The 2π electron 1,3‐dipole boradigermaallyl, valence‐isoelectronic to an allyl cation, is synthesized from a bis(germylene). It reacts with benzene at room temperature by insertion of a boron atom ...into the benzene ring. Computational investigation of the mechanism shows the boradigermaallyl reacting with a benzene molecule in a concerted (4+3) or π4s+π2s cycloaddition reaction. Thus, the boradigermaallyl acts as a highly reactive dienophile in this cycloaddition reaction with nonactivated benzene as diene unit. This type of reactivity provides a novel platform for ligand assisted borylene insertion chemistry.
Boradigermaallyl featuring a delocalized π‐bond shows a boron atom insertion into benzene at room temperature. The mechanism starts by a concerted (4+3) reaction between the germanium atoms of the digermaboraallyl and the 1,4‐positions of a benzene molecule. Thus, boradigermaallyl acts as a highly reactive dienophile in this cycloaddition reaction with nonactivated benzene.
The cyclic azodicarbonyl 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) is a versatile and powerful reagent used mainly in cycloaddition chemistry. Though known for more than 50 years, its unsafe ...preparation, as well as purification by sublimation, hampered its widespread applicability on a larger scale. Herein we report a scalable and safe route to MTAD, which avoids the generation of methyl isocyanate. Moreover, we demonstrate that sublimation can be circumvented by the application of judicious oxidation conditions, followed by simple filtration. Overall, up to 25 g of MTAD was prepared in a single batch from commercial starting materials in three steps, with recrystallization serving as the only purification in the sequence. When employed in dearomative methodologies, the MTAD obtained by this protocol displayed synthetic efficiency equivalent to that of MTAD purified by sublimation.
Lack of the repulsion type interaction at exo TS held responsible for stereoselectivity in the exo TS of 4+2 cycloaddition left. The π-π aromatic stacking, appears to have significant destabilizing ...effect on the endo TS of this hetero-Diels-Alder reaction right.
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•H—bonding and suitable interaction of exo TS in water leads to stereo-specific cycloaddition.•The π—aromatic stacking leads to destabilization of the endo TS.•Decision on submission to Inorganic Chemistry Communications.
Four commercially available asymmetric thioindoles including (E)-3-X-indoline-2-thiones (where X = phenyl, furan-2-yl, 1H-pyrrol-2-yl, and thiophene-2-yl, I to IV, respectively) are known as selective and potent inhibitors in contradiction of different receptors for tyrosine kinases. A specifically interesting report for these biologically active species is the effect of media on their stability and stereo-selectivity in inter-molecular cycloaddition as drug delivery involving I-IV hetero Diels–Alder (as diene) with 20fullerene (as dienophile). Here, we have tackled this survey using the SCRF method in the gas phase, C7H8, CH2Cl2, MeOH, H2O, CH3CN and DMSO, at DFT. Stability of each solute (I-IV) and Diels–Alder cycloadducts (Ia-IVa) depends on the dielectric constant of the solvent, the possibility of the hydrogen bonding and dipole–dipole interactions. Formation of the endo isomer appears energetically less favorable due to the non-bonding electrostatic repulsions between the heteroatoms and C20 (nheteroatom ↔ πC20), also the π-π aromatic stackings among the substituted rings and C20 (πsubstituted ring ↔ πC20), which affect the stability of the transition states (TSs). Even though, the endo isomer appears thermodynamically more stable, we propose formation of the kinetically more stable exo isomer due to lack of π-π aromatic stackings. These appear completely comparable to interactions of the acyclic electron rich 1,3-dienes and dienophile C60 previously held responsible for the origin of region-selections in the exo 4 + 2 cycloadditions. Theoretical predictions are waiting for inter-molecular donor–acceptor experimental testing and verifications.
A stereoselective synthesis of the decahydrofluorene core of the hirsutellones was accomplished in eight steps and in 43% overall yield. The key step of the synthesis is the highly stereoselective ...intramolecular Diels–Alder cyclization of the siloxacyclopentene-constrained tetraene
1.
An efficient approach to the type III lepadin alkaloids (lepadins F and G) has been developed through a key Diels–Alder reaction, in which a novel ketolactone‐type dienophile with chiral diol unit is ...employed to generate the desirable all‐cis‐trisubstituted cyclohexene with excellent regio‐ and stereoselectivity control. The subsequent selective sulfonylation of the diol unit followed by SN2 cyclization under hydrogenation conditions could construct the substituted piperidine ring. By using this approach, (−)‐lepadin F is synthesized from ethyl l‐lactate for the first time.
An efficient approach to the type III lepadin alkaloids (lepadins F and G) has been developed through a key Diels–Alder reaction, in which a novel ketolactone‐type dienophile with a chiral unit is employed to generate the desirable all‐cis‐trisubstituted cyclohexene with complete regio‐ and stereoselectivity control. By using this approach, (−)‐lepadin F is synthesized for the first time.
In this paper, one of the selective and potent inhibitors named (E)‐3‐benzylidene‐indoline‐2‐one (I), as against different receptor tyrosine kinase in metastasis, angiogenesis, and tumor growth, is ...inspected in the gas phase and in solution, at B3LYP/6‐311++G** and B3LYP/AUG‐cc‐pVTZ level of theory. A stimulating issue for this biologically active species is the effect of different media on its stability, structure, and energy gap in intermolecular 4 + 2 adsorption of I (as diene) to C20 (as dienophile) to yield (E)‐3‐benzylidene‐indoline‐2‐one20fullerene: Ia complex. In going from gas phase to C6H6, C2H4Cl2, EtOH, MeNO2, DMSO, and H2O solvents, individually, the optimization of complex (Ia) leads to the following: (1) The thermodynamic stability; the adsorption energy difference between liquid and gas phase (∆El–g) and dipole moment (μ) seem proportional to the dielectric constant (ε) of the scrutinized media. (2) The kinetic stability; energy difference (∆EL–H) between the frontier molecular orbitals; FMO in different media is altered in the opposite direction of ε. (3) Despite of popular belief that the endo isomer emerges thermodynamically more stable than its corresponding exo isomer, we suggest formation of kinetically more stable exo isomer because of π–π stacking among the benzyl ring and C20 nanocage. (4) The possibility of hetero 4 + 2 cycloaddition is anticipated by the lowest energy barrier of 3.8 kcal/mol probed for exo transition state (TS) in gas phase, while the highest energy barrier of 7.9 kcal/mol corresponds to the endo TS in water. (5) Due to lack of the repulsion type interaction, the exo 4 + 2 cycloaddition of unstable C20 fullerene with the scrutinized oxindole can be carried out thermally at r.t. and currently hold responsible for the origin of stereoselectivity.
Lack of the repulsion at exo TS held responsible for stereoselectivity of cycloaddition. The π–aromatic stacking has significant destabilizing effect on the endo TS.
The 2π electron 1,3‐dipole boradigermaallyl, valence‐isoelectronic to an allyl cation, is synthesized from a bis(germylene). It reacts with benzene at room temperature by insertion of a boron atom ...into the benzene ring. Computational investigation of the mechanism shows the boradigermaallyl reacting with a benzene molecule in a concerted (4+3) or π4s+π2s cycloaddition reaction. Thus, the boradigermaallyl acts as a highly reactive dienophile in this cycloaddition reaction with nonactivated benzene as diene unit. This type of reactivity provides a novel platform for ligand assisted borylene insertion chemistry.
Boradigermaallyl featuring a delocalized π‐bond shows a boron atom insertion into benzene at room temperature. The mechanism starts by a concerted (4+3) reaction between the germanium atoms of the digermaboraallyl and the 1,4‐positions of a benzene molecule. Thus, boradigermaallyl acts as a highly reactive dienophile in this cycloaddition reaction with nonactivated benzene.
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•An elusive 1,3-butadiene having 2-carboxy and 4-alkoxy substituents is prepared.•This reactive diene is trapped with dienophiles to give cycloaddition products.•The cycloadduct from ...fumarate ester can be elaborated to oseltamivir (Tamiflu).
A reactive diene, ethyl 2-methylene-4-(pent-3-oxy)but-2-enoate, bearing electron-withdrawing carboxy and electron-donating pentoxy substituents is prepared and trapped in situ by a variety of dienophiles to form 4+2 cycloaddition products. Diels–Alder reaction of this diene with fumarate esters gives multiply substituted cyclohexenes that are useful for building the scaffold of oseltamivir.
This article provides an overview about specifically modified Mannich reactions where the process involves an
-quinone methide (
-QM) intermediate. The reactions are classified on the basis of the
...-QM source followed by the reactant, e.g., the dienophile partner in cycloaddition reactions (C=C or C=N dienophiles) or by the formation of multicomponent Mannich adducts. Due to the important pharmacological activities of these reactive
-QM intermediates, special attention is paid to the biological activity of these compounds.
Making use of a Diels-Alder approach based on various α,β-unsaturated 2-carbomethoxy-4,4-dimethyl-1-tetralones as novel dienophiles, the corresponding polycyclic adducts could be efficiently ...synthesized in good to high yields (74~99%) in the presence of Lewis acid (e.g., SnCl
). Accordingly, a synthetically useful platform is established to provide a focused aromatic polyketide-like library for screening of potential natural and non-natural antimicrobial agents.
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