Synthesis of seven-membered lactones via nickel- and zinc-catalyzed highly regio- and stereoselective cyclization of 2-iodobenzyl alcohols with propiolates

A new class of substituted seven-membered lactones 3 were conveniently synthesized via cyclization of o-iodobenzyl alcohol 1 (o-IC(6)H(4)CH(2)OH) with various propiolates 2 (RC triple bond CCOOMe) in the presence of Ni(dppe)Br(2) and Zn powder in acetonitrile at 80 degrees C. The catalytic reaction is highly regio- and stereoselective affording seven-membered lactones in moderate to good yields. This methodology can be successfully extended to various substituted o-iodobenzyl alcohols. An intermediate 7 was obtained from the reaction of 1a with methyl 2-octynoate (2a) in the presence of Ni(dppe)Br(2) and Zn at room temperature. A mechanism involving an unusual E/Z isomerization of the carbon-carbon double bond of 7 prior to lactone formation is proposed to account for the catalytic reaction.     

An experimental and computational investigation of the Diels-Alder cycloadditions of halogen-substituted 2(H)-pyran-2-ones

[reaction: see text] Diels-Alder reactions of 3- and 5-halo-subsituted 2(H)-pyran-2-ones with both electron-rich and electron-deficient dienophiles afford stable and readily isolable bridged bicyclic lactone cycloadducts. These cycloadditions proceed with excellent regioselectivity and very good stereoselectivity. In contrast, Diels-Alder reactions of 4-halo-subsituted 2(H)-pyran-2-ones afford cycloadducts which are very prone to loss of bridging CO(2) and the subsequent formation of barrelenes ([2.2.2]cyclooctenes). Furthermore, these cycloadditions proceed with only moderate regio- and stereoselectivity. For both series of the 3- and 5-halo-subsituted 2(H)-pyran-2-ones and 4-halo-subsituted 2(H)-pyran-2-ones, the reactivity patterns do not significantly change between the halogens. The regio- and stereochemical preferences of the cycloadditions of halo-substituted 2(H)-pyran-2-ones are investigated computationally. Calculations were carried out on the transition states leading to the four possible regio- and stereoisomeric cycloadducts by using density functional theory (B3LYP/6-31G). These studies allow prediction of the regio- and stereoselectivity in these reactions which are broadly in line with experimental observations.     

1,3-Dipolar addition of diazocyclopropane to eudesmane-type methylidene lactones and thermolysis of the resulting spiro-fused pyrazolines

Reactions of alanto-, isoalanto-, and alloalantolactones, which are unsaturated eudesmane-type lactones, with diazocyclopropane generated in situ from N-cyclopropyl-N-nitrosourea under the action of sodium methoxide proceed alike, are highly regio- and stereoselective, and always give spiro-fused pyrazolines via cycloaddition to the exocyclic double bond of the methylidene group of the lactone ring. Their thermolysis at 195?C210 °C results in elimination of molecular nitrogen, mainly yielding spiropentane-containing lactones. Minor thermolysis products (10?C12%) are isomeric 13-cyclopropyl lactones.     

Reactions selectives des organonagnesiens avec les lactols et les lactones. Synthese des diols primaires-secondaires

The reactionz of organomagnesium compounds with cyclic lactols and the phthalde show a high chemioselectivity and provide respectively corresponding monoalkylated cyclic lactones and diols We also observe that the formation of bridged tricyclic lactones stereoselectively yields to thetransisomer. In the same way, we describe an easy and general method for the synthesis of diols, precursors of dibromides and cyclic ethers.     

Synthesis of methylene bridged C-disaccharides

Addition of glycosyl radicals to the α-methylene lactones 8 obtained from the corresponding glycopyranosyl phenylsulfoxides 5a,b in convenient two step procedures provides methylene bridged C-disaccharides in high diastereoselectivities. Thus, after reduction of the lactone moiety the methylene bridged analogs 9–11 of kojibiose, ristobiose, and α-L-fucopyranosyl (1→2)-D-galactose, respectively, were obtained.     

Investigation of the Diels-Alder cycloadditions of 2(H)-1,4-oxazin-2-ones

[Reaction: see text]. A variety of 5-chloro-2(H)-1,4-oxazin-2-ones bearing a range of substituents at their 3- and 6-positions undergo Diels-Alder cycloaddition as a 2-azadiene component with electron-rich, electron-deficient, and electron-neutral dienophiles. These reactions proceed with moderate regio- and stereoselectivity to afford relatively stable and readily isolable bridged bicyclic lactone cycloadducts. Chemical manipulation of these cycloadducts affords highly substituted and functionally rich piperidines. The regio- and stereochemical preferences of the cycloadditions of 5-chloro-2(H)-1,4-oxazin-2-ones are investigated computationally using density functional theory (B3LYP/6-31G).     

Cobalt- and nickel-catalyzed regio- and stereoselective reductive coupling of alkynes, allenes, and alkenes with alkenes

Transition-metal-catalyzed coupling of two different C-C pi components through a metallacycle intermediate is a highly atom economical method to construct C-C bonds in organic synthesis. The metal-catalyzed coupling of an alkene and alkyne generally gives an Alder-ene or reductive coupling product. In this article, we focus on the cobalt- and nickel-catalyzed reductive coupling of alkynes, allenes, and alkenes with alkenes. These reductive coupling reactions provide convenient methods for the synthesis of various alkenes, dienes, functionalized alkanes, lactones, lactams, and cyclic alcohols in a highly regio- and stereoselective manner. A chemselective formation of metallacyclopentene intermediate from the two different C-C pi components and a low-valence metal species plays a key role for the high regio- and stereoselectivity of the catalytic reaction.     

Skeletal rearrangements of bicyclo[2.2.2]lactones: a short and efficient route towards Corey’s lactone

The application of a unique tandem radical-initiated, Brönsted acid-catalysed, skeletal rearrangement of bicyclo[2.2.2]lactones provides a novel route towards Corey’s lactone 2. The strategy also features a high-pressure promoted inverse electron-demand Diels-Alder (IEDDA) reaction of 3-carbomethoxy-2-pyrone (3-CMP), which proceeds with complete regio- and diastereocontrol.     

An expedient domino three-component [3+2]-cycloaddition/annulation protocol: regio- and stereoselective assembly of novel polycyclic hybrid heterocycles with five contiguous stereocentres

A novel three-component strategy for the efficient synthesis of unprecedented polycyclic hybrid heterocycles comprising fused, bridged, and spiro rings with five contiguous stereocentres in a regio- and stereoselective manner is described. This transformation proceeds via 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of sarcosine/thiazolidine-4-carboxylic acid and acenaphthoquinone to a series of 2-[arylmethylidene]-3,4-dihydro-1(2H)-acridinones and concomitant annulation through an intramolecular aldol-type reaction.     

Regio and diastereoselective lactonisation of enolisable 1,3-dicarbonyls by reaction with mesoionic 1,3-oxazolium-5-olates

The one-pot reaction of enolisable 1,3-dicarbonyls and N-methyl-1,3-oxazolium-5-olate derivatives provided enol lactones directly in good yield and with excellent regio- and diastereocontrol.     

An aluminum ate base: its design, structure, function, and reaction mechanism

An aluminum ate base, i-Bu(3)Al(TMP)Li, has been designed and developed for regio- and chemoselective direct generation of functionalized aromatic aluminum compounds. Direct alumination followed by electrophilic trapping with I(2), Cu/Pd-catalyzed C-C bond formation, or direct oxidation with molecular O(2) proved to be a powerful tool for the preparation of 1,2- or 1,2,3-multisubstituted aromatic compounds. This deprotonative alumination using i-Bu3Al(TMP)Li was found to be effective in aliphatic chemistry as well, enabling regio- and chemoselective addition of functionalized allylic ethers and carbamates to aliphatic and aromatic aldehydes. A combined multinuclear NMR spectroscopy, X-ray crystallography, and theoretical study showed that the aluminum ate base is a Li/Al bimetallic complex bridged by the nitrogen atom of TMP and the alpha-carbon of an i-Bu ligand and that the Li exclusively serves as a recognition point for electronegative functional groups or coordinative solvents. The mechanism of directed ortho alumination reaction of functionalized aromatic compounds has been studied by NMR and in situ FT-IR spectroscopy, X-ray analysis, and DFT calculation. It has been found that the reaction proceeds with facile formation of an initial adduct of the base and aromatic, followed by deprotonative formation of the functionalized aromatic aluminum compound. Deprotonation by the TMP ligand rather than the isobutyl ligand was suggested and reasoned by means of spectroscopic and theoretical study. The remarkable regioselectivity of the ortho alumination reaction was explained by a coordinative approximation effect between the functional groups and the counter Li(+) ion, enabling stable initial complex formation and creation of a less strained transition state structure.     

Regio- and stereoselective cycloadditions of dichloroketene to bridged bicyclic olefins

Dichloroketene cycloadditions to selected bridged bicyclic compounds are described. The regio- and stereochemical course of these cycloadditions is discussed.     

Etude de l'action des alkylmagnesiens primaires et arylmagnesiens sur les anhydrides tricycliques pontes

The reaction of primary alkyl and aromatic Grignard reagents with bridged tricyclic di-carboxylic anhydrides gives the corresponding dialkylated tricyclic lactones via di-addition process. The lactones were transformed by retro-Diels-Alder reactions into 4,4-dialkylated butenolides.     

Trichloromethylative Olefin Lactonization by Photoredox Catalysis

A trichloromethylative olefin lactonization reaction using an iridium photoredox catalyst was developed. The reactions proceeded at room temperature for olefins with various substituents and substitution patterns, and a variety of lactones with a tetrasubstituted carbon and trichloromethyl group were obtained regio- and stereoselectively. The reaction mechanism was elucidated through isotope labeling experiments. The chemical properties of the lactones containing the trichloromethyl groups were investigated, and synthetic transformations of the product were realized.     

Regio- and stereoselective synthesis of tetrahydroindolysines,tetrahydropyridin-6-olates,and cyclopropanes from pyridinium ylides and unsaturated nitriles

The regio- and stereoselectivity of the reactions of pyridinium ylides with unsaturated nitriles are dependent on the electronic nature of the substituent in position 3 of the pyridine ring. The reaction of 1-carbamoylmethylide-3-cyanopyridinium with arylmethylenemalononitriles or arylmethylcyanoacetic esters proceeds regio- and stereoselectively with the formation of substituted 2-aryl-3-carbamoyl-6-cyano-2,3-trans- or 2,3-cis-1,2,3,8a-tetrahydroindolysines. The condensation of pyridinium 1-carbamoylmethylide with arylmethylenecyanoacetic ether leads to 4-aryl-2-oxo-3-(1-pyridinio)-5-cyano-3,4-trans-1,2,3,4-tetrahydropyridin-6-olates. The reaction of pyridinium (3-methylpyridinium) 1-carbamoylmethylide with arylmethylenemalononitriles results in the formation of 2-aryl-1,1-dicyano-3-carbamoyl-3-(1-pyridinio)- or (3-methyl-1-pyridinio)-1-propanides, which undergo stereoselective 1,3-transelimination with the formation of 3-aryl-1,1-dicyano-2-carbamoylcyclopropanes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 146–155. January, 1991.     

Additions of allenyl/propargyl organometallic reagents to 4-oxoazetidine-2-carbaldehydes: novel palladium-catalyzed domino reactions in allenynes

Metal-mediated carbonyl allenylation and propargylation of 4-oxoazetidine-2-carbaldehydes were investigated in aqueous environment. Different propargyl bromide and metal promoters showed varied regio- and stereoselectivities on product formation. In addition, an unprecedented one-pot stereoselective synthesis of beta-chlorinated allylic alcohols, which can also be considered as functionalized allylsilanes, has been developed, which involves tin(IV) chloride-mediated reaction of propargyltrimethylsilane and 4-oxoazetidine-2-carbaldehydes. Some of the resulting coupling products were submitted to transition metal catalyzed reactions, such as the allenic Pauson-Khand and palladium-catalyzed reactions, leading to novel fused or bridged tricyclic beta-lactams. Remarkably, a novel domino process, namely the allene cyclization/intramolecular Heck reaction was found. A likely mechanism for the cascade reaction should involve an intramolecular cyclization on a (pi-allyl)palladium complex and a Heck-type reaction.     

Enantioselective bromolactonization of cis-1,2-disubstituted olefinic acids using an amino-thiocarbamate catalyst

A facile, highly regio- and enantioselective amino-thiocarbamate-catalyzed bromolactonization of cis-1,2-disubstituted olefinic acids has been developed. The use of the enantio-enriched lactones in the synthesis of chiral synthetic intermediates is also demonstrated.     

Conformationally locked bridged bicyclic diselenides: synthesis, structure, Se...O interaction, and theoretical studies

A general synthetic methodology has been developed for the synthesis of a conformationally locked, bridged diselena-bicyclo[3.2.1]octane skeleton by regio- and stereospecific tandem nucleophilic ring opening of cis-1,4-aziridino-epoxides with tetraethylammonium tetraselenotungstate [Et4N]2WSe4, 1, in a one-pot synthesis. Some correlations have been made on the physicochemical characteristics of the diselenides with a change in the dihedral angles.     

Acid-Catalysed Cyclisation of p-Mentha-1,8(9)-diene- and p-Mentha-1,8(10)-diene-9-carboxylic Acid. Novel Access to the Bicyclo[3.2.1]octane Skeleton

Treatment of the title compounds with either H₃PO₄ or BF₃ · Et₂O affords the bridged tricyclic lactones 3 and 7 as main products (57 and 70% yield, resp.). This is an efficient and novel access to specifically functionalised molecules possesing the bicyclo[3.2.1]octane skeleton. Lactones 4 and 5 and the bicyclic ketone 6 were formed as by-products (2, 7, and 10% yield, resp.).     

Regio- and stereodirectivity in the reactions of isoquinolinium ylides with unsaturated nitriles

Reactions of isoquinolinium ylides with arylmethylenemalonitriles involve 1,3-dipolar cycloaddition, with the highly regio- and stereoselective formation of 2-aryl-3-benzoyl(or carbamoyl)1,1-dicyano-2,3-trans-1,2,3,10b-tetrahydropyrrolo[2, 1-a]isoquinolines. In contrast, N-phenacylisoquinolinium ylide reacts with aryl-methylenecyanothioacetamides differently, proceeding regio- and stereoselectively to give 4-aryl-2-hydroxy-3-(1-isoquinolinio)-2-phenyl-3-cyano-3,4-trans-1,2,3,4-tetrahydropyridine-6-thiolates.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2593–2599, November, 1990.