Effect of Extended Benzannelation Orientation on Bergman and Related Cyclizations of Isomeric Quinoxalenediynes.

A combined computational and experimental study was conducted to examine the effect of extended benzannelation orientation on C1-C5 and C1-C6 cyclization of acyclic quinoxalenediynes. Calculations (mPW1PW91/cc-pVTZ//mPW1PW91/6-31G(d,p)) on terminal and phenylethynyl-substituted 5,6-diethynylquinoxaline and 6,7-diethynylquinoxaline showed C1-C6 Bergman cyclization as the favored thermodynamic reaction pathway, with larger C1-C6 preference for the angular quinoxalenediynes due to gain of a new aromatic sextet. Kinetic studies, as a function of 1,4-cyclohexadiene concentration, revealed retro-Bergman ring opening predominates over hydrogen atom abstraction (k-1 > k2) for 6,7-diethynylquinoxaline while 5,6-diethynylquinoxaline undergoes irreversible Bergman cyclization indicative of a large retro-Bergman ring opening barrier (k2 > k-1). The effect of extended linear versus angular benzannelation on reaction pathway shows in the contrasting photocyclizations of phenylethynyl derivatives. While angular 5,6-diethynylquinoxalines gave exclusive C1-C6 photocyclization, linear 6,7-diethynylquinoxaline afforded C1-C5 fulvene products. Computed singlet-triplet gaps and biradical stabilization energies indicated weak interaction between the nitrogen lone pair and proximal radical center in angular 5,6-diethynylquinoxalines. The overall data indicates extended angular benzannelation effectively renders Bergman cyclization irreversible due to favorable aromatic stabilization energy, while extended linear benzannelation results in increased retro-Bergman ring opening, allowing C1-C5 cyclization to become a competitive reaction channel.

Syntheses, thermal reactivities, and computational studies of aryl-fused quinoxalenediynes: effect of extended benzannelation on Bergman cyclization energetics.

A series of [b]-fused 6,7-diethynylquinoxaline derivatives have been synthesized through an imine condensation strategy to examine the effect of extended benzannelation on the thermal reactivity of enediynes. Absorption and emission spectra of the highly conjugated quinoxalenediynes were red-shifted approximately 100-200 nm relative to those of 1,2-diethynylbenzene. Strong exotherms indicative of enediyne cyclization were observed by differential scanning calorimetry, while solution cyclizations in the presence of 1,4-cyclohexadiene confirmed C(1)-C(6) Bergman cyclization. To provide further insight into Bergman cyclization energetics, computational studies were performed to compare changes in the cyclization enthalpy barrier, reaction enthalpy, and barrier of retro-Bergman ring-opening. Extension of benzannelation from 1,2-diethynylbenzene to either 2,3-diethynylnaphthalene or the 6,7-diethynylquinoxalines had a minimal effect on the cyclization barrier. In comparison, the enthalpies of cyclization were increased upon linearly extended benzannelation, which resulted in reduced barriers to retro-Bergman ring-opening. In addition, the orientation of extended benzannelation was found to have a significant effect on the cyclization endothermicity. In particular, 5,6-diethynylquinoxaline exhibited a 6.9 kcal/mol decrease in cyclization enthalpy compared to 6,7-diethynylquinoxaline due to increased aromatic stabilization energy in the respective angularly versus linearly fused azaacene cyclized products.

Syntheses and reactivity of naphthalenyl-substituted arenediynes.

A series of naphthalenyl-substituted arenediynes were prepared to examine photochemical reactivity. For naphthalen-1-ylethynyl arenediyne, 350 nm photolysis resulted in a tandem [2 + 2] photocycloaddition to afford cyclobutene adducts. For naphthalen-2-ylethynyl derivatives, electron-donating methoxy substituents were found to facilitate C(1)-C(6) Bergman cyclization at 300 nm. Theoretical calculations provided further insight into thermal and photochemical reactivity.

Synthesis of diazacalix[8]arene and triazacalix[12]arene methyl ethers via intramolecular aryl amination.

Azacalixarenes derived from p-tert-butylphenol are generated by an intramolecular aryl amination strategy as the ring-closing step. The reaction produces the first examples of larger p-tert-butylcalixarenes with regioselective substitution of bridging methylenes with nitrogen atoms.

Synthesis and Bergman cyclization of a beta-extended porphyrenediyne.

Condensation of a porphyrin-2,3-dione with a 1,2-diaminoarenediyne affords a [small beta]-extended porphyrinic-enediyne: upon thermal Bergman cyclization the quinoxaline spacer positioned between the macrocycle and the enediyne prevents tandem radical cyclization to a picenoporphyrin.

Regioselective oxidations of benzocarbaporphyrins with ferric chloride: a facile synthesis of bridged [18]annulene ketals with strong absorptions in the far red and an unexpected halogenation reaction at the interior carbon atom.

Benzocarbaporphyrins 4 were found to undergo regioselective oxidations with ferric chloride in methanol, ethanol, isopropyl alcohol, or ethylene glycol to give bridged benzo[18]annulene ketal derivatives 5 in excellent yields. These polar derivatives were generally isolated in a monoprotonated form and the corresponding free bases appeared to be relatively unstable. Addition of TFA resulted in the formation of spectroscopically distinct dications. The ketals 5 were highly diatropic in nature, showing the internal alkoxy substituents upfield beyond -1 ppm in their proton NMR spectra. The external meso-protons resonated near 10 ppm, confirming the presence of a strong aromatic ring current. The UV-vis spectra for 5 showed a Soret band at 422 nm, and two strong absorptions in the far red at 751 and 832 nm. A carbaporphyrin with a fused acenaphthylene ring was also oxidized with ferric chloride and this produced a ketal derivative with still further bathochromically shifted absorptions particularly for the Soret band. Also, the use of different alcohols in these reactions allows the overall polarity of these ketal products to be controlled and this could have merit in biomedical applications. Reaction of carbaporphyrin 4a with aqueous ferric chloride afforded the corresponding 21-chloro derivative 20 in good yields, and at longer reaction times a nonaromatic dione was isolated. Aqueous ferric bromide gave a 21-bromocarbaporphyrin product but in this case very poor yields (<10%) were noted. Mechanisms are proposed to explain the formation of these unusual oxidation products. The structure of 21-chlorocarbaporphyrin 20 was further demonstrated by X-ray crystallography. The presence of the interior chlorine atom was found to tilt the indene moiety by 29.59(4) degrees relative to the [18]annulene macrocyclic ring. The crystal packing for 20 shows offset face-to-face pi-stacking interactions that link the porphyrinoid molecules as closely paired dimers.

Conjugated macrocycles related to the porphyrins. 21. Synthesis, spectroscopy, electrochemistry, and structural characterization of carbaporphyrins.

The "3 + 1" variant of the MacDonald condensation has been shown to be an excellent methodology for synthesizing carbaporphyrins. In particular, 1,3-indenedicarbaldehyde condenses with tripyrranes in the presence of TFA to give, following oxidation with DDQ, a series of benzocarbaporphyrins in excellent yields. Triformylcyclopentadienes also afford carbaporphyrin products, albeit in low yields ranging from 5 to 8%. These hybrid bridged annulene structures have porphyrin-like electronic absorption spectra with strong Soret bands near 420 nm and a series of Q-bands through the visible region. The proton NMR spectrum confirms the presence of a strong diamagnetic ring current, and the meso-protons show up at 10 ppm, while the internal CH is shielded to approximately -7 ppm. Carbaporphyrins undergo reversible protonation with TFA. Initial addition of acid affords a monocation, although mixtures of protonated species are observed in the presence of moderate concentrations of TFA. However, in the presence of 50% TFA a C-protonated dication is generated. The dications relocate the pi-delocalization pathway through the benzo moiety of benzocarbaporphyrins, and these therefore represent bridged benzo[18]annulenes, although they nevertheless retain powerful macrocyclic ring currents. Carbaporphyrins with fused acenaphthylene and phenanthrene rings have been prepared, and the former demonstrated significantly larger bathochromic shifts in UV-vis spectroscopy that parallel previous observations for acenaphthoporphyrins. A diphenyl-substituted benzocarbaporphyrin 19b was also characterized by X-ray crystallography, and these data show that the macrocycle is reasonably planar although the indene subunit is tilted out of the mean macrocyclic plane by 15.5 degrees. The structural data indicates that the preferred tautomer in the solid state has the two NH's flanking the pyrrolene unit in agreement with previous spectroscopic and theoretical studies. Cyclic voltammetry for carbaporphyrin 19a was more complex than for true porphyrins, showing five anodic waves and two quasi-reversible reductive couples.

Actuating Cycloaromatization of a Bicyclo[7.3.1]enediyne by Annelation: An Example of Inverse Dependence on Bridge Atom Hybridization.

Although the acetylenic carbon atoms in 2 are closer together than those in 1, only the latter undergoes Bergman cyclization. In contrast, in analogous enediynes without an annelated cyclohexane ring a change in the hybridization of the bridging carbon atom from sp2 to sp3 leads to a dramatic increase in the cyclization rate.

Stereogenic Propargylic Centers via Base-Mediated Terminal Allene Isomerization.

A study of alkali metal amide-mediated isomerizations of terminal allenes is described. The isomerizations of substituted ethenylidenecyclohexanes to form diastereomeric mixtures of terminal alkynes have been conducted to determine factors which may influence the stereochemistry at the newly formed propargylic centers. An initial base screen revealed that potassium N-methylbutylamide (KMBA) exhibits the highest level of equatorial to axial alkyne diastereoselectivity. With the severely hindered terminal allene 26, the use of potassium 3-aminopropylamide is required to effect isomerization. A general synthesis of deuterated terminal allenes has also been achieved, and a mechanistic study using d(2)-allenes 18a,b has revealed the involvement of a propargylic anion in the course of the KMBA-mediated isomerizations.