Reaction of allenyl esters with sodium azide: an efficient synthesis of e-vinyl azides and polysubstituted pyrroles

The nucleophilic addition of sodium azide to 1,2-allenyl esters can generate vinyl azides in excellent yields with excellent regio- and stereoselectivities. Moreover, pyrroles are synthesized using 1-allyllic 1,2-allenyl esters as substrates in t-BuOH at 65 degrees C. The sequential reaction for pyrroles is developed on the basis of a novel domino process involving nucleophilic addition, cycloaddition, denitrogenation, and aromatization.     

Synthesis of polysubstituted N-H pyrroles from vinyl azides and 1,3-dicarbonyl compounds

Two synthetic methods for tetra- and trisubstituted N-H pyrroles are presented: (i) the thermal pyrrole formation by the reaction of vinyl azides with 1,3-dicarbonyl compounds via the 1,2-addition of 1,3-dicarbonyl compounds to 2H-azirine intermediates generated in situ from vinyl azides; (ii) the Cu(II)-catalyzed synthesis of pyrroles from alpha-ethoxycarbonyl vinyl azides and ethyl acetoacetate through the 1,4-addition reaction of the acetoacetate to the vinyl azides. By applying these two methods, regioisomeric pyrroles can be prepared selectively starting from the same vinyl azides.     

Iodine-mediated electrophilic cyclization of 2-alkynyl-1-methylene azide aromatics leading to highly substituted isoquinolines and its application to the synthesis of norchelerythrine

The reaction of 2-alkynyl-1-methylene azide aromatics 1 with iodine and/or other iodium donors, such as the Barluenga reagent (Py2IBF4/HBF4) and NIS, gave highly substituted cyclization products, namely, the 1,3-disubstituted 4-iodoisoquinolines 2, in good to high yields. Not only simple 2-alkynyl benzyl azides 1a-j and their substituted analogues 1k-u and 6 but also heteroaromatic analogues, including pyridine 8, pyrroles 10a-c, furane 10d, and thiophenes 10e-g, gave the corresponding isoquinoline derivatives in excellent to allowable yields. Electron-donating and electron-accepting substituents on the aromatic ring were equally tolerated, and either acidic or basic (or even neutral) reaction conditions, depending on the reactivity of the substrate, could be applied to smoothly convert the azide starting materials into the desired isoquinoline products in moderate to good yields. Limits were found only in connection with the substituent at the alkyne terminus, where electron-neutral or electron-donating substituents are clearly favored. The iodine-mediated electrophilic cyclization of 1 most probably proceeds through the iodonium ion intermediate 4 followed by nucleophilic cyclization of the azide and subsequent elimination of N2. This new methodology was successfully applied to the short synthesis of norchelerythrine.     

Efficient amidation from carboxylic acids and azides via selenocarboxylates: application to the coupling of amino acids and peptides with azides

A facile one-pot procedure for the coupling of carboxylic acid and azide via selenocarboxylate and selenatriazoline has been developed and successfully applied to the coupling of amino acids and peptides with azides. Selenocarboxylates are readily prepared by the reaction of the activated carboxylic acids with LiAlHSeH under mild conditions. The selenocarboxylates formed in situ are used to react directly with azides to form the corresponding amides via a selenatriazoline intermediate. Excellent yields were obtained for electron-deficient azides, and moderate to good yields were obtained for electron-rich azides. The selenocarboxylate/azide amidation reaction is clean and chemoselective. It provides an attractive alternative method to the conventional acylation of amines when an amide bond needs to be formed without going through an amine intermediate.     

Rapid and facile synthesis of acyl azides from acyl halides using a polymer-supported azide ion under heterogeneous conditions

In this article a rapid and facile method for synthesis of acyl azide is described. The cross-linked poly(N-methyl-4-vinylpyridinium) azide ion, [P₄-VP]N₃ is prepared and used as an efficient polymeric reagent for synthesis of acyl azides from acyl halides at room temperature under heterogeneous conditions. Various benzoyl halides, with electron-withdrawing groups as well as electron-donating groups, were transformed into the corresponding benzoyl azides in high to excellent yields in short reaction times. The acyl azide products were characterized by FT-IR, and some of them were also characterized by ¹H-and/or ¹³C-NMR spectroscopy, and physical properties were compared to literature values of known compounds. The spent polymeric reagents can be regenerated and reused for several times without losing their activity. Relative to the reported methods, the present method has the advantages of operational simplicity, mild reaction conditions, fast reaction rates, simple reaction work-up and lower hazardous and potentially explosive nature. Also the present method is the first procedure for the synthesis of acyl azides from acyl halides by using a polymer-supported azide ion under heterogeneous conditions.     

Gold(I)-catalyzed intramolecular acetylenic Schmidt reaction

Substituted pyrroles were prepared by a gold(I)-catalyzed acetylenic Schmidt reaction of homopropargyl azides. The reaction allows for regiospecific substitution at each position of the pyrrole ring under mild conditions. A mechanism in which azides serve as nucleophiles toward gold(I)-activated alkynes with subsequent gold(I)-aided expulsion of dinitrogen is proposed.     

Rhodium/Silver‐Cocatalyzed Transannulation of N‐Sulfonyl‐1,2,3‐triazoles with Vinyl Azides: Divergent Synthesis of Pyrroles and 2 H‐Pyrazines

The first cyclization reaction between vinyl azides and N‐sulfonyl‐1,2,3‐triazoles is reported. A Rh/Ag binary metal catalyst system proved to be necessary for the successful cyclization. By varying the structure of vinyl azides, such reaction allows the divergent synthesis of pyrroles and 2H‐pyrazines. The cyclization reactions feature a broad substrate scope, good functional group tolerance, high reaction efficiency, and good to high product yields.     

One‐Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides

A general and efficient one‐pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper‐catalyzed alkyne and azide cycloaddition to N‐sulfonyl‐1,2,3‐triazole, rhodium‐catalyzed selective insertion of α‐iminocarbenes onto the C3?H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH₃ or palladium catalyst, in one‐pot. The reaction also showed excellent functional‐group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one‐pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro‐β‐carboline and tryptoline.     

Synthesis of aryl azides and vinyl azides via proline-promoted CuI-catalyzed coupling reactions

The coupling reaction of aryl halides or vinyl iodide with sodium azide under catalysis of CuI/L-proline works at relatively low temperature to provide aryl azides or vinyl azides in good to excellent yields.     

Selective reduction of anomeric azides to amines with tetrathiomolybdate: synthesis of beta-D-glycosylamines

A number of beta-d-glycosyl azide derivatives undergo reduction on treatment with tetrathiomolybdate to produce the corresponding beta-d-glycosylamines exclusively without anomerization under very mild and neutral reaction conditions. Acetyl, allyl, benzoyl, and benzyl protective groups are left untouched under the reaction conditions. An exclusive selectivity in the reduction of anomeric azides is observed, while the C-2 and C-6 azides are left untouched.     

Radical azidonation of aldehydes

Aliphatic and aromatic aldehydes can be converted to acyl azides by treatment with iodine azide at 0-25 degrees C. If the reaction is performed at reflux Curtius rearrangement occurs and carbamoyl azides are obtained in 70-97% yield from the aldehyde. The reaction was shown to have a radical mechanism.     

Mechanism of thio acid/azide amidation

A combined experimental and computational mechanistic study of amide formation from thio acids and azides is described. The data support two distinct mechanistic pathways dependent on the electronic character of the azide component. Relatively electron-rich azides undergo bimolecular coupling with thiocarboxylates via an anion-accelerated [3+2] cycloaddition to give a thiatriazoline. Highly electron-poor azides couple via bimolecular union of the terminal nitrogen of the azide with sulfur of the thiocarboxylate to give a linear adduct. Cyclization of this intermediate gives a thiatriazoline. Decomposition to amide is found to proceed via retro-[3+2] cycloaddition of the neutral thiatriazoline intermediates. Computational analysis (DFT, 6-31+G(d)) identified pathways by which both classes of azide undergo [3+2] cycloaddition with thio acid to give thiatriazoline intermediates, although these paths are higher in energy than the thiocarboxylate amidations. These studies also establish that the reaction profile of electron-poor azides is attributable to a prior capture mechanism followed by intramolecular acylation.     

Reactions of the nitrosonium ion. VII. Syntheses of dihydroisoquinolines and oxazoles from azides in nitrile solvents

N-Alkylnitrilium salts are cleanly produced from alkyl azides by reaction with nitrosonium salts in nitrile solvents. Syntheses of 3,4-dihydroisoquinolines from nitrilium ions formed in this method from 2-phenylethyl azide are described. Oxazoles are readily formed from phenacyl azides by this general method; the advantages of oxazole syntheses through azide nitrosation are discussed.     

Time-resolved resonance Raman observation of the dimerization of didehydroazepines in solution

Time-resolved resonance Raman (TR3) studies of the photochemistry of phenyl azide, 3-hyroxyphenyl azide, 3-methoxyphenyl azide and 3-nitrophenyl azide in acetonitrile:water solutions is reported. After photolysis of these four aryl azides in room temperature solutions, only one species was observed in the TR3 spectra for each azide, respectively at the probe wavelengths employed in the TR3 experiments. The species observed after photolysis of 3-nitrophenyl azide was assigned to 3,3'-dinitroazobenzene, an azo compound formed from the dimerization reaction of triplet 3-nitrophenylnitrene. In contrast, the species observed after photolysis of phenyl azide, 3-hydroxyphenyl azide and 3-methoxyphenyl azide were tentatively assigned to intermediates formed from the dimerization of didehydroazepines that are produced from the ring expansion reaction of the respective singlet arylnitrene. To our knowledge, this is the first time-resolved vibrational spectroscopic observation of the dimerization reaction of didehydroazepines in solution. In addition, these are the first resonance Raman spectra reported for dimers formed from didehydroazepines. We briefly discuss the structures, properties and chemical reactivity of the dimer species observed in the TR3 spectra and possible implications for the photochemistry of aryl azides.     

Glycosylthiomethyl chloride: a new species for S-neoglycoconjugate synthesis. Synthesis of 1-N-glycosylthiomethyl-1,2,3-triazoles

Reaction of O-acyl-protected glycosylthiols with dichloromethane afforded readily glycosylthiomethyl chlorides, which gave with sodium azide the corresponding glycosylthiomethyl azides 17-22. Reaction of these azides with dicyclopentadiene as dipolarophile led to tandem 1,3-dipolar cycloaddition/retro-Diels-Alder reaction furnishing the parent 1-glycosylthiomethyl-1,2,3-triazoles 23-25. Reaction of azides with acetylene derivatives gave directly 1-glycosylthiomethyl-1,2,3-triazoles which are ring-substituted.     

Theoretical investigation of the decomposition of acyl azides: Molecular orbital treatment

The thermal decomposition of formyl, acetyl, and benzoyl azides to the corresponding isocyanate and nitrogen has been treated theoretically using ab initio molecular orbital calculations at the Møller–Plesset type 2 (MP2)(full)/6‐31G* level. The reaction is stimulated by elongation of N N bond and is followed until the formation of the isocyanate and expulsion of nitrogen. The decomposition of formyl azide proved to be a concerted one‐step reaction without the formation of a nitrene intermediate. In contrast, the conversion of both acetyl and benzoyl azides to the corresponding isocyanate and nitrogen is a two‐step reaction, and a nitrene intermediate is formed. One transition state is located and identified during the course of the conversion of formyl azide, but two transition states are located and identified during the course of the conversion of acetyl and benzoyl azides. The thermodynamic functions, ΔE_r and ΔH_r, of the studied reactions are calculated. The results predict that the ease of conversion of the acyl azide to the isocyanate and nitrogen goes in the order: formyl azide > acetyl azide > benzoyl azide. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Azide rearrangements in electron-deficient systems

The azide group has a diverse and extensive role in organic chemistry, reflected in the power of azide anion as a strong nucleophile, the role of organic azides as excellent substrates for cycloaddition reactions, the uses of azides as precursors of amines and nitrenes, and azide rearrangements known as the Curtius and Schmidt reactions. In recent years the scope of the Schmidt reaction has begun to be explored in depth, so that it now represents an important reaction in synthetic chemistry. This tutorial review analyses and summarises key recent developments in the field of Schmidt reactions.     

Introduction of click chemistry to carotenoids

We describe the synthesis of carotenoid derivatives via the azide–alkyne click reaction and optimize the conditions for these sensitive molecules. After finding the mildest conditions possible for the reaction we were able to use the click reaction for the synthesis of PEG–carotenoid conjugates starting from carotenoid pentynoates and PEG azides.     

Triazolines. XXXIII. Nonregiospecific 1,3-cycloaddition of aryl azides to vinylpyridines: A unique route to the synthesis of 2-pyridyl substituted aziridines via unstable 4-pyridyltriazoline intermediates

The 1,3-cycloaddition of aryl azides to the olefinic bonds of 4- and 2-vinylpyridines has been found to yield pyridyl substituted aziridines as the main reaction products with only smaller amounts of the normally expected l-aryl-5-pyridyl-1,2,3-triazolincs. Theoretical and experimental evidence are provided to explain the results: based on the fact that the olefinic bonds in 4- and 2-vinylpyridines are electron-deficient, azide addition can be expected to be not regiospecific. In the bidirectional addition reaction, the HOMO_azide- LUMO_olefin interaction predominates leading to unstable l-aryl-4-pyridyl-1,2,3-triazolines, which, unlike the more stable 5-pyridyl compounds, lose nitrogen under thermal conditions to yield the aziridines. At room temperature, the reactions yield the aziridine along with the l-aryl-4-pyridyltriazole, providing evidence for the formation of the 4-pyridyltriazoline intermediate. Reaction of the vinylpyridines with variously substituted phenyl azides, clearly indicates that the electron donating methyl and methoxy groups on the phenyl azide facilitate reaction, while the electron withdrawing nitro group has a retarding effect. This is consistent with an increase in the HOMO_azide energy and hence in azide reactivity. According to the FMO model, the 1,3-cycloaddition of aryl azides to vinylpyridines appears to be predominantly, but not exclusively, a HOMO_azide-LUMO_olefin interaction and provides a unique route to the synthesis of 2-pyridyl substituted aziridines.     

Rhodium promoted intramolecular [4 + 2] cycloaddition of 2-azidodiene with alkyne: A transition metal catalysis approach to challenging fused bicyclic vinyl azide

Although vinyl azide is an important class of functional group that possesses diverse reactivities and is a convenient synthon for N-heterocycles, cyclic vinyl azide remains underdeveloped due to difficult preparation. This work discloses a rhodium catalyzed intramolecular [4?+?2] cycloaddition reaction that can afford challenging fused bicyclic vinyl azides efficiently in ambient conditions and paves a facile route for the research in the chemistry of cyclic vinyl azides.