Synthesis of 7-oxa-phomopsolide E and its C-4 epimer

A flexible, enantioselective route to highly functionalized α,β-unsaturated δ-lactones has been applied to the synthesis of 7-oxa-phomopsolide E and its C-4 epimer. This approach relies on the application of the Noyori asymmetric hydrogenation of furyl ketone to produce the secondary furyl alcohol in high enantioexcess, which can be stereoselectively transformed into α,β-unsaturated-δ-lactones by a short, highly diastereoselective oxidation and reduction sequence. DCC and Mitsunobu coupling were used to introduce the side chains of the two natural product analogs.     

Synthesis of α-amino γ-butyrolactone derivatives by aziridination of α-ylidene γ-butyrolactones

The reactions of exocyclic α,β-unsaturated γ-lactones with NsONHCO₂Et and CaO produce N-(ethoxycarbonyl) spiroaziridino γ-lactones. By reaction with acetic acid these products give ring opening reaction and acetylated N-protected α-amino γ-butyrolactones are obtained. The ring opening reaction is quantitative and highly regioselective.     

Syntheses of furo[3,4-c]coumarins and related furyl coumarin derivatives via intramolecular Wittig reactions

A new and general strategy for highly functional furo[3,4-c]coumarins and related furyl coumarin derivatives has been developed, which is based on an extraordinarily facile intramolecular Wittig reaction, starting from α,β-unsaturated ketones, tributylphosphine, and acyl chlorides. The phosphorus ylides were proposed to be the key intermediates for constructing the crucial furan ring, leading to a wide variety of substituted furyl coumarins in one step.     

Bifunctional cinchona alkaloids-catalyzed asymmetric [4+2] cycloaddition reaction of β,γ-unsaturated α-keto esters with oxazolones

A highly enantioselective [4+2] cycloaddition reaction of β,γ-unsaturated α-keto esters with oxazolones was realized with readily available cinchona alkaloids as the catalysts. Using this reaction, a series of highly functionalized δ-lactones with adjacent α-quaternary-β-tertiary stereocenters were obtained in high yields (up to 97%) and with good-to-excellent enantioselectivities (up to 97% ee).     

Synthesis of functionalised β-lactones via silylcarbocyclisation/desilylation reactions of propargyl alcohols

Functionalised β-lactones were prepared starting from propargyl alcohols by means of an efficient rhodium-catalysed silylcarbocyclisation reaction. This process took place in high yields and complete stereoselectivity using DBU as the base, a sterically hindered alcohol and/or hydrosilane. Otherwise, a silylformylation competitive reaction occurred affording 3-hydroxy-2-[(aryldimethylsilyl)methylene]alkanals with complete regioselectivity. Indeed, while α-(aryldimethylsilylmethylene)-β-lactones were generated exclusively starting from an alkynol characterised by two alkyl groups on the propargyl carbon atom, significant amounts of the aldehydes were observed for secondary alcohols. In these cases, the use of ortho-substituted arylsilanes improved the chemoselectivity towards the α-methylene-β-lactones. Such molecules were then successfully converted into α-methylaryl-β-lactones by a fluoride-induced rearrangement of the aryl group that migrates from silicon to carbon with retention of configuration.     

Molecular complexity from aromatics: synthesis of highly functionalized spiro δ-lactones

A novel, general, and efficient method has been developed for the synthesis of highly functionalized spiro δ-lactones from aromatic precursors. Our methodology involves a tandem oxidative dearomatization-rearrangement of tertiary furyl carbinols and ring-closing metathesis as key features. This method allows an access to the spirolactones attached to carbocycles of various sizes.     

An enantioselective synthesis of phomopsolide D

A short enantioselective route to the highly functionalized α,β-unsaturated δ-lactone natural product phomopsolide D and three of its stereoisomers, has been accomplished. All of the carbon atoms of phomopsolide D come from tiglic acid and 2-furyl-1-penta-1′,3′-dienylketone (furan plus hexadienal). This approach derives its asymmetry from the sequential use of two catalytic asymmetric reactions; these being a Sharpless dihydroxylation reaction and a Noyori furylketone reduction. The resulting furfuryl alcohols were stereoselectively transformed into α,β-unsaturated δ-lactones via a short highly diastereoselective oxidation and reduction sequence.     

Synthesis and reactions of sulfur-substituted α,β-unsaturated δ- and γ-lactones

A new synthetic method for the preparation of sulfur-substituted α,β-unsaturated δ- and γ-lactones has been developed by reaction of the allylic bromides of 5,6-dihydro-2-pyridinones with NaOH in refluxing MeOH or t-BuOH. The substituents at C5 and C6 of these substrates are very important for the success of this reaction. Some synthetic transformations of the α,β-unsaturated δ-lactones have also been carried out.     

A new synthesis of α,β-unsaturated γ- and δ-lactones via intramolecular acylation of α-sulfinyl carbanion

A new synthesis of α,β-unsaturated γ- and δ-lactones involving the intramolecular acylation of α-sulfinyl carbanion followed by pyrolysis is described.     

Novel methodologies for the synthesis of functionalized pyroglutamates

Alkylation of amino-acid derived iminoesters with Baylis-Hillman (BH) template based allyl bromides furnished α-methylene-β-substituted-pyroglutamates, while the corresponding alkylation with BH derived allylic acetates provided α-alkylidene-pyroglutamates. These methodologies have been applied in the synthesis of fused [3.2.0]-γ-lactam-β-lactones.     

Synthese de β-ethoxycarbonyl λ-lactones

β-ethoxycarbonyl β, λ-insaturated λ-lactones 2 are easily prepared by dehydration of β-acyl β-ethoxycarbonyl α-alkyl propionic acids. Otherwise the condensation of these acids with allylzinc reagents produces β-ethoxycarbonyl λ-lactones 3 with a β-ethylenic carbon chain branched on the λ-carbon of the lactone.     

A concise and stereoselective synthesis of both enantiomers of altholactone and isoaltholactone

A concise and flexible stereoselective route to synthesize both enantiomers of the highly functionalized α,β-unsaturated-δ-lactones, altholactone and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulphonic acid.     

Highly stereoselective synthesis of antitumor agents: both enantiomers of goniothales diol,altholactone, and isoaltholactone

A flexible stereoselective route to synthesize both enantiomers of the highly functionalized substituted tetrahydrofurans and α,β-unsaturated-δ-lactones, goniothales diol, altholactone, and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulfonic acid.     

Ligand-Controlled Palladium-Catalyzed Carbonylation of Alkynols: Highly Selective Synthesis of α-Methylene-β-Lactones

The first general and regioselective Pd-catalyzed cyclocarbonylation to give α-methylene-β-lactones is reported. Key to the success for this process is the use of a specific sterically demanding phosphine ligand based on N-arylated imidazole ( L11 ) in the presence of Pd(MeCN)₂Cl₂ as pre-catalyst. A variety of easily available alkynols provide under additive-free conditions the corresponding α-methylene-β-lactones in moderate to good yields with excellent regio- and diastereoselectivity. The applicability of this novel methodology is showcased by the direct carbonylation of biologically active molecules including natural products.     

Stereoselective synthesis of 3-(ω-hydroxyalkyl)-2-pyrrolidinones from α-alkylidenelactones and nitromethane

Enantiopure 3-(ω-hydroxyalkyl)-2-pyrrolidinones 7 and 9 were synthesised by Michael-addition of nitromethane to chiral α-alkylidenelactones 1 followed by reduction of the resulting 3-(β-nitroalkyl)-lactones and ring transformation of the intermediate 3-(β-aminoalkyl)-lactones. In an analogous manner the naturally occurring costuslactone 10 was transformed into the butyrolactam 12.     

Efficient synthesis of α,β-unsaturated γ-lactones linked to sugars

A series of structurally diverse unsaturated sugar-derived lactones has been prepared. α,β-Butenolides were introduced to the sugar moiety starting from epoxides, while α-methylene-γ-lactones were constructed from a carbonyl precursor, either an aldehyde, a ketone or a lactone. In the last case, an unprecedented Reformatsky-type reaction has been developed.     

Synthesis of γ,γ-difluoro-β-hydroxy-δ-lactones as new precursors of HMG-CoA reductase inhibitor

A series of γ,γ-difluoro-β-hydroxy-δ-lactones 1 were efficiently synthesized as new precursors of HMG-CoA reductase inhibitor in one pot by treatment of readily prepared gem-difluoromethylenated acetonides 3 with trifluoroacetic acid. Contrarily, acetonides 3 could be transformed to the γ,γ-gem-difluoromethylenated α,β-unsaturated δ-lactones 2 through hydrolyzation and lactonization in refluxing toluene.     

Indium(III)-catalyzed asymmetric hetero-Diels-Alder reaction of Brassard-type diene with aliphatic aldehydes

A highly diastereo- and enantioselective hetero-Diels-Alder (HDA) reaction of a Brassard-type diene with aliphatic aldehydes has been developed. The chiral N,N'-dioxide L2/In(OTf)(3) complex was efficient toward the obtention of the corresponding β-methoxy-γ-methyl α,β-unsaturated δ-lactones in good yields (up to 86%) as well as dr and ee values (up to 97:3 cis/trans and 94% ee). In addition, the product 4a could be easily transformed into the methyl-protected epi-prelactone B by hydrogenation.     

Studies in the syntheses of sesquiterpene lactones—II : Chemical transformation of α-santonin into reynosin,santamarine, epoxysantamarine and 1β-hydroxyarbusculin A

Eudesmane type α-methylene-γ-lactones, reynosin (1), santamarine (2), epoxysantamarine (3) and 1β-hydroxyarbusculin A (4) have been synthesized from α-santonin.     

氮杂环卡宾催化α,β-不饱和酰氯与亚硝基化合物的[4+2]环化反应

报道氮杂环卡宾催化的α,β-不饱和酰氯与亚硝基化合物的形式[4+2]环化反应合成氮杂-δ-内酯([1,2]嗪-6-酮)化合物.反应机理推测可能是卡宾进攻现场生成的烯基烯酮,得到烯基烯醇负离子,然后与取代的亚硝基苯发生[4+2]环合反应,从而得到的氮杂-δ-内酯产物.