Ligand-free palladium-catalyzed cyanation of aryl halides

[reaction: see text] A practical, ligand-free cyanation of aryl bromides that utilizes as little as 0.1 mol % Pd(OAc)(2) in combination with a nontoxic cyanide source, M(4)[Fe(CN)(6)] (M = K, Na), is described. The reactions are performed in DMAC at 120 degrees C and provide the corresponding aryl nitrile in 83-96% yield, typically in less than 5 h. TON values of up to 7100 were attained.     

Unexpected conversion of a hexacyanometallate to a homoleptic nitrile complex with triphenylborane substituents

The homoleptic, triphenylborane adduct of the hexacyanochromate anion was structurally characterized and found to be a product in which all six cyanide ligands have undergone isomerization to nitrile groups.     

Novel synthesis of isoquinolines using isobenzofuran-nitrile Diels-Alder reactions

[reaction: see text] The synthesis of isoquinolines through coupling of 2-alkynylbenzaldehyde derivatives with beta-cyanocarbene complexes has been examined. The reaction involves formation of an isobenzofuran followed by intramolecular Diels-Alder reaction with the nitrile, a process with limited precedent. The unique success of this process in this system has been attributed to deoxygenation of the initial adduct to form the isoquinoline ring system.     

Metalated nitriles: electrophile-dependent alkylations

[reaction: see text] Sequential carbonyl addition-conjugate addition to oxonitriles generates a C-magnesiated nitrile exhibiting electrophile-dependent alkylation stereoselectivities. Alkylations with alkyl halides, sulfonates, and ketones proceed with retention of stereochemistry, whereas aldehyde and acyl cyanide acylations proceed with inversion of stereochemistry. BuLi-initiated conversion of the C-magnesiated nitrile to the corresponding N-lithiated nitrile reverses the alkylation stereoselectivity, providing a facile route to diastereomeric nitriles that vary at a single, quaternary stereocenter.     

Postmodification of poly(9‐alkyl‐9H‐carbazole‐2,7‐diyl)s as a route to new main‐chain‐functionalized carbazole polymers

The postmodification of poly[9‐(2‐hexyldecyl)‐9H‐carbazole‐2,7‐diyl] ( P1 ) upon its reaction with N‐bromosuccinimide affords exclusive and full bromination of the 3,6‐positions of the carbazole repeat units to yield poly[3,6‐dibromo‐9‐(2‐hexyldecyl)‐9H‐carbazole‐2,7‐diyl] ( P2 ). Brominated polymer P2 can be used as a precursor for further functionalization at the 3,6‐positions with the desired functional group to afford other useful polymers. Polymer P2 has hence been reacted with copper(I) cyanide to afford poly[3,6‐dicyano‐9‐(2‐hexyldecyl)‐9H‐carbazole‐2,7‐diyl] ( P3 ). Full substitution of the bromide groups with nitrile‐functional groups has been achieved. The preparation and structural characterization of polymers P2 and P3 are presented together with studies on their electronic conjugation and photoluminescence properties. Cyclic voltammetry studies on polymer P3 indicate that the new polymer is easier to reduce (n‐dope) but more difficult to oxidize than its unsubstituted counterpart ( P1 ) as a result of the introduction of the electron‐withdrawing nitrile‐functional groups at the 3,6‐positions on the carbazole repeat units on the polymer chains. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3336–3342, 2006     

Huisgen's 1,3-Dipolar Cycloadditions to Fulvenes Proceed via Ambimodal [6+4]/[4+2] Transition States

Huisgen's 1960 announcement of the concept of 1,3-dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry.     

Generation of gas-phase VO2+, VOOH+, and VO2+-nitrile complex ions by electrospray ionization and collision-induced dissociation

Cationic metal species normally function as Lewis acids, accepting electron density from bound electron-donating ligands, but they can be induced to function as electron donors relative to dioxygen by careful control of the oxidation state and ligand field. In this study, cationic vanadium(IV) oxohydroxy complexes were induced to function as Lewis bases, as demonstrated by addition of O2 to an undercoordinated metal center. Gas-phase complex ions containing the vanadyl (VO2+), vanadyl hydroxide (VOOH+), or vanadium(V) dioxo (VO2+) cation and nitrile (acetonitrile, propionitrile, butyronitrile, or benzonitrile) ligands were generated by electrospray ionization (ESI) for study by multiple-stage tandem mass spectrometry. The principal species generated by ESI were complexes with the formula [VO(L)n]2+, where L represents the respective nitrile ligands and n=4 and 5. Collision-induced dissociation (CID) of [VO(L)5]2+ eliminated a single nitrile ligand to produce [VO(L)4]2+. Two distinct fragmentation pathways were observed for the subsequent dissociation of [VO(L)4]2+. The first involved the elimination of a second nitrile ligand to generate [VO(L)3]2+, which then added neutral H2O via an association reaction that occurred for all undercoordinated vanadium complexes. The second [UO(L)4]2+ fragmentation pathway led instead to the formation of [VOOH(L)2]+ through collisions with gas-phase H2O and concomitant losses of L and [L+H]+. CID of [VOOH(L)2]+ caused the elimination of a single nitrile ligand to generate [VOOH(L)]+, which rapidly added O2 (in addition to H2O) by a gas-phase association reaction. CID of [VONO3(L)2]+, generated from spray solutions created by mixing VOSO4 and Ba(NO3)2 (and precipitation of BaSO4), caused elimination of NO2 to produce [VO2(L)2]+. CID of [VO2(L)2]+ produced elimination of a single nitrile ligand to form [VO2(L)]+, a V(V) analogue to the O2-reactive V(IV) species [VOOH(L)]+; however, this V(V) complex was unreactive with O2, which indicates the requirement for an unpaired electron in the metal valence shell for O2 addition. In general, the [VO2(L)2]+ species required higher collisions energies to liberate the nitrile ligand, suggesting that they are more strongly bound than the [VOOH(L)2]+ counterparts.     

Thermodynamic, kinetic, and mechanistic study of oxygen atom transfer from mesityl nitrile oxide to phosphines and to a terminal metal phosphido complex

The enthalpies of oxygen atom transfer (OAT) from mesityl nitrile oxide (MesCNO) to Me(3)P, Cy(3)P, Ph(3)P, and the complex (Ar[(t)Bu]N)(3)MoP (Ar = 3,5-C(6)H(3)Me(2)) have been measured by solution calorimetry yielding the following P-O bond dissociation enthalpy estimates in toluene solution (±3 kcal mol(-1)): Me(3)PO [138.5], Cy(3)PO [137.6], Ph(3)PO [132.2], (Ar[(t)Bu]N)(3)MoPO [108.9]. The data for (Ar[(t)Bu]N)(3)MoPO yield an estimate of 60.2 kcal mol(-1) for dissociation of PO from (Ar[(t)Bu]N)(3)MoPO. The mechanism of OAT from MesCNO to R(3)P and (Ar[(t)Bu]N)(3)MoP has been investigated by UV-vis and FTIR kinetic studies as well as computationally. Reactivity of R(3)P and (Ar[(t)Bu]N)(3)MoP with MesCNO is proposed to occur by nucleophilic attack by the lone pair of electrons on the phosphine or phosphide to the electrophilic C atom of MesCNO forming an adduct rather than direct attack at the terminal O. This mechanism is supported by computational studies. In addition, reaction of the N-heterocyclic carbene SIPr (SIPr = 1,3-bis(diisopropyl)phenylimidazolin-2-ylidene) with MesCNO results in formation of a stable adduct in which the lone pair of the carbene attacks the C atom of MesCNO. The crystal structure of the blue SIPr·MesCNO adduct is reported, and resembles one of the computed structures for attack of the lone pair of electrons of Me(3)P on the C atom of MesCNO. Furthermore, this adduct in which the electrophilic C atom of MesCNO is blocked by coordination to the NHC does not undergo OAT with R(3)P. However, it does undergo rapid OAT with coordinatively unsaturated metal complexes such as (Ar[(t)Bu]N)(3)V since these proceed by attack of the unblocked terminal O site of the SIPr·MesCNO adduct rather than at the blocked C site. OAT from MesCNO to pyridine, tetrahydrothiophene, and (Ar[(t)Bu]N)(3)MoN was found not to proceed in spite of thermochemical favorability.     

Metalated nitriles: halogen-metal exchange with alpha-halonitriles

[reaction: see text] Alpha-halonitriles react with organometallic reagents in a facile halogen-metal exchange. The halogen-metal exchange is extremely fast with Grignard and alkyllithium reagents, generating metalated nitriles in situ with aldehyde, ketone, acid chloride, and acyl cyanide electrophiles. Sequential halogen-metal exchange and methylation of conformationally constrained nitriles is highly stereoselective and consistent with a retentive alkylation of a C-magnesiated nitrile.     

Highly diastereoselective cyanation of methyl ketimines obtained from (R)-glyceraldehyde

[reaction: see text] Addition of trimethylsilyl cyanide to ketimines derived from (R)-2,2-dimethyl-1,3-dioxolan-4-yl methyl ketone to generate a quaternary stereocenter has been achieved with high yields and excellent diastereoselectivity. The stereoselectivity was found to be temperature and solvent dependent. The beta-hydroxy-alpha-amino nitrile of syn configuration was the major compound in kinetically controlled reactions, whereas the anti stereoisomer was obtained in excess in thermodynamically controlled reactions. Double stereodifferentiation under kinetic control conditions was successful, and the cyanation reaction occurred with complete syn diastereoselectivity using the matched pair. The versatility of the resulting amino nitrile as a synthetic intermediate was tested by performing the synthesis of orthogonally protected (R)-(2-aminomethyl)alanine.     

Huisgen's 1,3‐Dipolar Cycloadditions to Fulvenes Proceed via Ambimodal [6+4]/[4+2] Transition States

Huisgen's 1960 announcement of the concept of 1,3‐dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry.     

Synthesis of ammonium [14C]thiocyanate

Ammonium [¹⁴C]thiocyanate was prepared from potassium [¹⁴C]cyanide with a radiochemical yield of 90%. [¹⁴C]hydrocyanic acid, generated from potassium [¹⁴C]cyanide by sulphuric acid, reacts with aqueous ammonia and elemental sulphur in the presence of trace amounts of ammonium sulphide to yield ammonium [¹⁴C]thiocyanate.     

Synthesis of the new ring system,Pyrazolo[3,4-d][1,3]diazepine. A novel route for the synthesis of azolo[1,3]diazepines

A reduction of the nitrile group of 5-amino-4-cyano-1-methylpyrazole ( 3 ) has provided the very versatile compound 5-amino-1-methylpyrazole-4-carboxaldehyde ( 4 ). The amino group of 4 was protected using di-methylformamide dimethylacetal and the aldehyde group was then reacted with trimethylsilyl cyanide to afford the moisture sensitive compound 5-[[(dimethylamino)methylene]amino]-4-[cyano(trimethylsiloxy)-methyl]-1-methylpyrazole ( 10 ). The cyano group of the cyanohydrin 10 was reduced using a cobalt boride catalyst to afford an intermediate aminomethyl group which was involved in an in situ annulation. This reaction provided 1-methyl-1,4,5,6-tetrahydropyrazolo[3,4-d][1,3]diazepin-4-ol, a derivative of the new ring system, pyrazolo[3,4-d][1,3]diazepine.     

Saponification Kinetics of Acrylonitrile Terpolymer and Polyacrylonitrile

Saponification kinetics of acrylic terpolymer and polyacrylonitrile were studied. The influence of alkali concentration and the time of hydrolysis on the degree of saponification were determined by the residual nitrogen content. The order of reaction was graphically determined and the rate of saponification was found to be faster in the terpolymer than in the homopolymer. Chemical and infrared spectroscopy methods reveal that the reaction is initiated through cyclization of nitrile groups, followed by hydrolysis to amide and carboxylic groups of the [sbnd](C[dbnd]N)_n[sbnd] segments produced.

The saponification of nitrile groups in the terpolymer initially yields amide groups, then slows down to yield carboxylic groups.     

Revisit to the reaction of [60]fullerene with nitrile ylides generated from imidoyl chlorides and triethylamine

The reaction of [60]fullerene (C₆₀) with nitrile ylides generated from N-benzyl-4-nitrobenzimidoyl chloride/N-(4-chlorobenzyl)-4-nitrobenzimidoyl chloride and triethylamine gave only isomeric monoadducts of C₆₀ with [6,6]-closed structure. No [5,6]-open adduct of C₆₀ could be identified from these reactions. The previously reported [5,6]-open product of C₆₀ should be reassigned as a [6,6]-closed product.     

Synthesis of 4,4-disubstituted piperidine analogs of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide

Condensation of (±)-1-benzyl-3-methyl-4-piperidone ( 1 ) with aniline followed by trapping of the intermediate imine with cyanide generated a mixture of isomeric nitriles 2A and 2B , the structures of which were established unambiguously by obtaining an X-ray crystal structure on nitrile 2B . Subsequent elaboration of the nitrile intermediates provided analogs of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide having a second substituent (carbomethoxyl, carboethoxyl, methoxymethyl) at the piper-idine 4-position. The conversion of the carboxamide intermediates 3A and 3B to the carboalkoxyl intermediates 5A, 5B and 6A was accomplished utilizing a modified esterification procedure. Proton nmr data are presented for both the final products and the key synthetic intermediates.     

[6+2] Cycloaddition of N-phenyltriazolinedione with cycloheptatriene derivatives mediated and stereodirected by a chiral 3-oxy substituent

The addition of N-phenyltriazolinedione to a 7,7-dimethylcycloheptatriene derivative afforded a [6+2] adduct, which was found to be produced by the rearrangement of an initially formed [4+2] adduct. The regioselectivity of the initial addition was controlled by the 3-oxy-substituent, which also mediates the PTAD addition to the tropilidene form. The chiral 3-substituent also controlled the stereoselectivity of the addition to a high degree.     

2-quinoxalinylnitrenes and 4-quinazolinylnitrenes: rearrangement to cyclic and acyclic carbodiimides and ring-opening to nitrile ylides

This work was undertaken with the aim to obtain direct evidence for the interrelationships between hetarylnitrenes, their ring-expanded cyclic carbodiimide isomers, and ring-opened nitrile ylides. Tetrazolo[1,5-a]quinoxaline 11T and tetrazolo[5.1-c]quinazoline 13T undergo valence tautomerization to the corresponding azides 11A and 13A on mild flash vacuum thermolysis (FVT). Photolysis in Ar matrixes at ca. 15 K affords the triplet nitrenes 12 and 14, identified by ESR, UV, and IR spectroscopy. The nitrenes are converted photochemically to the seven-membered ring carbodiimide 15 followed by the open-chain carbodiimide 22. The 3-methoxy- and 3-chloro-2-quinoxalinylnitrenes 24 yield the ring-expanded carbodiimides 26 very cleanly on matrix photolysis, whereas FVT affords N-cyanobenzimidazoles 28. The ring-opened nitrile ylides 36 and 49 are identified as intermediates in the photolyses of 2-phenyl-4-quinazolinylnitrene 32 and 7-nitro-2-phenyl-4- quinazolinylnitrene 47. In these systems, a photochemically reversible interconversion of the seven-membered ring carbodiimides 35 and 48 and the nitrile ylides 36 and 49 is established. Recyclization of open-chain nitrile ylides is identified as an important mechanism of formation of ring contraction products (N-cyanobenzimidazoles).     

1,3‐dipolar cycloaddition reactions of nitrile oxides to prop‐1‐ene‐1,3‐sultone

The reaction of prop‐1‐ene‐1,3‐sultone 1 with a variety of nitrile oxides 3 afforded novel [3+2] cycloaddition products 4 in good yield. The cycloaddition reaction achieved excellent regioselectivity.     

Rhodium-catalyzed annulation reactions of 2-cyanophenylboronic acid with alkynes and strained alkenes

[reaction: see text]. A new [3 + 2] annulation reaction was developed in which 2-cyanophenylboronic acid reacted as a three-carbon component with alkynes or alkenes to afford substituted indenones or indanones. The use of an alkynoate even produced benzotropone, a formal [3 + 2 + 2] adduct. The cyclic skeletons were constructed by intramolecular nucleophilic addition of an intermediate organorhodium(I) species to a cyano group.