C–C Bond Cleavage of Unactivated 2-Acylimidazoles

Xin, Hai Long; Pang, Bo; Choi, Jeesoo; Akkad, Walaa; Morimoto, Hiroyuki; Ohshima, Takashi

doi:10.1021/acs.joc.0c01458

Cited by 18 publications

(6 citation statements)

References 90 publications

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“…Recently, our group developed the iridium(III)-catalyzed C(sp 2 )–H and C(sp 3 )–H alkynylation of 2-acylimidazoles with alkynyl bromides (Scheme B) . 2-Acylimidazole derivatives are widely utilized in organic synthesis as useful building blocks, and applying this functionality as a directing group for C–H activation enables efficient access to a variety of desirable compounds . As part of our mechanistic studies directed at understanding the pathway for such reactions, we conducted a number of experiments and confirmed the existence of several intermediates by X-ray crystallography, nuclear magnetic resonance (NMR), and fast atom bombardment mass spectrometry (FAB-MS) .…”

Section: Introductionmentioning

confidence: 75%

Double 1,2-Migration of Bromine and Silicon in Directed C–H Alkynylation Reactions with Silyl-Substituted Alkynyl Bromides through an Iridium Vinylidene Intermediate

et al. 2021

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The iridium(III)-catalyzed C–H alkynylation of 2-acylimidazoles with alkynyl bromides, which was recently developed by our group, provides an efficient strategy for the construction of both C(sp)–C(sp2) and C(sp)–C(sp3) bonds. The mechanism for this reaction was extensively studied using density functional theory (DFT) calculations. The computed catalytic cycle is initiated by C–H activation, and the formed iridacycle undergoes a strain-controlled regioselective migratory insertion of an alkynyl bromide. The resulting α-bromovinyl iridium species is rapidly converted into a more stable iridium vinylidene intermediate by a 1,2-bromine migration, and the adjacent silyl group subsequently migrates to furnish a C–H-alkynylated product. The origin of the unique difference in reactivity with respect to the substituent on the alkynyl bromide is the 1,2-migration step, in which a silyl group can highly stabilize the transition state by the β-silicon effect.

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Section: Introductionmentioning

confidence: 75%

Double 1,2-Migration of Bromine and Silicon in Directed C–H Alkynylation Reactions with Silyl-Substituted Alkynyl Bromides through an Iridium Vinylidene Intermediate

et al. 2021

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“…Using the method described by Morimoto and Ohshima, 15 acylimidazole 3 was subjected to solvolysis in MeOH at 150 °C in a sealed pressure tube for 48 h. The solvolysis of 3 afforded ester 5 in 71% yield after column chromatography purification. Compound 5 was then treated with TFA in CH 2 Cl 2 at room temperature, providing lactam 4 in 73% yield and 94:6 er after workup, without the necessity of further purification ( Scheme 4 A).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of the Brivaracetam Employing Asymmetric Photocatalysis and Continuous Flow Conditions

Franco,

Silva,

Rosa

et al. 2023

ACS Omega

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An original total synthesis of the antiepileptic drug brivaracetam (BRV) is reported. The key step in the synthesis consists of an enantioselective photochemical Giese addition, promoted by visible-light and the chiral bifunctional photocatalyst Δ-RhS. Continuous flow conditions were employed to improve the efficiency and allow an easy scale-up of the enantioselective photochemical reaction step. The intermediate obtained from the photochemical step was converted into BRV by two different pathways, followed by one alkylation and amidation, thus giving the desired active pharmaceutical ingredients (API) in 44% overall yield, 9:1 diastereoisomeric ratio (dr) and >99:1 enantiomeric ratio (er).

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“…To date, numerous catalytic strategies have been developed for the cleavage and functionalization of C(CO)–C bond. The pre-functionalization of the α -C–H in ketones as the directing group is one of the efficient protocols for C(CO)–C bond cleavage 19 – 21 . However, the protocol is only available for specific substrates and the pre-functionalization steps are tedious, which limit its wide application.…”

Section: Introductionmentioning

confidence: 99%

Zn-Nx sites on N-doped carbon for aerobic oxidative cleavage and esterification of C(CO)-C bonds

et al. 2021

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Selective cleavage of C-C bonds is very important in organic chemistry, but remains challenging because of their inert chemical nature. Herein, we report that Zn/NC-X catalysts, in which Zn2+ coordinate with N species on microporous N-doped carbon (NC) and X denotes the pyrolysis temperature, can effectively catalyze aerobic oxidative cleavage of C(CO)-C bonds and quantitatively convert acetophenone to methyl benzoate with a yield of 99% at 100 °C. The Zn/NC-950 can be applied for a wide scope of acetophenone derivatives as well as more challenging alkyl ketones. Detail mechanistic investigations reveal that the catalytic performance of Zn/NC-950 can be attributed to the coordination between Zn2+ and N species to change the electronic state of the metal, synergetic effect of the Zn single sites with their surrounding N atoms, as well as the microporous structure with the high surface area and structural defects of the NC.

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C–C Bond Cleavage of Unactivated 2-Acylimidazoles

Cited by 18 publications

References 90 publications

Double 1,2-Migration of Bromine and Silicon in Directed C–H Alkynylation Reactions with Silyl-Substituted Alkynyl Bromides through an Iridium Vinylidene Intermediate

Double 1,2-Migration of Bromine and Silicon in Directed C–H Alkynylation Reactions with Silyl-Substituted Alkynyl Bromides through an Iridium Vinylidene Intermediate

Synthesis of the Brivaracetam Employing Asymmetric Photocatalysis and Continuous Flow Conditions

Zn-Nx sites on N-doped carbon for aerobic oxidative cleavage and esterification of C(CO)-C bonds

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