Vinyl Cyclopropanes Research Articles

Rapid and Modular Access to Vinyl Cyclopropanes Enabled by Air-stable Palladium(I) Dimer Catalysis.

While vinyl cyclopropanes are valuable functional groups in drugs or natural products as well as established precursors to trigger a rich variety of synthetic transformations, their reactive nature can make their installation via direct catalytic approaches challenging. We herein present a modular access to (di)vinyl cyclopropanes under very mild conditions and full conservation of stereochemistry, allowing access to the cis or trans cyclopropane- as well as E or Z vinyl-stereochemical relationships. Our protocol relies on air-stable dinuclear PdI catalysis, which enables rapid (<30 min) and selective access to a diverse range of vinyl cyclopropane motifs at room temperature, even on gram scale.

Asymmetric cascades of the π-allyl complex: a journey from transition-metal catalysis to metallaphotocatalysis.

The enantioselective catalytic cascade involving Tsuji-Trost allylation has provided a viable strategy for the construction of multiple asymmetric C-C and C-X centres and numerous methods have been developed around it for the synthesis of various vital scaffolds. The synthetic utility of this strategy was enhanced by replacing the customary allyl acetates with ethylene diacetates/dicarbonates, vinyl epoxides, vinyl oxetanes, vinyl ethylene carbonates, vinyl cyclopropanes, enynes, and dienes using transition-metal catalysis. One more milestone was achieved when metallaphotocatalysis provided the necessary platform for these cascades by using a cheaper metal. This review will provide a summary of these enantioselective catalytic cascades from 2015.

Taming Chiral Quaternary Stereocenters via Remote H-Bonding Stereoinduction in Palladium-Catalyzed (3+2) Cycloadditions.

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

Taming Chiral Quaternary Stereocenters via Remote H‐Bonding Stereoinduction in Palladium‐Catalyzed (3+2) Cycloadditions

AbstractRing‐opening transformations of donor‐acceptor (D‐A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium‐catalyzed highly diastereo‐ and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron‐withdrawing groups, a subset of D‐A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five‐membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and &gt;19 : 1 dr). In‐depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H‐bonding in stereocontrol.

Catalyst-Controlled Chemodivergent Reactivity of Vinyl Cyclopropanes: A Selective Approach toward Indoles and Aniline Derivatives.

Herein, we disclose a catalyst-controlled chemodivergent approach to access C2-substituted indoles and diverse aniline derivatives with good chemo- and stereoselectivity by employing vinylcyclopropanes (VCPs) as coupling partners via a tandem C-H/C-C activation/annulation strategy. The key feature of this work is the divergent reactivity profile showcased by VCPs, going beyond allylation under a high-valent Rh-/MPAA catalyst system.

The Effect of Hydrogen Bonding on Polymerization Behavior of Monofunctional Vinyl Cyclopropane‐Amides with Different Side Chains

AbstractThe synthesis of four different monofunctional vinyl cyclopropane (VCP) amides and their photopolymerization behavior are presented. All VCPs can form hydrogen bonds, with one being the amide linkage of the VCP unit and the other one being the side chain. The number of additional hydrogen bonds is regulated by the different side chains being, carbonate, urethane, urea, and amide. Hydrogen bonds should lead to a preorganization of the monomers, leading to a fast polymerization. Kinetic studies of the photopolymerization, analysis of hydrogen bond strength via solid‐state nuclear magnetic resonance (NMR) experiments, and theoretical calculations are used to correlate the degree of conversion and the amount of preorganization. A fast polymerization could be observed due to hydrogen bonding near the active site, while hydrogen bonds in the side chain make a minor difference.

Palladium-Catalyzed Intermolecular Asymmetric Dearomative Annulation of Phenols with Vinyl Cyclopropanes.

Herein, we report the Pd(0)-catalyzed intermolecular asymmetric dearomative [3 + 2] annulation of phenols with vinyl cyclopropanes via in situ generated ortho-quinone methide intermediates. A series of highly functionalized spiro-[5,6] bicycles which bear three contiguous stereogenic centers including one all-carbon quaternary were obtained with excellent stereoselectivities. Density functional theory (DFT) calculations indicate that the reactions were controlled by thermodynamics.

Functionalized Cyclopentenes via the Formal [4+1] Cycloaddition of Photogenerated Siloxycarbenes from Acyl Silanes.

This work describes the first formal cycloaddition reaction of photogenerated nucleophilic carbenes derived from acylsilanes with electrophilic dienes. The resulting transient donor-acceptor cyclopropane rearranges to its stable and highly functionalized cyclopentene isomer in an unprecedented metal-free process. The cyclopropanation-vinyl cyclopropane rearrangement sequence was corroborated by computational calculations. The cyclopropane formation corresponds to a higher energetic barrier, and the vinylcyclopropane-cyclopentene rearrangement proceeds through different mechanisms, although of comparable energies, depending on the stereochemistry of the cyclopropane.

Recent Advances in [5+2] Cycloadditions

Abstract: The existence of a seven-membered cyclic core in several natural products and biomolecules vitalized the research on its synthesis. [5+2] cycloaddition has become a promising strategy for the construction of seven-membered ring systems by the formation of carboncarbon bonds in a single step, with strong regioselectivity and stereoselectivity. This review mainly focuses on recent developments in the area of [5+2] cycloaddition since 2019. Total synthesis of natural products involving [5+2] cycloaddition as a key step leading to the heptacyclic core has also been discussed. Synthesis of fused and bridged ring systems via the reactions involving inter and intramolecular [5+2] cycloadditions like oxidopyrylium-mediated [5+2] cycloadditions, [5+2] cycloadditions of vinyl cyclopropanes (VCPs), vinyl phenols, etc. is explained in the review with the latest examples. This review provides a useful guide for researchers exploring this powerful strategy to create more elegant heptacycles in their future research.

Dearomative Cyclopropanation of Naphthols via Cyclopropene Ring-Opening.

The dearomatization of 2-naphthols represents a simple method for the construction of complex 3D structures from simple planar starting materials. We describe a cyclopropanation of 2-naphthols that proceeds via cyclopropene ring-opening using rhodium and acid catalysis under mild conditions. The vinyl cyclopropane molecules were formed with high chemoselectivity and scalability, which could be further functionalized at different sites. Both computational and experimental evidence were used to elucidate the reaction mechanism.

Dearomative Cyclopropanation of Naphthols via Cyclopropene Ring‐Opening

AbstractThe dearomatization of 2‐naphthols represents a simple method for the construction of complex 3D structures from simple planar starting materials. We describe a cyclopropanation of 2‐naphthols that proceeds via cyclopropene ring‐opening using rhodium and acid catalysis under mild conditions. The vinyl cyclopropane molecules were formed with high chemoselectivity and scalability, which could be further functionalized at different sites. Both computational and experimental evidence were used to elucidate the reaction mechanism.

Palladium-catalyzed hydroamination of vinylidenecyclopropane-diester with pyrroles and indoles: an approach to azaaromatic vinylcyclopropanes.

A new method for the synthesis of azaaromatic vinylcyclopropanes (VCPs) has been disclosed in this paper by using pyrrole or indole derivatives as nucleophilic reagents to react with vinylidenecyclopropane-diesters (VDCP-diesters) in the presence of a Pd catalyst, a phosphine ligand and a base under mild conditions in up to 98% yield with a reasonable substrate scope. This reaction is one of the few examples of hydroamination at electron-rich allene's β-position. A plausible reaction mechanism has also been proposed through a zwitterionic π-propargyl N-palladium species according to the previous work and the obtained deuterium labeling experimental result.

Palladium-Catalyzed Arylative Ring Expansion of Fused Bicyclic Vinyl Cyclopropanes

Palladium-Catalyzed Arylative Ring Expansion of Fused Bicyclic Vinyl Cyclopropanes

Kinetic Analysis of a Cysteine-Derived Thiyl-Catalyzed Asymmetric Vinylcyclopropane Cycloaddition Reflects Numerous Attractive Noncovalent Interactions.

Kinetic studies of a vinylcyclopropane (VCP) cycloaddition, catalyzed by peptide-based thiyl radicals, are described. Reactions were analyzed by using reaction progress kinetic analysis, revealing that ring-opening of the VCP is both rate- and enantio-determining. These conclusions are further corroborated by studies involving racemic and enantiopure VCP starting material. Noncovalent interactions play key roles throughout: both the peptide catalyst and VCP exhibit unproductive self-aggregation, which appears to be disrupted by binding between the catalyst and VCP. This in turn explains the requirement for the key catalyst feature, a substituent at the 4-position of the proline residue, which is required for both turnover/rate and selectivity.

Radical 1,5-Chloropentafluorosulfanylation of Unactivated Vinylcyclopropanes and Transformation into α-SF5 Ketones.

The radical 1,5-chloropentafluorosulfanylation of vinyl cyclopropanes (VCPs) initiated by Et3B/O2 affords allylic pentafluorosulfanyl/homoallylic chloride products through the ring-strain release of the cyclopropane. The VCP substitution pattern was investigated. The utility of this reaction was illustrated in post-transformation of the C═C bond by ozonolysis, giving access to valuable α-SF5 carbonyl compounds.

Visible-Light-Induced Dearomatization of Indoles/Pyrroles with Vinylcyclopropanes: Expedient Synthesis of Structurally Diverse Polycyclic Indolines/Pyrrolines

Visible-light-induced cycloaddition reactions initiated via energy-transfer processes have recently evolved as powerful methods for the construction of strained cyclic molecules that are not easily accessed using known ground-state synthetic methods. Particularly, the reactions initiated by the excitation of aromatic rings provide an alternative solution to the direct transformations of aromatic feedstocks under the scheme of dearomatization. Vinylcyclopropanes (VCPs) are well-known reagents in radical clock experiments, working as a probe to detect transient radical intermediates. However, the synthetic applications in this regard still remain limited due to uncontrollable selectivities. Herein, we report visible-light-induced dearomatization of indole- or pyrrole-tethered VCPs, in which several competitive reaction pathways, including [5 + 2], [2 + 2], interrupted [5 + 2], and [5 + 4] cycloadditions, can be well regulated by engineering substrate structures and tuning reaction conditions. The reaction mechanism has been explored by combined experimental and computational investigations. These reactions provide a convenient method to synthesize structurally diverse polycyclic molecules with high efficiency and good selectivity.

Porous 2D and 3D Covalent Organic Frameworks with Dimensionality‐Dependent Photocatalytic Activity in Promoting Radical Ring‐Opening Polymerization

AbstractDimensionality is a fundamental parameter to modulate the properties of solid materials by tuning electronic structures. Covalent organic frameworks (COFs) are a prominent class of porous crystalline materials, but the study of dimensional dependence on their physicochemical properties is still lacking. Herein we illustrate photocatalytic performances of N,N‐diaryl dihydrophenazine (PN)‐based COFs are heavily dependent on the structural dimensionality. Six isostructural imine‐bonded 2D‐PN COFs and one 3D‐PN COF were prepared. All can be heterogeneous photocatalysts to promote radical ring‐opening polymerization of vinylcyclopropanes (VCPs), which typically produces polymers with a combination of linear (l) and cyclic (c) repeat units. The 2D‐PN COFs have much higher catalytic activity than the 3D‐PN COF, allowing the efficient synthesis of poly(VCPs) with controlled molecular weight, low dispersity and high l/c selectivity (up to 97 %). The improved performance can be ascribed to the 2D structure which has a larger internal surface area, more catalytically active sites, higher photosensitizing ability and photoinduced electron transfer efficiency.

Porous 2D and 3D Covalent Organic Frameworks with Dimensionality-Dependent Photocatalytic Activity in Promoting Radical Ring-Opening Polymerization.

Dimensionality is a fundamental parameter to modulate the properties of solid materials by tuning electronic structures. Covalent organic frameworks (COFs) are a prominent class of porous crystalline materials, but the study of dimensional dependence on their physicochemical properties is still lacking. Herein we illustrate photocatalytic performances of N,N-diaryl dihydrophenazine (PN)-based COFs are heavily dependent on the structural dimensionality. Six isostructural imine-bonded 2D-PN COFs and one 3D-PN COF were prepared. All can be heterogeneous photocatalysts to promote radical ring-opening polymerization of vinylcyclopropanes (VCPs), which typically produces polymers with a combination of linear (l) and cyclic (c) repeat units. The 2D-PN COFs have much higher catalytic activity than the 3D-PN COF, allowing the efficient synthesis of poly(VCPs) with controlled molecular weight, low dispersity and high l/c selectivity (up to 97 %). The improved performance can be ascribed to the 2D structure which has a larger internal surface area, more catalytically active sites, higher photosensitizing ability and photoinduced electron transfer efficiency.

Development of Dipolarophiles for Catalytic Asymmetric Cycloadditions through Pd-π-Allyl Zwitterions.

The development of new and efficient methodology for the construction of optically active molecules is of great interest in both synthetic organic and medicinal chemistry fields. To this end, the personal account summarizes our studies on the development of electron-deficient alkenes, allenes, and alkynes containing single activator as new dipolarophiles for Pd-catalyzed asymmetric cycloaddition reactions. These new dipolarophiles can participate in Pd-catalyzed asymmetric [3+2] and [4+2] cycloadditions through Pd-π-allyl 1,3- and 1,4-zwitterions in-situ generated by the reaction of Pd(0) catalyst with vinyl aziridines, vinyl epoxides, vinyl cyclopropanes, 4-vinyl-1,3-dioxan-2-ones, and vinyl benzoxazinanones. These [3+2] and [4+2] cycloadditions provide efficient approaches to a wide range of enantiomerically enriched five- and six-membered ring compounds containing contiguous chiral centers with high to excellent chemo-, diastereo-, and enantioselectivities. The utilities of these protocols are demonstrated by transformation of the cycloadducts into other useful chiral building blocks. DFT calculations reveal the dissimilar reactivity of different electron deficient alkenes and rationalize the mechanism and stereo-control of the reaction. A Pd-catalyzed inverse [3+2] cycloaddition is disclosed.

Molecular design and synthesis of crosslinked polyimides using radical isomerization of vinylcyclopropane with thiols

AbstractReactive polyimides bearing a vinylcyclopropane (VCP) moiety in the main chain were successfully synthesized from the corresponding diamine with the VCP moiety. Their radical crosslinking using a dithiol proceeded with the radical ring‐opening reaction (RROR) of the VCP moiety to afford the corresponding crosslinked polyimides with the CC bonds in crosslinking moieties. Thermal properties of those crosslinked polyimides were evaluated by thermal gravimetry and differential scanning calorimetry. As a result, the increase of the crosslinking degree in the crosslinked polymer exhibited great residual weight at 600°C. In contrast, the tendency of the glass transition temperature was inverse because the increase in the amount of dithiol unit as a crosslinker would enhance the mitigation of the polymer packing structure and activates the mobility of polymer chains.