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Chemoselectivity is one of the most challenging issues facing the chemical sciences. In this study, the first highly chemoselective reactions of N -acylpyrroles via either an anionic Fries rearrangement (pyrrole dance) or a C–H functionalization of toluene to provide aryl benzyl ketones are advanced. This efficient and operationally simple approach enables the synthesis of either 2-aroylpyrroles or aryl benzyl ketones in good to excellent yields under transition metal-free conditions. The choice of base plays a crucial role in controlling the chemoselectivity. The aroylation of toluene derivatives was observed with N -acylpyrroles when subjected to KN(SiMe 3 ) 2 , while anionic Fries rearrangement products were produced with LiN(SiMe 3 ) 2 . Surprisingly, cross-over experiments indicate that the anionic Fries rearrangement is an intermolecular process. The aroylation reaction has the advantage over Weinreb amide chemistry in that it does not require preformed organometallic reagents or cryogenic temperatures.
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Pyrrole-stabilized free carbenes generated from alkynyl imidates or aldimines and electrophilic alkynes give pyrrolone- or pyrrole-containing products
Pyrrole and 2-pyrrolone derivatives are valuable heterocyclic compounds and while classical condensation methods for their synthesis have a long history, many of the recent developments for their preparation involve the use of transition metal catalysis. Here we report a complementary, metal-free strategy for constructing structurally diverse derivatives of these heterocycles. The key feature of the approach is the in situ creation of a reactive intermediate by an initial facile event that simultaneously generates a pyrrole ring bearing a free carbene. This is straightforwardly accessed via a spontaneous, net [3 + 2] cyclization reaction of a linear alkynyl O-silylimidate or alkynyl aldimine with an electrophilic alkyne. The carbene then undergoes either 1,4-silyl migration (to produce 2-pyrrolone derivatives) or C–H insertion, cycloaddition, cyclopropanation or macrocyclization reactions (leading to pyrrole derivatives).
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- PAR ID:
- 10673771
- Publisher / Repository:
- Springer Nature
- Date Published:
- Journal Name:
- Nature Synthesis
- Volume:
- 5
- Issue:
- 1
- ISSN:
- 2731-0582
- Page Range / eLocation ID:
- 95 to 102
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Carbenes (R1R2C:) [like radicals, arynes, and nitrenes] constitute a significant family of neutral, high-energy, reactive intermediates – fleeting chemical entities that undergo rapid reactions. An alkyne (R3C≡CR4) is a fundamental functional group that houses a high degree of potential energy; however, the substantial kinetic stability of alkynes renders them conveniently handleable as shelf-stable chemical commodities. The ability to generate metal-free carbenes directly from alkynes, fueled by the high potential (that is, thermodynamic) energy of the latter, would constitute a significant advance. We report here that this can be achieved simply by warming a mixture of a 2-alkynyl-iminoheterocycle (a cyclic compound containing a nucleophilic nitrogen atom) with an electrophilic alkyne. We demonstrate considerable generality for the process: many shelf-stable alkyne electrophiles engage many classes of (2-alkynyl)heterocyclic nucleophiles to produce carbene intermediates that immediately undergo many types of transformations to provide facile and practical access to a diverse array of heterocyclic products. Key mechanistic aspects of the reactions are delineated.more » « less
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The catalytic uses of metal carbenes for addition, insertion, and cycloaddition reactions are dependent on their carbene precursor. The limited methods available for the preparation of diazo esters, which are the most common carbene precursors, restricts their ability to impart structural diversity in metal carbene reactions. Here we report a new methodology for the preparation of diverse vinyldiazoacetate esters and their effective uses in highly enantiocontrolled cyclopropanation, N-H bond insertion, O-H bond insertion, and [3+2] cycloaddition reactions. 1,2,3-Triazine 1-oxides with a sp3-C-H bond at the 5-position undergo base catalyzed Dimroth-type rearrangement to form multiply substituted oximidovinyldiazoacetates in high yields at or below room temperature, and these diverse vinyldiazo compounds undergo catalytic metal carbene transformations to produce oximidovinylcyclopropanes, α-oximidovinyl-α-amino acids and α-hydroxy acids, as well as tricyclic indole derivatives in high yields and enantioselectivities. The new access to vinyldiazo compounds has applicability to a vast array of metal carbene transformations.more » « less
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Abstract Donor–acceptor (D–A)‐conjugated polymers have achieved promising performance metrics in numerous optoelectronic applications that continue to motivate studying structure–property relationships and discovering new materials. Here, the materials toolbox is expanded by synthesizing D–A copolymers where 1,4‐dihydropyrrolo[3,2‐b]pyrrole (DHPP) is directly incorporated into the main chain of D–A copolymers for the first time via direct heteroarylation polymerization. Notably, the synthetic complexity of DHPP‐containing polymers coupled with thieno[3,2‐b]pyrrole‐4,6‐dione (TPD) or 3,6‐bis(2‐thienyl)‐2,5‐dihydropyrrolo[3,4‐c]pyrrole‐1,4‐dione (Th2DPP) comonomers is calculated to be lower compared to many common conjugated polymers synthesized via direct arylation. The electron‐rich nature of DHPPs when coupled with TPD or DPP enables optoelectronic properties to be manipulated, evident by measuring distinctly different absorbance and redox properties. Additionally, these D–A copolymers demonstrate their potential in organic electronic applications, such as electrochromics and organic photovoltaics. The reported DHPP‐alt‐Th2DPP copolymer is the first DHPP‐based colored‐to‐transmissive electrochrome and achieves power conversion efficiencies of ~2.5% when incorporated into bulk heterojunction solar cells. Overall, the synthetic accessibility of DHPP monomers and their propensity to participate in robust polymerizations highlights the value of establishing structure–property relationships of an underutilized scaffold. These fundamental attributes serve to inform and advance efforts in the development of DHPP‐containing copolymers for various applications.more » « less
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Following previous work on helicene–porphyrin conjugates in which carbo[6]helicene are connected to zinc‐porphyrin via phenyl‐bis‐ethynyl bridges (Por(Zn)‐H[6]1, series 1), and displaying clear exciton coupling (EC) chirality, novel carbo[6]helicenes derivatives substituted at their 2,15 positions by zinc‐porphyrin units are prepared, either through a triple bond (Por(Zn)‐H[6]2, series 2), or through an alkynyl‐phenyl bridge (Por(Zn)‐H[6]3, series 3). Series 2 is also synthesized with free porphyrins or different metals [Ni(II) and Pd(II)]. Their photophysical and chiroptical properties (electronic circular dichroism and circularly polarized luminescence) are characterized, and it is examined how i) the distance between the porphyrin units and ii) the metal type impacted these properties. Experimental and theoretical analyses highlight strong responses originating from EC chirality in combination with the typical helicene‐centered optical activity. ThePor(Zn)‐H[6]2system displaying strong absorption dissymmetry factors is then selected to experimentally examine the chiral‐induced spin selectivity effect by magnetic conductive atomic force microscopy; a spin polarization of 50% is measured.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1038/s44160-025-00899-0
