A highly selective method for the synthesis of(E)-α-methyl-α,β-unsaturated aldehydes

Anhydrous acidic treatment of E,Z mixtures of α-methyl-α,β-unsaturated imines followed by hydrolysis gives the corresponding aldehydes with ≥ 100:1 E:Z ratios.     

Microwave-assisted Pd-catalyzed synthesis of fused steroidal and non-steroidal pyrimidines from β-halo-α,β-unsaturated aldehydes

A Pd-catalyzed protocol has been developed for the synthesis of fused steroidal and non-steroidal pyrimidines from β-halo-α,β-unsaturated aldehydes under microwave irradiation. The β-halo-α,β-unsaturated aldehydes are synthesized from corresponding ketones using Vilsmeier formylation reaction. This synthetic protocol is utilized to synthesize some more novel steroidal pyrimidine derivatives and are currently being evaluated for their biological activities.     

α-Bromo-β,γ-unsaturated ketenes for the synthesis of α-benzylamino-β,γ-unsaturated acids

The synthesis of α-benzylamino-β,γ-unsaturated acids has been developed starting from α-bromo-α,β-unsaturated chlorides. Via treatment of the acyl chlorides with (R)-pantolactone in the presence of TEA, the in situ formation of the deconjugated ketenes and their direct transformation into chiral esters was performed. The substitution of bromine with benzylamine, followed by acid hydrolysis, allowed to us obtain enantiomerically enriched α-benzylamino-β,γ-unsaturated acids.     

A novel route for the synthesis of α,β-unsaturated esters,ketones and nitriles using dibutyl telluride

In the presence of dibutyl telluride, α-halo-ester, nitrile, and ketone were found to condense easily with aromatic aldehydes to afford α,β-unsaturated esters, nitriles and ketones in high yields as one-pot reaction. A possible reaction machanism was proposed.     

Regioselective synthesis of β-fluoro-α,β-unsaturated ketones by the reaction of β-diketones with DFMBA

The deoxyfluorination reaction of β-diketones with N,N-diethyl-α,α-difluoro-m-methylbenzylamine (DFMBA) gave β-fluoro-α,β-unsaturated ketones in good yields. The reaction proceeded regioselectively, and only one regioisomer was obtained from the unsymmetrical 1-aryl-1,3-diketones. The reaction is applicable to diketones with a trifluoromethyl group, obtaining good yields of 3,4,4,4-tetrafluorobutenones. We used the resulting β-fluoro-α,β-unsaturated ketones for the reaction with lithium dialkyl cuprates.     

A general route to α-alkyl (E)-α,β-unsaturated aldehydes

Bis(trimethylsilyl)-tert-butylaldimines 3 react with aldehydes in the presence of zinc bromide at room temperature to give, after hydrolysis, the desired α-alkyl α,β-ethylenic aldehydes in good yield and with very high E stereoselectivity. The reaction was believed to proceed via the α-silyl β-siloxyimines 4.     

N-heterocyclic carbene catalyzed reactions of α-bromo-α,β-unsaturated aldehydes/α,β-dibromoaldehydes with 1,3-dinucleophilic reagents

Carbenes ring true: N-Heterocyclic carbene (NHC) catalyzed reactions of α-bromo-α,β-unsaturated aldehydes/α,β-dibromoaldehydes with 1,3-dinucleophilic reagents, such as 1,3-dicarbonyl compounds, β-enamino ketones, and β-enamino esters through umpolung processes gave functionalized 3,4-dihydropyranones and 3,4-dihydropyridinones. The availability of the starting materials, lack of external oxidant, and usefulness of the products make this strategy attractive.     

Organocatalytic enantioselective Michael addition reactions of fluoromalonates with α,β-unsaturated aldehydes

A new organocatalytic enantioselective Michael addition of α-fluoromalonate to enals has been developed.The process is efficiently catalyzed by readily available chiral diphenylpyrolinol TES ether under mild reaction conditions to afford versatile highly enantioenriched fluorinated aldehydes.     

Reactions of α-halo-α, β-unsaturated aldehydes with secondary amines

Reactions of 2-halo-2-alkenals R(R)C=CX-CHO with secondary amines R₂NH occur asipso-substitution of the halogen atom, along with fragmentation and condensation, yielding 1,2-diaminoethenes R₂NCH=CHNR₂, carbonyl compounds RC(O)R, 1,3-bis(amino)-2-haloolefins R(R)C(NR₂)CX=CHNR₂, and formamides R₂NCHO. The ratio between the competing reactions depends on the structure of the starting compounds and the experimental conditions.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp, 135–138, January, I996.     

New polymer-supported phosphonate reagents for the synthesis of Z-α,β-unsaturated esters

New polymer-supported phosphonate reagents have been prepared and evaluated for the synthesis of Z-α,β-unsaturated esters. High Z-selectivity was obtained using the reagent having two o-t-BuC₆H₄ groups.     

Cinchona-based primary amine-catalyzed enantioselective aza-Michael reactions of pyrroles with α,β-unsaturated aldehydes

The cinchona-based primary amine-catalyzed enantioselective aza-Michael reaction of α,β-unsaturated aldehydes with 4,5-dihalo-1H-pyrrole-2-carbonitriles as the N-centered heteroaromatic nucleophile, followed by chemoselective reduction provided the corresponding chiral aza-Michael products in good yields and with excellent enantioselectivities (90–97% ee).     

Regioselective synthesis of α-bromo-α,β-unsaturated carbonyl compounds via photocatalytic α-bromination reactions

A visible light-mediated approach for the preparation of α-bromo-α,β-unsaturated ketones and aldehydes was developed. In comparison to traditional methods that generally take two steps to afford the above compounds, this protocol was highlighted by its operational simplicity, avoiding using hazardous bromine and mild reaction conditions.     

New protocols for the synthesis of 3,4-annulated and 4-substituted quinolines from β-bromo-α,β-unsaturated aldehydes and 1-bromo-2-nitrobenzene or 2-bromoacetanilide

The palladium[0]-mediated Ullmann cross-coupling of readily available β-bromo-α,β-unsaturated aldehydes of the general form 2 with 1-bromo-2-nitrobenzene (3, X = Br) delivers products, 4, that undergo reductive cyclization to novel quinolines (5) upon exposure to indium in aqueous ammonium chloride or to Raney-nickel in the presence of dihydrogen. Analogous cross-coupling of 2-bromoacetanilide (6) with 2 affords products of type 7 that undergo in situ and K₂CO₃-mediated cyclization to give the same types of quinolines (5).     

Palladium catalyzed ring opening of furans as a route to α,β-unsaturated aldehydes

Furans may be ring opened via pallado-catalyzed reactions leading to α,β-unsaturated aldehydes and ketones tethered to indole and isoquinoline moieties. Besides their synthetic interest, these fragmentations bring interesting elements into the discussion around the reaction mechanisms involved in palladium C-H activations of electron-rich heterocycles.     

Two-carbon homologation of aldehydes and ketones to α,β-unsaturated aldehydes

Phosphonate reagents were developed for the two-carbon homologation of aldehydes or ketones to unbranched- or methyl-branched α,β-unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2-phosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with a variety of aldehydes and ketones. Overall isolated yields of unsaturated aldehyde products ranged from 71% to 86% after the condensation and deprotection steps.     

Organocatalytic asymmetric nitrocyclopropanation of α,β-unsaturated aldehydes

A novel organocatalytic highly enantioselective nitrocyclopropanation reaction of α,β-unsaturated aldehydes is presented. The 1-nitro-2-formylcyclopropane derivatives synthesized from this catalytic transformation were converted to the corresponding β-nitromethyl-acid esters, which are excellent precursors of GABA analogues such as Baclofen, by subsequent organocatalytic chemoselective ring-opening.     

Catalytic asymmetric aziridination of α,β-unsaturated aldehydes

The development, scope, and application of the highly enantioselective organocatalytic aziridination of α,β-unsaturated aldehydes is presented. The aminocatalytic azirdination of α,β-unsaturated aldehydes enables the asymmetric formation of β-formyl aziridines with up to >19:1 d.r. and 99% ee. The aminocatalytic aziridination of α-monosubstituted enals gives access to terminal α-substituted-α-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted α,β-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure β-formyl-functionalized aziridine products (99% ee). A highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis (AHCC) is also disclosed. This one-pot three-component co-catalytic transformation between α,β-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy-protected β-amino acid esters with ee values ranging from 92-99%. The mechanisms and stereochemistry of all these catalytic transformations are also discussed.     

Regioselective synthesis of multisubstituted pyrazoles via cyclocondensation of β-thioalkyl-α,β-unsaturated ketones with hydrazines

Multisubstituted pyrazoles were efficiently synthesized by cyclocondensation of β-thioalkyl-α,β-unsaturated ketones with hydrazines under relatively mild conditions. A one-pot synthetic protocol through tandem Liebeskind-Srogl cross-coupling/cyclocondensation using α-oxo ketene dithioacetals as the starting materials was also realized for the same purpose.