Esters from enals

The initially formed chromate ester, from this very hindered secondary alcohol, suffers a transposition to an isomeric chromate ester. The isomeric chromate ester produces the transposed enal. Alternatively, the transposed chromate ester can produce the epoxidation of the alkene, giving an epoxy alcohol that is further oxidized to an epoxy aldehyde. 

However, during the addition of -keto esters onto enals, ytterbium triflate proved to be an efficient catalyst [171] as in the Michael additions of a-nitro esters [172]. Several water-soluble phosphines gave the corresponding phos-phonium salts in good yields when added to a,j9-unsaturated acids [173] or activated alkynes [174]. With alkynes, vinyl phosphine oxides or alkenes were formed depending on the pH of the aqueous solution. Significantly, the reaction of nitroalkanes with buten-2-one is considerably accelerated when going from... 

Homoenolates generated from enals by NHC catalysis undergo annulation with chalcones in methanol to afford methyl hydroxycyclopentanecarboxylates stereose-lectively (Scheme 6.18). Construction of four contiguous stereocenters in a stereoselective manner is noteworthy. Mechanistically, the reaction undergoes events analogous to those in Scheme 6.16 until the intramolecular aldol reaction. Further, the catalyst gets eliminated by methanol to give the cyclopentanecarboxylates. Evidently, the interference of methanol before the intramolecular addition delivers the acyclic esters [22]. 

Consideration of the reaction pathways shown in Scheme 14.12 for the NHC-catalyzed generation of activated carboxylates from enals reveals the intermediacy of an NHC-bound ester enol or enolate equivalent that could be trapped by a suitable electrophile. This was first achieved by Bode, who in 2006 reported highly enantioseleetive inverse electron-demand Diels-Alder reactions of the catalytically generated enolate equivalents and ot,p-unsaturated N-sul-fonyl imines (Scheme 14.19). At the time, this was the first report of a highly... 

Acyl azoliums generated from enals have been converted to cyclopropyl carboxylic esters with ee < 99% by reaction with sulfur ylides. Some FLPs have been found to i react by conjugate P/B addition to unsaturated ketones and esters, whereas 1,2-addition to corresponding aldehydes is usual. ... 

Oxidation Processes Scheidt and co-workers have employed cascade oxidation pathways from aUyhc or propargylic alcohols to afford unsaturated ester products 25. In situ oxidation of an unsaturated alcohol 21 to the enal 22 using MnO, ... 

Homoenolate Protonation The p-protonation of homoenolates has been observed by Scheidt and co-workers, resulting in a redox transformation of enals to afford saturated esters 48. This process is catalysed by the NHC derived from imidazolium salt 46 and utilises phenol as a proton source [14]. A range of primary and secondary alcohols, and phenol itself, are competent nucleophiles with which to trap the acylazolium intermediate 47 generated by protonation (Scheme 12.8). 

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

Whereas the Markovnikov addition of carboxylic acids to propargylic alcohols produces P-ketoesters, resulting from intramolecular transesterification [30, 31], the addition to propargylic alcohols in the presence of Ru(methallyl)2(dppe) 1 at 65 °C leads to hydroxylated alk-l-en-l-yl esters via formation of a hydroxy vinylidene intermediate [32, 33]. The stereoselectivities are lo ver than those obtained from non-hydroxylated substrates. These esters, which are protected forms of aldehydes, can easily be cleaved under thermal or acidic conditions to give conjugated enals, corresponding to the formal isomerization products of the starting alcohols (Scheme 10.6). 

Thanks to the addition of p-TsOH that catalyzes the equilibration of the intermediate allylic chromate ester the major product is the desired enal, resulting from an oxidative transposition. Failure to add p-TsOH leads to the major formation of the untransposed enone, ... 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

The control of the legiochemistiy of addition of organometallic a-enones, a-enals and a-ene esters has attracted the attention of many chemists from the early age of organic chemistry. Not only have a-sele-noalkyllithiums not escaped the rule, but fundamental discoveries made at the occasion of this work have been successfully extended to other organometallics. ... 

It is interesting to observe that the loss in affinity caused by the replacement of the mercapto function by a carboxyl rest was compensated, thanks to an additional hydrophobic interaction. Thus, scientists from Merck developed enal-aprilat 6a, a compound of comparable effectiveness and for which the additional hydrophobic interaction is provided by a phenethyl rest. But enalaprilat is poorly absorbed orally therefore the commercial compound is enalapril 6b, the corresponding ethyl ester. 

Tandem reactions. The multiple activities of the Ru catalysts enable development of valuable tandem reactions. Further extension of the carbon chain of a conjugated enal obtained from a cross-metathesis reaction is readily achieved on treatment with diazoacetic esters to give alkadienoic esters. ... 

The f.Z-diene of the seco acid 2 would result from Horner-Emmons and Wittig reactions from aldehyde 3 (Scheme 2). The trimethoxyaniline functionality is carried along as a stable nitrobenzene that would be unmasked at a late stage prior to macrolactam formation. The syn methoxy-hydroxy functionality at C6-7 in 3 is installed using the newly developed glycolate aldol reaction with enal 4 and norephedrine glycolate ester auxiliary 5. This new method is an application of Masamune s recent work with propionate norephedrine aldol reactions.The CIO methyl is installed using the aforementioned hydroboration reaction,... 

In the acylcyanation of l-alkynes" two for Pd. For hydroarylation of enals and eot Deallylation. Ally carbonates and c ment with Pd(OAc>2. There is a useful ch dimethylallyl esters and cinnamyl esters j isoflavanones and isoflavones from allyl ch lation with ArPb(OAc>3 and treatment with ester group to give isoflavanones" when HCOOH, and EtyN. Isoflavones are obtain Pd(OAc)2 and Ph2PCH2CH2PPh2 in refluxm... 

By the employment of other bromides O-desmethylmycophenolic acid was obtained. Thus, the C7 bromoester methyl 6-bromo-4-methylhex-4-enoate, BrCH2CH=C(Me)CH2CH2C02Me, was prepared from tritylgeraniol which was first converted in several steps to the terminal diol, Malaprade oxidation of which furnished 4-methy-6-trityloxylhex-4-enal. Mild oxidation to, the corresponding acid with silver oxide, formation of the methyl ester with diazomethane and derivation of the required allylic bromide by treatment of the alcohol, liberated from the trityl derivative, with carbon tetrabromide containing triphenylphosphine completed the synthesis. 

The use of esters of a (substituted-methyl)phosphonic acid to provide the carbanion site next to phosphoryl phosphorus was a natural step forward. The most successful development has been the use of the carbanion 346 derived from esters of methylenebisphospho-nic acid (or its monoalkylated derivatives). The anion 346 reacts with an aldehyde to afford the alkenylphosphonic diester 347 (R = Et, Ph, PhCH—CH, 2-thienyl, 2-pyridinyl, etc,) ". Use of the protected 3-pyridinylcarboxaldehyde 348 allowed the preparation of the ester 349, which, after reduction of the C=C bond and hydrolysis, afforded the phosphonic acid 350 Such reactions have also been carried out under phase-transfer condi-tions. Reactions between the lithium salt of the ester 351 and benzaldehyde or but-2-enal give the (alk-1 -enyl)phosphonic esters 352 and 353 in the ratio 1 4 the lithium salts 354 and 355 are formed concomitantly in the ratio 4 1. ... 

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