Schmittel Cyclization Research Articles

Hidden intermediate activation: a concept to elucidate the reaction mechanism of the Schmittel cyclization of enyne-allenes.

The mechanistic paradigm in which the Schmittel cyclization transitions from one-step to stepwise has been investigated through the stabilization of a full hidden intermediate in the framework of the Diabatic Model of Intermediate Stabilization. Hidden intermediate activation was studied in silico employing quasi-classical trajectories and the Electron Localization Function. The stabilization of hidden intermediates achieved by substituting enyne-allenes with cyano and nitro groups generates the appearance of a partially hidden and an explicit intermediate, leading to one-step asynchronous biradical and stepwise biradical/zwitterionic mechanisms, respectively. The mechanistic feature associated with the activation level of the hidden intermediate arises from the Thornton effect and non-RRKM dynamics, where in the case of the CN-substituted system, despite having a single transition state, 54% of the effective trajectories remain in the intermediate zone after 540 fs, indicating that a mixture of mechanisms is observed.

Copper(I)-Catalyzed Syntheses of Benzo[b]fluorenes by the Cascade Reactions of 2-Alkynylbenzaldehyde N-Tosylhydrazones and Aromatic Terminal Alkynes.

Benzo[b]fluorenes were synthesized via CuI-catalyzed cascade reactions of 2-alkynylbenzaldehyde N-tosylhydrazones and aromatic terminal alkynes in the presence of base including the formation of the benzoenyne-allene intermediate in situ and its Schmittel cyclization. Density functional theory calculation was performed to give the energy difference for the formation of 5-phenyl-11H-benzo[b]fluorene and 1,2-diphenyl-1H-cyclobuta[a]indene from the proposed diradical intermediates.

Synthesis of Divergent Benzo[ b]fluorenones through Cycloaromatization Reactions of 1,5-Enynols and 1,5-Diynols.

A facile and efficient synthesis of divergent benzo[ b]fluorenones is described through the use of dichlorobenzoquinone-promoted oxidative cycloaromatization reactions of acyclic 1,5-enynols and 1,5-diynols. The success of these cascade reactions depends on the chemoselectivity of the initial Meyer-Schuster rearrangement to produce allenol intermediate, which is followed by regioselective Schmittel cyclization and the subsequent Friedal-Crafts alkylation or radical attack at the terminal Ar moiety. Only an oxidant and a solvent were required in the reaction, thus delivering a small library of the expected polycarbocyclic products with excellent functional group tolerance under metal-free conditions. The absorption and photoluminescence properties of the selected benzo[ b] fluorenones were also investigated. The results indicated that the compound (2h) which contained an electron-donating 4-OMe group at the phenyl moiety displayed deep green color emission (491 nm).

Enynone-enabled migratory insertion and Schmittel cyclization cascade for the synthesis of furan-fused fluorenes

A new method for the synthesis of furan-/benzo-fused fluorenes through copper(i)-catalyzed coupling of conjugated enynones or α-diazocarbonyl compounds with dialkynylbenzenes has been developed.

ChemInform Abstract: Ambient Schmittel Cyclization Promoted by Chemoselective Triazole‐Gold Catalyst.

AbstractTriazole‐gold‐catalyzed Propargyl vinyl ether rearrangement according to A) followed by cyclization allows an access to the previously challenging benzannulated indenes at room temperature.

Ambient Schmittel Cyclization Promoted by Chemoselective Triazole-Gold Catalyst

The Schmittel cyclization was achieved at room temperature through triazole-gold (TA-Au) catalyzed propargyl vinyl ether rearrangement. Other tested [L-Au](+) catalysts gave complex reaction mixtures under identical conditions with no desired products observed. Importantly, because of the employment of mild conditions, sterically hindered groups (such as t-Bu) on allene termini were no longer required, which allowed successful synthesis of previously challenging substrates.

Theoretical Studies on Myers−Saito and Schmittel Cyclization Mechanisms of Hepta-1,2,4-triene-6-yne

The mechanisms of the Myers-Saito cyclization and the Schmittel cyclization of hepta-1,2,4-triene-6-yne are studied by ab initio multireference MO methods (CASSCF and MRMP2 methods). For the Myers-Saito cyclization, two transition states with C(s) and C₁ symmetries are located. The transition state with C1 symmetry is only 1.5 kcal/mol lower in energy than that with C(s) symmetry at the MRMP2 calculation level. The obtained activation energy at the transition state with C₁ symmetry and the reaction energy are 16.6 and 16.2 kcal/mol exothermic, respectively. For the Schmittel cyclization, two transition states with C(s) and C₁ symmetry are also obtained. The transition state with C₁ symmetry is 7.9 kcal/mol lower in energy than that with C(s) symmetry. The transition state with C₁ symmetry for Schmittel cyclization is 6.7 kcal/mol higher in energy than that for the Myers-Saito cyclization. The reaction mechanisms are analyzed by a CiLC-IRC method. The interactions of orbitals for the Myers-Saito and Schmittel cyclizations can be distinguished.

ChemInform Abstract: Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence

AbstractA stepwise process involving Sonogashira coupling, propargyl‐allenyl isomerization and Schmittel cyclization has been realized, leading to an efficient synthesis of polycyclic fluorene derivatives from readily available starting materials. The reaction features the formation of three new carbon‐carbon bonds to construct the benzene unit together with an efficient assembly of three or four rings in a single operative step.

Molybdenum‐Mediated Cyclocarbonylation of 1‐Ethynyl‐2‐allenylbenzenes to 1H‐Cyclopenta[a]inden‐2‐ones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access the actual ChemInform Abstract, please click on HTML or PDF.

Synthesis of Indeno‐Fused Derivatives of Quinolizinium Salts, Imidazo[1,2‐a]pyridine, Pyrido[1,2‐a]indole, and 4H‐Quinolizin‐4‐one via Benzannulated Enyne—Allenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Molybdenum-mediated cyclocarbonylation of 1-ethynyl-2-allenylbenzenes to 1 H-cyclopenta[ a]inden-2-ones

Although 1-ethynyl-2-allenylbenzenes readily undergo Myers–Saito or Schmittel cyclization under mild conditions, cyclocarbonylation of these moieties to 1 H-cyclopenta[ a]inden-2-ones proceeds smoothly using suitable molybdenum carbonyl reagents, with Mo(CO) 3(CH 3CN) 3 being the most efficient. The yields of desired bicyclic ketones were up to 87–93%.

Myers–Saito and Schmittel cyclizations of enyne-(hetero)-1,2,3-trienes: A DFT study on the structure–reactivity relationship

The Myers–Saito (C 2–C 7) cyclization and the alternative Schmittel (C 2–C 6) cyclization of enyne-1,2,3-triene 1R and its hetero analogues 2R– 5R were investigated by using pure density functional theory method (BPW91) in connection with the 6-311G(d, p) basis set. It has been shown that heteroatom-containing reactants lower significantly reaction barriers for both cyclization modes and reduce the difference between the barrier of the C 2–C 7 cyclization mode and that of the C 2–C 6 one. The Myers–Saito cyclization of 4R is associated with the smallest reaction barrier and the highest exothermicity. Whereas the Schmittel cyclization of 4R is exothermic, all the others are predicted to be endothermic.

Synthesis of Indeno-Fused Derivatives of Quinolizinium Salts, Imidazo[1,2-a]pyridine, Pyrido[1,2-a]indole, and 4H-Quinolizin-4-one via Benzannulated Enyne−Allenes

The benzannulated enediynyl propargylic alcohol 8 was prepared from 1-bromo-2-iodobenzene by two consecutive Sonogashira cross-coupling reactions. The subsequent transformation to mesylate 9 followed by treatment with 4-substituted pyridines 10 then furnished the benzannulated enediynes 11. On exposure of 11 to triethylamine, the indeno-fused quinolizinium salts 15 were produced in quantitative yield. Presumably the reaction proceeded through a 1,3-prototropic rearrangement to form the benzannulated enyne-allenes 12, which then underwent either a concerted Diels-Alder reaction or a two-step process involving a Schmittel cyclization reaction to form biradical 13 followed by an intramolecular radical-radical coupling to afford 14. A subsequent prototropic rearrangement then produced 15. Similarly, 21a and 21b were produced from 19a and 19b, respectively. The use of the Sonogashira reaction for cross-coupling between 1-iodo-2-(phenylethynyl)benzene (7) and 1-(2-propynyl)-1H-imidazole (25) followed by treatment of the resulting adduct with potassium tert-butoxide gave the indeno-fused imidazo[1,2-a]pyridine 24 in 98% yield. Similarly, the indeno-fused pyrido[1,2-a]indole 32 and 4H-quinolizin-4-one 35 were obtained by starting from 7 for cross-coupling with 1-(2-propynyl)-1H-indole (30) and 1-(2-propynyl)-2(1H)-pyridinone (33), respectively, followed by treatment with potassium tert-butoxide.

Substituent Effects on the Cyclization Mode of 7‐Sulfonyl‐3‐hepten‐1,5‐diynes and 11‐Sulfonylundeca‐3,7‐dien‐1,5,9‐triynes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Substituent effects on the cyclization mode of 7-sulfonyl-3-hepten-1,5-diynes and 11-sulfonylundeca-3,7-dien-1,5,9-triynes

In probing of cycloaromatization of 7-phenylsulfonyl-3-hepten-1,5-diyne systems to generate biradical intermediates under an alkaline condition suggested that the aryl moiety on C3–C4 also plays an important role to switch the Myers cyclization to Schmittel cyclization in the allen–enyne system, although the aryl group on the alkyne terminus does not work in the proceeding of the cycloaromatization. For example, treatment of 1-phenyl-7-phenylsulfonyl-3-hepten-1,5-diyne ( 8 ) with triethylamine in the presence of 1,4-cyclohexadiene in benzene offered biphenyl 13 in 51% yield. Under the same reaction conditions, cyclization of 1-(2-phenylethynyl)-2-(3-phenylsulfonyl-1-propynyl) benzene ( 28 ) gave naphthalene 34 in 42% yield along with indene 35 in 32% yield. Moreover, the substituent effect also occurred in the cyclization of 11-phenylsulfonylundeca-3,7-diene-1,5,9-triyne ( 38 ), which provided indene 39 in 50% yield as the major product.

Polycyclic Aromatic Compounds via Radical Cyclizations of Benzannulated Enyne‐Allenes Derived from Ireland—Claisen Rearrangement.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Polycyclic aromatic compounds via radical cyclizations of benzannulated enyne-allenes derived from Ireland-Claisen rearrangement.

A new synthetic sequence involving the use of Ireland-Claisen rearrangement of propargylic acetates to form the corresponding benzannulated enyne-allenes followed by Schmittel cyclization to generate benzofulvene biradicals for radical cyclizations leading to polycyclic aromatic compounds was established. Treatment of 9-fluorenone (8) with the lithium acetylide 9 followed by acetic anhydride produced the propargylic acetate 10. A sequence of reactions occurred after 10 was converted to the corresponding silyl ketene acetal 11. An initial Ireland-Claisen rearrangement produced the benzannulated enyne-allene 12, which then underwent a Schmittel cyclization reaction to generate the benzofulvene biradical 13. A subsequent intramolecular radical-radical coupling then produced the formal Diels-Alder adduct 14, which in turn underwent a prototropic rearrangement to give the silyl ester 15 and, after hydrolysis, the carboxylic acid 16 in 57% overall yield from 10 in a single operation. An intramolecular acylation reaction of 16 produced the ketone 17. The carboxylic acids 24-26 were likewise prepared from the diaryl ketones 18-20, respectively. However, the intramolecular [2 + 2] cycloaddition reaction of the benzannulated enyne-allene 33 having a tert-butyl group at the allenic terminus occurred preferentially, producing the 1H-cyclobut[a]indenyl acetic acid 35 as the predominant product.

Biradicals from benzoenyne-allenes. Application in the synthesis of 11H-benzo[b]fluoren-11-ols, 1H-cyclobut[a]indenes, and related compounds.

New synthetic pathways to 11H-benzo[b]fluoren-11-ols, 1H-cyclobut[a]indenes, and related compounds via biradicals generated from benzoenyne-allenes were developed. Treatment of the diacetylenic propargylic alcohols 13, derived from condensation between benzophenones and the lithium acetylide of 1-(2-ethynylphenyl)-2-phenylethyne, with thionyl chloride produced the 11-chloro-11H-benzo[b]fluorene 14 and, after hydrolysis, the corresponding 11H-benzo[b]fluoren-11-ols 15. The transformation involved a sequence of reactions, including a biradical-forming C2-C6 cyclization (Schmittel cyclization) reaction of the chlorinated benzoenyne-allene intermediates followed by an intramolecular radical-radical coupling to form the formal Diels-Alder adducts. Interestingly, in the case of the diacetylenic propargylic alcohol 26, obtained from dibenzosuberenone (25), an intramolecular [2 + 2] cycloaddition reaction of the chlorinated benzoenyne-allene intermediate occurred, furnishing the 1H-cyclobut[a]indene 27 exclusively. The dramatic change of the reaction pathway could be attributed to the emergence of a steric strain due to the nonbonded interactions with the chloro substituent along the pathway toward the formal Diels-Alder adduct 31. On the other hand, the non-chlorinated benzoenyne-allene, derived from prototropic isomerization of the diacetylenic hydrocarbon 60, underwent a formal Diels-Alder reaction to furnish the 11H-benzo[b]fluorene-type hydrocarbon 61 exclusively.

Myers–Saito and Schmittel cyclization of hepta-1,2,4-triene-6-yne: A theoretical REKS study

Spin-restricted ensemble-referenced Kohn–Sham (REKS) calculations have been performed on the cyclization process of hepta-1,2,4-triene-6-yne leading to a five-membered ring (Schmittel cyclization) or a six-membered ring (Myers–Saito process), both products being biradicals. Geometries compare well with density functional as well as ab initio calculations and experimental measurements from the literature. Relative energies and singlet–triplet gaps were studied and compared with BCCSD(T) calculations.