Aldehydes, conjugated anion

Aldehyde 54 and the hydroxamic acids 55 were generated together in an acid-catalysed elimination reaction (Scheme 7 pathway (ii)). A crossover experiment indicated that esters are formed in a concerted rearrangement concomitant with the likely formation of the hydroxynitrene 57 (Scheme 7 pathway (iii)) while there is no evidence to date for the formation of hydroxynitrene, joint solvolysis of equimolar quantities of /V-acetoxy-/V-butoxy-/>-chlorobenzamide 26e and N- acetoxy-/V-benzyloxybenzamide 27a afforded significant quantities of butyl p-chlorobenzo-ate (36%) and benzyl benzoate (54%) as the only esters. This is an example of a HERON reaction, which has been identified in these laboratories as a characteristic rearrangement of bisheteroatom-substituted amides.32,33,42 43 155 158 Since ester formation was shown to prevail in neutral or low acid concentrations, it could involve the conjugate anion of the hydroxamic acid (vide infra).158... 

Reactions alkylations, reactions with epoxides and aldehydes, conjugate additions Heterocyclic synthesis with allyl silanes Reactions with Co-stabilised cations An Allyl Dianion The Role of Tin in Anion Formation Halide Exchange with Chelation Indium Allyls Allyl Anions by Deprotonation The synthesis ofall-trans dienes The synthesis ofall-trans retinol... 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

An interesting application of the Paal thiophene synthesis was documented for the synthesis of a polystyrene-oligothiophene-polystyrene copolymer. In the Stetter reaction of aldehyde 13 and P-dimethylaminoketone 14, in situ generation of the a,p-unsaturated ketone preceded nucleophilic 1,4-conjugate addition by the acyl anion... 

Pyridinium p-toluenesulfonylmethylide 91 has been used as a formyl anion equivalent for conjugate addition to N-substituted maleimides to give the enol ethers 92, which were readily deprotected to give the aldehydes 93 (80TL705). 

Similarly, monobasic forms of other trivalent phosphorus species have been used successfully in such conjugate addition processes, including monoesters of phosphonous acids375 425 426 and secondary phosphine oxides.427-429 The notable exception to the last of these species is the addition of the anion from diphenyl phosphine oxide to unsaturated aldehydes, which appears always to proceed by addition to the carbonyl carbon.427... 

However, cyanide ion is not suitable for inducing a benzoin-type condensation between two aliphatic aldehydes, since the basic character of this ion induces an aldol condensation between them. In Nature, nevertheless, condensations of this type take place easily. As Breslow proposed in 1958 [8], such condensations are catalysed by thiamine pyrophosphate 6 (or cocarboxylase), the active part of which is the conjugate base of the "thiazolium cation present in it. According to Breslow [8a], the mechanism is, in fact, identical to that described for the cyanide ion (see Scheme 5.7) that is to say, the conjugate base of thiamine (TPP ) reacts with an "aldehyde equivalent -such as an a-ketoacid 2- to generate the corresponding "active aldehyde" 8 with umpoled reactivity, which then reacts with the electrophile to give finally, after elimination of "thiamine anion", a 1,2-D system (9). 

The conjugate addition of organometallic reagents R M to an electron-deficient alkene under, for instance, copper catalysis conditions results in a stabilized car-banion that, upon protonation, affords the chiral yS-substituted product (Scheme 7.1, path a). Quenching of the anionic intermediate with an electrophile creates a disubstituted product with two new stereocenters (Scheme 1, path b). With a pro-chiral electrophile, such as an aldehyde, three new stereocenters can be formed in a tandem 1,4-addition-aldol process (Scheme 1, path c). 

The Michael-type conjugate addition of an alkoxide such as methoxide to an a,p-unsaturated nitrile or aldehyde proceeds in solution quite readily, being complete in 5—10 minutes. In the gas phase however, it was found that reaction (6a) does not occur there is no evidence of the addition product even at the longest trapping times, nor in the unquenched mode. Rather, the sole product observed is due to proton loss from the nitrile, to form a nominal vinyl anion, reaction (6b). 

The a-hydrogens of carboxylic acid derivatives show enhanced acidity, as do those of aldehydes and ketones, and for the same reasons, that the carbonyl group stabilizes the conjugate base. Thus, we can generate enolate anions from carboxylic acid derivatives and use these as nucleophiles in much the same way as we have already seen with enolate anions from aldehydes and ketones. 

The conjugate addition of a thiol, methanethiol, to the a,(5-unsaturated aldehyde acrolein may be used in the synthesis of the amino acid methionine. Under basic conditions, the nucleophile will be the thiolate anion, and 1,4-addition leads to the thia-aldehyde. Methionine may then be obtained via... 

The first reaction involves a ketone reaction with an aldehyde under basic conditions, so enolate anion chemistry is likely. This is a mixed aldol reaction the acetone has acidic a-hydrogens to form an enolate anion, and the aldehyde is the more reactive electrophile. The reaction is then driven by the ability of the intermediate alcohol to dehydrate to a conjugated ketone. 

The efficiency of the amination methodology of enolates with 0-phoshinylhydroxyl-amine-type reagents was further demonstrated by Boche and Schrodt in the high-yield amination of 0-(trimethylsilyl)cyanohydrin anions with 4c (Scheme 44)". 0-(Trimethyl-silyl)cyanohydrins prepared by treatment of aryl, hetaryl and conjugated aldehydes with trimethylsilyl cyanide were lithiated to the eniminates. This is a practical method that enables the easy conversion of aldehydes to iV,Ai-dimethylamides under mild conditions. 

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