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Hexafluoroisopropanol is typically considered as an unreactive solvent and not as a reagent in organic synthesis. Herein, we report on a mild and efficient photochemical reaction of aryl diazoacetates with hexafluoroisopropanol that enables, under stoichiometric reaction conditions, the synthesis of fluorinated ethers in excellent yield. Mechanistic studies indicate there is a preorganization of hexafluoroisopropanol and the diazoalkane acts as an unreactive hydrogen‐bonding complex. Only after photoexcitation does this complex undergo a protonation‐substitution reaction to the reaction product. Investigations on the applicability of this photochemical transformation show that a broad variety of acidic alcohols can be subjected to this transformation and thus demonstrate the feasibility of this concept for O‐H functionalization reactions (54 examples, up to 98 % yield). [ABSTRACT FROM AUTHOR]

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Three visible‐light responsive photoswitches are reported, azobis(1‐methyl‐benzimidazole) (1), azobis(benzoxazole) (2) and azobis(benzothiazole) (3). Photostationary distributions are obtained upon irradiation with visible light comprising approximately 80 % of the thermally unstable isomer, with thermal half‐lives up to 8 min and are mostly invariant to solvent. On protonation, compound 1H+ has absorption extending beyond 600 nm, allowing switching with yellow light, and a thermal half‐life just under 5 minutes. The two isomers have significantly different pKa values, offering potential as a pH switch. The absorption spectra of 2 and 3 are insensitive to acid, although changes in the thermal half‐life of 3 indicate more basic intermediates that significantly influence the thermal barrier to isomerization. These findings are supported by high‐level ab initio calculations, which validate that protonation occurs on the ring nitrogen and that the Z isomer is more basic in all cases. [ABSTRACT FROM AUTHOR]

Tropylium bromide undergoes noncatalyzed, regioselective additions to a large variety of Michael acceptors. In this way, acrylic esters are converted into β‐bromo‐α‐cycloheptatrienylpropionic esters. The reactions are interpreted as nucleophilic attack of bromide ions at the electron‐deficient olefins and the approach of the tropylium ion to the incipient carbanion. Quantum chemical calculations were performed to elucidate the analogy to the amine‐ or phosphine‐catalyzed Rauhut–Currier reactions. Subsequent synthetic transformations of the bromo‐cycloheptatrienylated adducts are reported. [ABSTRACT FROM AUTHOR]

The functionalization of C−H bonds with non‐precious metal catalysts is an important research area for the development of efficient and sustainable processes. Herein, we describe the development of iron porphyrin catalyzed reactions of diazoacetonitrile with N‐heterocycles yielding important precursors of tryptamines, along with experimental mechanistic studies and proof‐of‐concept studies of an enzymatic process with YfeX enzyme. By using readily available FeTPPCl, we achieved the highly efficient C−H functionalization of indole and indazole heterocycles. These transformations feature mild reaction conditions, excellent yields with broad functional group tolerance, can be conducted on gram scale, and thus provide a unique streamlined access to tryptamines. An iron porphyrin catalyst furnishes acetonitrile‐functionalized indole derivatives by C−H functionalization reactions of protected and unprotected indole heterocycles with diazoacetonitrile. This process streamlines the synthesis of valuable tryptamines for applications in total synthesis and drug discovery. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Predicting the fragmentation patterns of proteins would be beneficial for the reliable identification of intact proteins by mass spectrometry. However, the ability to accurately make such predictions remains elusive. An approach to predict the specific cleavage sites in whole proteins resulting from collision‐induced dissociation by use of an improved electrostatic model for calculating the proton configurations of highly‐charged protein ions is reported. Using ubiquitin, cytochrome c, lysozyme and β‐lactoglobulin as prototypical proteins, this approach can be used to predict the fragmentation patterns of intact proteins. For sufficiently highly charged proteins, specific cleavages occur near the first low‐basicity amino acid residues that are protonated with increasing charge state. Hybrid QM/QM′ (QM=quantum mechanics) and molecular dynamics (MD) simulations and energy‐resolved collision‐induced dissociation measurements indicated that the barrier to the specific dissociation of the protonated amide backbone bond is significantly lower than competitive charge remote fragmentation. Unlike highly charged peptides, the protons at low‐basicity sites in highly charged protein ions can be confined to a limited sequence of low‐basicity amino acid residues by electrostatic repulsion, which results in highly specific fragmentation near the site of protonation. This research suggests that the optimal charge states to form specific sequence ions of intact proteins in higher abundances than the use of less specific ion dissociation methods can be predicted a priori. Specific bond cleavage of highly charged protein ions can result from the protonation of low‐basicity amino acid residues. An approach to predict the specific cleavage sites in whole proteins was developed, using ubiquitin, cytochrome c, lysozyme, and β‐lactoglobulin as prototypical proteins. [ABSTRACT FROM AUTHOR]

Three Pd(II) phthalocyanine–carotenoid dyads featuring chromophores linked by amide bonds were prepared in order to investigate the rate of triplet–triplet (T‐T) energy transfer from the tetrapyrrole to the covalently attached carotenoid as a function of the number of conjugated double bonds in the carotenoid. Carotenoids having 9, 10 and 11 conjugated double bonds were studied. Transient absorption measurements show that intersystem crossing in the Pd(II) phthalocyanine takes place in 10 ps in each case and that T‐T energy transfer occurs in 126, 81 and 132 ps in the dyads bearing 9, 10 and 11 double bond carotenoids, respectively. To identify the origin of this variation in T‐T energy transfer rates, density functional theory (DFT) was used to calculate the T‐T electronic coupling in the three dyads. According to the calculations, the primary reason for the observed T‐T energy transfer trend is larger T‐T electronic coupling between the tetrapyrrole and the 10‐double bond carotenoid. A methyl group adjacent to the amide linker that connects the Pd(II) phthalocyanine and the carotenoid in the 9 and 11‐double bond carotenoids is absent in the 10‐double bond carotenoid, and this difference alters its electronic structure to increase the coupling. Three Pd(II) phthalocyanine–carotenoid dyads with the two chromophores linked by amide bonds were prepared to study the triplet–triplet (T‐T) energy transfer from the tetrapyrrole to the carotenoid as a function of the number of conjugated double bonds in the carotenoid. Experimentally T‐T energy transfer was found to be faster in the 10 double bond carotenoid than in ones having 9 or 11 double bonds. DFT calculations indicated that the methyl group on the polyene chain adjacent to the amide linker was a primary structural feature that modulates the T‐T electronic coupling and therefore the T‐T energy transfer rate. [ABSTRACT FROM AUTHOR]

The hydration of alkynes is one of the most atom‐economic and versatile synthetic protocols to access carbonyl compounds. This fundamental reaction, however, often requires transition‐metal catalysts or harsh reaction conditions to promote the addition of water to the carbon–carbon triple bond. In this work, it is demonstrated that the non‐benzenoid aromatic tropylium ion can be used as an organic Lewis acid promoter for the hydration of alkynes under simple reaction conditions with excellent outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Macrophage migration inhibitory factor (MIF) activates CD74, which leads to severe disorders including inflammation, autoimmune diseases and cancer under pathological conditions. Molecular dynamics (MD) simulations up to one microsecond revealed dynamical correlation between a residue located at the opening of one end of the MIF solvent channel, previously thought to be a consequence of homotrimerization, and residues in a distal region responsible for CD74 activation. Experiments verified the allosteric regulatory site and identified a pathway to this site via the MIF β‐strands. The reported findings provide fundamental insights on a dynamic mechanism that controls the MIF‐induced activation of CD74. [ABSTRACT FROM AUTHOR]

Abstract: Dual H‐bond donors are widely used as recognition motifs in anion receptors. We report the synthesis of a library of dual H‐bond receptors, incorporating the deltic and croconic acid derivatives, termed deltamides and croconamides, respectively, and a comparison of their anion binding affinities (for monovalent species) and Brønsted acidities to those of the well‐established urea and squaramide dual H‐bond donor motifs. For dual H‐bonding cores with identical substituents, the trend in Brønsted acidity is croconamides>squaramides>deltamides>ureas, with the croconamides found to be 10–15 pKa units more acidic than the corresponding ureas. In contrast to the trends displayed by ureas, deltamides and squaramides, N,N′‐dialkyl croconamides displayed higher binding affinity to chloride than the N,N′‐diaryl derivatives, which was attributed to partial deprotonation of the N,N′‐diaryl derivatives at neutral pH. A number of differences in anion binding selectivity were observed upon comparison of the dual H‐bond cores. Whereas the squaramides display similar affinity for both chloride and acetate ions, the ureas have significantly higher affinity for acetate than chloride ions and the deltamides display higher affinity for dihydrogenphosphate ions than other oxoanions or halides. These inherent differences in binding affinity could be exploited in the design of anion receptors with improved ability to discriminate between monovalent anions. [ABSTRACT FROM AUTHOR]

The development of efficient methods for the metathesis and phosphorylation reactions of disulfide compounds is of widespread interest due to their important synthetic utility in polymer, biological, medicinal and agricultural chemistry. Herein, we demonstrate the use of N-heterocyclic carbenes (NHCs) as versatile organocatalysts to promote these challenging reactions under mild conditions. This metal- and oxidant-free protocol is operationally simple with very short reaction times. The interplay between the nucleophilicity and basicity of NHCs in these reactions were also elucidated by NMR studies and high-level ab initio calculations. [ABSTRACT FROM AUTHOR]

Review: 54 refs. [ABSTRACT FROM AUTHOR]