Expedient one-pot synthesis of N-aryliminoethers via mild electrophilic activation of secondary amides

Abstract  

The direct transformation of various secondary amides into N-aryliminoethers via mild electrophilic activation with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine is described. Low temperature amide activation followed by warming to 0 °C and subsequent treatment with phenols provides the desired products with short overall reaction times and moderate to high reaction yields.     

Molecular oxygen dianions trapped in lithium cluster cages

In an important recent report, Coles and Hitchcock (Chem. Commun. 2005, 3165) have synthesized a unique compound of the form Li9O2(hpp)7, with an O2 unit encapsulated in the Li cluster. The group hpp is the bicyclic guanidinate 1,3,4,6,7,8-hexahydropyrimido[1,2-a]pyrimidinate. Coles and Hitchcock raise the interesting possibility that the trapped species is the O2 dianion. We have theoretically investigated (with full geometry optimization) the structural, vibrational, and electronic properties of this fascinating system with 165 atoms. Every indication supports the qualitative conclusion that this system is best represented as an O2 dianion embedded in a Li cluster. Several smaller model systems, including replacement of the hpp ligands by Cl atoms, are also examined and provide some interesting comparisons.     

Efficient preparation of chiral diamines via Red-Al reduction of N-Boc-protected amino acid-derived secondary amides

Conditions have been developed for the selective reduction of N-Boc-protected amino acid-derived secondary amides, avoiding the formation of overreduction and cyclic urea byproducts. The method is showcased by the efficient formal synthesis of NK-1 antagonist LY303870.     

Anionic polymerization of methyl methacrylate by initiating systems based on lithium amides of various secondary amines

The anionic polymerization of methyl methacrylate in toluene at −78 °C with lithium amides of various secondary amines (diisopropylamine, N‐isopropylaniline, N‐n‐butylaniline, indoline, and N‐ethyl‐o‐toluidine) as initiators was studied. The tacticity of the resulting poly(methyl methacrylate)s (PMMAs) was dependent on the kind of secondary amine, and highly isotactic PMMAs (91–93% mm) were obtained when lithium amides of N‐isopropylaniline and N‐n‐butylaniline were employed. The isotacticity of the PMMAs further increased up to 98% mm with initiating systems composed of the lithium amides, n‐butyllithium, and transition‐metal halides (WCl₆, MoCl₅, and NbCl₅). © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4405–4411, 2005     

Hydroamination of cinnamyl alcohol using lithium amides

Hydroamination of cinnamyl alcohol is possible by reaction with lithium amides derived from primary or cyclic secondary amines.     

Acetylenic amides. 2. The generation and reactions of dianions derived from 2-propynamides

The dianion of N-benzyl-2-propynamide can be generated by the treatment of 4 with two equivalents of LDA at ?65° or ethylmagnesium bromide at ?20°. The trilithio species 6 is readily formed using 3 equivalents of LDA. Reaction of 5 with aldehydes or ketones produce hydroxypropynamides 9 in good yields. Silation of 5a with chlorotrimethylsilane produces N-benzyl-3-trimethylsilyl-2-propynamide ( 13 ) in high yield. Reduction of 9 furnishes either fully saturated amides 15 or partially reduced cis-olefins 16 or 18 . Compounds 16 , on heating, rearrange to 4-ketoamides 17 . Carboxylation of 5a with carbon dioxide produces 3-benzyl-2,4-dioxo-5-oxazidinylacetic acid ( 11 ). Warming 11 in dimethyl sulfoxide results in the loss of carbon dioxide and the formation of N-benzylpyruvamide ( 21 ).     

Multiple lithium exchange under lithium cationization of cyclodextrins

Multiple lithium exchange is observed during electrospray ionization of alpha-, beta- and gamma-cyclodextrins from aqueous methanolic solution containing LiOH. Apart from [M + Li](+) and [M + nLi - (n - 1)H](+) ions, abundant multiply lithiated doubly charged ions corresponding to [M + nLi - (n - 2)H](2+) ions were observed. At least six lithium exchanges in alpha-cyclodextrin, seven in beta-cyclodextrin and eight in gamma-cyclodextrin were noted. The propensity of multiply lithiated doubly charged ions is much less in the open-ended maltoheptaose. It appears that during droplet or cluster formation and subsequent desolvation, LiOH trapped in the cavity of cyclodextrin reacts to form multiply lithiated ions. The singly charged [M + Li](+) and doubly charged [M + 2Li](2+) ions fragment by glycosidic cleavages, giving B series of ions, whereas the multiply lithiated ions fragment by cross ring cleavages ((2, 4)A or (O, 2)X) followed by glycosidic cleavage. From the tandem mass spectra, it appears that a maximum of two lithium exchanges occur in one sugar unit in these cyclodextrins.     

Enantioselective conjugate addition of a lithium ester enolate catalyzed by chiral lithium amides

Mixed aggregates of chiral lithium amide and lithium ester enolate have been employed in the enantioselective conjugate addition on alpha,beta-unsaturated esters. Michael adducts were obtained in ee's up to 76% combining a lithium enolate and a chiral 3-aminopyrrolidine lithium amide. The sense of the induction was found to be determined by both the relative configuration of the stereogenic centers borne by the amide and the solvent in which the reaction was conducted. [reaction: see text]     

Enamines from terminal epoxides and hindered lithium amides

A new reactivity mode of lithium amides with epoxides leads to hindered enamines. The reaction of some of these enamines with unactivated primary and secondary alkyl halides is described, which expands the range of electrophiles that one can use in the synthesis of mono-alkylated aldehydes.     

New Heck coupling strategies for the arylation of secondary and tertiary amides via palladium-catalyzed intramolecular cyclization

A new synthetic protocol has been developed for the arylation of secondary and N-alkylated amide Heck precursors by the implementation of the palladium-catalyzed intramolecular Heck reaction strategies.     

Stereoselective synthesis of pinane-based β- and γ-amino acids via conjugate addition of lithium amides and nitromethane

Michael addition of dibenzylamine to (?)- and (+)-tert-butyl myrtenate, (?)-2 and (+)-2, derived from (?)- and (+)-myrtenal, furnished monoterpene-based β-amino acid derivatives in highly stereospecific reactions. The resultant amino esters (?)-3 and (+)-3 were transformed to unsubstituted, mono- and disubstituted and Fmoc-protected amino acids (?)-6-11 and (+)-6-11, which are promising building blocks for the synthesis of β-peptides and 1,3-heterocycles. The microwave-assisted conjugate addition of nitromethane to α,β-unsaturated esters (?)-12 and (+)-12 likewise resulted in nitro esters (?)-13 and (+)-13 in highly stereospecific reactions. Compounds (?)-13 and (+)-13 were successfully transformed into γ-amino acids (?)-16 and (+)-16 in two steps.     

Synthesis of aminopyridines from 2-fluoropyridine and lithium amides

Lithium amides promote the amination of 2-fluoropyridine under mild reaction conditions, providing 2-aminopyridines in good yields and purity. Treatment of 2-fluoropyridine with 1 equiv of lithium amide at room temperature affords complete conversion after 2 h. To our knowledge, this is the first study of lithium amide-promoted amination of fluoropyridines that are not further activated by electron-withdrawing groups.     

Electrochemical insertion of lithium in thin tin films

The behavior of model electrodes made of lithiated thin films of tin during their cycling is studied. The electrodes show high values of useful specific capacity for the extension of several tens of operation cycles. Dependences of the diffusion coefficient for lithium into tin on the initial electrode potential, temperature, and direction of the electrode process are determined by a chronopotentiometric method. The dependences have a complex character, which is connected with the phase composition of the lithium-tin alloy.     

Synthesis of beta,gamma-unsaturated lactams via a magnesium iodide promoted ring expansion of secondary methylenecyclopropyl amides

A novel and efficient route to exo-beta,gamma-unsaturated lactams from substituted and non-substituted secondary methylenecyclopropyl amides is reported. Subsequent modification of the resulting exo-beta,gamma-unsaturated lactams provides access to several pharmaceutically relevant scaffolds. [reaction: see text].     

Nitration of N-Chloromethyl-substituted secondary amides by nitronium tetrafluoborate

Conclusions When treated with nitronium tetrafluoborate the N-chloromethyi derivatives of the secondary amides of the carbonic, sulfonic, and nitric acids form either the corresponding N-alkyl-N-nitramides, methylenebis-N-alkylamides, or their mixture.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1182–1184, May, 1982.