A widely applicable triazole‐substituted chiral aryl iodide is described as catalyst for enantioselective oxidation reactions. The introduction of a substituent in ortho‐position to the iodide is key for its high reactivity and selectivity. Besides a robust and modular synthesis, the main advantage of this catalyst is the excellent performance in a plethora of mechanistically diverse enantioselective transformations, such as spirocyclizations, phenol dearomatizations, α‐oxygenations, and oxidative rearrangements. DFT‐calculations of in situ generated [hydroxy(tosyloxy)iodo]arene isomers give an initial rational for the observed reactivity.
We report the application of a chiral triazole-substituted iodoarene in a direct enantioselective hydroxylation of alkyl arenes. This method allows the rapid synthesis of chiral benzyl alcohols in high yields and exceptional stereocontrol despite its non-templated nature. In a unique cascade activation comprising of an initial irradiation-induced radical C-Hbromination and a consecutive enantioconvergent hydroxylation, the iodoarene catalyst has a dual role. It initiates the radical bromination in its oxidized state through an in situ formed bromoiodane and in the second, Cu-catalyzed step, it acts as a chiral ligand. To the best of our knowledge this the first example demonstrating the ability of a chiral aryl iodide catalyst acting both, as an oxidant and as a chiral ligand in a highly enantioselective C-H-activating transformation. Furthermore, this is the first example for an enantioconvergent hydroxylation. zylic C-H-bond in the presence tertiary C-H-bonds was observed. This unique reaction cascade offers great potential for other enantioselective oxidative benzylic C-H-activations, although the mechanism of the enantioconvergent step still needs to be further elaborated. ASSOCIATED CONTENTSupporting Information. The Supporting Information is available free of charge on the ACS Publications website at DOI: XXX. Including all experimental procedures and characterization data.
Aw idely applicable triazole-substituted chiral aryl iodide is described as catalyst for enantioselective oxidation reactions.The introduction of asubstituent in ortho-position to the iodide is key for its high reactivity and selectivity.B esides ar obust and modular synthesis,t he main advantage of this catalyst is the excellent performance in ap lethora of mechanistically diverse enantioselective transformations,s uch as spirocyclizations,p henol dearomatizations, a-oxygenations, and oxidative rearrangements.D FT-calculations of in situ generated [hydroxy(tosyloxy)iodo]arene isomers give an initial rational for the observed reactivity.Hypervalentiodinecompoundsareversatileoxidantswhich have been utilized with great success in aplethora of oxidative coupling reactions [1] and in natural product synthesis. [2] In related enantioselective processes,achiral aryl iodide precursor can be used in catalytic amounts in combination with aterminal co-oxidant to generate achiral hypervalent iodine compound in situ. This chiral oxidant is subsequently capable of transferring its chirality onto the desired coupling products through diastereotopic transition states in the key oxidative C-X bond forming step. [3] Since the discovery of the first enantioselective transformation catalyzed by ac hiral aryl iodide in 2007 by Wirth and co-workers, [4] more than ad ozen highly diverse C1-and C2-symmetric chiral aryl iodides have been developed. [5] Successful catalysts,s uch as 1-4 ( Figure 1), usually show ag ood reactivity and selectivity in only one distinct class of oxidative transformation. So far there is no omnipotent chiral aryl iodide available that performs well throughout the most important oxidative transformations and hence can be seen as broadly applicable catalyst for iodane-based enantioselective couplings.Our group is heavily interested in the development of N-heterocycle-stabilized iodanes (NHIs) as an ew class of stable and at the same time highly reactive hypervalent iodine compounds. [6, 7] With the aim to design novel chiral aryl iodides which are robust to synthesize in amodular sequence and show ag ood performance throughout adiverse range of enantioselective oxidations,w erecently developed the novel triazole-substituted aryl iodide 5 ( Figure 2) and evaluated its reactivity in the Kita-spirocyclization of 1-naphthols. [8] Even though this "first-generation" catalyst gave the so far highest enantioselectivities in direct comparison to other C1-symmetric aryl iodides for this reaction, reactivities were low.W ell-established C2-symmetric aryl iodides,s uch as spirobiindanes developed by Kita or resorcinol ethers 1 developed by Uyanik and Ishihara, showed significantly higher stereoinduction and yielded the desired chiral lactones in better yields. [9] Due to the promising initial results with catalyst 5 and its highly modular and robust synthesis,w e further developed "second-generation" triazole catalysts 6 ( Figure 2) bearing as imple ortho-modification at the aryl iodide.W et herefore synthesized orth...
Objective: To evaluate the knowledge, believes, psychological and behavioural impact of COVID-19 on the general population in the Middle East, exploring how it impacted public lives. Methods: A descriptive cross-sectional online survey was sent to a convenience sample in the Middle East through social media (Facebook and WhatsApp) between 16th of June and 30th of June 2020. The questionnaire was designed to collect the demographic, participant’s source of information regarding COVID-19, knowledge and believes about COVID-19, the psychological consequences of COVID-19, impact of COVID-19 on participant’s behaviour. The final version of the questionnaire was further tested for content validity by experts in the field. Results: A total of 2,061 participants completed the survey, with the majority being females (n=1394, 67.6%), from urban areas (n=1896, 92%) and the majority were from countries of The Levant (n=1199, 58.1%), followed by the Arabian Peninsula (n=392, 19.1%), Iraq (n=300, 14.6%) and Egypt (n=138, 6.7%). Few participants (3.0%) reported to have been infected and many (n=1847, 89.6%) were committed to quarantine at home. Social media platforms were the most common sources of information (41.2%). Many (63%) believed that COVID-19 is a biological weapon and were afraid of visiting crowded places (85%). The majority avoided public facilities (86.9%) such as prayer places and believed that the news about COVID-19 made them anxious (49.5%).
Exploration of three-dimensional structural space has become crucial for the development of novel bioactive molecules. In this context, polar spirocycles have emerged as key scaffolds due to their enhanced 3D character and well-defined spatial orientation. Herein, we report the development of a highly modular strategy to access beta-spirocyclic pyrrolidine derivatives from readily available starting materials, i.e., cyclic ketones and amino or oxamic acids. The sequence proceeds through a straightforward Knoevenagel condensation, followed by a domino Giese-type reaction/base-mediated cyclisation process, delivering a broad scope of polar spirocyclic scaffolds in good to excellent yields. The products can be readily diversified to access a wider range of spirocyclic cores (such as lactams or succinimides), thus increasing the versatility of our method to gain rapid access to libraries of potential drug-like molecules.
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