Acetals of γ-oxo-α,β-unsaturated esters in nitrone cycloadditions. Regio- and stereochemical implications

Several acetals of γ-oxo-α,β-unsaturated esters have been prepared, mainly from enantiopure C₂-symmetric diols, and their 1,3-dipolar cycloaddition to 2,3,4,5-tetrahydropyridine 1-oxide has been studied. All the reactions showed complete regioselectivity and a high preference for the endo approach of the reactants in the transition state. The enantiopure acetals derived from (cis,cis)-spiro[4.4]nonane-1,6-diol gave the highest diastereofacial selectivity.     

Anionic versus photochemical diastereoselective deconjugation of diacetone d-glucose α,β-unsaturated esters

Deconjugation of diacetone d-glucose α,β-unsaturated esters has been conducted by deprotonation using NaHMDS with HMPA as co-solvent followed by stereoselective protonation at low temperature. High selectivities (>95%) were obtained with α-methyl linear compounds.     

Enzyme mediated kinetic resolution of δ-hydroxy-α,β-unsaturated esters as a route to optically active δ-lactones

A novel synthetic route to optically active saturated and unsaturated δ-lactones based on enzymatic kinetic resolution and ring-closing metathesis reactions has been proposed. The influence of temperature, co-solvent, organic additives and the substrate structure on the catalytic behavior of selected hydrolases was studied. The substantial impact of the organic co-solvent and surfactant type on the enzymatic activity and enantioselectivity was observed providing enantiomerically pure δ-hydroxy-α,β-unsaturated esters. The established protocol combining enzymatic kinetic resolution with ring closing metathesis was successfully applied in the synthesis of the enantiomerically pure (6R)-phenyl-5,6-dihydro-2H-pyran-2-one which plays crucial role in the synthesis of the number of bioactive compounds.     

The asymmetric addition of malononitrile to α,β-unsaturated ketones catalyzed by RuCl2[(R,R)-DPEN](PPh3)2 as the precatalyst

Non-borohydride ruthenium complex, RuCl₂[(R,R)-DPEN](PPh₃)₂ (1f), was demonstrated to catalyze asymmetric Michael addition of malononitrile to acyclic enones with weak bases. Michael addition of malononitrile to chalcone and analogues was promoted by combining CsOAc with CsOH in the presence of 1f and gave good yields and up to 82% ee.     

Synthesis of (Z)-α-chloro-α,β-unsaturated esters with complete stereoselectivity promoted by samarium diiodide

Stereoselective β-elimination in α,α-dichloro-β-hydroxyesters 2 was achieved by using samarium diiodide, yielding (Z)-α-chloro-α,β-unsaturated esters 1. The starting compounds 2 were easily prepared by reaction of the lithium enolate of ethyl dichloroacetate with different aldehydes at −78 °C. A mechanism to explain this process is proposed.     

Reaction of δ-silyl-γ,δ-epoxy-α,β-unsaturated acylsilanes with cyanide ion: possibility of the formation of silicate intermediate in anion-induced ring opening of epoxysilanes

Reaction of trans- and cis-δ-silyl-γ,δ-epoxy-α,β-unsaturated acylsilanes 1 and 9 with cyanide ion in the presence of an electrophile affords double Brook rearrangement products 10 in an E/Z ratio depending on the cis/trans geometry of the epoxysilanes.     

SmI2-induced reductive cross-coupling of carbonyl compounds with (α,β-unsaturated esters

Reductive cross-coupling of carbonyl compounds with(α,β-unsaturated esters by SmI₂ to ?-lactones was highly accelerated by the addition of hexamethylphosphoric triamide (HMPA).     

Stereoselective cycloaddition of N-acyliminium cations withα,β-unsaturated ketones and esters

The cycloaddition of N-acyliminium cations with some deactivated alkenes such asα,β-unsaturate ketones and esters has been investigated.In most cases,the N-acyliminium cations produced from 3-hydroxy-2-arylisoindol-1-ones in the presence of BF_3·OEt_2 could be reacted withα,β-unsaturated ketones and esters to afford stereoselectively the cycloaddition products 6-acylisoindolo[2,1-a] quinolin-11-ones in moderate to high yields.     

TsNBr2 promoted decarboxylative bromination of α,β-unsaturated carboxylic acids

A rapid process for decarboxylative bromination of α,β-unsaturated carboxylic acids have been developed using N,N-dibromo-p-toluenesulfonamide (TsNBr₂). Treatment of cinnamic acids with TsNBr₂ in presence of potassium carbonate in acetonitrile produces corresponding β-bromostyrenes at room temperature. Exclusive formation of (E)-β-bromostyrenes was observed in a stereoselective manner within a very short period of time (5–15?min). This method was further extended for obtaining 1-bromoalkynes from corresponding propiolic acids. Instantaneous formation of bromoalkynes was observed when the reaction was carried out in presence of DBU as a base in acetonitrile at room temperature. A wide variety of cinnamic acids and propiolic acids could be converted to corresponding β-bromostyrenes and 1-bromoalkynes respectively under mild reaction condition with high to excellent yield.     

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.     

Copper-catalyzed iminohalogenation of γ, δ-unsaturated oxime esters with halide salts: Synthesis of 2-halomethyl pyrrolines

A copper-catalyzed iminohalogenation of unactivated alkenes of γ, δ-unsaturated oxime esters is achieved by using readily available halide salts. Utilizing this protocol, a sequence of structurally diversiform 2-halomethyl pyrrolines are efficiently synthesized and a mechanism involving iminyl radical intermediates, which were initiated by Cu(I) species, was proposed.     

Oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones into N-(α-ketoacyl)anthranilic acids

N-(α-Ketoacyl)anthranilic acids were prepared by oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones by using paraperiodic acid (H₅IO₆) or sodium periodate (NaIO₄). The optimisation of the reaction conditions is described as well as the utilisation of N-(α-ketoacyl)anthranilic acids in the preparation of anthranilic acid hydrochlorides.     

Facile synthesis of α, β-unsaturated esters through a one-pot copper-catalyzed aerobic oxidation-Wittig reaction

An efficient one-pot synthesis of α, β-unsaturated esters through the aerobic oxidation – Wittig tandem reaction of alcohols and phosphorous ylide is developed. This new method operates under mild reaction conditions, and uses CuI/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) as co-catalyst and air (O₂) as the oxidant. It tolerates a wide range of functionalized benzylic alcohol and aliphatic alcohols.     

Reactivity of the 30-electron dimolybdenum anion [Mo2(η-C5H5)2(μ-PCy2)(μ-CO)2] towards β,γ-unsaturated organic halides: Alkenyl, allenyl and alkoxycarbyne derivatives

The 30-electron dimolybdenum anion [Mo₂Cp₂(μ-PCy₂)(μ-CO)₂]⁻ reacts at room temperature with allyl chloride to give the unsaturated σ:π-bonded alkenyl derivative trans-[Mo₂Cp₂(μ-η¹:η²-CMeCH₂)(μ-PCy₂)(CO)₂], this requiring a 2,1-hydrogen shift in the allyl moiety probably induced by the unsaturated nature of the dimetal center. In a similar way, the dimolybdenum anion reacts with trans-1-chloro-2-butene (crotyl chloride) to give a mixture of the alkenyl complexes trans-[Mo₂Cp₂(μ-η¹:η²-CEtCH₂)(μ-PCy₂)(CO)₂] and trans-[Mo₂Cp₂(μ-η¹:η²-CMeCHMe)(μ-PCy₂)(CO)₂] in a 3:2 ratio, which could not be separated by column chromatography. All these alkenyl species exhibit a dynamic behavior in solution (fast on the NMR timescale even at low temperatures) involving alternative π-bonding of the alkenyl ligand to each metal center. In contrast, the title anion reacts with propargyl chloride (ClCH₂-CCH) without further rearrangement of the propargyl moiety, to afford the allenyl derivative trans-[Mo₂Cp₂{μ-η²:η³-CH₂CCH)}(μ-PCy₂)(CO)₂] as the major species. Acryloyl chloride (ClC(O)-CHCH₂) also reacts with the title anion to give a mixture of two products, the carbyne complex [Mo₂Cp₂{μ-COC(O)CHCH₂}(μ-PCy₂)(μ-CO)] and the vinyl trans-[Mo₂Cp₂(μ-η¹:η²-CHCH₂)(μ-PCy₂)(CO)₂], in a 1:1 ratio. This reaction is a unique case in which a single electrophile can attack both nucleophilic positions in the dimolybdenum anion, these being located at the O(carbonyl) and metal sites, respectively. The formation of the vinyl derivative requires the decarbonylation of a metal-bound acryloyl group, which proved to be an irreversible reaction, since the addition of CO to the above alkenyl complex gave instead the tricarbonyl vinyl derivative cis-[Mo₂Cp₂(μ-η¹:η²-CHCH₂)(μ-PCy₂)(CO)₃]. The structure of this electron-precise complex was confirmed through a single-crystal X-ray diffraction analysis (Mo−Mo = 3.0858(7) Å).     

Chemoselective hydrogenation of α,β-unsaturated ketones to allylic alcohols, catalyzed by a mononuclear ruthenium complex containing trans PBu3 and PPh3 ligands

The ruthenium(II) bis(acetate) complex Ru(CO)₂(OAc)₂(PⁿBu₃)(PPh₃) (OAc = acetate) containing two different trans phosphine ligands, has been employed as pre-catalyst for the chemoselective hydrogenation of α,β-unsaturated ketones to allylic alcohols. Analogous catalytic reactions with the homodiphosphine pre-catalysts Ru(CO)₂(OAc)₂(PⁿBu₃)₂ and Ru(CO)₂(OAc)₂(PPh₃)₂ gave lower conversions and selectivities. Batch catalytic reactions and operando high-pressure NMR experiments have contributed to establish that the hydrogenation of the CO group is performed by the heterodiphosphine monohydride RuH(CO)₂(OAc)(PⁿBu₃)(PPh₃) generated in situ by hydrogenation of the bis(OAc) precursor. PPh₃ unfastening from this monohydride complex is an essential condition for the occurrence of catalytic activity.     

A facile stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones

Palladium-catalyzed hydrostannylation of acetylenic sulfones 1 in benzene at room temperature gives highly regio- and stereoselectively (E)-α-stannylvinyl sulfones 2 in high yields. (E)-α-Stannylvinyl sulfones 2 are new difunctional group reagents which undergo Stille coupling reactions with acyl chlorides 3 to afford stereoselectively (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 in good yields. A one-pot stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 has also been achieved by tandem hydrostannylation-Stille coupling reaction of acetylenic sulfones 1 under mild conditions.     

Synthesis and hetero-Diels-Alder reactions of (E)-α-perfluoroalkanesulfonyl-α,β-unsaturated ketones

Catalyzed by ammonium acetate, the Knoevenagel reactions of β-keto perfluoroalkanesulfones 1 with aromatic aldehydes 2 afforded α-perfluoroalkanesulfonyl-α,β-unsaturated ketones 4 in moderate to good yields. The possible mechanism for the reactions was proposed. These fluorine-containing α,β-unsaturated ketones, which are electron-poor 1-oxa-1,3-butadienes, could be used in inverse electron demand hetero Diels-Alder (HDA) reaction with electron-rich olefins to give tetrasubstituted dihydropyrans 6 in quantitative yields.     

Double asymmetric induction in the osmylation of -γ-alkoxy-α,β-unsaturated esters

OsO₄ promoted cis-dihydroxylation of enantiomerically pure (E)-α,β- unsaturated esters derived from alkoxyaldehydes occurs with noticeable levels (up to⩾ 45:1) of stereoselection when carried out in the presence of alkaloid derived ligands. Matching and mismatching substrate-ligand pairs have been identified.     

An efficient synthesis of (E)-α,β-unsaturated ketones and esters with total stereoselectivity by using chromium dichloride

(E)-α,β-Unsaturated ketones 1 or esters 2 can be obtained with complete stereoselectivity by reaction of different 2-chloro-3-hydroxy ketones 3 or esters 4 and CrCl₂. A comparative study of the results of synthesis of ketones 1 with CrCl₂ or samarium is performed. A mechanism to explain both β-elimination reactions has been proposed.     

Synthesis of dipyrrolo[2,3-a:1′,2′,3′-fg]acridin-12(1H)-ones

Acylation reactions of 4,6-dimethoxyindoles with glyoxyloyl chlorides were achieved by the use of graphite powder in 1,2-dichloroethane at reflux. The products were monoketones as a result of decarbonylation, rather than the expected 1,2-diketones. Treatment of these monoketones with base led to their cyclisation and elimination of methanol to afford the novel dipyrrolo[2.3-a:1′,2′,3′-fg]acridin-12(1H)-ones.