A new synthesis of β,γ-unsaturated esters and allenic esters with construction of a carbon-carbon bond between α- and β-positions by the reaction of magnesium alkylidene carbenoids with lithium ester enolates

Treatment of lithium ester enolates with magnesium alkylidene carbenoids, generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride via the sulfoxide-magnesium exchange reaction, gave β,γ-unsaturated esters in moderate to good yields. When this reaction was conducted with the lithium ester enolates of α-chlorocarboxylic acid esters, allenic esters were obtained. This procedure provides an unprecedented way for the synthesis of β,γ-unsaturated esters and allenic esters from ketones with the construction of a carbon-carbon bond between α- and β-positions.     

A short synthesis of 3-oxa- and 3-azabicyclo[3.1.0]hexanes from α,β-unsaturated esters based on the 1,5-CH insertion reaction of cyclopropylmagnesium carbenoids

1-Chlorocyclopropyl p-tolyl sulfoxides bearing an alkoxymethyl group at the 2-position were easily prepared from α,β-unsaturated esters with dichloromethyl p-tolyl sulfoxide and alkylhalides in three steps in good overall yields. Treatment of the 1-chlorocyclopropyl p-tolyl sulfoxides with i-PrMgCl resulted in the formation of 3-oxabicyclo[3.1.0]hexanes in up to 89% yield as a single diastereomer via the 1,5-CH insertion reaction of the generated cyclopropylmagnesium carbenoid intermediates. This procedure provides a good way for the synthesis of 3-oxabicyclo[3.1.0]hexanes from α,β-unsaturated esters in only four steps. 3-Aza- and 3-thiabicyclo[3.1.0]hexanes were also obtained from the corresponding precursors via the 1,5-CH insertion reaction of the cyclopropylmagnesium carbenoid intermediates, though the yields were low to moderate.     

Synthesis of β-carbolines from aldehydes and ketones via the α-siloxy α,β-unsaturated esters

We report an efficient method for the synthesis of β-carbolines from α-siloxy α,β-unsaturated esters, which are accessible from a variety of aldehydes and ketones.     

Novel synthesis of β-siloxy esters by condensation of carbonyls and trimethylsilane with α,β-unsaturated esters catalyzed by RhCl3

A novel one pot reaction of α,β-unsaturated esters with carbonyls and trimethylsilane gave good yields of β-siloxy esters. This RhCl₃ catalyzed method improves upon the two step reaction of silyl ketene acetals with carbonyls.     

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.     

γ-Oxygenation of α,β-unsaturated esters by vinylogous O-nitroso Mukaiyama aldol reaction

A practical procedure has been developed for γ-oxygenation of α,β-unsaturated esters by a vinylogous O-nitroso Mukaiyama aldol reaction followed by a one-pot N-O bond heterolysis of the in situ generated γ-aminoxy-α,β-unsaturated esters.     

β-Nitroacrylates and silyl enol ethers as key starting materials for the synthesis of polyfunctionalized β-nitro esters and 1,2-oxazine-2-oxides

The reaction of silyl enol ethers with β-nitroacrylates, in the presence of tetrabutyl ammonium fluoride as catalyst, allows the formation of polyfunctionalized β-nitro esters, or hexahydro-4H-benzoxazine-2-oxides, depending on the nature of the starting silyl enol ethers.     

Thiourea-catalyzed asymmetric domino Michael-cyclization reaction of 3-isothiocyanato oxindoles with β,γ-unsaturated α-keto esters for the synthesis of spirocyclic oxindoles

A reaction between 3-isothiocyanato oxindoles and β,γ-unsaturated α-keto esters catalyzed by a chiral thiourea organocatalyst via a domino Michael-cyclization process is described, which delivers a range of biologically important 2′-thioxospiro[indoline-3,4′-oxazolidin]-2-one compounds in high yields with good diastereo- and enantioselectivities (up to 99% yield, >99:1 dr, >99% ee). Moreover, two of 2′-thioxospiro[indoline-3,4′-oxazolidin]-2-one compounds were found to significantly behave in anti-inflammatory activities in a preliminary biological evaluation.     

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.     

Merging domino and redox chemistry: stereoselective access to di- and trisubstituted β,γ-unsaturated acids and esters

Merging is the game! The coupling of a domino reaction and an internal neutral redox reaction constitutes an excellent manifold for the stereoselective synthesis of di- and trisubstituted olefins featuring a malonate unit, an ester, or a free carboxylic acid as substituents at the allylic position (see scheme; MW=microwave). The reaction utilizes simple starting materials (propargyl vinyl ethers), methanol or water as solvents, and a very simple and bench-friendly protocol.     

Lewis acid-promoted reaction of β,γ-unsaturated α,α-dimethoxy esters with silyl nucleophiles

The Lewis acid-promoted reaction of β,γ-unsaturated α,α-dimethoxy esters, which are easily prepared by the acetalization of β,γ-unsaturated α-keto esters, with silyl nucleophiles is presented. By employing trimethylsilyl enolate and allyltrimethylsilane as nucleophiles, the BF₃-promoted reactions of a series of β,γ-unsaturated α,α-dimethoxy esters bearing aromatic and aliphatic substituents proceeded at the γ-position in an SN2′ manner to furnish γ-substituted α,β-unsaturated α-methoxy esters in good yields with high regioselectivity. In contrast, the reaction using trimethylsilyl cyanide predominantly occurred at the α-position, and the reaction of silyl hydride resulted in a mixture of α- and γ-regioisomers in favor of the γ-substitution products.     

A facile synthesis of trisubstituted alkenes from β-diketones and aldehydes with AlCl3 as catalyst

Preparation of trisubstituted alkenes from low-activity β-diketones and aldehydes with aluminum chloride as catalyst has been studied. The frequently used catalyst AlCl₃ is used for the first time to promote this condensation. The procedure is a convenient, low toxicity, and highly efficient method for industrial synthesis of trisubstituted alkenes in high yield.     

Lanthanum-pyBOX complexes as catalysts for the enantioselective conjugate addition of malonate esters to β,γ-unsaturated α-ketimino esters

Abstract

In this paper, we report the application of chiral complexes of La(III) with pyBOX ligands as Lewis acid catalysts in the conjugate addition of malonic esters to N-tosyl imines derived from β,γ-unsaturated α-keto esters to give the corresponding chiral α,β-dehydroamino esters. pyBOX complexes with La(III), Yb(III), Sc(III), and In(III) triflates were assessed in this reaction but only La(III) showed good activity and enantioselectivity, while Yb(III) provided the expected product with low yield and stereoselectivity, and the Sc(III) and In(III) complexes were completely inactive. The complex of La(OTf)₃ with the diphenyl-pyBOX ligand prepared in situ provided the best results and allowed obtaining chiral α,β-dehydroamino esters 3 with excellent yields, E:Z diastereomeric ratios (29:71–99:1) and high enantiomeric excesses (20–95%). The reaction could be applied to imines having a substituted aromatic ring or a heterocycle attached to the double bond, although the presence of electron-withdrawing groups on the aromatic ring was detrimental for stereoselectivity. The reaction products were obtained with the S configuration at the stereogenic center and the Z configuration at the enamine double bond as determined by NOESY experiments and X-ray analysis. Based on the experimental results a stereochemical model involving a nine-coordinate La(III) species has been proposed.     

Facile synthesis of highly functional pyrrolizidine derivatives from β,γ-unsaturated α-keto esters and proline via a tandem cycloaddition

A new tandem cycloaddition between proline and β,γ-unsaturated α-keto esters was disclosed. Highly functional and diastereomerically pure pyrrolizidine derivatives were obtained in moderate to high yields.     

A generalised route for the synthesis of β-furyl-α,β-unsaturated aldehydes through Suzuki reactions

A general method for the synthesis of β-(2-furyl)-α,β-unsaturated aldehydes is described using the Suzuki coupling reaction of furan-2-boronic acids and β-bromo-α,β-unsaturated aldehyde derivatives.     

Synthesis of β,γ-unsaturated primary amides from α,β-unsaturated acids and investigation of the mechanism

α,β-Unsaturated acids, through their acid chlorides, react with tritylamine in the presence of triethylamine under mild conditions, to afford in high yield and high regioselectivity the corresponding β,γ-unsaturated tritylamides. Detritylation with TFA generates quantitatively β,γ-unsaturated primary amides. An investigation of this deconjugative isomerization was performed.     

Tetramic acids and indole derivatives from amino acid β-keto esters. Fine-tuning the conditions of the key Cu-catalyzed reaction

1,3,5-Trisubstituted tetramic acids and 2,3-disubstituted indole derivatives were prepared from β-keto esters derived from amino acids by their reaction with iodophenyl-2-trifluoroacetylamine under Cu-catalysis. Both heterocyclic systems were generated from the same starting materials by choice of the appropriate reaction conditions.     

DABCO-catalyzed regioselective cyclization reactions of β,γ-unsaturated α-ketophosphonates or β,γ-unsaturated α-ketoesters with allenic esters

Highly efficient DABCO-catalyzed [4 + 2] cycloaddition of β,γ-unsaturated α-ketophosphonates or β,γ-unsaturated α-ketoesters with allenic esters gives the corresponding highly functionalized tetrahydropyran and dihydropyran derivatives in good to excellent yields and moderate to good regioselectivities under mild conditions.     

Stereoselective synthesis of new vicinal diaminoalkyl naphthols by three component Mannich type reaction of α,β-unsaturated aldehydes

The application of the aromatic Mannich reaction to α,β-unsaturated aldehydes, affords a series of new diaminoalkyl naphthols, by a convenient solventless reaction, starting from inexpensive and easily available starting materials. The absolute configurations of the products obtained are attributed on the basis of the coupling constant values of ¹H NMR spectra, joined with the conformational analysis of the molecules by molecular modelling. A mechanistic hypothesis is proposed, which involves an imino–amino intermediate.     

Highly enantioselective aldol reaction of acetone with β,γ-unsaturated α-keto esters promoted by simple chiral primary-tertiary diamine catalysts

A series of primary-tertiary diamine catalysts were successfully applied to promote the enantioselective aldol reaction of acetone with β,γ-unsaturated α-keto esters in excellent yields (up to 99%) and enantioselectivities (up to 96% ee).