Tetrahedron Letters (v.52, #52)

Synthesis and cross coupling of a highly substituted 2-pyridylboronate: application to the large scale synthesis of a mineralocorticoid antagonist by Charles Boos; Daniel M. Bowles; Cuiman Cai; Agustin Casimiro-Garcia; Xiangyang Chen; Catherine A. Hulford; Sandra M. Jennings; E. Jason Kiser; David W. Piotrowski; Matthew Sammons; Robert A. Wade (7025-7029).
The large scale synthesis of functionalized 2-pyridylboronate 8 and optimization of its Suzuki–Miyaura coupling to chloropyrazoline (R)-7 to provide a scalable synthesis of mineralocorticoid antagonist (R)-1 is described.
Keywords: Suzuki–Miyaura coupling; 2-Pyridylboronate; Pyrazoline; Large-scale synthesis;

A multistep approach to construct novel 3-(1H-benzo[d]imidazol-2-yl)imidazolidine-2,4-diones and 3-(1H-benzo[d]imidazol-2-yl)-2-thioxoimidazolidin-4-ones from commercially available amino acids, amines, and carboxylic acids is described. Coupling of Fmoc-amino acid to resin-bound aminobenzimidazole provided following Fmoc elimination free amine. Treatment of the free amine with 1,1′-carbonyldiimidazole or 1,1′-thiocarbonyldiimidazole furnished the corresponding hydantoins and thiohydantoins via intramolecular cyclization. The desired aminobenzimidazole tethered hydantoins or thiohydantoins were isolated in good yields.
Keywords: Solid phase synthesis; Benzimidazole; Amino acid; Hydantoin; Thiohydantoin; Heterocycles; Intramolecular cyclization;

l-Prolinamide derivatives as efficient organocatalysts for aldol reactions on water by Gongkun Tang; Xianming Hu; Hans Josef Altenbach (7034-7037).
A series of l-prolinamide derivatives have been evaluated as potential organocatalysts for aldol reactions. To synthesize these catalysts, a novel and simple route has been developed using proline N-carboxyanhydride (proline-NCA). A new catalyst with a trifluoromethyl-sulfonamide group has been found exhibiting excellent diastereoselectivity (anti/syn: 97/3) and enantioselectivity (99% ee) with 10 mol % loading and being easily recyclable in water.
Keywords: Aldol reaction; Enantioselecitvity; Organocatalysis; Proline amide derivative; Proline-NCA;

This study describes a general palladium-catalyzed cyanation of aryl bromides using K4[Fe(CN)6] as the cyanide surrogate. The reactions can be successfully conducted under mild reaction conditions (at 50 °C) in mixed solvents (water/MeCN = 1:1) without any surfactant additives, and afford the desired aryl nitriles in good-to-excellent yields. Particularly noteworthy is that this system allows the mildest reaction temperature reported so far for palladium-catalyzed cyanation of aryl bromides with K4[Fe(CN)6] source in general. Common functional groups, including keto, aldehyde, free amine, and heterocyclic substrates are compatible under this system. Interestingly, the phosphine ligands bearing –PCy2 moiety, which usually show excellent activity in aryl halide couplings, are found less effective than the corresponding ligands with –PPh2 group.

Suberoyl bis-hydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, led to significant changes in the secondary metabolism of an entomopathogenic fungus, Torrubiella luteorostrata, and induced the production of three new prenylated tryptophan analogs, luteorides A–C (13). The structures are characterized by the presence of an (E)-oxime group, which is an unusual functional group in natural products, and a 3-methylbuta-1,3-dienyl unit as a common substituent. The method of culturing entomopathogenic fungi in the presence of HDAC inhibitors, such as SBHA, is convenient and attractive for obtaining novel secondary metabolites.
Keywords: Entomopathogenic fungi; Secondary metabolites; Histone deacetylase inhibitor; Epigenetics; Tryptophan analogs;

First total synthesis of (±)-adunctin B by Kenji Arimitsu; Sayo Nomura; Hiroki Iwasaki; Minoru Ozeki; Masayuki Yamashita (7046-7048).
The first total synthesis of (±)-adunctin B (1), a natural product isolated from Piper aduncum (Piperaceae) and having antibacterial activity, was achieved in 1.26% overall yield in 15 steps from 5,7-dimethoxycoumarin-3-carboxylate (8).
Keywords: Adunctin B; Total synthesis; Ylide; Skeleton transformation; Stereoselective alkylation;

Solid-phase synthesis of an apoptosis-inducing tetrapeptide mimicking the Smac protein by Sebastian T. Le Quement; Mette Ishoey; Mette T. Petersen; Pernille M. Simonsen; Nanna S. Holck; Thomas E. Nielsen (7049-7053).
An approach for the solid-phase synthesis of apoptosis-inducing Smac peptidomimetics is presented. Using a Rink linker strategy, tetrapeptides mimicking the N-4-terminal residue of the Smac protein [(N-Me)AVPF sequence] were synthesized on PEGA resin in excellent purities and yields. Following two synthetic routes, a known tetrapeptide, incorporating a substituted proline, previously shown to exhibit excellent biological activity in vitro as well as low toxicity, was synthesized effectively on a solid support.
Keywords: Apoptosis; Peptides Smac mimetics; Solid-phase synthesis; Peptidomimetics;

An unusual transformation of 5-acyl-1,2,4-triazines into 3-pyridyl-1,2,4-triazines via tandem Stille cross-coupling/aza Diels–Alder reaction by Danuta Branowska; Olga Siuchta; Zbigniew Karczmarzyk; Waldemar Wysocki; Ewa Wolińska; Mariusz Mojzych; Robert Kawęcki (7054-7057).
A new route to 3-heteroaryl-1,2,4-triazines possessing a keto substituent at C-5 of the 1,2,4-triazine core using a Stille cross-coupling procedure and their unexpected ring transformation into pyridyltriazines as a result of enolization of an acyl group catalyzed by metal ions, are reported.
Keywords: 1,2,4-Triazine; Stille coupling reaction; Cycloaddition; Pyridyltriazines;

Bis-furyl alditols via SnCl4- or ZnCl2-catalysed reaction of furans with sugars by Flavio Cermola; Fabio Temussi; Maria Rosaria Iesce (7058-7060).
Alditols have been obtained in very high yield using an excess of electron-rich furans with respect to the protected sugars. The scope and limitation of the reaction have been explored.
Keywords: Furans; Electron rich-furans; Sugars; Coupling reaction; Bis-alditols;

Sulfenylation of nitroalkanes and hydroxyaryls by Guillermo A. Blanco; Maria T. Baumgartner (7061-7063).
The sulfenylation of nitroalkanes and hydroxyaryls in DMSO using aryl disulfides as sulfenylating reagents was studied. The corresponding arylthionitroalkanes and arylthiohydroxyaryls were obtained in moderate to good yields in very mild conditions, thus improving the reported procedures for the synthesis of these compounds.
Keywords: Sulfenylation; Disulfides; Nitroalkanes; Hydroxyaryls; Dimethylsulfoxide;

An organocatalytic asymmetric tandem 1,5-hydride transfer/ring closing reaction of o-aminobenzoketones with anilines to give cyclic aminals in fairly good diastereo- and enantioselectivities.
Keywords: Asymmetric catalysis; 1,5-Hydride shift; Brønsted acid; Cyclic aminals;

Synthesis of linear and cyclic aromatic peptides with fixed conformation owing to intramolecular hydrogen bonding by condensation polymerization method by Tomoyuki Ohishi; Toshiya Suzuki; Tetsurou Niiyama; Koichiro Mikami; Akihiro Yokoyama; Kosuke Katagiri; Isao Azumaya; Tsutomu Yokozawa (7067-7070).
Chain-growth condensation polymerization of 3-(4-octyloxybenzylamino)benzoic acid esters bearing an alkoxy group on the benzene ring was investigated for the synthesis of polyamides having a specific conformation owing to intramolecular hydrogen bonding of CONH⋯OR. The 4-octyloxybenzyl group on the nitrogen of the amide linkage was easily removed with trifluoroacetic acid after polymerization to afford the desired polyamides, which had lower solubility than expected. Furthermore, we found that a cyclic triamide was selectively obtained by slow addition of the base to a solution of the monomer.
Keywords: Chain-growth condensation polymerization; Aromatic peptide; Poly(m-benzamide); Hydrogen bond; Macrocycles;

Generation and spectroscopic properties of syn-1,6:9,14-bismethanodicyclodeca[cd,gh]pentalene dianion by Shigeyasu Kuroda; Yoshihiro Terada; Ryuta Miyatake; Yoshikazu Horino; Takako Abe; Yurie Fujiwara; Mitsunori Oda (7071-7074).
The hydrocarbon precursor, 8,16-dihydro-syn-1,6;9,14-bismethano[cd,gh]pentalene (5), to the title structure, dianion 4, was synthesized from ethyl 4-bromo-1,6-methano[10]annulene-3-carboxylate (6) in three steps, which included a nickel-catalyzed stereoselective homo-coupling, LiAlH4 reduction of the ester groups, and scandium triflate-catalyzed double intramolecular cyclization of the biarylmethyldiol. Deprotonation of 5 with n-butyllithium in THF-d 8 provided 4, whose structure was confirmed by NMR analysis. Aspects of chemical shifts in the 1H NMR spectrum and the calculated structure of 4 establish its diatropic nature.
Keywords: Carbanions; Methano[10]annulenes; Ni-catalyzed coupling; Scandium triflate; NICS values;

Total synthesis of (+)-varitriol via a symmetrical furanose diol as the key intermediate by Lingaiah Nagarapu; Venkateswarlu Paparaju; Apuri Satyender; Rajashaker Bantu (7075-7078).
Synthesis of (+)-varitriol has been achieved from d-ribose via a symmetrical furanoside diol as the key intermediate, which is also a very useful furanoside building block in synthesizing novel analogues of (+)-varitriol.Alternative, simple and efficient route for (+)-varitriol (1), a marine-derived natural product with potent biological activity, has been synthesized from d-ribose. In this synthetic strategy symmetrical diol (6) with mono alcohol protection, the key intermediate, was produced in eight steps with 35% overall yield and the significance of 6 as the key furanoside building block for the synthesis of novel analogues of 1 for SAR studies was explained.
Keywords: (+)-Varitriol; Anti-cancer activity; Symmetrical diol; Total synthesis; Analogues;

Molybdenum oxide/bipyridine hybrid material {[MoO3(bipy)][MoO3(H2O)]}n as catalyst for the oxidation of secondary amines to nitrones by Marta Abrantes; Isabel S. Gonçalves; Martyn Pillinger; Carolina Vurchio; Franca M. Cordero; Alberto Brandi (7079-7082).
The inorganic–organic hybrid material {[MoO3(bipy)][MoO3(H2O)]}n (bipy = 2,2′-bipyridine) can be used as a water-tolerant catalyst for the oxidation of secondary amines under mild conditions using either urea hydrogen peroxide (UHP) or tert-butylhydroperoxide (TBHP) as the oxidant. Under optimized reaction conditions (2 mol % catalyst, 3–4 equiv TBHP, CH2Cl2 as the solvent, 40 °C), the corresponding nitrones were obtained with different efficiency depending on the nature of the cyclic or acyclic amine used.
Keywords: Inorganic–organic hybrid materials; Oxomolybdenum catalysts; Oxidation; Secondary amines; Nitrones;

Reductive dechlorination of atrazine using sodium-borohydride catalysed by cobalt(II) phthalocyanines by Poonam; Pratibha Kumari; Sohail Ahmad; Shive Murat Singh Chauhan (7083-7086).
A series of functional metallophthalocyanines have been synthesized to study their role as a catalyst towards the reductive dechlorination of atrazine using sodium borohydride as a mild reducing agent. The cobalt(II) phthalocyanine bearing nitro groups at the peripheral position is the most efficient catalyst with exceptionally high catalytic activity in comparison to other functional cobalt(II) phthalocyanines.
Keywords: Metallophthalocyanines; Atrazine; Sodium borohydride; Reductive dechlorination;

A nickel-catalyzed process for the cross-coupling of mixed arylzincs and primary alkyl halides has been developed. The reaction of a methylarylzinc with a primary alkyl halide in THF in the presence of NiCl2/PPh3 takes place with selective aryl transfer at room temperature in moderate yields. This protocol provides an atom-economic alternative to aryl–primary alkyl coupling using diarylzincs.
Keywords: Alkylarylzincs; Mixed diorganozincs; Alkylation; Triphenylphosphine;

Investigation of copper(II) tetrafluoroborate catalysed epoxide opening by Amy S. Capes; Arthur T. Crossman; Lauren A. Webster; Michael A.J. Ferguson; Ian H. Gilbert (7091-7094).
We report the extension of the copper(II) tetrafluoroborate catalysed opening of epoxides with alcohols to include a wider variety of alcohols, a range of solvents and a method to purify the products from the reaction.
Keywords: Epoxide; Copper(II) tetrafluoroborate; Lewis acid; Alcohols;

Facile syntheses of 7,9-dimethoxypyrrolo[3,2,1-ij]quinolin-6-ones by Santosh Rajput; Chao-wei Leu; Kasey Wood; David StC Black; Naresh Kumar (7095-7098).
The activated dimethoxypyrrolo[3,2,1-ij]quinolin-6-one ring system was synthesized via two approaches, starting from an indole and quinolin-4-one, respectively. Subsequent demethylation led to both monohydroxy- and dihydroxypyrrolo[3,2,1-ij]quinolin-6-ones.
Keywords: Pyrrolo[3,2,1-ij]quinoline; Indole; Isoflavonoid; Phytoestrogen;

A new, one-pot, four-component condensation of 3-methyl-1H-pyrazol-5(4H)-one, ammonium acetate, aromatic aldehydes, and meldrum’s acid in [bmim]BF4 as solvent is described for the synthesis of 3-(5-amino-3-methyl-1H-pyrazol-4-yl)-3-arylpropanoic acid derivatives. This methodology resulting in excellent isolated yields in short reaction time is characterized by simple work up procedure and little environmental impact.
Keywords: Green chemistry; Multi-component reaction; [bmim]BF4; Aldehyde; Meldrum’s acid;

Direct synthesis of diamines has been efficiently realized from the N-alkylation of amines with diols by means of heterogeneous bimetallic Pt–Sn/γ-Al2O3 catalyst (0.5 wt % Pt, molar ratio Pt:Sn = 1:3) through a ‘Borrowing Hydrogen’ strategy under ligand-free conditions. The present methodology provides an environmentally benign route to diamines.

Lathrophytoic acids A and B: two novel polyprenylated phloroglucinol derivatives from Kielmeyera lathrophyton by Miquéias F. de Almeida; Maria L.S. Guedes; Frederico G. Cruz (7108-7112).
Two novel polyprenylated phloroglucinol derivatives were isolated from the trunk of Kielmeyera lathrophyton (Clusiaceae). Lathrophytoic acid A presented an unusual caged carbon skeleton with a 1,3-dione-4-cyclopentanol moiety. Lathrophytoic acid B exhibited a highly substituted bicycle[3.3.1]nonane skeleton and an isopropylfuran system which was formed by unusual cyclization of a prenyloxy side chain.
Keywords: Clusiaceae; Kielmeyera; Lathrophytoic acid; Phloroglucinol derivative; Natural product;

We report a very convenient laboratory preparation of pentachloroacetone (PCA) by selective dechlorination of hexachloroacetone (HCA) via reaction with triphenylphosphine in the presence of methanol or aromatic alcohols.
Keywords: Hexachloroacetone; Pentachloroacetone; Triphenylphosphine; Appel reaction; Chlorophosphonium salt; Aryloxyphosphonium salt;

Supramolecular AA/BB-type oligomer formation from a heterotetratopic bis-calix[5]arene monomer and octanediyldiammonium dichloride by Claudia Gargiulli; Giuseppe Gattuso; Anna Notti; Sebastiano Pappalardo; Melchiorre F. Parisi (7116-7120).
A novel bis-calix[5]arene (1) with divergent cavities was prepared in four steps starting from p-methylcalix[5]arene. This molecule is composed of two calix[5]-bis-crown-3 units held together, via their narrow rims, by a N,N″-1,4-phenylene-bis[N′-(2-ethenyloxyethyl)]diureido bridging moiety. Owing to the anion-binding ability of the ureido moieties embedded in its framework, bis-calix[5]arene 1 acts as a heterotetratopic monomer and, in the presence of 1,8-octanediyldiammonium dichloride, self-assembles into AA/BB-type polycapsular oligomers. Extensive 1H NMR investigations have demonstrated that the nature and stoichiometry of these supramolecular oligomers are strongly dependent on the concentration and the ratio of the two monomers.
Keywords: Calixarenes; Supramolecular polymers; Capsules; Diammonium ions; Ion pair complexation;

A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins by Nitin S. Nandurkar; Rico Petersen; Katrine Qvortrup; Vitaly V. Komnatnyy; Kennedy M. Taveras; Sebastian T. Le Quement; Robin Frauenlob; Michael Givskov; Thomas E. Nielsen (7121-7124).
An efficient method for the solid-phase synthesis of hydroxamic acids is described. The method comprises the nucleophilic displacement of esters immobilized on PEGA resins with hydroxylamine/sodium hydroxide in isopropanol. The hydroxyaminolysis protocol is compatible with a broad range of PEGA-supported peptide and peptidomimetic esters. The methodology was found to be compatible with two new strategies for the synthesis of solid-supported lactams and diketopiperazines, respectively, both relying on the high inter- and intramolecular reactivity of cyclic N-acyliminium ions with electron-rich aromatics and heteroaromatics, ultimately affording hydroxamic acid derivatives in high purities.
Keywords: Hydroxamic acids; Solid-phase synthesis; Hydroxylamine; HDAC inhibitor; PEGA resin;

Ikirydinium A: a new indole alkaloid from the seeds of Hunteria umbellata (K. Schum) by Olusegun S. Ajala; Andrew M. Piggott; Fabien Plisson; Zeinab Khalil; Xiao-cong Huang; Sunday A. Adesegun; Herbert A.B. Coker; Robert J. Capon (7125-7127).
Chemical investigations into samples of Hunteria umbellata (K. Schum) collected in Osun State, Nigeria, led to the discovery of a new indole alkaloid, ikirydinium A, featuring an unprecedented 3-alkylpyridinium-indole-2-carboxylate scaffold. Ikirydinium A was found to exhibit antimicrobial activity (IC50  0.6 μM) against Bacillus subtilis ATCC 6051. The involvement of a common intermediate in the biosynthesis of ikirydinium A and vinblastine is hypothesized.
Keywords: Indole alkaloids; Hunteria umbellata; Nigerian medicinal plant; Natural products chemistry;

A ring-closing metathesis approach to secosteroidal macrocycles by Malika Ibrahim-Ouali; Jamel Zoubir; Eugénie Romero (7128-7131).
An efficient synthesis of B- and C-secosteroids is described via a ring-closing metathesis reaction.An efficient synthesis of secosteroidal macrocycles has been achieved via an oxidative ring-expansion/ring-opening sequence and a ring-closing metathesis reaction as the key steps.
Keywords: Secocholane; Baeyer–Villiger oxidation; Macrocyclization; Ring-closing metathesis (RCM);

The N-hydroxybenzotriazole (HOBt) sulfonate esters undergo amidation under ambient conditions in the presence of di-isopropylethyl amine. This method can be applied to varieties of amines including sterically hindered amino acid esters in less time with reasonably good yields.HOBt ester of sulfonic acids can be a replacement for pentafluorophenyl and trichlorophenyl ester as well as chloride moiety of sulfonyl chloride for amidation.
Keywords: N-Hydroxybenzotriazole sulfonate; Sulfonamide; Aminolysis; Di-isopropyl ethyl amine;

Reversible modification of oligodeoxynucleotides: click reaction at phosphate group and alkali treatment by Kazuhito Tanabe; Yuichirou Ando; Sei-ichi Nishimoto (7135-7137).
We characterized click reaction between oligodeoxynucleotides (ODNs) possessing acetylene groups at the phosphate unit and azide compounds. Cu(I)-catalyzed cycloaddition proceeded efficiently to form the corresponding functional ODNs. The resulting ODNs could be converted into ordinary ODNs by treatment with aqueous methylamine. The present method successfully achieved a reversible modification of ODNs.
Keywords: Click reaction; Postsynthetic-modification method; Oligodeoxynucleotides; Alkali treatment;

Neighbouring group participation in the reaction of 7-oxo-ent-kaur-16-ene derivatives with diacetoxyiodobenzene. Synthesis of gibberellin analogues by Braulio M. Fraga; Carlo Bressa; Victoria González-Vallejo; Sergio Suárez; Ricardo Guillermo (7138-7140).
The reaction of different 7-oxo-ent-kaur-16-ene derivatives with diacetoxyiodobenzene has been evaluated for the preparation of gibberellin analogues. Thus, the reaction of 7-oxo-ent-kaur-16-en-18-oic acid methyl ester (3) with this reagent afforded 4-epi-GA12 dimethyl ester (6). This reaction constitutes a good procedure for the preparation of this type of compounds. In some cases, alternative reactions that led to the introduction in the substrate of a conjugated 5,6-double bond or to the formation of a ketal at the 6-position were also produced. The formation of these compounds, or of gibberellin analogues, depends on the neighbouring group participation of the different C-18 and C-19 substituents at C-4.
Keywords: Diacetoxyiodobenzene; ent-Kaur-16-ene; Ring contraction; Anchimeric assistance; 4-epi-Gibberellin A12;

p-Iodinations in hydrocarbon media: continuous flow reactor application by D.W. Slocum; Kristen C. Tekin; Quang Nguyen; Paul E. Whitley; Thomas K. Reinscheld; Begum Fouzia (7141-7145).
Regiospecific iodination of aryl amines, that is, aryl compounds possessing strong electron donating groups (EDG’s) in the p-position, is described. This procedure features not only the unique use of hydrocarbon media for such substitutions but also the absence of any oxidants aside from iodine itself. Further potential of this hydrocarbon media based electrophilic aromatic substitution is demonstrated by the coupling of the iodination with an in situ halogen/lithium exchange and product forming nucleophilic addition in a batch process. The protocol was ultimately scaled to a continuous flow reactor using an isolated p-iodoarylamine. Constituted as described, these procedures possess enhanced atom-economical, green and safety aspects compared to existing literature protocols.
Keywords: Iodination; Continuous flow reactor; Electrophilic aromatic substitution; Green chemistry; Halogen/metal exchange;

Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide by Youhei Sohma; Hitomi Kitamura; Hiroyuki Kawashima; Hironobu Hojo; Masayuki Yamashita; Kenichi Akaji; Yoshiaki Kiso (7146-7148).
By using dimethylformamide to suppress the O-to-N acyl migration, we efficiently synthesized an O-acyl isopeptide by native chemical ligation of a peptide-thioester and a Cys-O-acyl isopeptide. The reaction mixture was then loaded onto an octadecylsilane reverse-phase HPLC column, and the isopeptide was purified by using a linear gradient of CH3CN in 0.1% aqueous trifluoroacetic acid. The recovery rate of the O-acyl isopeptide was considerably higher than that of the corresponding native polypeptide. Synthesis of O-acyl isopeptides via native chemical ligation, with O-to-N acyl migration as the final step to give the native form, has potential as an efficient method of constructing hydrophobic polypeptides.
Keywords: O-Acyl isopeptide; HPLC; Hydrophobic peptide; Native chemical ligation; Purification;

A simple conversion of azlactones into indenones via H3PW12O40/Al2O3 catalyzed intramolecular Friedel–Crafts reaction by Mahboubeh Rostami; Ahmad R. Khosropour; Valiollah Mirkhani; Majid Moghadam; Shahram Tangestaninejad; Iraj Mohammadpoor-Baltork (7149-7152).
A rapid and simple procedure for the synthesis of the indenone derivatives, N-(1-oxo-1H-inden-2-yl)benzamides, via intramolecular Friedel–Crafts (IFC) reaction of (Z)-4-arylidene-2-phenyl-5(4)-oxazolones (azlactones) catalyzed by H3PW12O40 supported on neutral alumina under microwave irradiation has been developed. The reaction is straightforward and allows easy isolation of the product. The catalyst could be re-used up to four times after simple filtration.
Keywords: Indenones; Azlactones; Intramolecular Friedel–Crafts reaction; Microwave irradiation; H3PW12O40/Al2O3;

N-heterocyclic carbene (NHC) has been employed as an efficient catalyst for cyanation reaction of carbonyl compounds. Under catalysis of 1 mol % NHCs, various aldehydes and 2,2,2-trifluoroacetophenone coupled with ethyl cyanoformate in THF to provide cyanohydrins ethyl carbonates in excellent yields. While in the presence of 10 mol % catalyst, different types of aldehydes and 2,2,2-trifluoroacetophenone reacted with acetyl cyanide in dichloroethane to give acylated cyanohydrins in moderate to high yields.
Keywords: N-heterocyclic carbenes; Cyanation reaction; Carbonyl compounds; Ethyl cyanoformate; Acetyl cyanide;

A facile and operationally simple route to diastereomerically pure, natural-like 3-azabicyclo[3.3.1]non-6-enes via microwave-assisted, BF3·OEt2-promoted aza-Prins reaction has been developed. Complexity-generating transformations based on these products involving reactive functionalities introduced during the aza-Prins step have been developed.
Keywords: Microwave-assisted organic synthesis; aza-Prins reaction; Diastereoselective synthesis; Bicyclic piperidines; Lycopodium alkaloids; Complexity-generating synthesis;

Microwave-assisted aza-Prins reaction. Part 2: straightforward access to 2,6-disubstituted 1-azaadamantanes by Vladislav Parchinsky; Alexei Shumsky; Mikhail Krasavin (7161-7163).
Novel symmetrically and unsymmetrically disubstituted 1-azaadamantanes were prepared as a single, chiral diastereomer via double microwave-assisted aza-Prins cyclization in one-pot or sequential reaction format.
Keywords: Azaadamantanes; Aza-Prins reaction; Microwave-assisted organic synthesis; Diastereoselective reaction; Chiral base; Reversible reaction;

Fabrications of potential imaging probes based on a β-alkyl substituted porphyrin with a terpyridine external coordination site by Masaaki Suzuki; Tomoya Uehara; Yasushi Arano; Tyuji Hoshino; Saburo Neya (7164-7167).
We report synthesis and coordination properties of β-alkyl porphyrin derivatives bearing terpyridylphenyl substituents at the meso-position and propionate side chains at the β-positions. Rhenium(I) carbonyl ion was encapsulated not in the core but in the external terpyridyl ligand. Such porphyrin–terpyridine hybrid porphyrins can be potentially available for less-invasive imaging like SPECT.
Keywords: Porphyrin; Terpyridine; Metal complex; Rhenium tricarbonyl; SPECT;

Intermolecular hydroamination of vinylarenes and anilines was studied using zinc triflate as catalyst. NMR experiments supported a Lewis acid activation of the C=C double bond. Electronic/steric effect study indicated that Lewis acidity of the catalyst as well as the coordination property of the amine were the governing factors for successful hydroamination of the substrates. More nucleophilic amine would bind more tightly to the central metal, leading to an unproductive coordination. Approach of bulky amine to C=C bond would be hindered, and an alternative electrophilic substitution on benzene ring of the amine would become the major reaction. Electrophilic substitution would become predominant when strong electron-donating group is presented on aniline benzene ring.
Keywords: Zinc triflate; Styrene; Aniline; Hydroamination; Hydroarylation;

An efficient and convenient bimetallic MnF2/CuI catalyst in combination with trans-1,2-diaminocyclohexane has been developed for the cross-coupling of nitrogen heterocycles with aryl halides in water.An efficient and convenient bimetallic MnF2/CuI catalyst in combination with trans-1,2-diaminocyclohexane has been developed for the cross-coupling of nitrogen heterocycles with aryl halides in water at moderate temperature. A variety of nitrogen nucleophiles including pyrazole, 7-azaindole, indazole, indole, pyrrole and imidazole afforded the corresponding products in moderate to good yields (up to 94%) under the described arylation conditions.
Keywords: Manganese; Copper; Bimetallic; Coupling; N-arylation;

Total synthesis of 3,5-O-dicaffeoylquinic acid and its derivatives by K. Saki Raheem; Nigel P. Botting; Gary Williamson; Denis Barron (7175-7177).
We report the first total synthesis of 3,5-O-dicaffeoylquinic acid and its derivatives, 3,5-O-diferuloylquinic acid and 3,5-(3,4-dimethoxycinnamyl)quinic acid, in a nine-step sequence. The key step involves Knoevenagel condensations between vanillin, 3,4-dimethoxybenzaldehyde or 4-hydroxy-3-methoxybenzaldehyde and the dimalonate ester of quinic acid.
Keywords: Dicaffeoylquinic acids; Natural product synthesis; Knoevenagel condensation; Metabolism references; Plant natural products;

Improved Hiyama cross-coupling reactions using HOMSi® reagents: a novel application of a palladacycle by Sebastian M. Marcuccio; Ruwan Epa; Maisa Moslmani; Andrew B. Hughes (7178-7181).
Various parameters in the Hiyama cross-coupling reaction of HOMSi® reagents with ethyl bromobenzoate were studied. These included solvent, ligand, palladium source, and added water. DMF and THF were found to be excellent solvents. Palladium chloride was found to be the best palladium source and no added water was required. The use of tri-o-tolylphosphine as the ligand proved to be particularly effective.
Keywords: HOMSi®; Hiyama reaction; Palladacycle; Tri-o-tolylphosphine; Cross-coupling;

A facile synthesis of novel 1,4-benzoxazepin-2-one derivatives by Fatemeh Khaleghi; Laily Bin Din; Ibrahim Jantan; Wan Ahmad Yaacob; Mohammad A. Khalilzadeh (7182-7184).
An efficient and simple synthesis of 1,4-benzoxazepin-2-one derivatives has been achieved via the reaction of isoquinoline, activated acetylenes, and 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone in water without using any catalyst. This one-pot reaction occurs in high yields under mild conditions.

Ring cleavage of dihydropyrimidine skeleton by Hidetsura Cho; Eunsang Kwon; Yoshizumi Yasui; Satoshi Kobayashi; Shin-ichiro Yoshida; Yoshio Nishimura; Masahiko Yamaguchi (7185-7188).
The first observation of ring cleavage between positions 1 and 2 of a 1,4-dihydropyrimidine skeleton was reported upon the nucleophilic addition of 4,6-unsubstituted 1,4-dihydropyrimidine with 3 equiv of an aniline derivative or phenylhydrazine in the presence of 0.1 equiv of pyridinium p-toluenesulfonate (PPTS) in CH2Cl2; the nucleophilic reactions of 4-methyl-6-unsubstituted 1,6(3,4)-dihydropyrimidine with the same amines gave conventional substituted products at position 2. The effect of this ring opening was found to be due to the electron density of the benzene ring of a nucleophilic amine. On the other hand, aralkylamines, alkylamines, or heterocyclic amines did not cleave the skeleton. The ring-opening chemical structure was confirmed by X-ray crystallographic analysis. This characteristically different phenomenon may be due to the pattern of two C=C double bonds of 1,4-DP and 1,6(3,4)-DP as well as to the effect of two substituted groups on the DP ring.
Keywords: Dihydropyrimidine; Ring cleavage; Ring opening; Dihydropyrimidine skeleton;

A new synthetic approach toward the synthesis of flavones and pyranoflavone has been developed by light induced intramolecular photochemical Wittig reaction in water onto aryloxycarbonyl groups and suitably substituted phosphonium bromides sans any phase transfer catalyst or promoter.
Keywords: Intramolecular photochemical Wittig reaction; Phosphoranyl radical; Betaine; Flavones; Water;

A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6 has been developed by domino coupling of phthalhydrazide, 1,3-diketones, and aldehydes under solvent-free conditions at 80 °C as well as under solvent-free ultrasound irradiation at room temperature promoted by (S)-camphorsulfonic acid.
Keywords: Ultrasound irradiation; Solvent-free conditions; Indazolo[2,1-b]phthalazine-1,6,11-triones; Pyrazolo[1,2-b]phthalazine-5,10-diones; (S)-Camphorsulfonic acid; One-pot three-component reaction;

Base-induced photorearrangements from 3-styrylfurans to 2-methylnaphthalenes by Jinn-Hsuan Ho; Tunng-Hsien Lee; Chia-Kai Lo; Chao-Li Chuang (7199-7201).
Irradiation of 3-(4-substituted styryl)furans in basic media yielded a series of 7-substituted-2-methylnaphthalenes, including methoxy, isopropyl, ethyl, methyl, fluoro, and cyano substituents. This base-induced photorearrangement involves cistrans photoisomerization, 6e photocyclization, base-induced elimination, and a Norrish Type I photoreaction and is a novel method to synthesize unsymmetrical 2,7-disubstituted naphthalenes.
Keywords: Base-induced photorearrangement; Photocyclization; 3-Styrylfurans; 2-Methylnaphthalenes;

Synthesis of medium-sized carbocyclic ketones via the intramolecular B-alkyl Liebeskind–Srogl coupling reaction is described. The sequence of hydroboration of ω-alkenyl thiol ester with 9-BBN and the Liebeskind–Srogl reaction results in the formation of medium-sized carbocyclic ketones with good yield.
Keywords: Medium-sized carbocyclic ketone; Intramolecular coupling reaction; Liebeskind–Srogl coupling reaction; Palladium-mediated reaction;