A practical synthesis of 2-(N-substituted)-aminobenzimidazoles utilizing CuCl-promoted intramolecular cyclization of N-(2-aminoaryl)thioureas

A practical protocol for synthesis of 2-(N-substituted)-aminobenzimidazoles was developed. N-(2-Aminoaryl)thioureas undergo a CuCl-promoted intramolecular cyclization to give the corresponding 2-(N-substituted amino)benzimidazoles in good to excellent isolated yields.     

A facile synthesis of 2-(N-alkylamino)-pyrimidin-4-one derivatives

Substituted 2-(N-alkylamino)-pyrimidin-4-ones were synthesized from N-alkyl β-amino acid esters starting with guanidinylation using Pbf-activated thiourea. The six-membered pyrimidinones were obtained in good yields via intramolecular cyclization during TFA cleavage of the Pbf protecting group.     

A simple and convenient synthesis of 2-(perfluoroalkyl)-4H-chromenes from salicyl N-tosylimines or salicylaldehydes and methyl 2-perfluoroalkynoates

Et₃N-catalyzed reactions of salicyl N-tosylimines or salicylaldehydes with methyl 2-perfluoroalkynoates proceed smoothly at room temperature in dichloromethane (DCM) or dimethyl sulfoxide (DMSO) to give the corresponding fluorinated chromenes in good to excellent yields with high regioselectivity.     

Efficient enantioselective synthesis of orthogonally protected (R)-α-alkylserines compatible with the solid phase peptide synthesis

The Schöllkopf methodology for the asymmetric synthesis of α-amino acids, which was previously not applicable to the construction of quaternary α-amino acids, has been rendered not only suitable but also practical for this purpose and applied to a highly efficient enantioselective synthesis of orthogonally protected (R)-α-alkylserines suitable for the solid phase synthesis.     

PTSA catalyzed straightforward protocol for the synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles in PEG

An efficient PTSA catalyzed synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles has been described using S-ethylated-N-acylthioureas as substrates and polyethylene glycol as solvent.     

N-(Diethoxyphosphoryl)-O-benzylhydroxylamine—a convenient substrate for the synthesis of N-substituted O-benzylhydroxylamines

Easily available N-(diethoxyphosphoryl)-O-benzylhydroxylamine was shown to be convenient, orthogonally protected substrate for regioselective N-alkylation by means of diverse halides under basic conditions (sodium hydride/tetrabutylammonium bromide). An efficient procedure for dephosphorylation of N-substituted N-(diethoxyphosphoryl)-O-benzylhydroxylamine to provide N-substituted O-benzylhydroxylamines was also established.     

Syntheses and structures of iron carbonyl complexes derived from N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine and N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine

The reaction of N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine (1) with Fe₂(CO)₉ in refluxing acetonitrile yielded di-(μ₃-thia)nonacarbonyltriiron (2), μ-[N-(5-methyl-2-thienylmethyl)-η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido]hexacarbonyldiiron (3), and N-(5-methyl-2-thienylmethylidene)amine (4). If the reaction was carried out at 45 °C, di-μ-[N-(5-methyl-2-thienylmethylidene)-η¹(N);η¹(S)-2-thiolethylamino]-μ-carbonyl-tetracarbonyldiiron (5) and trace amount of 4 were obtained. Stirring 5 in refluxing acetonitrile led to the thermal decomposition of 5, and ligand 1 was recovered quantitatively. However, in the presence of excess amount of Fe₂(CO)₉ in refluxing acetonitrile, complex 5 was converted into 2-4. On the other hand, the reaction of N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine (6) with Fe₂(CO)₉ in refluxing acetonitrile produced 2, μ-[N-(6-methyl-2-pyridylmethyl)-η¹ (N_py);η¹:η¹(N); η¹:η¹(S)-2-thiolatoethylamido]pentacarbonyldiiron (7), and μ-[N-(6-methyl-2-pyridylmethylidene)-η²(C,N);η¹:η¹(S)-2- thiolethylamino]hexacarbonyldiiron (8). Reactions of both complex 7 and 8 with NOBF₄ gave μ-[(6-methyl-2-pyridylmethyl)-η¹(N_py);η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido](acetonitrile)tricarbonylnitrosyldiiron (9). These reaction products were well characterized spectrally. The molecular structures of complexes 3, 7-9 have been determined by means of X-ray diffraction. Intramolecular 1,5-hydrogen shift from the thiol to the methine carbon was observed in complexes 3, 7, and 9.     

A facile synthesis of 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones by the reaction of 1,1-dimethylethyl 2-isocyanobenzoates with N,N-dialkyliminium iodides

A convenient synthetic approach to 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones has been developed. Thus, 1,1-dimethylethyl 2-isocyanobenzoates, which can be readily prepared from 2-nitrobenzoic acids by a simple four-step sequence, react with N,N-dialkyliminium iodides without using any catalysts under mild conditions to give the desired products in generally fair-to-good yields.     

An efficient synthesis of optically pure α-alkyl-β-azido- and α-alkyl-β-aminoalanines via ring opening of 3-amino-3-alkyl-2-oxetanones

N-Boc-α-alkylserine β-lactones on ring opening with sodium azide provide N-Boc-α-alkyl-β-azidoalanines, as N-protected amino acids are suitable for direct incorporation into peptides. N-Boc-α-alkyl-β-azidoalanines can be transformed by catalytic hydrogenation into the corresponding N-Boc-α-alkyl-β-aminoalanines.     

Dimolybdenum complexes containing anions of N,N′-bis(pyrimidine-2-yl)formamidine and N-(2-pyrimidinyl)formamide

The reactions of Mo₂(O₂CCH₃)₄ with different equivalents of N,N′-bis(pyrimidine-2-yl)formamidine (HL1) and N-(2-pyrimidinyl)formamide (HL2) afforded dimolybdenum complexes of the types Mo₂(O₂CCH₃)(L1)₂(L2) (1) trans-Mo₂(L1)₂(L2)₂ (2) cis-Mo₂(L1)₂(L2)₂ (3) and Mo₂(L2)₄ (4). Their UV–Vis and NMR spectra have been recorded and their structures determined by X-ray crystallography. Complexes 2 and 3 establish the first pair of trans and cis forms of dimolybdenum complexes containing formamidinate ligands. The L1 ligands in 1–3 are bridged to the metal centers through two central amine nitrogen atoms, while the L2 ligands in 1–4 are bridged to the metal centers via one pyrimidyl nitrogen atom and the amine nitrogen atom. The Mo–Mo distances of complexes 1 [2.0951(17) Å], 2 [2.103(1) Å] and 3 [2.1017(3) Å], which contain both Mo?N and Mo?O axial interactions, are slightly longer than those of complex 4 [2.0826(12)–2.0866(10) Å] which has only Mo?O interactions.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

A convenient and new approach to the synthesis of ω-heterocyclic amino acids from carboxy lactams through ring-chain-transformation. Part 2: Synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid

Making use of amide activation, a convenient and short path synthesis of optically pure ω-heterocyclic-β-amino acids has been achieved from (1R,3R)- and (1R,3S)-5-oxo-1-(1-phenyl-ethyl)-pyrrolidine-3-carboxylic acid methyl ester. The key step of the synthesis involves a regiospecific ring-chain-transformation of the enaminones when subjected to 1,2-binucleophilic attacks. The method is illustrated by the synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid.     

Mild, convenient and versatile Cu-mediated synthesis of N-aryl-2-imidazolidinones

A mild, general, convenient and practical methodology for the selective copper-mediated mono N-arylation of unprotected 2-imidazolidinone was developed. Strong electron-donating groups and free hydroxy and amino groups on the aryl iodide substrates were well tolerated. The use of n-butanol as the solvent for the copper-catalysed mono-arylation of 2-imidazolidinone is unprecedented.     

Stereoselective synthesis of cis and trans-fused 3a-aryloctahydroindoles using cyclization of N-vinylic α-(methylthio)acetamides: synthesis of (−)-mesembrane

Treatment of N-(2-arylcyclohex-1-en-1-yl)-α-(methylthio)acetamides with N-chlorosuccinimide (NCS) gave 3a-aryl-2,3,3a,4,5,6-hexahydro-3-(methylthio)indol-2-ones. Desulfurization of the cyclization products followed by a catalytic hydrogenation of the resulting hexahydroindol-2-ones gave predominantly or exclusively trans-fused octahydroindol-2-ones. On the other hand, reduction of the desulfurization products with Et₃SiH in CF₃CO₂H exclusively provided cis-fused octahydroindol-2-ones. A chiral induction of N-[2-(3,4-dimethoxy)phenylcyclohex-1-en-1-yl]-α-(methylthio)acetamide having an (R)-1-(1-naphthyl)ethyl group on the nitrogen atom led to the synthesis of (−)-mesembrane and (−)-trans-mesembrane.     

Stereoselective synthesis of (Z)-β-fluoro-α,β-unsaturated esters from (Z)-2-fluoro-1-alkenyliodonium salts

(Z)-β-Fluoro-α,β-unsaturated esters were stereoselectively synthesized from (Z)-2-fluoro-1-alkenyliodonium salts by the Pd-catalyzed methoxycarbonylation reaction. The reaction proceeded at room temperature and various functional groups on the substrate can tolerate the reaction conditions.     

A versatile synthesis of poly(lauryl acrylate) using N-(n-octyl)-2-pyridylmethanimine in copper mediated living radical polymerization

A facile synthesis of poly(lauryl acrylate) has been achieved by atom transfer radical polymerization using benzyl-2-bromoisobutyrate, copper (I) bromide, and N-(n-octyl)-2-pyridylmethanimine (OPMI). The latter was of great interest as its synthesis was very easy to carry out and as it allowed the reaction mixture to be homogeneous, which was essential for the control of the reaction. The polymerization was controlled under these conditions and was optimized with the addition of copper (II) bromide as deactivator. We proved that the synthesis of poly(lauryl acrylates) with well defined molecular weights and narrow polydispersities was possible using a ligand which does not require difficult synthesis and purification. We also showed the ability of pyridylmethanimine ligands to control ATRP of an acrylate derivative. Best results were obtained at 130 °C in xylene for [Initiator]₀/[Cu(I)Br]₀/[Cu(II)Br₂]₀/[OPMI]/[lauryl acrylate] equal to 1/1/0.05/2.2/181, respectively (M_n = 19,942, DPI = 1.28).     

A general and convenient synthesis of N-aryl piperazines

A general and convenient synthesis of N-aryl piperazines from bis(2-chloroethyl)amine hydrochloride and a broad range of anilines in diethylene glycol monomethyl ether is described.     

A convenient transformation of α-alkylserines into α-halogenomethyl-α-alkylglycines

An efficient and facile synthesis of N-Boc-α-chloromethyl- and α-bromomethyl-α-alkylglycines is reported that involves cyclization of N-Boc-α-alkylserines to the corresponding β-lactones under Mitsunobu reaction conditions, followed by ring opening with anhydrous MgCl₂ or MgBr₂.     

Synthesis of the end-capped 5-(N,N-dimethylamino)naphthyl-1-ethynyl derivatives and their 1,4-di[5-(N,N-dimethylamino)naphthyl]-1,3-butadiynes: anti rotamer structure

A new family of the end-capped 5-(N,N-dimethylamino)naphthylethynyl chains were synthesized, as terminal acetylenes or poly(yne) structures, by heterocoupling between 5-iodo-N,N-dimethylnaphthalen-1-amine and 2-methyl-3-butyn-2-ol or 4-(5-iodo-1-naphthyl)-2-methyl-3-butyn-2-ol, catalyzed by the palladium-copper system. Catalytic homocoupling of the terminal acetylenes, affords to 1,4-dinaphthyl-1,3-butadiyne nanostructures. X-ray diffraction analysis of 1,4-di(α-naphthyl)-1,3-butadiyne shows that the naphthalene rings are in the anti configuration along the acetylene axis. All the conjugated compounds show an important fluorescent emission radiation.     

Acylation of α-(N-carbamoyl)alkylcuprates and alkyl- or aryl(halo)cuprates

α-(N-Carbamoyl)alkylcuprates [R₂CuLi·LiX or RCuXLi (X=CN, Cl)] when prepared from THF soluble CuX·2LiCl (X=Cl, CN) undergo a reliable and generally high yield reaction with aroyl, alkanoyl, and alkenoyl chlorides to provide a rapid and efficient synthesis of α-carbamoyl ketones. Cuprates prepared from acyclic, cyclic, and a functionalized carbamate can be utilized. Although yields are a function of cuprate reagent and substrate structure, nearly quantitative yields can be obtained with reagents generated from 2RLi+CuCN·2LiCl. The use of reagents generated from CuCl·2LiCl are more efficient in the α-(N-carbamoyl)alkyl ligand, although yields are slightly lower. Acylation of alkyl(chloro)cuprates generated from one equivalent of CuCl·2LiCl and organolithium or Grignard reagents provides an efficient and high yield procedure for ketone synthesis.