkylation, a quaternary bromide [PhC(Br)(Me)CN] reacted with allyl bromide, in the presence of a Grignard reagent, to give the alkylated product [PhC(CN)(Me)CH2CH=CH2]. ... 

A number of so-called double ion-pair methods have been described for the analysis of hydrophobic amines in which the mobile phase contains both a quaternary ammonium ion and an alkyl sulfate or sulfonate. At first glance, this combination of mobile phase additives is counterintuitive because one would expect the effect of the anionic and cationic additives to cancel. However, the combination of cationic masking agents to reduce peak tailing and an anionic ion-pairing agent to enhance retention is sometimes necessary for the reversed-phase separation of hydro-phobic amines. 

In dithioacetals the proton geminal to the sulfur atoms can be abstracted at low temperature with bases such as Bu"Li. Lithium ion complexing bases such as DABCO, HMPA and TMEDA enhance the process. The resulting anion is a masked acyl carbanion, which enables an assortment of synthetic sequences to be realized via reaction with electrophiles. Thus, a dithioacetal derived from an aldehyde can be further functionalized at the aldehyde carbon with an alkyl halide, followed by thioacetal cleavage to produce a ketone. Dithiane carbanions allow the assemblage of polyfunctional systems in ways complementary to traditional synthetic routes. For instance, the p-hydtoxy ketone systems, conventionally obtained by an aldol process, can now be constructed from different sets of carbon groups. ... 

Asymmetric Synthesis via Alkylations cf Anions of Masked Carboxylic Acid Derivatives... 

Sulfolenes are valuable precursors of 1,3-dienes. Thermolytic desulfonylations of 2,S-disubstituted derivatives lead exclusively to ( ,Z)-dienes in agreement with the symmetry rules. The stereoselectivity of the reaction is dramatically changed however by carrying out the reaction in a protic solvent and in the presence of a base (which probably isomerizes the trans sulfolene to the cis isomer), since ( , )-dienes are now obtained exclusively and contrary to the symmetry rules. a-Metallo sulfolenes may be viewed therefore as masked 1,3-dienyl anion equivalents ( C =>C—C =C—R). The above mentioned set of reactions has been used for the regioselective syntheses of 6- and 16-alkyl-substituted vitamin D3 analogs, as well as rrani-3-ocimene and oi-famesene. ... 

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

Regiospecific alkylation of dimethylhydrazone anions with the masked acrolein equivalent, 3-bromo-propionaldehyde dimethyl acetal, has brcn used as an alternative to a conventional Michael reaction in Corey s total synthesis of picrotoxinin (c/. equation 13). Azaallyllithium reagents derived from aldehyde and ketone hydrazones, unlike enolates, yield monoalkylation products with control of both regio-chemistry and stereochemistry. In appropriate cases, alkylation followed by deprotection to form a dicarbonyl product can be a very effective synthetic strategy. 

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