Development of C?N Coupling Using Mechanochemistry: Catalytic Coupling of Arylsulfonamides and Carbodiimides

Reported herein is the mechanochemical synthesis of sulfonyl guanidines, a family of molecules which are relevant as pharmaceuticals and herbicides, by direct coupling of sulfonamides and aromatic or aliphatic carbodiimides. Attempts to conduct the coupling in solution have either failed or given very low conversions, thus demonstrating mechanochemistry as the necessary component for the discovery of this synthetic strategy.     

Laboratory Real‐Time and In Situ Monitoring of Mechanochemical Milling Reactions by Raman Spectroscopy

Mechanistic understanding of mechanochemical reactions is sparse and has been acquired mostly by stepwise ex situ analysis. We describe herein an unprecedented laboratory technique to monitor the course of mechanochemical transformations at the molecular level in situ and in real time by using Raman spectroscopy. The technique, in which translucent milling vessels are used that enable the collection of a Raman scattering signal from the sample as it is being milled, was validated on mechanochemical reactions to form coordination polymers and organic cocrystals. The technique enabled the assessment of the reaction dynamics and course under different reaction conditions as well as, for the first time, direct insight into the behavior of liquid additives during liquid‐assisted grinding.     

Onion-shell metal-organic polyhedra (MOPs): a general approach to decorate the exteriors of MOPs using principles of supramolecular chemistry

Metal-organic polyhedra with surface-exposed organic groups have been designed. The polyhedra are based on concentric shells of alternating negative-positive-negative charges and have been used to design homochiral hosts.     

Scope of the asymmetric intramolecular stetter reaction catalyzed by chiral nucleophilic triazolinylidene carbenes

A highly enantioselective intramolecular Stetter reaction of aromatic and aliphatic aldehydes tethered to different Michael acceptors has been developed. Two triazolium scaffolds have been identified that catalyze the intramolecular Stetter reaction with good reactivity and enantioselectivity. The substrate scope has been examined and found to be broad; both electron-rich and -poor aromatic aldehydes undergo cyclization in high yield and enantioselectivity. The tether can include oxygen, sulfur, nitrogen, and carbon linkers with no detrimental effects. In addition, the incorporation of various tethered Michael acceptors includes amides, esters, thioesters, ketones, aldehydes, and nitriles. The catalyst loading may be reduced to 3 mol % without significantly affecting the reactivity or selectivity of the reaction.     

Nucleophilic carbene catalyzed synthesis of 1,2 amino alcohols via azidation of epoxy aldehydes

We report herein a nucleophilic carbene catalyzed redox azidation of epoxyaldehydes. The intermediate beta-hydroxy acyl azides undergo thermal Curtius rearrangement followed by trapping with excess azide to form carbamoyl azides or, in a complementary sequence, by the hydroxy group to form oxazolidinones. Both products are formed in modest to good yields and diastereoselectivities. The use of an enantioenriched triazolium catalyst leads to modest asymmetric induction.     

Evaluation and clinical impact of MALDI Biotyper Mycobacteria Library v6.0 for identification of nontuberculous mycobacteria by MALDI-TOF mass spectrometry

Major challenges in the identification of non-tuberculous mycobacteria (NTM) by MALDI-TOF MS include protein extraction protocol and updating of the NTM database. The aim of this study was to evaluate MALDI Biotyper Mycobacteria Library v6.0 (Bruker Daltonics GmbH, Bremen, Germany) for identification of clinical NTM isolates and its impact on clinical management. NTM isolates cultivated from clinical samples in 101 patients were identified simultaneously by PCR-reverse hybridization (Hain Lifescience GmbH, Nehren, Germany) as a routinely used reference molecular method and using MALDI Biotyper Microflex LT/SH after protein extraction. Each isolate was applied to eight spots, and mean scores were used in analysis. MALDI-TOF MS obtained correct identification to the species level for 95 (94.06%) NTM isolates. The majority of correctly identified isolates (92/95; 96.84%) were identified with high-confidence score of ≥1.80 and only 3.16% (3/95) with a score of <1.80. Mean value ± SD of RGM NTM isolates (2.127 ± 0.172) was statistically significant higher in comparison to SGM NTM isolates (2.027 ± 0.142) with a p value of 0.007. In comparison to PCR-reverse hybridization, discordant identification results by MALDI-TOF MS were found in six (6/101; 5.94%) NTM isolates for which clinical data were analyzed. We demonstrated a high confidence NTM identifications using Mycobacterium Library v 6.0 on routine clinical isolates. This is the first study that analyzed MALDI-TOF MS identification results of NTM isolates in the context of clinical data, and it showed that MALDI-TOF MS with its updated databases could help clarify the epidemiology, clinical characteristics, and course of infections caused by less frequent NTM species.     

On the existence of multiply connected monolayered cyclofusenes with given parameters

For a given bipartite graph G its skewness is defined as the difference between the sizes of its classes of bipartition. We show that a multiply connected monolayered cyclofusene with m ≥ 2 internal holes and skewness k exists if and only if 0 ≤ k ≤ 2m − 2, thus settling in affirmative two conjectures raised in a recent paper by Karimi et al.     

Selective substituent transfer from mixed zinc reagents in Ni-catalyzed anhydride alkylation

The use of mixed zinc reagents in Ni-catalyzed anhydride alkylation results in preferential transfer of substituents (Ph > Me > Et > iPr approximately TMSCH2) for the ligands bipy, dppe, and iPrPHOX. Utilization of such mixed species allows the use of 0.55 equiv of the diorganozinc reagent, effectively transferring both desired substituents when used in conjunction with a suitable second zinc reagent.     

Enantioselective rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and terminal alkynes: application to the total synthesis of (+)-lasubine II

The use of TADDOL-based phosphoramidite ligands on rhodium allows for the incorporation of terminal alkynes in the [2+2+2] cycloaddition with alkenyl isocyanates. Terminal aliphatic alkynes provide bicyclic lactams, while the use of aryl alkynes provides complementary access to vinylogous amides. Product selectivity seems to be governed by a combination of electronics and sterics, with smaller and/or more electron-deficient substituents favoring lactam formation. The use of homologous alkenyl isocyanates leads to an expedient asymmetric total synthesis of the alkaloid lasubine II.