Singlet oxygenation of 7-aryl and 7-alkyl-1,3,5-cycloheptatrienes: substituent effects on the product distribution of tropilidene- and nocaradiene-derived endoperoxides

The N/T ratio, i.e. the proportion of norcaradiene ($\text{N}$) versys tropilidene ($\text{T}$) endoperoxides in the cycloaddition of singlet oxygen with 7-substituted 1,3,5-cycloheptrines, decreases in the order p-C1C₆H₄ > C₆H₅ > p-MeOC₆H₄ and t-Bu > iPr > Et > Me, prresumably reflecting the ability of these substituents in promoting the tropilidene to norcaradiene valence isomerization.     

Primary dependence of 7-aryl-2,5-di-t-butyl-1,3,5-cycloheptatriene valence tautomerism on the π-acceptor strength of the 7-aryl substituent

¹³C NMR studies showed that the population of the norcaradiene form of the title systems containing p-CH₃O, H, and p-CF₃ on the 7-aryl group increases in this order. The result is consistent with the prediction from the π-acceptor strength of the aryl group estimated by INDO calculations.     

Generation and notable position dependent electrocyclization of cycloheptatrienylphenylcarbonium ions -electrocyclization of a norcaradiene

While (1- and 2-cycloheptatrienyl)phenylcarbonium ions undergo electrocyclizations through the cycloheptatriene forms giving dihydrobenz[a]azulenes, (3-cycloheptatrieny])-diphenylcarbonium ion does through the norcaradiene form. (7-Cycloheptatrienyl)diphenyl- carbnium ion undergoes a rearrangement. A possible rationalization is discussed.     

The Norcaradiene Problem

Compounds having the norcaradiene structure are stable if one of the double bonds of the norcaradiene also belongs to a benzene ring or if C atoms 1 and 6 are fixed in position by a bridge. A similar effect that favors the norcaradiene form is produced by the incorporation of nitrogen atoms in positions 3 and 4. Cycloheptatriene and most of the simply substituted tropilidenes exist exclusively in the monocyclic triene form. It has been possible in some cases to detect a valence-tautomeric equilibrium between the norcaradiene and the cycloheptatriene ring system. Non-classical stabilization of compounds having norcaradiene or cycloheptatriene structure in the sence of a pseudoaromatic “homobenzene” is only very slight, if it occurs at all.     

Development of domino processes by using 7-silylcycloheptatrienes and its analogues

7-Silyl- and 7-silylmethylcycloheptatrienes were shown to react with acylnitroso reagents at room temperature, through their norcaradiene forms, to generate the corresponding cycloadducts 5?a-b and 6?a-b as single diastereomers. The course of the reaction was dramatically modified by changing the reaction conditions. Using a polar medium, functionalized cyclohexa-1,3-dienes 7?a-b and bicyclic compounds 13?a-b were instead generated, incorporating one or two amino groups. Similar behavior was observed by using other dienophiles, including triazolinedione, but also activated aldehydes and ketones. A tentative mechanism has been proposed to rationalize the formation of both classes of products that relies on a domino process involving four consecutive elementary steps, in this order: 1)?electrocyclic process, 2)?hetero-Diels-Alder reaction, 3)?cyclopropane ring opening, and 4)?hetero-Diels-Alder reaction. Trapping of the cationic intermediate and isolation of the primary cycloadduct provide support for this hypothesis. An enantioselective version of the cascade using cycloheptatriene 4?b and aldehydes and ketones, under copper(II) catalysis was also carried out, leading to cyclohexa-1,3-dienes 21, 28, and 30 with enantioselectivities up to 93?% ee. Finally, elaboration of the intermediates above has been carried out, opening a straightforward access to sugar mimics 42-43 and complex polycyclic systems 36 and 39.     

Enantioselective total synthesis of (+)-salvileucalin B

An enantioselective total synthesis of the diterpenoid natural product (+)-salvileucalin B is reported. Key findings include a copper-catalyzed arene cyclopropanation reaction to provide the unusual norcaradiene core and a reversible retro-Claisen rearrangement of a highly functionalized norcaradiene intermediate.     

Rearrangement and hydrogen scrambling pathways of the toluene radical cation: a computational study

A computational study is undertaken to provide a unified picture for various rearrangement reactions and hydrogen scrambling pathways of the toluene radical cation (1). The geometries are optimized with the BHandHLYP density functional, and the energies are computed with the ab initio CCSD(T) method, in conjunction with the 6-311+G(d,p) basis set. In particular, four channels have been located, which may account for hydrogen scrambling, as they are found to have overall barriers lower than the observed threshold for hydrogen dissociation. These are a stepwise norcaradiene walk involved in the Hoffman mechanism, a rearrangement of 1 to the methylenecyclohexadiene radical cation (5) by successive [1,2]-H shifts via isotoluene radical cations, a series of [1,2]-H shifts in the cycloheptatriene radical cation (4), and a concerted norcaradiene walk. In addition, we have also investigated other pathways such as the suggested Dewar-Landman mechanism, which proceeds through 5, via two consecutive [1,2]-H shifts. This pathway is, however, found to be inactive as it involves too high reaction barriers. Moreover, a novel rearrangement pathway that connects 5 to the norcaradiene radical cation (3) has also been located in this work.     

Acid-catalyzed rearrangement of ethynylcycloheptatriene to phenylallene

7-Ethynylcycloheptatriene (1) cleanly isomerizes to phenylallene in the presence of acid. A mechanism involving the protonation of ethynylnorcaradiene, which is in equilibrium with 1, followed by the cleavage of a three-membered ring to give an arenium ion, is proposed. The rearrangement is accelerated by a factor of 370 by introducing tert-butyl groups on C-2 and C-5, indicating the importance of the equilibrium concentration of the norcaradiene form as a rate-controlling factor.     

Homobenzene: homoaromaticity and homoantiaromaticity in cycloheptatrienes

Cycloheptatriene (C(s)) is firmly established to be a neutral homoaromatic molecule based on detailed analyses of geometric, energetic, and magnetic criteria. Substituents at the 7 (methylene) position, ranging from the electropositive BH2 to the electronegative F, favor the equatorial conformation but influence the aromaticity only to a small extent. By the same criteria, the planar transition state (C(2v)) for cycloheptatriene ring inversion is clearly antiaromatic. This is attributed to the involvement of the pseudo-2pi-electrons of the CH2 group with the 6pi-electrons of the ring to give an 8pi-electron system. Similarly, the participation of the CH2 groups into C(2v) cyclopentadiene and cyclononatetraene lead to significant 4n + 2 pi electron aromaticity. The cyclization of cycloheptatriene to norcaradiene proceeds via a highly aromatic transition structure, but norcaradiene itself is less aromatic than cycloheptatriene. An annelated cyclopropane ring does not function as effectively as a double bond in promoting cyclic electron delocalization.     

Conversion of C5 into C6 cyclic species through the formation of C7 intermediates

We have recently proposed that the addition of C2H2 to the cyclopentadienyl radical can lead to the rapid formation of the cycloheptatrienyl radical and, in succession, of the indenyl radical. These reactions represent an interesting and unexplored route for the enlargement of gas-phase cyclic species. In this work we report ab initio calculations we performed with the aim of investigating in detail the gas-phase reactivity of cycloheptatrienyl and indenyl radicals. We found that the reaction of the cycloheptatrienyl radical with atomic hydrogen can lead to its fast conversion into the more stable benzyl radical. This reaction pathway involves the intermediate formation of heptatriene, norcaradiene, and toluene. Successively we investigated whether this reaction mechanism can be extended to polycyclic aromatic hydrocarbons (PAHs). For this purpose we studied the reaction of C2H2 with the indenyl radical, which can be considered as a superior homologue of the cyclopentadienyl radical. This reaction proceeds through a pathway similar to that proposed for C5H5 but with a reaction rate about an order of magnitude smaller. The present calculations extend thus the previously proposed C5-C7-C9 mechanism to bicyclic PAH and suggest a fast route for the conversion of C5 into C6 cyclic radicals, mediated by the formation of C7 cyclic species.     

Development of Domino Processes by Using 7‐Silylcycloheptatrienes and Its Analogues

7‐Silyl‐ and 7‐silylmethylcycloheptatrienes were shown to react with acylnitroso reagents at room temperature, through their norcaradiene forms, to generate the corresponding cycloadducts 5 a – b and 6 a – b as single diastereomers. The course of the reaction was dramatically modified by changing the reaction conditions. Using a polar medium, functionalized cyclohexa‐1,3‐dienes 7 a – b and bicyclic compounds 13 a – b were instead generated, incorporating one or two amino groups. Similar behavior was observed by using other dienophiles, including triazolinedione, but also activated aldehydes and ketones. A tentative mechanism has been proposed to rationalize the formation of both classes of products that relies on a domino process involving four consecutive elementary steps, in this order: 1) electrocyclic process, 2) hetero‐Diels–Alder reaction, 3) cyclopropane ring opening, and 4) hetero‐Diels–Alder reaction. Trapping of the cationic intermediate and isolation of the primary cycloadduct provide support for this hypothesis. An enantioselective version of the cascade using cycloheptatriene 4 b and aldehydes and ketones, under copper(II) catalysis was also carried out, leading to cyclohexa‐1,3‐dienes 21 , 28 , and 30 with enantioselectivities up to 93 % ee. Finally, elaboration of the intermediates above has been carried out, opening a straightforward access to sugar mimics 42 – 43 and complex polycyclic systems 36 and 39 .     

A ring walk of methylene groups in toluene radical cations. An extension of the toluene-cycloheptatriene rearrangement of aromatic radical cations. Theory and experiment

The minimum energy reaction pathway (MERP) of the toluene-cycloheptatriene radical cation rearrangement (TOL/CHT-rearrangement) has been calculated by the UHF and DFT model at the level UHF/6-311+G(3df,2p)//UHF/6-31G(d) and B3LYP/6-311+G(3df,2p)//B3LYp/6-31G(d), respectively, including the ring walk of the substituent by a 1,2-shift around the aromatic ring. This ring walk corresponds to interconversion of distonic ions and norcaradiene radical cations (the two intermediates of the TOL/CHT-rearrangement) by making and breaking of the external C-C bonds of the cyclopropane moiety of the intermediate norcaradiene structure. For toluene radical cation 1, UHF calculations adequately reproduce earlier results(4) and show, that the ring walk of the CH(3)-substituents requires slightly more energy than formation of the cycloheptatriene radical cation. By the DFT model, the distonic ion, which is formed initially by a 1,2-H shift from CH(3) to the benzene ring, is not stable but the transition state of an interconversion of norcaradiene radical cations along a ring walk of the CH(3) substituent. The activation energy for this ring walk exceeds that for formation of the cycloheptatriene radical cation by c. 30 kJ mol(-1). Thus, isomerization of 1 by a ring walk of the CH(3)-substituent competes with the TOL/CHT-rearrangement likely only for excited 1. The calculation was repeated for the MERPs of a TOL/CHT-rearrangement of para-xylene radical cation 5 and ethylbenzene radical cation 2, yielding basically the same results as for 1. According to the calculation, polar substituents alter significantly the relative energies of the competing routes of isomerization. For benzylcyanide 3 (X = CN), the activation energy for a ring walk of the NC-CH(2)-substituent is distinctly below that of a ring enlargement. For benzyl methyl ether 4 (X = OCH(3)), the distonic intermediate along the UHF-MERP is unusually stable. Further, the 7-methoxy-norcaradiene radical ion is unstable and corresponds to a transition state between isomeric distonic intermediates differing by a 1,2-shift of the side chain. In contrast, the 7-methoxy-norcaradiene radical ion is the only intermediate of the DFT-MERP, and the distonic ion is the transition state for a 1,2-shift of the cyclopropane ring. A ring walk of the CH(3)OCH(2)-substituent is much more favorable than formation of a 7-methoxy-cycloheptatriene radical cation in both MERPs. The findings of the theoretical calculation are substantiated by the mass spectrometric fragmentations of meta- and para-methoxymethylated 1-phenylethanols 8 and 9 and of para-methoxymethyl substituted benzyl ethyl ether 10 and benzyl n-propyl ether 11. Important fragmentation routes of metastable molecular ions of these compounds correspond to elimination of alcohols. Use of deuterated derivatives shows that the elimination occurs by a "false" ortho-effect which requires migration of a ROCH(2)-substituent around the benzene ring. Results of particular interest are obtained for the asymmetric bis-ethers 10 and 11. Here, the MIKE spectra of the molecular ions of deuterated analogs reveal a selective ring walk of the C(2)H(5)OCH(2)- and n-C(3)H(7)OCH(2)-side chain, respectively.     

Antarafacial role of an aromatic nucleus; a novel regiospecific [π4a + π2a] intramolecular cycloaddition of the ene-ketene with an aromatic ring

The thermally generated ene-ketene undergoes a facile and regiospecific intramolecular cycloaddition with N,N-dimethylaniline to result in the novel formation of the azulenone derivative via a norcaradiene intermediate.     

Manganese(III) Acetate Catalyzed Oxidative Radical Additions of α‐Dicarbonyl Compounds to 1‐ and 2‐Phenylcyclohepta‐1,3,5‐triene

Manganese(III) acetate catalyzed oxidative radical‐addition reactions of α‐dicarbonyl compounds such as methyl acetoacetate ( 6 ), acetylacetone ( 7 ), and dimedone ( 8 ) to the mixture of 1‐ and 2‐phenylcyclohepta‐1,3,5‐triene ( 4 and 5 ) were investigated (Scheme 1). The 1‐phenylcyclohepta‐1,3,5‐triene ( 4 ) formed mainly [2+3] and [4+3] dihydrofuran addition products derived from cycloheptatriene and [2+3] dihydrofuran addition products derived from the norcaradiene structure. The 2‐phenylcyclohepta‐1,3,5‐triene ( 5 ) formed mainly [6+3] dihydrofuran addition products derived from cycloheptatriene and [4+3] dihydrofuran addition products derived from the norcaradiene structure. The structures of isolated products were established by their spectroscopic data (IR, ¹H‐ and ¹³C‐NMR, MS, and elemental analysis) and comparison with literature data. The formation mechanism of the products is discussed.     

8-Oxoheptafulvene III. One Step Synthesis of Heptafulvalene and Benzoheptafulvalenes

In the previous paper,¹ we have reported that 8-oxoheptafulvene (1) reacts with monocyclic tropones to from adducts (2) containing a novel norcaradiene and cycloheptatriene moieties according to apparent 8 + 2 cycloaddition process.     

Position and dienophile dependent Diels-Alder reactions of vinylcycloheptatrienes

While 1-vinyl- and 2-vinylcycloheptatrienes undergo Diels-Alder reactions exclusively from cycloheptatriene forms at the diene part including the vinyl group, 3-vinylcycloheptatriene reacts site-selectively from either cycloheptatriene or norcaradiene form depending on electron affinity of dienophiles.     

Synthesis and properties of 5-(2,3-diphenylcyclopropenylidene)-1,6-methano-2(5h)-[10]- annulenone (or 10,11-diphenyl-4,9-methano[3.10]quinaren-3-one). Contribution of a homobenzene structure annelated on [3.6]quinaren-3-one

The title quinarenone 2 has been prepared and proved that the three-membered ring possesses a larger diatropicity than diphenylcyclopropenone and the seven-membered ring exists in a cycloheptatriene (not norcaradiene) tautomer having a contribution of a homobenzene structure. The rotational barrier about the intercyclic bond of 2 is 13.3 Kcal/mol.     

An unusual norcaradiene/tropylium rearrangement from a persistent amino-phosphonio-carbene

An amino-phosphonio-carbene featuring a bromobiphenyl backbone was prepared and spectroscopically characterized at low temperature. This carbene was found to readily rearrange upon warm up, affording an original tricyclic phospholium derivative, presumably via a norcaradiene/tropylium isomerization.     

Preparation of some 2,4,6-cycloheptatriene-1-yl ketones. Strong preference for the norcaradiene isomer in the case of the 2,4,6-cycloheptatriene-1-yl t-butyl ketone

t-Butyl, i-propyl and phenyl 2,4,6-cycloheptatriene-1-yl ketone ({=1a},{=c},{=d}, respectively) have been synthesized. At ?139°C, rather unexpectedly, the t-butyl ketone {=1a} exists in a 1:1 equilibrium with its norcaradiene isomer {=2a}.     

Total synthesis of the tropoloisoquinoline alkaloid pareitropone via alkynyliodonium salt chemistry and related studies

The first chemical synthesis of pareitropone, by a route featuring application of alkynyliodonium salt chemistry, is described. The key transform initiates with addition of an alkylidenecarbene, derived by intramolecular nucleophile addition to the alkynyliodonium moiety, to a proximal aromatic ring. This addition delivers a highly strained norcaradiene substructure that rapidly reorganizes to furnish the pareitropone skeleton.