Stereospecific 1,4‐Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes

Reported herein is a stereospecific 1,4‐metallate rearrangement for single‐geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N‐oxides, and amides having a single configuration.     

Aryl C-N bond formation by electrophilic amination of diarylcadmium reagents with O-substituted ketoximes

Diorganocadmium reagents cannot react with ketoxime at room temperature. CuCN catalysis allows diarylcadmium reagents to react with ketoxime and to give corresponding arylamines in good to high yields at room temperature. According to the electronic effects of the substituent attached to the aromatic ring, functionalized diarylcadmium reagents show meta-para selectivity in their amination reactions. Also compared to diarylzinc reagents, diarylcadmium reagents react with O-substituted ketoxime under milder reaction conditions and they form corresponding arylamines in higher yields. CuCN cannot help dialkyl-, dicycloalky-, and dibenzylcadmium reagents to react with ketoxime. Our Aryl C-N bond formation method does not include cadmium excretion into the environment.     

Copper-Catalyzed Carbonylative Cross-Coupling of Alkyl Iodides and Amines

A general copper-catalyzed carbonylative cross-coupling between amines and alkyl iodides is reported. Using a simple combination of catalytic amounts of copper(I) chloride and N,N,N’,N”,N”-pentamethyldiethylenetriamine in the presence of sodium hydroxide under carbon monoxide pressure, a broad range of alkyl iodides and amines can be efficiently coupled to the corresponding amides that are obtained in good to excellent yields. Notable features of this process – the first one relying on a base metal catalyst – include the availability and low cost of the catalytic system, its successful use with primary, secondary, tertiary alkyl iodides and all classes of amines – with no or limited competing nucleophilic substitution without CO incorporation – as well as its efficiency with complex alkyl iodides and amines. Mechanistic studies demonstrated that a radical pathway is operative and the key role of CO.     

Alkyl ketoximes as analytical reagents: The chloroform extraction of the alkyl ketoxime complexes of palladium (II) chloride

Summary The syntheses of four symmetrical alkyl ketoxime complexes of palladium(II) chloride and a study of their extraction into chloroform from an aqueous-alcohol solution ofph 3.0 are described.

---

Zusammenfassung Die Synthese vier verschiedener Komplexverbindungen von PdCl₂ mit symmetrischen Alkylketoximen wurde beschrieben. Deren Extrahierbarkeit mit Chloroform aus wäßrig-alkoholischer Lösung beiph 3,0 wurde untersucht.

     

The Mitsunobu Reaction: An Alternative Synthesis of 1-(Primary Alkyl)benzotriazoles

1-(Primary alkyl)benzotriazoles are obtained in convenient yields by treating the corresponding alcohol with triphenylphosphine, N-bromosuccinimide and benzotriazole. Under these conditions, the alcohols gave exclusively the corresponding 1-alkyl-benzotriazoles. Allyl and propargyl alcohols also reacted regiospecifically in a typical Sn2 manner, and no products derived from prototropic rearrangement were found.     

O-Alkylation of furan and thiophene ketoximes in conditions of interphase catalysis in a liquid/solid system

Alkylation of 2 furanyl- and 2-thienylalkyl ketoximes with alkyl, allyl, and propargyl halides in the two phase catalytic system sol. K₂CO₃/C₆H₆/18-crown-6 at room temperature causes the formation of mixtures of E- and Z-isomers of the corresponding O-ethers with yields of 32–74%. Partial E/Z-isomerization takes place during the reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 18–23, January, 1994.     

Ruthenium(II)‐Catalyzed C−H Difluoromethylation of Ketoximes: Tuning the Regioselectivity from the meta to the para Position

A highly para‐selective C_Ar?H difluoromethylation of ketoxime ethers under ruthenium catalysis has been developed. A wide variety of ketoxime ethers are compatible with the reaction, which leads to the corresponding para‐difluoromethylated products in moderate to good yield. A mechanistic study clearly showed that chelation‐assisted cycloruthenation is the key factor in the para selectivity of the difluoromethylation of ketoxime ethers. Density functional theory was used to gain a theoretical understanding of the para selectivity.#     

Synthesis of Alkyl 4-(1-Alkyl-2-aryl-2-oxoethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylates

Zinc enolates derived from 1-aryl-2-bromoalkanones react with alkyl 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylates to give alkyl 4-(1-alkyl-2-aryl-2-oxoethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylates. Reactions of the latter with amines, such as p-toluidine, cyclohexylamine, and piperidine, lead to the corresponding carboxamides.     

Triphenylphosphine-Catalyzed Stereoselective Synthesis of Alkyl 3-(2-Naphthylsulfanyl)-2-propenoate from Alkyl Acetylenecarboxylates and 2-Naphthalenethiol

Protonation of the highly reactive 1:1 intermediates, produced in the reaction between triphenylphosphine and alkyl acetylenecarboxylates by 2-naphthalenethiol, leads to vinyltriphenylphosphonium salts, which undergo an addition–elimination reaction to produce the corresponding S-vinyl thioethers. The NMR spectra indicated that the compounds contained two stereoisomers for each S-vinyl thioether; their ratio was determined on the basis of ¹ H NMR spectra. The reaction is fairly stereoselective.     

(o-Phenylenediamino)borylstannanes: Efficient Reagents for Borylation of Various Alkyl Radical Precursors

(o-Phenylenediamino)borylstannanes were newly synthesized to achieve radical boryl substitutions of a variety of alkyl radical precursors. Dehalogenative, deaminative, decharcogenative, and decarboxylative borylations proceeded in the presence of a radical initiator to give the corresponding organic boron compounds. Radical clock experiments and computational studies have provided insights into the mechanism of the homolytic substitution (S_H2) of the borylstannanes with alkyl radical intermediates. DFT calculation disclosed that the phenylenediamino structure lowered the LUMO level including the vacant p-orbital on the boron atom to enhance the reactivity to alkyl radicals in S_H2. Moreover, C(sp³)-H borylation of THF was accomplished using the triplet state of xanthone.     

A Novel Synthesis of tert- Alkyl Sulfides

tert- Alkyl sulfides are conveniently prepared from α-(1H-benzotriazol-1-yl)alkyl sulfides by displacement of the 1H-benzotriazol-1-yl group with Grignard reagents. The 1-[α-(alkylthio)alkyl]- and 1-[α-(arylthio)alkyl]-1H-benzotriazole intermediates are easily available by several routes: (i) displacement of the halogen from appropriate halides by sodium salts of thiols, (ii) condensation of 1H-benzotriazole and thiols with carbonyl compounds, or (iii) lithiation of N-substituted 1H-benzotriazoles and subsequent treatment with electrophiles.     

Distance‐Dependent Attractive and Repulsive Interactions of Bulky Alkyl Groups

The stabilizing and destabilizing effects of alkyl groups on an aromatic stacking interaction were experimentally measured in solution. The size (Me, Et, iPr, and tBu) and position (meta and para) of the alkyl groups were varied in a molecular balance model system designed to measure the strength of an intramolecular aromatic interaction. Opposite stability trends were observed for alkyl substituents at different positions on the aromatic rings. At the closer meta‐position, smaller groups were stabilizing and larger groups were destabilizing. Conversely, at the farther para‐position, the larger alkyl groups were systematically more stabilizing with the bulky tBu group forming the strongest stabilizing interaction. X‐ray crystal structures showed that the stabilizing interactions of the small meta‐alkyl and large para‐alkyl groups were due to their similar distances and van der Waals contact areas with the edge of opposing aromatic ring.     

Radical Copolymerization Behavior of Alkyl Vinyl Sulfides

In order to clarify the effects of the sulfur atom and the alkyl groups in alkyl vinyl sulfides (RVS) on their reactivities, the radical copolymerizations of eight RVS (M₂) with styrene, methyl methacrylate, and acrylonitrile (Mi) were investigated at 60°C, and the copolymerization parameters were determined. It was found that the Q and e values for RVS were estimated as 0.3 ～ 0.5 and -1.1 ～ -1.7, respectively, from the copolymerizations with styrene, and these values were almost unchanged, regardless of the type of alkyl group in RVS. These results indicated that the electron-sharing, 3d orbital resonance between the growing radical derived from electron-donating RVS monomer and the adjacent sulfur atom was important in the transition state of copolymerizations.

It was also found that the copolymer composition curves in the copolymerizations of RVS varied widely with the comonomers used, and the tendency for alternative copolymerizations increased with an increase in the electron-accepting nature of the comonomers in the order: styrene ≤ methyl methacrylate ≤ acrylonitrile. The selectivities between RVS and alkyl vinyl ether toward various polymer radicals were determined, and they were found to correlate with the e values of the monomers corresponding to the attacking polymer radicals.     

Comparing Cyclophellitol N‐Alkyl and N‐Acyl Cyclophellitol Aziridines as Activity‐Based Glycosidase Probes

The synthesis and evaluation as activity‐based probes (ABPs) of three configurationally distinct, fluorescent N‐alkyl cyclophellitol aziridine isosteres for profiling GH1 β‐glucosidase (GBA), GH27 α‐galactosidase (GLA) and GH29 α‐fucosidase (FUCA) is described. In comparison with the corresponding acyl aziridine ABPs reported previously, the alkyl aziridine ABPs are synthesized easily and are more stable in mild acidic and basic media, and are thus easier to handle. The β‐glucose‐configured alkyl aziridine ABP proves equally effective in labeling GBA as its N‐acyl counterpart, whereas the N‐acyl aziridines targeting GLA and FUCA outperform their N‐alkyl counterparts. Alkyl aziridines can therefore be an attractive alternative in retaining glycosidase ABP design, but in targeting a new retaining glycosidase both N‐alkyl and N‐acyl aziridines are best considered at the onset of a new study.     

An Efficient One-Pot Conversion of Alkyl Bromides Into Imines Via the Staudinger Reaction

A new one-pot procedure for transforming primary alkyl bromides into the corresponding imines via the Staudinger reaction has been developed. Acetonitrile was found to be an excellent solvent for azidation as well as the reaction of organic azide with triphenylphosphine and a carbonyl compound.     

Intramolecular and Intermolecular Schmidt Reactions of Alkyl Azides with Aldehydes

Despite recent advances in the use of alkyl azides in ring expansion reactions of ketones, there has been little work done on the corresponding chemistry of aldehydes. In the present study, the Lewis acid-promoted reactions of alkyl azides with aldehydes were studied in both intermolecular and intramolecular contexts. The intramolecular reactions of azidoalkyl aldehydes in which the azide and carbonyl groups were separated by 2-5 carbons were examined. Although the examples having the shortest tether failed (3-azidopropanals), each of the other systems gave good yields of either NH-substituted lactams (resulting from hydride migration in the initially formed azidohydrin adduct) or formamides (alkyl migration). The product formed was dependent on the chain length of the starting azido aldehyde. The intermolecular reactions were less efficient, requiring TiCl₄ promotion for even moderate yields, and in each case gave mixtures of products resulting from hydride and alkyl migration.     

C-Acylation of rhodanine derivatives

The corresponding 5-aroyl derivatives were obtained by reaction of aromatic carboxylic acid chlorides with 3-ethylrhodanine, and their chemical and physicochemical properties were studied. It is shown that they are completely enolized and stabilized by intramolecular hydrogen bonding; the side-chain carbonyl group undergoes enolization. Methylation with diazomethane gives O-ethers -methoxyarylidene derivatives of 3-ethylrhodanine and S-ethers, which exist as dipolar ions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1491–1495, November, 1972.     

Regioselective Arene Functionalization: Simple Substitution of Carboxylate by Alkyl Groups

Arenes with various alkyl side‐chains were synthesized in high yields and excellent regioselectivities. Starting from toluic and naphthoic acids, the carboxylate group was conveniently substituted by alkyl halides by Birch reduction and subsequent decarbonylation. The method is characterized by inexpensive starting materials and reagents, and methylation of arenes was realized. Besides simple alkyl substituents, the scope of arene functionalization was extended by benzyl, fluoro, amino, and ester groups. We were able to control the alkylation of 1‐naphthoic acid during Birch reduction by the addition of tert‐butanol. This allowed the regioselective synthesis of mono and bis‐substituted naphthalenes from the same starting material.     

Reactions of Alkyl 1H,1H-Perfluoroalkyl Sulfones with Ammonia, Amines, and Hydrazines

2,2,3,3-Tetrafluoropropyl and 2,2,3,3,4,4,5,5-octafluoropentyl alkyl sulfones react with ammonia, primary and secondary amines, hydrazine hydrate, phenylhydrazine, and N,N-dimethylhydrazine to afford, depending on the length of the polyfluoroalkyl chain and reaction conditions, the corresponding enamines, imines, or mono- and bis-hydrazones. The bis-hydrazone obtained from phenylhydrazine and 2,2,3,3,4,4,5,5-octafluoropentyl benzyl sulfone is capable of undergoing further dehydrofluorination to give 5-difluoromethyl- or 5-unsubstituted 1-phenylpyrazole.     

Alkyl radical hyperconjugation in phosphorus compounds

Conclusions The³¹P and¹⁹F chemical shifts in phosphorus compounds of various conformations vary with the number of hydrogen or fluorine atoms attached to the-C atom of the phosphorus atom alkyl or perfluoroalkyl radical. This effect can be explained in terms of alkyl radical hyperconjugation.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2435–2439, September, 1976.