A method for the radical chlorodifluoromethylation of (hetero)arenes using chlorodifluoroacetic anhydride is reported. This operationally simple protocol proceeds under mild photochemical conditions ...with high functional group compatibility and complements the large body of literature for the trifluoromethylation of (hetero)arenes. Introduction of the chlorodifluoromethyl motif enables rapid diversification to a wide array of aromatic scaffolds. This work showcases the chlorodifluoromethyl group as an attractive entryway to otherwise synthetically challenging electron-rich difluoromethyl(hetero)arenes. Furthermore, facile conversion of the CF2Cl moiety into the corresponding aryl esters, gem-difluoroenones, and β-keto-esters is demonstrated.
Iron(III)-catalyzed carbonyl-olefin ring-closing metathesis represents a new approach toward the assembly of molecules traditionally generated by olefin–olefin metathesis or olefination. Herein, we ...report detailed synthetic, spectroscopic, kinetic, and computational studies to determine the mechanistic features imparted by iron(III), substrate, and temperature to the catalytic cycle. These data are consistent with an iron(III)-mediated asynchronous, concerted 2+2-cycloaddition to form an intermediate oxetane as the turnover-limiting step. Fragmentation of the oxetane via Lewis acid-activation results in the formation of five- and six-membered unsaturated carbocycles.
Total Syntheses of Herqulines B and C Zhu, Xu; McAtee, Christopher C; Schindler, Corinna S
Journal of the American Chemical Society,
02/2019, Letnik:
141, Številka:
8
Journal Article
Recenzirano
Odprti dostop
An approach for the syntheses of herqulines B and C is reported that takes advantage of an l-tyrosine-derived diketopiperazine, a mycocyclosin analogue, as a synthetic precursor. The strategy relies ...on a series of consecutive reductions to adjust the mycocyclosin oxidation state to that observed in the herquline class of natural products. The strained and distorted l-tyrosine-based biaryl system characteristic for mycocyclosin is selectively converted to the 1,4-diketone structural motif common to the herqulines via initial hypervalent iodine-mediated dearomatization and a subsequent directed Birch reduction, enabled by an intramolecular H-source. Additionally, the piperazine oxidation state is accessible via an iron-catalyzed reduction of a diketopiperazine intermediate.
Scalable Synthesis of Mycocyclosin Zhu, Xu; McAtee, Christopher C; Schindler, Corinna S
Organic letters,
05/2018, Letnik:
20, Številka:
10
Journal Article
Recenzirano
We report herein the scalable total synthesis of the secondary metabolite, mycocyclosin, initially isolated from Mycobacterium tuberculosis. Mycocylosin bears a highly strained 3,3′-dityrosine biaryl ...system which arises biosynthetically from an intramolecular oxidative dehydrogenative cross-coupling of cyclo(l-Tyr-l-Tyr) (cYY) catalyzed by the P450 enzyme CYP121. CYP121 is found exclusively in M. tuberculosis. Scalable access to mycocyclosin and related derivatives via a Pd(II)-catalyzed macrocyclization is anticipated to facilitate the biological evaluation of these compounds as novel tuberculosis antimicrobials.
We report herein the intramolecular α-tert-alkylation of unsaturated β-ketoesters which gives rise to highly functionalized cyclopentanes. This transformation is characterized by its operational ...simplicity, mild reaction conditions and the use of scandium (III) triflate as a Lewis acid catalyst. Of interest, cyclopentanes bearing heterocycles, sites for post reaction functionalization and spirocyclic architectures are accessible with this strategy.
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Catalytic carbonyl-olefin metathesis reactions have recently been developed as a powerful tool for carbon–carbon bond formation. However, currently available synthetic protocols rely exclusively on ...aryl ketone substrates while the corresponding aliphatic analogs remain elusive. We herein report the development of Lewis acid-catalyzed carbonyl-olefin ring-closing metathesis reactions for aliphatic ketones. Mechanistic investigations are consistent with a distinct mode of activation relying on the in situ formation of a homobimetallic singly bridged iron(III)-dimer as the postulated active catalytic species. These “superelectrophiles” function as more powerful Lewis acid catalysts that form upon association of individual iron(III)-monomers. While this mode of Lewis acid activation has previously been postulated to exist, it has not yet been applied in a catalytic setting. The insights presented are expected to enable further advancement in Lewis acid catalysis by building upon the activation principle of “superelectrophiles” and to broaden the current scope of catalytic carbonyl-olefin metathesis reactions.
We describe herein formal syntheses of the indole alkaloids cis‐trikentrin A and herbindole B from a common meso‐hydroquinone intermediate prepared by a ruthenium‐catalyzed 2+2+1+1 cycloaddition that ...has not been used previously in natural product synthesis. Key steps include a sterically demanding Buchwald–Hartwig amination as well as a unique C(sp3)−H amination/indole formation. Studies toward a selective desymmetrization of the meso‐hydroquinone are also reported.
All of me(so): A ruthenium‐catalyzed 2+2+1+1 cycloaddition provided a common meso‐hydroquinone intermediate for formal syntheses of the indole alkaloids cis‐trikentrin A and herbindole B (see scheme). Key steps of the synthesis include a sterically demanding Buchwald–Hartwig amination and an unprecedented C(sp3)−H amination/indolization reaction.
The combination of SmI2 and the conjugate base of triethylurea (TEU–) has been shown to favor the cyclization of unsaturated halides over direct reduction to a much greater extent than other ...SmI2-based reductants. Aryl, heteroaryl, and alkyl halides (X = Br, Cl, F) readily undergo heterocyclization and carbocyclization in the presence of SmI2/TEU–.
A novel mode of SmI2 activation has been developed using ureates as reaction promoters. Several ureates formed by treatment of the corresponding ureas with n-BuLi have been shown to activate SmI2 to ...a substantial extent toward the reduction of 1-chlorodecane. Complexes formed from SmI2 and various ureates have been shown to be useful for the reduction of a variety of organohalides, including substrates of low reactivity such as aryl fluorides. Because of ease of synthesis and low molecular weight, the conjugate base of triethylurea (TEU–) was of primary focus. Visible spectroscopy and reactivity data are consistent with the hypothesis that the same complex is being formed when SmI2 is combined with either 2 or 4 equiv of TEU–, in spite of the greater reactivity of SmI2/4 TEU– with some alkyl halides. We propose that the active reductant is an N,O chelate formed between SmI2 and 2 equiv of TEU–.
Cyclopentadienes are scaffolds in organometallic chemistry, synthetic organic chemistry, and catalysis. We herein describe a regioselective Lewis-acid-catalyzed method for the synthesis of highly ...functionalized cyclopentadienes incorporating electronically and sterically diverse subunits. Our experimental and theoretical investigations support a mechanism that is related to catalytic carbonyl-olefin metathesis reactions wherein Lewis-acid-catalyzed cycloadditions between carbonyl and alkene functionalities afford reactive oxetane intermediates. However, in lieu of a 2+2-cycloreversion, stepwise oxetane fragmentation to intermediate carbocations results in the formation of functionalized cyclopentadienes via interrupted carbonyl-olefin metathesis. This work provides insights into the design of catalytic carbonyl-olefin metathesis reactions of aliphatic ketone substrates as stepwise oxetane fragmentation was previously only reported as a competing reaction pathway for aryl ketones.
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