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1. Ir( iii )-catalyzed ortho C–H alkylations of (hetero)aromatic aldehydes using alkyl boron reagents

   https://doi.org/10.1039/C8SC03606C  

   Chen, Xiao-Yang; Sorensen, Erik J. (December 2018, Chemical Science)

   Transition-metal-catalyzed C–H alkylation reactions directed by aldehydes or ketones have been largely restricted to electronically activated alkenes. Herein, we report a general protocol for the Ir( iii )-catalyzed ortho C–H alkylations of (hetero)aromatic aldehydes using alkyl boron reagents as the coupling partner. Featuring aniline as an inexpensive catalytic ligand, the method was compatible with a wide variety of benzaldehydes, heterocyclic aldehydes, potassium alkyltrifluoroborates as well as a few α,β-unsaturated aldehydes. An X-ray crystal structure of a benzaldehyde ortho C–H iridation intermediate was also successfully obtained. 

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2. Unconventional mechanism and selectivity of the Pd-catalyzed C–H bond lactonization in aromatic carboxylic acid

   https://doi.org/10.1038/s41467-022-27986-6  

   Xu, Li-Ping; Qian, Shaoqun; Zhuang, Zhe; Yu, Jin-Quan; Musaev, Djamaladdin G. (January 2022, Nature Communications)

   Abstract The search for more effective and highly selective C–H bond oxidation of accessible hydrocarbons and biomolecules is a greatly attractive research mission. The elucidating of mechanism and controlling factors will, undoubtedly, help to broaden scope of these synthetic protocols, and enable discovery of more efficient, environmentally benign, and highly practical new C–H oxidation reactions. Here, we reveal the stepwise intramolecular S_N2 nucleophilic substitution mechanism with the rate-limiting C–O bond formation step for the Pd(II)-catalyzed C(sp³)–H lactonization in aromatic 2,6-dimethylbenzoic acid. We show that for this reaction, the direct C–O reductive elimination from both Pd(II) and Pd(IV) (oxidized by O₂oxidant) intermediates is unfavorable. Critical factors controlling the outcome of this reaction are the presence of the η³-(π-benzylic)–Pd and K⁺–O(carboxylic) interactions. The controlling factors of the benzylic vs ortho site-selectivity of this reaction are the: (a) difference in the strains of the generated lactone rings; (b) difference in the strengths of the η³-(π-benzylic)–Pd and η²-(π-phenyl)–Pd interactions, and (c) more pronounced electrostatic interaction between the nucleophilic oxygen and K⁺cation in the ortho-C–H activation transition state. The presented data indicate the utmost importance of base, substrate, and ligand in the selective C(sp³)–H bond lactonization in the presence of C(sp²)–H. 

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3. Relation between Halogen Bond Strength and IR and NMR Spectroscopic Markers

   https://doi.org/10.3390/molecules28227520  

   Amonov, Akhtam; Scheiner, Steve (November 2023, Molecules)

   The relationship between the strength of a halogen bond (XB) and various IR and NMR spectroscopic quantities is assessed through DFT calculations. Three different Lewis acids place a Br or I atom on a phenyl ring; each is paired with a collection of N and O bases of varying electron donor power. The weakest of the XBs display a C–X bond contraction coupled with a blue shift in the associated frequency, whereas the reverse trends occur for the stronger bonds. The best correlations with the XB interaction energy are observed with the NMR shielding of the C atom directly bonded to X and the coupling constants involving the C–X bond and the C–H/F bond that lies ortho to the X substituent, but these correlations are not accurate enough for the quantitative assessment of energy. These correlations tend to improve as the Lewis acid becomes more potent, which makes for a wider range of XB strengths. 

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4. Photoelectron spectroscopy and thermochemistry of o -, m -, and p -methylenephenoxide anions

   https://doi.org/10.1039/C8CP05403G  

   Nelson, Daniel J.; Gichuhi, Wilson K.; Nichols, Charles M.; Bierbaum, Veronica M.; Lineberger, W. Carl; Lehman, Julia H. (October 2018, Physical Chemistry Chemical Physics)

   The anionic products following (H + H + ) abstraction from o -, m -, and p -methylphenol (cresol) are investigated using flowing afterglow-selected ion flow tube (FA-SIFT) mass spectrometry and anion photoelectron spectroscopy (PES). The PES of the multiple anion isomers formed in this reaction are reported, including those for the most abundant isomers, o -, m - and p -methylenephenoxide distonic radical anions. The electron affinity (EA) of the ground triplet electronic state of neutral m -methylenephenoxyl diradical was measured to be 2.227 ± 0.008 eV. However, the ground singlet electronic states of o - and p -methylenephenoxyl were found to be significantly stabilized by their resonance forms as a substituted cyclohexadienone, resulting in measured EAs of 1.217 ± 0.012 and 1.096 ± 0.007 eV, respectively. Upon electron photodetachment, the resulting neutral molecules were shown to have Franck–Condon active ring distortion vibrational modes with measured frequencies of 570 ± 180 and 450 ± 80 cm −1 for the ortho and para isomers, respectively. Photodetachment to excited electronic states was also investigated for all isomers, where similar vibrational modes were found to be Franck–Condon active, and singlet–triplet splittings are reported. The thermochemistry of these molecules was investigated using FA-SIFT combined with the acid bracketing technique to yield values of 341.4 ± 4.3, 349.1 ± 3.0, and 341.4 ± 4.3 kcal mol −1 for the o -, m -, and p -methylenephenol radicals, respectively. Construction of a thermodynamic cycle allowed for an experimental determination of the bond dissociation energy of the O–H bond of m -methylenephenol radical to be 86 ± 4 kcal mol −1 , while this bond is significantly weaker for the ortho and para isomers at 55 ± 5 and 52 ± 5 kcal mol −1 , respectively. Additional EAs and vibrational frequencies are reported for several methylphenyloxyl diradical isomers, the negative ions of which are also formed by the reaction of cresol with O − . 

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5. Nitrene C−H Bond Insertion Approach to Carbazolones and Indolones, and a Reactivity Departure for 7‐Membered Analogues**

   https://doi.org/10.1002/chem.202302995  

   Lakshman, Mahesh_K; Sebastian, Dellamol; Pradhan, Padmanava; Neary, Michelle_C; Piette, Alexis_M; Trzebiatowski, Samuel_P; Henriques, Alexander_E_K; Willoughby, Patrick_H (November 2023, Chemistry – A European Journal)

   Abstract A modular platform for facile access to 1,2,3,9‐tetrahydro‐4H‐carbazol‐4‐ones (H₄‐carbazolones) and 3,4‐dihydrocyclopenta[b]indol‐1(2H)‐ones (H₂‐indolones) is described. The requisite 6‐ and 5‐membered 2‐arylcycloalkane‐1,3‐dione precursors were readily obtained through a Cu‐catalyzed arylation of 1,3‐cyclohexanediones or by a ring expansion of aryl succinoin derivatives. Enolization of one carbonyl group in the diones, conversion to a leaving group, and subsequent azidation gave 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones. This two‐step, one‐pot azidation is highly regioselective with unsymmetrically substituted 2‐arylcyclohexane‐1,3‐diones. The regioselectivity, which is important for access to single isomers of 3,3‐disubstituted carbazolones, was analyzed mechanistically and computationally. Finally, a Rh‐catalyzed nitrene/nitrenoid insertion into theorthoC−H bond of the aryl moiety gave the H₄‐carbazolones and H₂‐indolones. One carbazolone was elaborated to an intermediate reported in the total synthesis ofN‐decarbomethoxychanofruticosinate, (−)‐aspidospermidine, (+)‐kopsihainanine A. With 2‐phenylcycloheptane‐1,3‐dione, prepared from cyclohexanone and benzaldehyde, the azidation reaction was readily accomplished. However, the Rh‐catalyzed reaction unexpectedly led to a labile but characterizable azirine rather than the indole derivative. Computations were performed to understand the differences in reactivities of the 5‐ and 6‐membered 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones in comparison to the 7‐membered analogue, and to support the structural assignment of the azirine. 

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