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Three-component coupling reactions of silylene, aldehydes and electron-deficient acetylenes proceed via 1,3-dipolar cycloaddition of silacarbonyl ylides with acetylenic dipolarophiles.

A new protocol for the cyclization of N-alkenylamides using chloramine-T and iodine is described. When N-alkenylsulfonamides are treated with chloramine-T and iodine, three- to six-membered N-heterocycles are obtained with complete stereoselectivity. The method is compatible with the cyclization of the allylbenzamide or allylbenzthioamide to afford an oxazoline or thiazoline derivative, respectively. Mechanistic studies indicate that the chloramine-T/I2 system functions as an effective iodonium species.

We present herein effective generation and cycloaddition of azomethine ylides and azomethine imines utilizing 1,4-metallatropic strategy in this. Since the metallatropy are based on the strong affinity between silicon/tin and oxygen/sulfur, the method does not require any additives and bases for the generation of the dipoles, which can avoid limitations in the functional groups of starting materials and dipolarophiles in their cycloaddition. Moreover, the present method could realize the efficient generation of less- or non-stabilized 1,3-dipoles.

A novel and efficient synthesis of 3,4,5-triaryltetrahydro-1,4-thiazine derivatives by treatment of β,β′-dichloro sulfides, 2:1 adducts of alkenes and sulfur dichloride, with aromatic amines in the presence of silica gel is described. The silica gel can be easily recovered and reused in up to four consecutive reactions without any significant decrease in product yield.

The ring opening of N-tosylaziridines with trimethylsilylated nucleophiles, catalyzed by N,N,N',N'-tetramethylethylenediamine, led to the production of beta-functionalized sulfonamides in good to excellent yields with high regioselectivity. [reaction: see text]

1,3-Dipolar cycloadditions of nitrones with alpha-alkyl- and alpha-arylacroleins are catalyzed with the DBFOX/Ph complexes of nickel(II) and magnesium(II) salts to produce the sterically controlled isoxazolidine-5-carbaldehydes, while the reactions with alpha-bromoacrolein are effectively catalyzed with the zinc(II) complexes to produce the electronically controlled isoxazolidine-4-carbaldehydes. Enantioselectivities up to 99.5% ee have been observed in the reactions performed at room temperature. [reaction: see text]

Reactions of malononitrile with 3-(2-alkenoyl)-2-oxazolidinones or 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles can be doubly activated by the use of catalytic amounts (10 mol% each) of both ( R , R )-DBFOX/Ph·Ni(ClO 4 ) 2 ·3H 2 O and amines, to give the Michael adducts in high chemical yields with satisfactory enantioselectivities.

The solid-phase synthesis of pyrrolidine and pyrrole derivatives using polymer-supported α-silylimines is described. Polymer-supported azomethine ylides were generated from the corresponding α-silylimine by thermal 1,2-silatropy onto the imino nitrogen or by treatment with a trifluorosilane as a quaternization and desilylation reagent, and the resulting species were then reacted with dipolarophiles to give five-membered heterocycles.

The 1,3-dipolar cycloaddition of polymer-supported azomethine ylides to dipolarophiles gave pyrrolidine derivatives in good yields. The azomethine ylides were generated from resin-bound alpha-silylimines via a 1,2-silatropic shift. The features of this method are not only a traceless synthesis but also a unique solid-phase route to pyrrolidines with extensive diversity. [reaction: see text]

A new synthetic method for chiral oxazolines has been developed by N1 unit transfer to olefins using a chiral nitridomanganese complex. When trans -disubstituted styrenes were treated with chiral complex 1 in the presence of an acid chloride, oxazolines were obtained with high enantioselectivities (up to 92% ee). Furthermore, the produced oxazolines could be easily converted into β-amino alcohols, which are ephedrine derivatives.

All possible combinations of a series of three fluorous benzyl tags and three acrylates have been made. The resulting acrylate esters were combined in groups of three (one of each tag) and the resulting mixtures were reacted with a mixture of four thiols under standard conditions to effect conjugate addition. Analysis of the resulting libraries by fluorous hplc showed a primary separation based on the tag and revealed reliable secondary separations based on the thiol and the acrylate. The primary and secondary separations were used together in a preparative ‘mixture of mixtures’ experiment in which one of the tagged acrylate mixtures was reacted with a mixture of three thiols. The resulting nine component mixture was demixed by fluorous and reverse phase hplc and then detagged to give all nine final products in pure form.

Temperature dependent 1 H NMR study has been performed on the substrate complex derived from zinc(II) perchlorate, ( R , R )-4,6-dibenzofurandiyl-2,2′-bis(4-phenyloxazoline), and 3-acetyl-2-oxazolidinone in deuteriodichloromethane. At room temperature, two isomers of octahedral substrate complexes are rapidly exchanging through a trigonal bipyramid intermediate. Liberation of the DBFOX/Ph ligand from the substrate complex can not be observed in a wide range of temperature, showing high stability of the DBFOX/Ph·Zn(ClO 4 ) 2 complex.

Cationic aqua complexes are prepared from a trans-chelating tridentate ligand, (R,R)-4,6-dibenzofurandiyl-2,2‘-bis(4-phenyloxazoline) (DBFOX/Ph), and various transition-metal(II) perchlorates. These complexes are effective catalysts in the Diels−Alder reactions of cyclopentadiene with 3-alkenoyl-2-oxazolidinone dienophiles and show excellent enantioselectivities. The active catalyst complex prepared from nickel(II) perchlorate hexahydrate has an octahedral structure with three aqua ligands, and it can be isolated and stored for months without loss of catalytic activity. Iron(II), cobalt(II), copper(II), and zinc(II) complexes are similarly active. The absolute configuration induced in the reaction can be readily predicted on the basis of the C2-symmetric structure of the complexes as well as the simple structure of the substrate complex. The aqua complex prepared from Ni(II) or Zn(II) perchlorate results in highly effective chiral amplification in the Diels−Alder reaction. Use of the DBFOX/Ph ligand of a ...

Cationic aqua complexes of a trans-chelating tridentate ligand, (R, R) -4, 6-dibenzofurandiyl-2, 2' -bis (4-phenyloxazoline), and transition metal (II) perchlorates are effective catalysts in the cyclopentadiene Diels-Alder reactions, nitrone cycloadditions, and diazomethane cycloadditions with 3-alkenoyl- 2-oxazolidinones to show excellent enantioselectivities. The active catalyst complex prepared from nickel (II) perchlorate hexahydrate has an octahedral structure with three aqua ligands, and it can be isolated and stored for months without loss of catalytic activity. The aqua complex prepared from Ni (II) or Zn (II) perchlorate results in highly effective chiral amplification in the Diels-Alder reaction. Two mechanisms for amplification are involved for this remarkable chiral amplification : (1) precipitation of S4-symmetric meso-2 : 1 complex between DBFOX/Ph and Ni (II) ion, and (2) associative formation of 1 : 1 heterochiral complexes by the aid of hydrogen bonds based on aqua ligands to produce stable meso oligomers.

A new synthetic procedure for the aminochlorination of olefins for the synthesis of vicinal chloroamine derivatives using a combination of Chloramine-T and carbon dioxide is described. The method can be applied to a variety of olefins, including an electron-sufficient olefin and a conjugated diene.

[reaction: see text] Pyrrolidines and bicyclic pyrrolidine derivatives can effectively be synthesized from gamma-iodoolefins using commercially available chloramine-T (CT) as a nitrogen source. The cyclization proceeds with high stereoselectivity via a cyclic iodonium intermediate.

A new procedure for the synthesis of silyl enol ethers from S-α-silylbenzyl thioesters without need for either bases or catalysts via CC bond formation is described. Solutions of S-α-silylbenzyl thioesters were simply heated at 180°C for 24 h in a sealed tube to give silyl enol ethers in good yields with high stereoselectivity. Cyclization of the dipoles generated by thermal rearrangement of the silyl group and elimination of sulfur afforded silyl enol ethers.

A new synthetic method for chiral oxazolines has been developed by N1 unit transfer to olefins using a chiral nitridomanganese complex. When trans -disubstituted styrenes were treated with chiral complex 1 in the presence of an acid chloride, oxazolines were obtained with high enantioselectivities (up to 92% ee). Furthermore, the produced oxazolines could be easily converted into β-amino alcohols, which are ephedrine derivatives.

Novel fluorophores, 1-aryl-3,4-diphenylpyrido[1,2-a]benzimidazoles were synthesized. They emit intense blue to green fluorescence in solution (Φ: ca. 0.7) and show weak negative solvatofluorochromism by about 10 nm which was caused by the combination of π–π* and n–π* transitions. In the powdered form, they emit intense fluorescence whose intensity is at least two times stronger than that of Alq3.

Cascade reactions of 4-alkenyl iodides, involving a carbonylation-cyclization-carbonylation sequence, were accomplished by a hnu/Pd system. The stereochemical outcomes suggest that radical carbonylation and subsequent acyl radical cyclization may be involved in this reaction.

Chiral nitridomanganese complex 1 was found to be a highly potential N1 unit source for the asymmetric synthesis of aziridines and 2-oxazolines from olefins such as styrene and its derivatives. When sulfonyl chlorides were employed as activators of the complex in the presence of pyridine, pyridine N-oxide, and a silver salt, the reaction of olefins with complex 1 proceeded smoothly to afford the N-sulfonylated aziridines. The aziridination of styrene derivatives with complex 1 using 2-trimethylsilylethanesulfonyl chloride (SESCl) gave the N-SES-aziridines, which were easily converted into chiral N-unsubstituted aziridines. It was found that the reaction was applicable to the asymmetric synthesis of 2-oxazolines from olefins when acyl chlorides were employed as activators. Complex 1 provided an effective asymmetric environment for trans-disubstituted styrenes in the reaction (up to 92% ee). This is the first example of a direct asymmetric synthesis of 2-oxazolines from olefins. Additional experiments, conducted during the course of this investigation, suggest that the isomerization of the N-acylaziridine intermediate is involved in this reaction.

Pyrrolidines and bicyclic pyrrolidine derivatives can effectively be synthesized from γ-iodoolefins using commercially available chloramine-T (CT) as a nitrogen source. The cyclization proceeds with high stereoselectivity via a cyclic iodonium intermediate.

A new and simple method for the synthesis of oxazolines from readily accessible olefins and amides using tert-butyl hypoiodite is described; aromatic/aliphatic olefins and amides can be used in the reaction to give a variety of oxazolines.

A new protocol for the cyclization of N-alkenylamides using chloramine-T and iodine is described. When N-alkenylsulfonamides are treated with chloramine-T and iodine, three- to six-membered N-heterocycles are obtained with complete stereoselectivity. The method is compatible with the cyclization of the allylbenzamide or allylbenzthioamide to afford an oxazoline or thiazoline derivative, respectively. Mechanistic studies indicate that the chloramine-T/I2 system functions as an effective iodonium species.

Ring-opening reactions of N-tosylaziridines with water-soluble nucleophiles proceeded in a silica−water reaction medium. The system is applicable to a ring expansion of an aziridine with potassium thiocyanate, leading to a thiazolidine derivative.

[reaction: see text] A new method for the generation of 1,5-dipoles from o-stannylmethylated thioanilides via 1,6-stannatropy under neutral conditions was developed. Cyclization of the 1,5-dipoles afforded indole derivatives effectively. The strategy has potential for application to the generation of alternative 1,5-dipoles from o-stannylmethylated aryl isothiocyanates leading to indole derivatives having a stannylthio group that was readily converted to other functional groups.

tert-Butyl hypoiodite (t-BuOI) was found to be a powerful reagent for synthesis of aziridines from olefins and sulfonamides. The aziridination of olefins was achieved by using sulfonamides with t-BuOI. Our preliminary findings represent the example of metal-free aziridination of olefins with readily accessible sulfonamides as a nitrogen source.

[Structure: see text] tert-Butyl hypoiodite (t-BuOI) was found to be a powerful reagent for the cyclization of N-alkenylamides leading to a variety of N-heterocycles under extremely mild conditions. When N-alkenylsulfonamides were employed in the reaction, three- to six-membered saturated N-heterocycles were obtained in good to excellent yields with complete stereoselectivity. The method was applicable to the cyclization of alkenylbenzamide derivatives to afford N-, O- or N-, S-heterocycles.

A facile method for the synthesis of thiophene derivatives via the reaction of readily accessible dienol silyl ethers with elemental sulfur is described. Dienol silyl ethers and elemental sulfur, when heated at 180 °C in the presence of MS4A, provided 3-siloxythiophene derivatives in yields up to 98%. In this reaction, thiophene derivatives might be formed through 1,2-dithiines and eight-membered cyclic tetrasulfides.

High diastereo- and enantioselectivities were obtained for the asymmetric 1,3-dipolar cycloaddition of azomethine ylides generated from N-alkylideneglycine esters with dipolarophiles using chiral phosphine-copper complexes as catalysts. Whereas the cycloaddition of azomethine ylides catalyzed by metal salts generally afforded endo-adducts as the predominant product, the present method is the first example of an exo-selective cycloaddition. [reaction: see text]

A novel convenient method for the generation of thiocarbonyl ylides from readily accessible starting materials and the first synthetic application of in situ generated ylides in the synthesis of silyl enol and dienol ethers, accompanied by C-C bond formation, is described. Under completely neutral conditions without any catalyst or additive, thermal reactions of S-alpha-silylbenzyl thioesters in sealed tubes at 180 degrees C provided silyl enol and dienol ethers in good to excellent yields with high stereoselectivities. This procedure consists of a multistep reaction in a one-pot process, i.e., 1,4-silatropy of S-alpha-silylbenzyl thioesters to give thiocarbonyl ylides, 1,3-electrocyclization of the ylides to give thiiranes, and the extrusion of sulfur from thiiranes to give silyl enol and dienol ethers.

Dibenzofuran-4,6-dicarboxylic acid (R,R)-Dibenzofuran-4,6-dicarboxylic acid bis(2-hydroxy-1-phenylethyl) amide (R,R)-4,6-Dibenzofurandiyl-2,2′(4-phenyloxazoline) Sec-Butyl lithium Dimethylformamide Diethylaminosulfur trifluoride Carbon dioxide Keywords: tridentate ligand; dibenzofurans; dicarbonyl chlorides; oxazoles; waste disposal; diaminosulfur trifluoride; Diels-Alder reactions; nitrone cycloadditions; chiral Lewis acid

Cascade reactions of 4-alkenyl iodides, involving a carbonylation-cyclization-carbonylation sequence, were accomplished by a hnu/Pd system. The stereochemical outcomes suggest that radical carbonylation and subsequent acyl radical cyclization may be involved in this reaction.

Chiral nitridomanganese complex 1 was found to be a highly potential N1 unit source for the asymmetric synthesis of aziridines and 2-oxazolines from olefins such as styrene and its derivatives. When sulfonyl chlorides were employed as activators of the complex in the presence of pyridine, pyridine N-oxide, and a silver salt, the reaction of olefins with complex 1 proceeded smoothly to afford the N-sulfonylated aziridines. The aziridination of styrene derivatives with complex 1 using 2-trimethylsilylethanesulfonyl chloride (SESCl) gave the N-SES-aziridines, which were easily converted into chiral N-unsubstituted aziridines. It was found that the reaction was applicable to the asymmetric synthesis of 2-oxazolines from olefins when acyl chlorides were employed as activators. Complex 1 provided an effective asymmetric environment for trans-disubstituted styrenes in the reaction (up to 92% ee). This is the first example of a direct asymmetric synthesis of 2-oxazolines from olefins. Additional experiments, conducted during the course of this investigation, suggest that the isomerization of the N-acylaziridine intermediate is involved in this reaction.

The solution-phase synthesis of organic compounds as mixtures rather than in individual pure form offers efficiency advantages that are negated by the difficulty in separating and identifying the components of the final mixture. Here, a strategy for mixture synthesis that addresses these separation and identification problems is presented. A series of organic substrates was tagged with a series of fluorous tags of increasing fluorine content. The compounds were then mixed, and multistep reactions were conducted to make enantiomers or analogs of the natural product mappicine. The resulting tagged products were then demixed by fluorous chromatography (eluting in order of increasing fluorine content) to provide the individual pure components of the mixture, which were detagged to release the final products.

Novel fluorophores, 1-aryl-3,4-diphenylpyrido[1,2-a]benzimidazoles were synthesized. They emit intense blue to green fluorescence in solution (Φ: ca. 0.7) and show weak negative solvatofluorochromism by about 10 nm which was caused by the combination of π–π* and n–π* transitions. In the powdered form, they emit intense fluorescence whose intensity is at least two times stronger than that of Alq3.