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1. Substituent Effects in the Cationic Green Fluorescent Protein Chromophore: Ultrafast Excited‐State Proton Transfer or Twisting?

   https://doi.org/10.1002/cptc.202400037  

   Liu, Jiawei; Chen, Cheng; Sokolov, Anatolii_I; Baranov, Mikhail_S; Fang, Chong (May 2024, ChemPhotoChem)

   Abstract Understanding the structure‐function relationships of the green fluorescent protein (GFP) chromophore is important in rationally developing new molecular tools for biological imaging and beyond. Herein, we systematically modified the GFP chromophore structure with electron‐withdrawing and ‐donating groups (EWGs and EDGs) to investigate the substituent effects on the excited‐state proton transfer (ESPT) and twisting dynamics of the cationic chromophore in solution. With key insights gained from femtosecond transient absorption and stimulated Raman spectroscopy, we reveal that the EWG substitution by –F increases photoacidity in an additive manner and leads to an ultrafast barrierless ESPT by difluorination, while the EDG substitution by –OCH₃also results in ultrafast ESPT despite the weak photoacidity as estimated by the Förster equation. We ascribe the unusually fast kinetics in methoxylated derivatives to the occurrence of a pre‐existing chromophore‐solvent complex that sets up the acceptor site for ESPT. Furthermore, the kinetic competition between ESPT and twisting pathways is crucial for the observation of ESPT in action, particularly for molecules undergoing efficient nonradiative decay in the excited state through torsional motions. Such flexible and highly engineerable molecules can enable more versatile photoswitches and sensors. 

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2. Catalytic Stereoselective 1,2- cis -Furanosylations Enabled by Enynal-Derived Copper Carbenes

   https://doi.org/10.1021/acscatal.3c05237  

   Ghosh, Bidhan; Alber, Adam; Lander, Chance W; Shao, Yihan; Nicholas, Kenneth M; Sharma, Indrajeet (January 2024, ACS Catalysis)

   Chang, Sukbok (Ed.)

   1,2-cis-Furanosides are present in various biomedically relevant glycosides, and their stereoselective synthesis remains a significant challenge. In this vein, we have developed a stereoselective approach to 1,2-cis-furanosylations using earth-abundant copper catalysis. This protocol proceeds under mild conditions at room temperature and employs readily accessible benchtop stable enynalderived furanose donors. This chemistry accommodates a variety of alcohols, including primary, secondary, and tertiary, as well as mannosyl alcohol acceptors, which have been incompatible with most known methods of furanosylation. The resulting 1,2-cisfuranoside products exhibit high yields and anomeric selectivity with both the ribose and arabinose series. Furthermore, the anomeric selectivity is independent of the C2 oxygen-protecting group and the anomeric configuration of the starting donor. Experimental evidence and computational studies support our hypothesis that copper chelation between the C2 oxygen of the furanose donor and an incoming alcohol nucleophile is responsible for the observed 1,2-cisstereoselectivity. 

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3. Umpolung Strategy for Arene C−H Etherification Leading to Functionalized Chromanes Enabled by I(III) N ‐Ligated Hypervalent Iodine Reagents

   https://doi.org/10.1002/adsc.202100809  

   Mikhael, Myriam; Guo, Wentao; Tantillo, Dean_J; Wengryniuk, Sarah_E (September 2021, Advanced Synthesis & Catalysis)

   Abstract The direct formation of aryl C−O bonds via the intramolecular dehydrogenative coupling of a C−H bond and a pendant alcohol represents a powerful synthetic transformation. Herein, we report a method for intramolecular arene C−H etherification via an umpoled alcohol cyclization mediated by an I(III)N‐HVI reagent. This approach provides access to functionalized chromane scaffolds from primary, secondary and tertiary alcohols via a cascade cyclization‐iodonium salt formation, the latter providing a versatile functional handle for downstream derivatization. Computational studies support initial formation of an umpoled O‐intermediate via I(III) ligand exchange, followed by competitive direct and spirocyclization/1,2‐shift pathways. magnified image 

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4. Excited-state proton transfer relieves antiaromaticity in molecules

   https://doi.org/10.1073/pnas.1908516116  

   Wu, Chia-Hua; Karas, Lucas José; Ottosson, Henrik; Wu, Judy I-Chia (October 2019, Proceedings of the National Academy of Sciences)

   Baird’s rule explains why and when excited-state proton transfer (ESPT) reactions happen in organic compounds. Bifunctional compounds that are [4 n + 2] π-aromatic in the ground state, become [4 n + 2] π-antiaromatic in the first 1 ππ* states, and proton transfer (either inter- or intramolecularly) helps relieve excited-state antiaromaticity. Computed nucleus-independent chemical shifts (NICS) for several ESPT examples (including excited-state intramolecular proton transfers (ESIPT), biprotonic transfers, dynamic catalyzed transfers, and proton relay transfers) document the important role of excited-state antiaromaticity. o- Salicylic acid undergoes ESPT only in the “antiaromatic” S 1 ( 1 ππ*) state, but not in the “aromatic” S 2 ( 1 ππ*) state. Stokes’ shifts of structurally related compounds [e.g., derivatives of 2-(2-hydroxyphenyl)benzoxazole and hydrogen-bonded complexes of 2-aminopyridine with protic substrates] vary depending on the antiaromaticity of the photoinduced tautomers. Remarkably, Baird’s rule predicts the effect of light on hydrogen bond strengths; hydrogen bonds that enhance (and reduce) excited-state antiaromaticity in compounds become weakened (and strengthened) upon photoexcitation. 

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5. Cu‐Catalyzed Hydroxymethylation of Unactivated Alkyl Iodides with CO To Provide One‐Carbon‐Extended Alcohols

   https://doi.org/10.1002/anie.201801814  

   Zhao, Siling; Mankad, Neal P. (April 2018, Angewandte Chemie International Edition)

   Abstract We have developed a reductive carbonylation method by which unactivated alkyl iodides can be hydroxymethylated to provide one‐carbon‐extended alcohol products under Cu‐catalyzed conditions. The method is tolerant of alkyl β‐hydrogen atoms, is robust towards a wide variety of functional groups, and was applied to primary, secondary, and tertiary alkyl iodide substrates. Mechanistic experiments indicate that the transformation proceeds by atom‐transfer carbonylation (ATC) of the alkyl iodide followed in tandem by two CuH‐mediated reductions in rapid succession. This radical mechanism renders the Cu‐catalyzed system complementary to precious‐metal‐catalyzed reductive carbonylation reactions. 

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