Expeditious approach to 5-aroyl-pyrrolidinones by a novel PIFA-mediated alkyne amidation reaction

[reaction: see text] A novel metal-free approach to the alkyne amidation reaction is presented. The oxidation of properly substituted amides by the hypervalent iodine reagent PIFA provides the generation of a nitrenium ion that can react intramolecularly with a triple bond, leading to the construction of the title compounds.     

Nitrenium ion azaspirocyclization-spirodienone cleavage: a new synthetic strategy for the stereocontrolled preparation of highly substituted lactams and N-hydroxy lactams

[reaction: see text] Although 1,4-cyclohexadienes 2, obtained through the Birch reduction of arenes 1, have found widespread use as masked beta-oxo carbonyl synthons 3, the possibility that 2,5-cyclohexadienones 5 might also be employed to the same end has been overlooked despite their ready availability. As part of our ongoing investigation of the synthetic chemistry of nitrenium ions, we have developed a novel and efficient strategy for the stereoselective preparation of di- and trisubstituted azetidinone, pyrrolidinone, and piperidinone derivatives, which features the ozonolytic cleavage of azaspirocyclic 2,5-cyclohexadienones 12. For example, ozonolysis of spirodienone 12c in CH2Cl2 and reductive workup with dimethyl sulfide generated unstable beta-formyl ester 21, whereas cleavage in MeOH followed by reduction with thiourea led to hemiacetal 22. While both 21 and 22 partially decompose upon exposure to silica gel, they can be trapped in situ, with a variety of weakly basic nucleophiles, to usefully substituted products. The requisite spirodienone substrates are readily accessible through the nitrenium ion cyclization of alkyl omega-arylhydroxamates 10, which proceeds with moderate to high diastereoselectivity.     

Synthesis of spirodienones by intramolecular ipso-cyclization of N-methoxy-(4-halogenophenyl)amides using [hydroxy(tosyloxy)iodo]benzene in trifluoroethanol

Spirodienones bearing the 1-azaspiro[4.5]decane ring system have been synthesized from N-methoxy-(4-halogenophenyl)amides by the intramolecular ipso attack of a nitrenium ion generated with [hydroxy(tosyloxy)iodo]benzene in trifluoroethanol.     

香豆素染料与羟基苯基碘鎓盐光敏引发体系的研究

本文通过吸收光谱、荧光猝灭、光聚合方法对羟基苯基碘盐(HTIB)的光敏引发体系进行了研究,发现具有给电子性的光敏剂香豆素1可以将引发剂羟基苯基碘盐的光响应移到长波区,而引发聚合效率与溶剂的性质有很大的关系.在一般极性溶剂中如DMSO中能有效地引发甲基丙烯酸甲酯(MMA)光聚合,而在电子受体性质的极性溶剂如乙腈中,光聚合反应受阻,这归结于香豆素1与羟基苯基碘盐形成络合物,使得光反应后生成不具活性的产物.该结果对研究其它单苯基碘盐的光敏体系提供了有价值的信息.     

Synthesis of dibenzo[g,p]chrysenes from bis(biaryl)acetylenes via sequential ICl-induced cyclization and Mizoroki-Heck coupling

We report a facile synthesis of functionalized dibenzo[g,p]chrysenes via initial ICl-promoted cyclization of bis(biaryl)acetylenes, followed by the Mizoroki-Heck coupling reaction. This new approach works well for various bis(biaryl)acetylenes to afford dibenzo[g,p]chrysenes bearing various functionalities. With substrates of one special type including 4'-methoxy-2-ethynylbiphenyls, we found that the ICl treatment led to ipso cyclization to give bicyclic spirocyclohexadienones. In the presence of MeOH/H2SO4, these spiroketone products undergo rearrangement to give 9-iodophenanthrenes through a selective 1,2-alkenyl migration. We prepared various 4'-methoxy-2-ethynylbiphenyl compounds to show the generalization of such an ipso cyclization and 1,2-alkenyl shift. This ipso-cyclization approach can be extended to the preparation of dibenzo[g,p]chrysenes.     

Reactivity and selectivity of the N-acetyl-Glu-P-1, N-acetyl-Glu-P-2, N-acetyl-MeIQx,and N-acetyl-IQx nitrenium ions: comparison to carbocyclic N-arylnitrenium ions

The model ultimate carcinogens 1a-d, related to the metabolites of the food-derived carcinogenic heterocyclic amines Glu-P-1, Glu-P-2, MeIQx, and IQx, spontaneously decompose in neutral aqueous solution to generate the heterocyclic nitrenium ions, 2a-d. The less reactive esters 1a and 1b also undergo acid-catalyzed ester hydrolysis to generate the corresponding hydroxamic acids at pH <2, while the more reactive 2c and 2d are prone to rearrangement in nonaqueous solvents. The reactions of the nitrenium ions with AcO(-), HPO(4)(2-), N(3)(-), and 2'-deoxyguanosine (d-G) were characterized in aqueous solution by using a combination of competitive trapping methods and product isolation and identification. The reactions with N(3)(-) and d-G generally follow patterns previously established for carbocyclic nitrenium ions, but the reactions with AcO(-) and HPO(4)(2-) are unusual. Similar reactions have previously only been reported for heterocyclic 1-alkyl-2-imidazolium ions. The N(3)(-)/solvent selectivities of these ions (5.1 x 10(6) M(-1) for 2a, 2.3 x 10(6) M(-1) for 2b, 1.2 x 10(5) M(-1) for 2c, and 5.2 x 10(4) M(-1) for 2d) are comparable to those of highly selective carbocyclic nitrenium ions. If k(az) for these ions is diffusion limited at ca. 5 x 10(9) M(-1) s(-1) the aqueous solution lifetimes of these ions range from 10 micros (2d) to 1 ms (2a). These ions are also highly selective for trapping by d-G, but comparisons to other nitrenium ions show that they are 10- to 50-fold less selective for trapping by d-G than they would be if both the N(3)(-) and d-G reactions were diffusion limited. This is not a consequence of their heterocyclic structures. Several carbocyclic ions show similar behavior. The relatively inefficient trapping of 2c and 2d by d-G may account for the observation of the unusual minor N-2 d-G adduct that is isolated for both of these nitrenium ions, but has not previously been observed for the reactions of other nitrenium ions with monomeric d-G.     

Reduction of digermenes with alkali metals: salts of formula M2[[Ge(H)Ar']2] (m = Li, Na, Or K, Ar' = terphenyl) with three different structures

The reduction of the digermene Ar'(H)GeGe(H)Ar' (Ar' = C6H3-2,6(C6H3-2,6-Pri2)2) with Li, Na, or K afforded [Li(THF)3Et2O][LiAr'(H)GeGe(H)Ar'] (1), Na2Ar'Ge(mu-H)2GeAr' (2), or K2{Ar'(H)GeGe(H)Ar'} (3), which have three different structures. 1 features a planar C(ipso)H)GeGe(H)C(ipso) dianion core with an associated Li+ cation. In contrast, 2 features a unique bridged hydride structure in which two Na+ ions also bridge the germaniums. In 3, the C(ipso)(H)GeGe(H)C(ipso) array has a nonplanar trans bent core with associated K+ ions. There is single Ge-Ge bonding in 1 and 3, but the Ge-Ge bonding in 2 may involve biradical character.     

[Hydroxy(tosyloxy)iodo]benzene-mediated regeneration of carbonyl compounds by cleavage of carbon nitrogen double bonds

[Hydroxy(tosyloxy)iodo]benzene (HTIB)-mediated regeneration of carbonyl compounds from various derivatives of carbonyl compounds of aryl and heteroaryl hydrazines containing adjacent nitrogen atoms is reported. These types of hydrazones cleaved oxidatively, giving back carbonyl compounds with HTIB, while cyclisation occurred with iodobenzene diacetate (IBD).     

Polycondensed nitrogen heterocycles. Part 25. Aminopyrrolo[1,2-f]-phenanthridines by decomposition of 2-(3-azidophenyl)-1-arylpyrroles

Acid catalyzed decomposition of the azido derivatives 4a-c gave rise to amino-hydroxy-phenylpyrroles of type 7 and 8 upon hydrolysis of the intermediate aryl nitrenium ions, together with the hydrogen abstraction compounds of type 3 . The aminopyrrolo[1,2-f]phenanthridines 10, 11 , and 12 were obtained by treatment with TFMSA of the azide 4d in which the ring being attacked was made more nucleophilic by the introduction of the methoxy group.     

Carbazolyl nitrenium ion: electron configuration and antiaromaticity assessed by laser flash photolysis, trapping rate constants, product analysis, and computational studies

Laser flash photolysis of 1-(carbazol-9-yl)-2,4,6-trimethylpyridinium tetrafluoroborate generates the carbazolyl nitrenium ion (tau = 333 ns, kobs = 3.0 x 106 M-1s-1) having absorption bands at 570 and 620 nm in CH3CN. The nitrenium ion is found to have reactivity comparable to structurally similar closed-shell diarylnitrenium ions, but spectroscopic evidence favors an open-shell singlet diradical assignment for the observed nitrenium ion. The carbazolyl nitrenium ion is also more reactive than diarylnitrenium ions as a likely result of antiaromatic character. Ab initio and hybrid DFT calculations were performed to address the degree of antiaromaticity in this and similar nitrenium ions through analysis of optimized geometries, nucleus independent chemical shifts, and isodesmic reactions.     

Sonogashira/N-acyliminium ion aromatic π-cyclisation processes: access to tetra- and pentacyclic lactams

Application of the Sonogashira reaction of N-alkynylimides with 2-iodophenol or 2-iodo-N-tosylaniline affords 2-(N-alkylimino)-benzofurans and indoles in good yield. Selective partial reduction of the latter followed by treatment with TsOH generates N-acyliminium ions, which cyclise to afford tetra- and pentacyclic lactams in good yield. The latter are reduced to the analogous cyclic amines by BH₃.     

Rate constants for the gas-phase reaction of OH with amines: tert-Butyl amine, 2,2,2-Trifluoroethyl amine,and 1,4-Diazabicyclo[2.2.2] octane

The title compounds were selected to test the current predictions of OH reaction rate constants. The reactions are studied employing flash photolysis/resonance fluorescence in 130 mbar He at room temperature and up to 420 K. Experimental difficulties were encountered due to the polar and hygroscopic properties of the compounds. The rate constants obtained at 298 K, 12, 0.9, and 22·10⁻¹²cm³/s for tert-Butyl amine (TBA), 2,2,2-Trifluoroethyl amine (TFEA), and 1,4-Diazabicyclo[2.2.2]octane (DABCO®), respectively, are much lower (up to a factor > 20) than calculated with the incremental system devised by Atkinson, indicating that electronic and steric effects should not be neglected. Activation energies are slightly negative for TBA and DABCO and some +450 K for TFEA. The reactivity of TFEA was also determined (as 1.2·10⁻¹²cm³/s) relative to a set of hydrocarbons employing continuous photolysis of H₂O₂ in a glass chamber. © 1996 John Wiley & Sons, Inc.     

Comparison of the relative stabilities of polycyclic aryl nitrenium ions and arylmethyl cations: ab initio and semiempirical molecular orbital calculations

Ab initio HF/3-21G calculations predict the stabilities of a series of nitrenium ions to increase in the order, phenyl < 2-naphthyl < 1-naphthyl < 2-fluorenyl. Quantitatively similar results are obtained at the MP/6-31G(d) level for the phenyl and naphthyl systems. The relative stabilities of the nitrenium ions qualitatively parallel those of the corresponding isoconjugate arylmethyl cations but are significantly more sensitive to the nature of the aryl group. Semiempirical AM1 calculations of the same quantities are in reasonable agreement with the ab initio values and are used to extend the comparison to a further 20 polycyclic aromatic derivatives. The relative stabilities of the larger set of nitrenium ions are found to be very precisely linearly related to those of the corresponding arylmethyl cations if allowance is made for the electron donating ability of the aryl group as measured by the charge on the exocyclic carbon atom. A similar but approximate relationship can also be demonstrated in terms of simple perturbational molecular orbital theory.     

Hydroxy(tosyloxy)iodo]benzene mediated alpha-azidation of ketones

Reaction of various ketones with [hydroxy(tosyloxy)iodo]benzene (HTIB) followed by treatment of the alpha-tosyloxy ketones thus generated in situ with NaN3 offers a one-pot procedure for the synthesis of alpha-azido ketones. The HTIB used in this conversion may also be generated in situ by using iodosobenzene in combination with p-toluene-sulphonic acid.     

瞬态吸收和共振拉曼光谱研究硝基对联苯氮宾、氮宾离子反应活性的影响

利用光解芳基叠氮化合物得到单重态氮宾,运用纳秒瞬态吸收光谱、瞬态共振拉曼光谱实验手段,辅以密度泛函理论(DFT)计算,研究了4'-硝基-4-联苯氮宾在乙腈和水溶液中的光化学反应中间体。实验结果表明,在非质子溶剂中, 4'-硝基-4-联苯氮宾发生系间窜越反应生成三线态氮宾;在质子溶剂中,单重态氮宾可被质子化产生氮宾离子。与4-联苯氮宾和氮宾离子相比,硝基对单重态氮宾系间窜越反应路径影响很小;降低了氮宾离子与水和叠氮阴离子的反应活性,却提高了其与鸟苷的反应活性。     

Nitrenium Salts in Lewis Acid Catalysis

Molecular compounds featuring nitrogen atoms are typically regarded as Lewis bases and are extensively employed as donor ligands in coordination chemistry or as nucleophiles in organic chemistry. By contrast, electrophilic nitrogen‐containing compounds are much rarer. Nitrenium cations are a new family of nitrogen‐based Lewis acids, the reactivity of which remains largely unexplored. In this work, nitrenium ions are explored as catalysts in five organic transformations. These reactions are the first examples of Lewis acid catalysis employing nitrogen as the site of substrate activation. Moreover, these compounds are readily accessed from commercially available reagents and exhibit remarkable stability toward moisture, allowing for benchtop transformations without the need to pretreat solvents.     

Zur Photochemie von 1H- und 2H-Indazolen in saurer Lösung

On the Photochemistry of 1H- and 2H-Indazoles in Acidic Solution It is shown that 1H- and 2H-indazoles (cf. Scheme 2) on protonation (0, 1N H₂SO₄ in water or alcoholic solution) give analogous indazolium ions (see Fig. 1 and 2) which on irradiation undergo heterolytic cleavage of the N (1), N (2) bond whereby aromatic nitrenium ions in the singlet ground state are formed (cf. Scheme 13). If the para position of these nitrenium ions is not occupied by a substituent (e.g. a methyl group) they are readily trapped by nucleophiles present (e.g. water, alcohols, chloride ions) to yield the corresponding 5-substituted 2-amino-benzaldehydes or acetophenones (cf. Schemes 4–10). Photolysis of indazole ( 4 ) and 3-methyl-indazole ( 5 ) in 0,75N H₂SO₄ in alcoholic solutions gives in addition minor amounts of the corresponding 3-substituted 2-amino-benzaldehydes and acetophenones, respectively (cf. Schemes 6 and 8 and Table 2). Phenylnitrenium ions carrying a methyl group in the para position give in aqueous sulfuric acid mainly the reduction products, i.e. 2-amino-5-methyl-benzaldehydes (cf. Schemes 11 and 12 and Table 3). In methanolic sulfuric acid, in addition to the reduction products, 6-methoxy substituted benzaldehydes are found (cf. Schemes 11 and 12 and Table 3) which are presumably formed by an addition-elimination mechanism (cf. Scheme 18). It is assumed that precursors of the reduction products are the corresponding nitrenium ions in the triplet ground state. Singlet-triplet conversion of the nitrenium ions may become efficient when addition of nucleophiles to the singlet nitrenium ions is reversible (cf. Scheme 22) thus, enhancing the probability of conversion or when conjugation in the singlet nitrenium ions is disturbed by steric effects (cf. Scheme 20) thus, destabilizing the singlet state relative to the triplet state.     

Synthesis of B/Ga and B/In heteronuclear bidentate Lewis acids: formation of intramolecular pi-arene-gallium(III) and -indium(III) complexes

Reaction of 1,8-dilithionaphthalene x TMEDA (TMEDA=tetramethylethylenediamine) with dimesitylboron fluoride in diethyl ether followed by treatment with THF affords the Li(THF)(4) salt of dimesityl-1,8-naphthalenediylborate (1). Compound 1-Li(THF)(4) undergoes a ring-opening reaction with trimethyltin chloride to afford high yields of 1-(dimesitylboron)-8-(trimethyltin)naphthalenediyl (2), a compound in which a boryl and a stannyl moiety coexist at the peri positions of a naphthalene core. Compound 2 has been characterized by multinuclear NMR spectroscopy, elemental analysis, and X-ray single-crystal analysis which reveal the existence of a sterically crowded structure. Compound 2 is a useful starting material for the synthesis of other heteronuclear naphthalene derivatives. Thus, the transmetalation reaction of 2 with GaCl(3) or InCl(3) in THF results in high yields of 1-(dichlorogallium)-8-(dimesitylboron)naphthalenediyl (3) and 1-(dichloroindium)-8-(dimesitylboron)naphthalenediyl (4), respectively. These unprecedented boron/gallium and boron/indium heteronuclear bidentate Lewis acids have been characterized by multinuclear NMR spectroscopy, elemental analysis, and X-ray single-crystal analysis. Owing to the presence of a short contact between the ipso-carbon atom of a mesityl group and the heavy Group 13 element (C(ipso)bondGa 2.279(4) A for 3, C(ipso)bondIn 2.442(6) A for 4), compounds 3 and 4 are best described as intramolecular pi-arene complexes and are the first examples of such complexes. As shown by (1)H and (13)C NMR spectroscopy, this pi interaction subsists in solution.     

Nitrenium ions. Reactions of N,N-dimethyl-p-benzoyloxyanilineiminium chloride with indoles and indolizines. X-ray structure of unexpected [2-chloro-4-(4-dimethylaminophenyl-ONN-azoxy)phenylldimethylamine (azoxy derivative)

N,N-Dimethyl-p-nitrosoaniline reacts with benzoyl chloride affording a complex salt containing a cation, a hybrid between a nitrenium ion and an iminium ion. The salt reacts with nucleophiles (indoles, indolizines) yielding compounds characterized by a new carbon-nitrogen bond, derived from the nitrenium ion form. According to the type of nucleophile, the reaction, to differing extents, is in competition with an electron transfer process which leads to the formation of the dimer of the nucleophile and of the azoxy corresponding to the N,N-dimethyl-p-nitrosoaniline. In one of the reactions studied, a chlorinated azoxy derivative was also isolated, and its structure was elucidated by X-ray analysis.     

Direct cyanation of heteroaromatic compounds mediated by hypervalent iodine(III) reagents: In situ generation of PhI(III)-CN species and their cyano transfer

Hypervalent iodine(III) reagents mediate the direct cyanating reaction of a wide range of electron-rich heteroaromatic compounds such as pyrroles 1, thiophenes 3, and indoles 5 under mild conditions (ambient temperature), without the need for any prefunctionalization. Commercially available trimethylsilylcyanide is usable as a stable and effective cyanide source, and the reaction proceeds in a homogeneous system. The N-substituent of pyrroles is crucial to avoid the undesired oxidative bipyrrole coupling process, and thus a cyano group was introduced selectively at the 2-position of N-tosylpyrroles 1 in good yields using the combination of phenyliodine bis(trifluoroacetate) (PIFA), TMSCN, and BF3.Et2O at room temperature. In the reaction mechanism, cation radical intermediates of heteroaromatic compounds are involved as a result of single electron oxidation, and the key to successful transformations seems to depend on the oxidation potential of the substrates used. Thus, the reaction was also successfully extended to other heteroaromatic compounds having oxidation potentials similar to that of N-tosylpyrroles such as thiophenes 3 and indoles 5. However, regioisomeric mixtures of the products derived from the reaction at the 2- and 3-positions were obtained in the case of N-tosylindole 5a. Further investigation performed in our laboratory provided insights into the real active iodine(III) species during the reaction; the reaction is induced by an active hypervalent iodine(III) species having a cyano ligand in situ generated by ligand exchange reaction at the iodine(III) center between trifluoroacetoxy group in PIFA and TMSCN, and effective cyanide introduction into heteroaromatic compounds is achieved by means of the high cyano transfer ability of the hypervalent iodine(III)-cyano intermediates. In fact, the reaction of N-tosylpyrrole 1a with a hypervalent iodine(III)-cyano compound (e.g., (dicyano)iodobenzene 8), in the absence of TMSCN, took place to afford the 2-cyanated product 2a in good yield, and an effective preparation of the intermediates is of importance for successful transformation. 1,3,5,7-Tetrakis[4-{bis(trifluoroacetoxy)-iodo}phenyl]adamantane 12, a recyclable hypervalent iodine(III) reagent, was also comparable in the cyanating reactions as a valuable alternative to PIFA, affording a high yield of the heteroaromatic cyanide by facilitating isolation of the cyanated products with a simple workup. Accordingly, after preparing the active hypervalent iodine(III)-CN species by premixing of a recyclable reagent 12, TMSCN, and BF3.Et2O for 30 min in dichloromethane, reaction of a variety of pyrroles 1 and thiophenes 3 provided the desired cyanated products 2 and 4 in high yields. The iodine compound 13, recovered by filtration after replacement of the reaction solvent to MeOH, could be reused without any loss of activity (the oxidant 12 can be obtained nearly quantitatively by reoxidation of 13 using m-CPBA).