Chiral tertiary 2-furyl alcohols: diversified key intermediates to bioactive compounds. Their enantioselective synthesis via (2-furyl)aluminium addition to ketones catalyzed by a titanium catalyst of (S)-BINOL

Novel asymmetric 2-furyl additions of (2-furyl)AlEt(2)(THF) to aromatic ketones and one alpha,beta-unsaturated ketone catalyzed by a titanium catalyst of 10-20 mol% (S)-BINOL are reported to furnish tertiary furyl alcohols in good to excellent enantioselectivities of 87-93% ee.     

PMR spectral study of the structure of 1-vinyl-2-(2-furyl)- and 2-(2-thienyl)pyrroles

Conclusions PMR spectral data indicate that the heterocycles in 1-vinyl-2-(2-fury1- and 1-vinyl-2-(2-thienyl) pyrroles lie in a single plane with syn arrangement of the heteroatoms and trans orientation of the vinyl group relative to the non-pyrrole heterocycle. Molecular coplanarity is lost in 3-alky1-1-vinyl-2-(2-furyl)- and 3-alkyl-1-vinyl-2-(2-thienyl) pyrroles.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 184–186, January.     

Stereoinversion of Unactivated Alcohols by Tethered Sulfonamides

The direct, catalytic substitution of unactivated alcohols remains an undeveloped area of organic synthesis. Moreover, catalytic activation of this difficult electrophile with predictable stereo‐outcomes presents an even more formidable challenge. Described herein is a simple iron‐based catalyst system which provides the mild, direct conversion of secondary and tertiary alcohols to sulfonamides. Starting from enantioenriched alcohols, the intramolecular variant proceeds with stereoinversion to produce enantioenriched 2‐ and 2,2‐subsituted pyrrolidines and indolines, without prior derivatization of the alcohol or solvolytic conditions.     

Formylation of Furyl-substituted Imidazo[1,2-a]pyridine, Imidazo[1,2-a]pyrimidine and Imidazo[2,1-b]thiazole

Vilsmeier formylation of 2-(2-furyl)-substituted imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine, and also 6-(2-furyl)imidazo[2,1-b]thiazole with 1 mole of reagent occurs at the free position of the imidazole ring, while with an excess of the reagent it also occurs at the position 5 of the furyl group.     

Synthesis of meso-furyl porphyrins with N4, N3S, N2S2 and N3O porphyrin cores

A series of meso-furyl porphyrins with four different porphyrin cores (N₄, N₃S, N₂S₂ and N₃O) were synthesized and characterized. The comparison of NMR, optical and fluorescence properties of meso-furyl porphyrins with porphyrins with six-membered aryl groups indicates that electronic properties of porphyrins were changed drastically on the introduction of furyl groups at meso positions. The maximum shifts in spectral bands were observed for meso-furyl porphyrins with N₂S₂ core. On protonation, the absorption bands of meso-furyl porphyrins were further red shifted. All these changes were ascribed to the possibility of more planarity of the meso-furyl porphyrins due to the small size of the furyl groups which results in extending the π-delocalisation of the porphyrin ring in to the furyl groups.     

Highly regioselective radical alkylation of 3-substituted pyrroles

It is reported that the intermolecular oxidative radical substitution on 3-substituted pyrroles gives the 2,3-disubstituted pyrroles in a highly regioselective manner. This behavior is explained on the basis of the relative stabilities of the intermediate radicals formed in the process. The methodology reported herein represents a direct entry into 2,3-disubstituted pyrroles, which might be used to construct more complex molecules.     

Stereoselective synthesis of highly enantioenriched (E)-allylsilanes by palladium-catalyzed intramolecular bis-silylation: 1,3-chirality transfer and enantioenrichment via dimer formation

Highly enantioenriched (E)-allylsilanes have been synthesized from optically active allylic alcohols on the basis of Pd-catalyzed intramolecular bis-silylation followed by highly stereospecific Si-O elimination reactions. The method involves three steps: 1) O-disilanylation of the allylic alcohols with chlorodisilanes, 2) intramolecular bis-silylation in the presence of a 1,1,3,3-tetramethylbutyl isocyanide/[Pd(acac)2] (acac = acetylacetonate) catalyst at 110 degrees C, and 3) treatment of the reaction mixture with organolithium reagents. The overall transformation proceeds with nearly complete conservation of the enantiopurity of the starting allyl alcohols by transposition of the C=C bond. For instance, (R)-(E)-3-decen-2-ol (99.6-99.7 % ee) produced (S)-(E)-4-(organosilyl)-2-decene of 98.8-99.4 % ee for a variety of silyl groups, including Me3Si, Me2PhSi, tBuMe2Si, Et3Si, and iPr3Si. In the bis-silylation step, the initially formed trans-1,2-oxasiletanes immediately dimerize to stereoselectively give 1,5-dioxa-2,6-disilacyclooctanes, which are isolated in high yield by carrying out the reaction at 70 degrees C. The eight-membered ring compounds undergo thermal extrusion of (E)-allylsilanes in high yield at 110 degrees C, along with formation of 1,3-dioxa-2,5-disilacyclohexane derivatives. These in turn undergo a Peterson-type elimination by treatment with nucleophiles such as BuLi and PhLi to give the (E)-allylsilanes. All of the steps involved in the sequence proceed with extremely high stereoselectivity and stereospecificity, leading to almost complete 1,3-chirality transfer through the overall transformation. The dimerization step, which forms diastereomeric intermediates, allows the synthesis of a highly enantioenriched allylsilane (99.4 % ee) from an optically active allylic alcohol with lower enantiopurity (79.2 % ee) by enrichment of enantiopurity. A general method for the determination of the enantiomeric excesses of (E)-allylsilanes is also described in detail.     

CuCl/DABCO/4-HO-TEMPO-catalyzed aerobic oxidative synthesis of 2-substituted quinazolines and 4H-3,1-benzoxazines

The Cu/N-ligand/TEMPO catalytic system was first applied to the aerobic oxidative synthesis of heterocycles. As demonstrated, 2-substituted quinazolines and 4H-3,1-benzoxazines were synthesized efficiently from the one-pot reaction of aldehydes with 2-aminobenzylamines and 2-aminobenzyl alcohols, respectively, by employing CuCl/DABCO/4-HO-TEMPO as the catalysts and oxygen as the terminal oxidant.     

Directed metalation and regioselective functionalization of 3-bromofuran and related heterocycles with NaHMDS

A mild and regioselective functionalization protocol for 3-bromofuran and analogs has been developed. Selective metalation and functionalization of C2 can be achieved as a result of the directing effect of the adjacent electron-withdrawing bromo group. In addition, the C5 position can also be selectively functionalized by blocking the C2 position via silylation or by simply controlling the reaction temperature. These functionalized compounds bearing a C3 bromo substituent may be further elaborated by utilizing a Suzuki–Miyaura cross-coupling procedure.     

Divergent reaction pathways of a cationic intermediate: rearrangement and cyclization of 2-substituted furyl and benzofuryl enones catalyzed by iridium(III)

In contrast to 2-substituted pyrrole enones, furyl and benzofuryl enones do not undergo the Nazarov electrocyclization. Instead, these furyl and benzofuryl enones exhibit unusual rearrangement sequences in the presence of catalytic amounts of [IrBr(CO)(DIM)((R)-(+)-BINAP)](SbF(6))(2) (1; DIM = diethylisopropylidene malonate) and AgSbF(6) (1:1). A 1,2-H shift followed by intramolecular Friedel-Crafts alkylation leads to synthetically valuable cyclohexanones with furanylic quaternary centers. The electrophilicity of 1 is essential for this rearrangement.     

Enzymatic kinetic resolution of 1-(3′-furyl)-3-buten-1-ol and 2-(2′-furyl)-propan-1-ol

The enzymatic kinetic resolution of the racemic alcohols 1-(3′-furyl)-3-buten-1-ol (±)-1 and 2-(2′-furyl)propan-1-ol (±)-2 was investigated by screening a range of lipases and esterases for enantioselective transacylation, as well as for enantioselective hydrolysis. For both alcohols, lipase-catalyzed hydrolysis of the derived racemic acetate gave the best results for accessing the desired (S)-enantiomers. In the case of the secondary alcohol (±)-1, ASL turned out to be the optimum enzyme, whereas PPL was found to be superior in the case of the primary alcohol (±)-2. Additionally, an alternative access to (S)-2 via Oppolzer's camphor sultam methodology is described.     

Reductive cyclization of o-nitrophenyl propargyl alcohols: facile synthesis of substituted quinolines

Reduction of secondary and tertiary o-nitrophenyl propargyl alcohols followed by acid-catalyzed Meyer-Schuster rearrangement gave 2-substituted and 2,4-disubstituted quinolines, respectively. Tertiary propargyl alcohols gave excellent yields of the quinoline derivative, while the yields of quinolines were slightly reduced when secondary propargyl alcohol derivatives were utilized.     

An atom-economic synthesis of nitrogen heterocycles from alkynes

A robust route to 2,4-disubstituted pyrrole heterocycles relying upon a cascade reaction is reported. The reaction benefits from operational simplicity: it is air and moisture tolerant and is performed at ambient temperature. Control over the reaction conditions provides ready access to isopyrroles, 2,3,4-trisubstituted pyrroles, and 3-substituted pyrollidin-2-ones.     

Nitration of Some 3-(2-Furyl)-2-propenones with Dinitrogen Tetraoxide

Nitration of 3-(2-furyl)-2-propenones with dinitrogen tetraoxide leads to the corresponding 3-(4-nitro-2-furyl)-2-propenones. If the furyl group contains a substituent in position 5, the nitration occurs at the side chain to afford 3-(5-R-2-furyl)-2-nitro-2-propenones.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 3, 2005, pp. 431–436.Original Russian Text Copyright © 2005 by Sitkin, Klimenko.     

A polarographic investigation of 5-nitrophenyl-2-furfurals and their derivatives

The polarographic behavior in dimethylformamide of the o-, p-, and m-isomers of 5-(nitrophenyl)-2-furfural and their benzoylhydrazones has been studied. These compounds give one one-electron and one three-electron wave of the reduction of the nitro group, the corresponding half-wave potentials being considerably more negative than the half-wave potentials of 5-nitro-2-furfural and the corresponding nitrobenzaldehydes. In the case of 5-(o-nitrophenyl)-2-furfural and its benzoylhydrazone, a hydrogen bond is formed between the nitro group and the furan ring or the amide grouping of the side chain, which leads to a considerable shift in the potentials in the negative direction. Because of the high electroreduction potentials, the benzoylhydrazones of the 5-(o-, p-, and m-nitrophenyl)-2-furfurals have no antibacterial and fungistatic activity.     

3-Furylchromones

-[2-(5-Methoxycarbonyl)furyl]-2,4-dihydroxy- and 2,4,6-trihydroxyacetophenones were obtained by the condensation of polyphenols with (2-methoxycarbonyl-5-furyl)acetonitrile. 7-Acetoxy- and 5,7-diacetoxy-2-methyl-3-[2-(5-methoxycarbonyl)furyl]chromones were obtained from them by reaction with acetic anhydride in the presence of triethylamine and were subsequently deacylated to 7-hydroxy and 5,7-dihydroxy compounds. 7-Hydroxy- and 5,7-dihydroxy-2-ethoxycarbonyl-3-[2-(5-methoxycarbonyl)furyl]chromones were obtained from the indicated acetophenones by reaction with ethoxalyl chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1317–1320, October, 1972.     

Novel catalytic kinetic resolution of racemic epoxides to allylic alcohols

[formula: see text] The kinetic resolution of racemic epoxides via catalytic enantioselective rearrangement to allylic alcohols was investigated. Using the Li-salt of (1S,3R,4R)-3-(pyrrolidinyl)methyl-2-azabicyclo [2.2.1] heptane 1 as catalyst allowed both epoxides and allylic alcohols to be obtained in an enantioenriched form.     

Copper Promoted Oxidative Coupling of SnAP Hydrazines and Aldehydes to Form Chiral 1,4,5‐Oxadiazepanes and 1,2,5‐Triazepanes

SnAP (Sn (tin) amine protocol) hydrazine reagents and aldehydes undergo oxidative, copper mediated coupling to form substituted 1,4,5‐oxadiazepanes and 1,2,5‐triazepanes. Unlike all prior reactions involving SnAP reagents, the SnAP hydrazine reagents undergo a molecular oxygen‐assisted oxidative cyclization. The air‐ and moisture tolerant transformation accommodates a broad range of groups including electron‐rich, electron‐poor aromatic, heteroaromatic, and aliphatic aldehydes and is amenable to gram scale synthesis. These unusual, chiral heterocycles have unexpectedly large optical rotations, which may find use in optical materials.     

Halogenation of thenyl and furyl cobaloximes

The reactions of thenyl and furyl cobaloximes with halogens (bromine and chlorine) in acetic acid and chloroform indicate that, CoC bond cleavage occurs in 2-thenyl and 2-furyl case whereas the ring substitution is faster than CoC band cleavage in 3-thenyl and 3-furyl cobaloximes.     

Synthesis of fused imidazoles, pyrroles, and indoles with a defined stereocenter α to nitrogen utilizing Mitsunobu alkylation followed by palladium-catalyzed cyclization

Nitrogen-containing fused heterocycles comprise many compounds that demonstrate interesting biological activities. A new synthetic approach involving Mitsunobu alkylation of imidazoles, pyrroles, and indoles followed by palladium-catalyzed cyclization has been developed providing access to fused heterocycles with a defined stereochemistry α to nitrogen. While ethyl imidazole or indole carboxylates are good substrates for Mitsunobu alkylation with optically pure secondary benzylic alcohols, the corresponding pyrroles are poor substrates presumably due to the increased pK(a) of the NH. The presence of a synthetically versatile trichloroacetyl functional group on the pyrroles significantly reduces the pK(a) and thereby facilitates Mitsunobu alkylation. Subsequent cyclization of the alkylated products mediated by palladium in the presence or absence of a ligand gave fused heterocycles in good to excellent yields.