Organic & Biomolecular Chemistry (v.17, #32)

Front cover (7429-7430).

Contents list (7431-7437).

Transition-metal-free direct nucleophilic substitution of carboranyllithium and 2-halopyridines by Ju-You Lu; Bo Zhao; Yongmei Du; Jianxin Yang; Jian Lu (7438-7441).
A practical and efficient C(cage)–heteroarylation of carborane is presented, via direct nucleophilic substitution of carboranyllithium with 2-halopyridines. This reaction does not need the aid of any transition metal and utilizes readily available carboranyllithium nucleophiles, thereby avoiding transmetalation of carboranyllithium. The process exhibits a broad scope, and a vast array of 2-halopyridines have proven to be suitable substrates. The method serves as a complement to C(cage)–arylation reactions and may find wide applications in materials science and medicinal and coordination chemistry.

The possible reaction mechanism and origin of stereoselectivity of the NHC-catalyzed annulation reaction between isatin-derived enals and hydrazones were theoretically studied by using density functional theory (DFT). According to the computational results, the Michael addition process was identified to be the stereoselectivity determining step and led to the experimentally observed S-configured product predominantly. The distortion–interaction analysis showed that the electrostatic interaction between two interactive fragments controls the stereoselectivity. Moreover, the types of interactions were further verified by non-covalent interaction analysis, in which the π⋯π, C–H⋯F and LP⋯π interactions involved in the favorable transition state are the key for determining the stereoselectivity.

In-depth, systematic photophysical studies have been performed on a series of ABAB, A3B and A4 ZnPcs functionalized with a varying number of bis(trifluoromethyl)phenyl units (i.e. at the B isoindoles) and other electron-withdrawing/electron-donating moieties (i.e. at the A isoindoles), to determine the influence of the susbtitution pattern on the aggregation features, fluorescence quantum yields and singlet oxygen (1O2) generation abilities of these molecules. As a general trend, the larger the number of bis(trifluoromethyl)phenyl units (i.e.ABAB crosswise functionalized ZnPcs), the lower the fluorescence quantum yield and the higher the 1O2 photosensitization. On the other hand, the electronic character of the substituents at the A isoindoles do not seem to have a clear effect on the photophysical properties of these ABAB ZnPcs. Overall, 1O2 quantum yields determined by the direct observation of the 1O2 phosphorescence are very high, with values ranging from 1 to 0.74 in THF solutions.

Copper(i)-catalyzed benzylation of triazolopyridine through direct C–H functionalization by Madhava Reddy Lonka; Jinquan Zhang; Thirupathi Gogula; Hongbin Zou (7455-7460).
A general and efficient copper-catalyzed benzylation reaction of triazolopyridine with N-tosylhydrazones was developed. This reaction forms a C(sp2)–C(sp3) bond through cross-coupling, and represents an exceedingly practical method to afford 3-benzylated triazolopyridines in moderate to good yields. A proposed mechanistic pathway underlying this reaction was outlined. This catalytic transformation should enable broad synthetic applications in functionalization chemistry, allowing the synthesis of new pharmaceutically relevant triazolopyridine derivatives.

An efficient tandem synthesis of chromones from o-bromoaryl ynones and benzaldehyde oxime by Jing-Wen Zhang; Wan-Wan Yang; Lu-Lu Chen; Pei Chen; Yan-Bo Wang; Dan-Yun Chen (7461-7467).
An effective transition-metal-free strategy was developed for the preparation of chromones from o-bromoaryl ynones and benzaldehyde oxime through sequential C–O bond formation. This cyclization reaction could well tolerate a wide range of functional groups, and the corresponding chromones were given in moderate to excellent yields. Mechanistically, benzaldehyde oxime as a hydroxide source and 1,3-diketone derivatives as reaction intermediates were involved in this transformation.

An unprecedented arylselenylation of aryl halides with trifluoromethyl aryl selenonium ylides in the presence of copper is described. The reaction proceeded at 100–140 °C under ligand- and additive-free conditions for 3–20 h to form a variety of unsymmetrical diaryl selenides in good to high yields. Arylselenylation is easy to operate, has good functional group tolerance, and demonstrates the different reaction profiles of trifluoromethyl aryl selenonium ylides from the homologous trifluoromethyl aryl sulfonium ylides.

TetraPh-Tol-BITIOPO: a new atropisomeric 3,3′-bithiophene based phosphine oxide as an organocatalyst in Lewis base-catalyzed Lewis acid mediated reactions by Abbinante Vincenzo Mirco; Benaglia Maurizio; Rossi Sergio; Benincori Tiziana; Cirilli Roberto; Pierini Marco (7474-7481).
A new chiral phosphine oxide based on a 3,3′-bithiophene scaffold (TetraPh-Tol-BITIOPO) was synthesized, fully characterized and separated into antipodes through chiral HPLC. This new compound was successfully employed as an organocatalyst in Lewis base-catalyzed Lewis acid mediated reactions involving trichlorosilyl compounds. The new atropisomeric catalyst was able to promote the allylation of aldehydes with allyltrichlorosilane in up to 98% yield and up to 96% enantiomeric excess (ee), and the direct aldol reaction to afford β-hydroxy ketones and β-hydroxy thioesters, with good chemical yields and modest stereochemical efficiency. Computational studies helped to elucidate and to rationalize the stereochemical outcome of the reactions catalyzed by TetraPh-Tol-BITIOPO that was found to favour the formation of the isomer with an opposite absolute configuration in comparison with the products obtained with the previously reported 3,3′-bithiophene-based catalyst.

A calix[4]arene with acylguanidine units as an efficient catalyst for phosphodiester bond cleavage in RNA and DNA model compounds by Riccardo Salvio; Stefano Volpi; Tommaso Folcarelli; Alessandro Casnati; Roberta Cacciapaglia (7482-7492).
A calix[4]arene scaffold, blocked in the cone conformation and decorated at the upper rim with two acylguanidine units, effectively catalyzes the cleavage of phosphodiester bonds of HPNP and BNPP under neutral pH conditions. The catalyst performance is discussed in terms of acceleration over background hydrolysis and effective molarity (EM). The combination of potentiometric acid–base titrations with pH-rate profiles for HPNP and BNPP cleavage in the presence of 2·2HCl additives points to a marked synergic action of an acylguanidine/acylguanidinium catalytic dyad in 2H+, via general base–electrophilic bifunctional catalysis. Acceleration factors over background larger than 3 orders of magnitude are obtained. The connection of the guanidine/guanidinium dyad to the calixarene scaffold by means of carbonyl joints has a double advantage: (i) the acidity of the guanidinium moiety is enhanced by the electron-withdrawing carbonyl group and maximum conversion into the catalytically active form 2H+ occurs at almost neutral pH, lower than the pH needed for the monoprotonated form 1H+ devoid of carbonyl groups; (ii) the EM value for HPNP cleavage with 2H+ is definitely higher than that with 1H+, suggesting a highly preorganized catalyst that perfectly fits in a strainless ring-shaped transition state in the catalyzed process. DFT calculations also provide useful insights into the reaction mechanisms and transition states.

An enzymatic Finkelstein reaction: fluorinase catalyses direct halogen exchange by Phillip T. Lowe; Steven L. Cobb; David O'Hagan (7493-7496).
The fluorinase enzyme from Streptomyces cattleya is shown to catalyse a direct displacement of bromide and iodide by fluoride ion from 5′-bromodeoxyadenosine (5′-BrDA) and 5′-iododeoxyadenosine (5′-IDA) respectively to form 5′-fluorodeoxyadenosine (5′-FDA) in the absence of l-methionine (l-Met) or S-adenosyl-l-methionine (SAM). 5′-BrDA is the most efficient substrate for this enzyme catalysed Finkelstein reaction.

Logic gate behavior and intracellular application of a fluorescent molecular switch for the detection of Fe3+ and cascade sensing of F in pure aqueous media by Romi Dwivedi; Divya P. Singh; Saumya Singh; Ashish K. Singh; Brijesh S. Chauhan; S. Srikrishna; Vinod P. Singh (7497-7506).
The nature and coordination sites of the Schiff base 3,3′-(1E,1′E)-(1,3-phenylenebis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)dinaphthalen-2-ol (APHN) were tuned by its selective reduction to design a highly efficient fluorescent probe, 3,3′-(pyridine-2,6-diylbis(azanediyl))bis(methylene)dinaphthalen-2-ol (RAPHN). The structures of APHN, RAPHN, and the RAPHN–Fe3+ complex were satisfactorily modeled from the results of density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. RAPHN worked in pure aqueous medium as a turn on–off–on probe of Fe3+ and F. The fluorescence nature of the probe in the presence and absence of Fe3+/F was regulated by a set of mechanisms including –CHN isomerization and LMCT. A 2 : 1 (M : L) binding stoichiometry was established from a fluorescence Job's plot and further substantiated from HR–MS studies. The limits of detection of RAPHN for Fe3+ and RAPHN–Fe3+ for F were found to be 2.49 × 10−7 M and 1.09 × 10−7 M, respectively. The RAPHN probe caused no cytotoxicity in gut tissue of Drosophila even at high concentrations. The probe displayed excellent bioimaging applications for detection of Fe3+ and F in gut tissue of Drosophila. A combinatorial logic gate was constructed for the proper understanding of the working principle of RAPHN.

Bio-inspired enantioselective total syntheses of (−)-viminalins A, B, H, I, and N, isolated from the Myrtaceae family, were accomplished in a convergent fashion in 5, 5, 1, 1, and 3 steps, respectively. A highly regio- and diastereoselective oxidative [3 + 2] cycloaddition reaction of acylphloroglucinols with α-phellandrene, diastereoselective modified Friedel–Crafts reaction of acylphloroglucinols with piperetol, and stereoselective epoxidation of extremely hindered β-face were described as key reactions.

Ruthenium(ii)-catalysed selective C(sp2)–H bond benzoxylation of biologically appealing N-arylisoindolinones by Yu-Chao Yuan; Christian Bruneau; Thierry Roisnel; Rafael Gramage-Doria (7517-7525).
Site- and regio-selective aromatic C–H bond benzoxylations were found to take place using biologically appealing N-arylisoindolinones under ruthenium(ii) catalysis in the presence of (hetero)aromatic carboxylic acid derivatives as coupling partners. Besides the presence of two potential C(sp2)–H sites available for functionalization in the substrates, exclusive ortho selectivity was achieved in the phenyl ring attached to the nitrogen atom. Notably, the reactions occurred in a selective manner as only mono-functionalized products were formed and they tolerated a large number of functional chemical groups. The ability of the cyclic tertiary amide within the isoindolinone skeleton to act as a weak directing group in order to accommodate six-membered ring ruthenacycle intermediates appears to be the key to reach such high levels of selectivity. In contrast, the more sterically demanding cyclic imides were unreactive under identical reaction conditions.

An efficient synthesis of oxazolines via a cascade reaction between azaoxyallyl cations and 1,2-benzisoxazoles by Li Sun; Yi Liu; Yankai Wang; Yuanyuan Li; Zhiwen Liu; Tao Lu; Wenhai Li (7526-7530).
A formal [3 + 2] cycloaddition reaction between the C and O terminals of azaoxyallyl cations formed in situ and 1,2-benzisoxazoles has been realized. This one-pot cycloaddition method provided an effective and practical pathway to synthesize oxazoline in good yields under mild conditions. The title products exhibited unique fluorescence properties.

Synthesis of glycosyl chlorides using catalytic Appel conditions by Imlirenla Pongener; Kirill Nikitin; Eoghan M. McGarrigle (7531-7535).
The stereoselective synthesis of glycosyl chlorides using catalytic Appel conditions is described. Good yields of α-glycosyl chlorides were obtained using a range of glycosyl hemiacetals, oxalyl chloride and 5 mol% Ph3PO. For 2-deoxysugars treatment of the corresponding hemiacetals with oxalyl chloride without phosphine oxide catalyst also gave good yields of glycosyl chloride. The method is operationaly simple and the 5 mol% phosphine oxide by-product can be removed easily. Alternatively a one-pot, multi-catalyst glycosylation can be carried out to transform the glycosyl hemiacetal directly to a glycoside.

We developed a catalyst-, reagent-, and additive-free protocol with 100% atom economy for the synthesis of diarylmethyl phosphine oxides via 1,6-hydrophosphonylation of p-quinone methides using water as a green solvent. The reaction showed broad scope with excellent functional group tolerance. The practicability of this method was demonstrated by carrying out the reaction on the gram scale whereby product was obtained in high yield by the filtration technique avoiding chromatographic purification.

A facile, one-pot method for the de novo synthesis of benzofurans from 2-hydroxy-1,4-diones is described. Using trifluoroacetic acid (TFA) as the catalyst and N-bromobutanimide (NBS) as the oxidant, 2-hydroxy-1,4-diones underwent a cyclization/oxidative aromatization cascade reaction to afford a variety of benzofuran derivatives in moderate to good yields. This is a practically useful method for the synthesis of benzofuran derivatives starting from 2-hydroxy-1,4-diones which is also a supplement of the Paal–Knorr furan synthesis. A preliminary mechanism study was undertaken to support the proposed mechanism during which a novel 1,6-conjugate addition reaction was revealed.

Copper-catalyzed acylation of pyrazolones with aldehydes to afford 4-acylpyrazolones by Yan Xiao; Xiaopeng Wu; Jiangang Teng; Song Sun; Jin-Tao Yu; Jiang Cheng (7552-7557).
Copper-catalyzed direct acylation of the alkenyl C–H bond in 1,2-dihydro-3H-pyrazol-3-ones has been developed, affording a series of 4-acylpyrazolones in moderate to good yields. Notably, this protocol involves readily accessible substrates and reagents, which have good functional group tolerance leading to pyrazolone derivatives under mild reaction conditions.

Trichloroacetonitrile as an efficient activating agent for the ipso-hydroxylation of arylboronic acids to phenolic compounds by Yuanding Fang; Rong Zhao; Yuan Yao; Yang Liu; Denghu Chang; Ming Yao; Lei Shi (7558-7563).
A metal-free and base-free Cl3CCN mediated method was developed for the ipso-hydroxylation of aryl boronic acids to their corresponding phenols, which was promoted by a key unstable Lewis adduct intermediate. This transformation has broad functional group tolerance, and late-stage functionalization was successful as well. After simple investigation, two pathways (radical/ionic mechanism) were suggested, and the beneficial action of blue light needs to be further studied.

Ruthenium-catalyzed remote C5-sulfonation of N-alkyl-8-aminoquinolines by Xuri Liu; Han Zhang; Fanzhi Yang; Bo Wang (7564-7568).
There is an increasing demand for the methodologies of positionally selective remote C–H functionalizations. We herein report the ruthenium-catalyzed remote C5-selective sulfonation of 8-aminoquinoline derivatives. Moderate to high yields were obtained with different substituted substrates. The catalytic system exhibited a high regio-selectivity, as well as good functional group tolerance. Mechanistic study supported a radical pathway. A bifunctional ruthenium-catalytic cycle is proposed.

Pd-Catalyzed sequential hydroarylation and olefination reactions of 3-allylchromones by Yi-En Liang; Chia-Ling Lu; Wen-Tai Li (7569-7583).
In this paper, a novel approach to regioselective α- or γ-hydroarylation of 3-allylchromones with electron-rich arenes has been presented. Results of this study indicated that the regioselectivity was dependent on the substituent at the γ-position of the allyl group. Hydrogen or alkyl substitution favored α-hydroarylation, whereas aryl substitution favored γ-hydroarylation. This methodology provides an efficient means to achieve the α- or γ-selective hydroarylation of 3-allylchromones. Application of α-hydroarylation to perform Pd-catalyzed one-pot sequential α-hydroarylation and π-chelation-assisted olefination has also been reported.

Back cover (7585-7586).