Electroreductive intramolecular coupling of N-(oxoalkyl)phthalimides: complementary method to samarium(II) iodide reduction

The electroreductive intramolecular coupling of phthalimides with ketones in the presence of chlorotrimethylsilane gave five- and six-membered trans-cyclized products stereospecifically (>99%). Similar electroreductive intramolecular coupling of phthalimides with aldehydes afforded five-, six-, and seven-membered trans-cyclized products stereoselectively (75-93%). On the other hand, the reductive coupling of N-(oxoalkyl)phthalimides with samarium(II) iodide gave cis-cyclized products stereoselectively (88->99%).     

Electroreductive intramolecular coupling of phthalimides with aromatic aldehydes: application to the synthesis of lennoxamine

The electroreductive intramolecular coupling of phthalimides with aromatic aldehydes in the presence of chlorotrimethylsilane and triethylamine led to five-, six-, and seven-membered cyclized products (58-84%). The electroreductive cyclization was applied to the total synthesis of lennoxamine.     

Reductive coupling of aliphatic cyclic imides with benzophenones by low-valent titanium

The reductive coupling of aliphatic cyclic imides with benzophenones by Zn–TiCl₄ in THF gave two- and four-electron reduced products selectively by controlling the reaction conditions. Although cyclic and acyclic products were formed as mixtures in most cases, cyclic dehydrated products could be selectively obtained by heating the product mixtures in the presence of cat. p-TsOH.     

Electroreductive intramolecular coupling of aromatic beta- and gamma-imino esters: a new synthetic method for N-alkoxycarbonyl-2-aryl-3-ones and cis-2-aryl-3-ols of pyrrolidines and piperidines

The electroreduction of aromatic beta- and gamma-imino esters prepared from beta-alanine and GABA in the presence of chlorotrimethylsilane and subsequent N-alkoxycarbonylation of the resulting five- and six-membered cyclized amines gave mixed ketals of N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones, respectively. The best result of the electroreductive intramolecular coupling was achieved using Bu(4)NClO(4) as a supporting electrolyte and a Pb cathode in THF. Acid hydrolysis of the mixed ketals afforded N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones in good yields. The reduction of these ketones with NaBH(4) in methanol afforded the corresponding N-alkoxycarbonyl-cis-2-arylpyrrolidin-3-ols and cis-2-arylpiperidin-3-ols diastereospecifically.     

Electroreductive crossed pinacol coupling of aromatic ketones with aliphatic ketones and aldehydes

The intermolecular crossed pinacol coupling of aromatic ketones with aliphatic aldehydes and ketones was effected by electroreduction in the presence of chlorotrimethylsilane. The best result was obtained using a Pb cathode in Bu₄NPF₆/THF. The electroreduction of aromatic 1,4-, 1,5-, and 1,6-diketones under the same conditions gave four-, five-, and six-membered 1,2-diols with trans-stereoselectivity, while the reduction of these diketones with TiCl₄-Zn produced the cis-isomers of the same intramolecular crossed pinacol coupling products predominantly.     

Stereoselective synthesis of N,N-acetals by cyclization of an N-acyliminium ion through interaction with an N-sulfonyl group

A new method for the stereoselective synthesis of five- and six-membered bicyclic N,N-acetals with trans configuration was developed using N-acyliminium ion cyclization. The N-sulfonyl substituted compounds were effectively cyclized to give the corresponding acetals in high yields and stereoselectivities, suggesting that the intramolecular interaction between the iminium and the sulfonyl group plays a key role in the cyclization.     

SmI2-Promoted novel tandem elimination and coupling reactions of aliphatic imides with carbonyl compounds: application to the synthesis of dl-isoretronecanol

Treatment of α-hetero-substituted cyclic imides with carbonyl compounds mediated by samarium(II) diiodide in the presence of HMPA was found to undergo novel tandem elimination and reductive coupling reactions to generate α-hydroxyalkylated imides in good to high yields. Stereochemistry of the coupling products was researched and the result that increasing the steric bulkiness of the N-substituents leads to an increase of threo-selectivity was observed. The mechanistic origins of this stereoselectivity are also briefly documented and the reaction was further applied to the convenient synthesis of a simple pyrrolizidine alkaloid, isoretronecanol.     

Tri(pentaflurophenyl)borane-catalyzed reduction of cyclic imides with hydrosilanes: Synthesis of pyrrolidines

B(C₆F₅)₃-catalyzed hydrosilylation of cyclic imides afforded an efficient synthetic method of pyrrolidines. In the presence of 5?mol% B(C₆F₅)₃, various aromatic, aliphatic and polycyclic imides were smoothly reduced by PhSiH₃ to generate the corresponding pyrrolidines in high yields. The reaction profiles monitored by ¹H NMR spectroscopy disclosed the reduction process of cyclic imides and the effect of difference structure of the hydrosilanes on the hydrosilylation.     

Domino Knoevenagel-hetero-Diels-Alder reactions: a stereoselective synthesis of sugar-annulated furo[3,2-b] pyrano[4,3-d]pyran derivatives

The O-propargyl derivative of a sugar aldehyde derived from d-glucose undergoes smooth intramolecular domino Knoevenagel-hetero-Diels-Alder reactions with 1,3-diketones in the presence of CuI/Et₃N system in refluxing methanol to afford a novel class of carbohydrate analogues, furopyranopyrans in good yields. 1-Aryl-pyrazol-5-ones also undergo smooth coupling with O-propargyl tethered sugar aldehyde under similar conditions to furnish pyrazole-annulated furopyranopyrans. The stereochemistry of the products was assigned by various NMR experiments.     

CpTiCl2-Catalyzed Cross-Coupling between Internal Alkynes and Ketones: A Novel Concept in the Synthesis of Halogenated,Conjugated Dienes

A novel concept for the synthesis of halogenated, conjugated dienes is disclosed: the CpTiCl₂-catalyzed coupling of keto-alkynes, in the presence of Me₃SiBr/Et₃N ⋅ HBr. This reaction provided five-, six-, and seven-membered carbocycles, nitrogenated heterocycles, as well as six-membered oxygenated heterocycles leading to a brominated conjugate diene. These products showed high reactivity in the Diels–Alder, Suzuki, and Sonogashira reactions, giving complex chemical structures in only three steps from the corresponding acyclic keto-alkyne. Hopefully, this strategy will pave the way towards the synthesis of bioactive natural products and new materials.     

Electroreductive intermolecular coupling of phthalimides with aldehydes: application to the synthesis of alkylideneisoindolin-1-ones

The electroreduction of N-methyl, N-p-anisyl, and N-unsubstituted phthalimides with aldehydes in the presence of chlorotrimethylsilane and triethylamine gave intermolecularly coupled products, 3-hydroxy-3-(1-hydroxyalkyl)isoindolin-1-ones. The coupling products were reduced with Et₃SiH/BF₃·Et₂O to 3-(1-hydroxyalkyl)isoindolin-1-ones, which were dehydrated to alkylideneisoindolin-1-ones. From N-unsubstituted phthalimides, Z-isomers of alkylideneisoindolin-1-ones were obtained stereospecifically.     

Formation of polysubstituted chlorocyclopropanes from electrophilic olefins and activated trichloromethyl compounds

Chlorocyclopropanes and bicyclic chlorocyclopropanes are prepared in non basic conditions by electroreductive or Mg-promoted Barbier activation of PhCCl₃ or Cl₃CCO₂Me in the presence of acyclic or cyclic α,β-unsaturated carbonyl compounds.     

A facile intramolecular azido/amido reductive cyclization approach: synthesis of pyrrolobenzodiazepines and their dimers

A new synthetic pathway has been developed for the preparation of imine-containing pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) and their dimers. Selective reduction of aromatic azides as well as aliphatic amides in a single step leading to an intramolecular reductive cyclization process by employing LiAlH₄ or LiBH₄ provides the cyclized imines.     

Untersuchungen zum elektronischen einfluss von organylliganden: IV. 13C-NMR-spektroskopische untersuchung der gegenseitigen beeinflussung von organylliganden in triethylzinnorganylverbindungen

By means of ¹³C NMR spectroscopy, the coupling constants ¹J(¹¹⁹Sn¹³C_Et) of 18 compounds of the SnEt₃R type (R = organo group) have been measured. These coupling constants have been shown to reflect the change induced by R in the s-content of the tin hybrid orbitals of the SnCEt bonds. The series of the influence of R obtained on the basis of the coupling constant mentioned as a parameter is compared with a trans-influence series of R obtained on organo-mercury compounds. Occurring differences are attributed to different modes of bonding of the group R at the central atom.     

Cascade synthesis of pyrido[3,2-a]indolizines by reaction of Kröhnke–Mukaiyama salts with malononitrile dimer

An efficient protocol for the synthesis of highly functionalized 2-aminoindolizines and pyrido[3,2-a]indolizines has been achieved via the reaction of N-RC(O)CH₂-2-chloropyridinium bromides with 2-amino-1,1,3-tricyanopropene in the presence of Et₃N. The reaction of N-allyl-2-chloropyridinium bromide with 2-amino-1,1,3-tricyanopropene in the presence of Et₃N gives 3-[1-allylpyridin-2(1Н)-ylidene]-2-aminoprop-1-ene-1,1,3-tricarbonitrile, which could be cyclized to give [2-amino-(2-amino-3-vinylindolizin-1-yl)methylene]malononitrile upon treatment with KOH–DMF.     

Reductive coupling of aliphatic cyclic imides and ω-amidoesters with benzophenones by low-valent titanium: Synthesis of 5-diarylmethylene-1,5-dihydropyrrol-2-ones, 6-diarylmethyl-2-pyridones,and ω-(diarylmethylene)lactams

The reductive coupling of cyclic imides and ω-amidoesters with benzophenones by Zn-TiCl₄ in THF and subsequent acid-catalyzed dehydration gave 5-diarylmethylene-1,5-dihydropyrrol-2-ones A, 6-diarylmethyl-2-pyridones B, and ω-(diarylmethylene)lactams C. In a similar manner, 3-((benzyloxy)carbonyl)amino substituted A, B, and C were synthesized from the corresponding 3-((benzyloxy)carbonyl)amino cyclic imides and ω-((benzyloxy)carbonyl)amino-ω-amidoesters prepared from L-aspartic and L-glutamic acids. In addition, 4- and 5-((benzyloxy)carbonyl)amino substituted C were also obtained by the same procedures from 2-((benzyloxy)carbonyl)amino-ω-amidoesters prepared from L-asparagine and L-glutamine, respectively.     

Synthesis and spectral characterization of N‐[2‐(4‐halophenoxy)‐3‐(3‐chlorophenyl)‐3, 4‐dihydro‐2H‐1,3,2‐λ5‐benzoxazaphosphinin‐2‐yliden]‐N‐substituted amines by the Staudinger reaction

The synthesis of the title compounds was accomplished in four steps. The synthetic route involves the preparation of Schiff's base by reacting salicylaldehyde with m‐chloroaniline in EtOH. The Schiff's base was then reduced with NaBH₄/MeOH. In the second step, PCl₃ was reacted with p‐chlorophenol/p‐bromophenol in THF in the presence of Et₃N to obtain P(III) dichloride derivatives. The reduced Schiff's base and dichloride derivatives were reacted in equimolar quantities in the presence of Et₃N in THF to get the cyclized product. Alkyl azides were prepared by reacting alkyl bromides with sodium azide, and then alkyl azides were treated with the cyclized product to obtain the title compounds. The structure of these novel compounds was elucidated by elemental analysis, IR, ¹H, ¹³C, ³¹P NMR, and mass spectroscopy. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:499–504, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20639     

Indium(III)-catalyzed intramolecular addition of silyl enolates to alkynes

In the presence of water and a catalytic amount of InBr₃, intramolecular trans-addition of silyl enolates derived from ketones and an aldehyde to alkynes proceeded smoothly to give 4 to 7-membered carbocycles bearing an acyl group. When carboxylic anhydrides were used as electrophiles instead of water, the cyclized products could be functionalized with an additional acyl group.     

A new diastereoselective intramolecular electroreductive coupling of unsaturated β-ketoesters and β-ketoamides in ionic liquids at a tin cathode

The diastereoselective intramolecular electroreductive coupling of several β-ketoesters and β-ketoamides has been accomplished at a tin cathode in ionic liquids and isopropanol (9:1). The ionic liquids used are 1-butyl-3-methylimidazolium bromide [BMIM]Br, 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF₄, 1-methoxyethyl-3-methylimidazolium trifluoroacetate [MOEMIM]CF₃COO and 1-methoxyethyl-3-methylimidazolium mesylate [MOEMIM]Ms. This methodology offers a clean and green process for the synthesis of functionalized carbocycles in good yields with excellent stereochemical control at three stereogenic centres.     

BF3·OEt2-catalyzed synthesis of 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran and trans-fused hexahydropyrano[3,2-c]chromene derivatives

A novel intramolecular Prins cyclization of (E)-5-(2-(hydroxymethyl)phenyl)pent-4-en-1-ol with aldehydes has been achieved using 10 mol % BF₃·Et₂O to produce 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran derivatives in good to excellent yields with high selectivity. Similar type of coupling with salicylaldehydes provides the trans-fused hexahydropyrano[3,2-c]chromene derivatives in excellent yields.