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A TBHP mediated carbonylation–peroxidation of styrene, α-peroxidation of α-substituted unsymmetrical internal alkenes and concurrent peroxidation–carbonylation–cycloalkylation/cycloetherifiction of internal cyclic alkene (indene) have been developed.

A method for the intramolecular addition of triarylmethanes to alkynes has been developed. The reaction was efficiently promoted by KOtBu/DMF without any transition-metal catalyst. A variety of indene derivatives were prepared in moderate to good yields. A cascade cyclization of 2-alkyl-substituted substrates at elevated reaction temperature gave bicyclic indene derivatives. The reaction is proposed to proceed through the generation of a triphenylmethyl radical.

Upon treatment with a substoichiometric amount of iodine in ethanol under reflux conditions, the Michael adducts of o-alkynylarene chalcones with diethyl malonate underwent 5-exo-dig Conia-ene cyclization followed by isomerization to yield highly functionalized 1H-indene derivatives in good yields.

A new synthesis of 2,3-dihydro-1,3-methano-1H-indene (3) has been designed with bicyclo[2.1.1]hex-2-ene serving as starting material, which was added onto chloro-substituted α-pyrones. The title hydrocarbon 3 was then obtained in two subsequent steps. The AA′MM′ 1H NMR spectrum of 3 was analyzed and simulated, leading to corrections of previously published coupling constants. The 13C NMR signal of the methylene carbon atoms appears at particularly low field (δ = 63.3 ppm). This finding is discussed together with anomalous low- and high-field absorptions of methylene carbon atoms of cyclobutanes and bridgehead carbon atoms of bicyclo[1.1.0]butanes, the 1,3- and 2,4-positions of which, respectively, are bridged by π electron systems. As a result, moieties with (4n + 2) π electrons cause deshieldings, whereas those having 4n π electrons evoke shieldings.

Enynes substituted with a tertiary hydroxyl group attached to one of the alkyne units react with iodobenzenes in a Pd-catalyzed domino reaction. The cascade consists of an intermolecular anti-carbopalladation and a terminating Heck reaction. This process leads to arene-substituted dienes. One tetrasubstituted double bond is embedded in a six-membered ring system, and the other trisubstituted alkene is located in an exocyclic position. On treatment with acid, the emerging tertiary carbocation is attacked by the arene to give a five-membered ring, and thus results in the formation of alkylated indenes.

A substoichiometric copper iodide catalysed synthesis of indene and dihydronaphthalene derivatives has been accomplished. This protocol is compatible with functional groups, and results in various scaffolds of indene and dihydronaphthalene derivatives in good to high yields. By employing this protocol, a functionalised cyclohexenone derivative is also achieved.

Palladium-catalyzed regio- and stereoselective synthesis of tetrasubstituted olefins incorporating an indene scaffold was developed through 6-exo-dig carbocyclization followed by Heck cyclization with anti β-hydrogen elimination. The starting materials for the domino reaction were designed through an A3-coupling reaction.

A palladium-catalyzed annulation reaction of alkynylborates with o-iodophenyl ketones to form indenes is described. Highly substituted indene skeletons are efficiently constructed with site-specific installation of the substituents.

A direct, asymmetric allylic alkylation of indenes withMorita–Baylis–Hillman (MBH) carbonates has been developed based on a Lewis base assisted Bronsted base catalysis strategy. This process is promoted by a modified cinchona alkaloid hydroquinidine (anthraquinone-1,4-diyl) diether [(DHQD)2AQN] and gives rise to multifunctional chiral indene derivatives with moderate to excellent enantioselectivities (53–95 % ee), albeit in low to modest yields (27–71 %).

The reaction of aldimine 1a, derived from ethyl glyoxalate, with activated dienophiles, such as styrene and indene, gave the tetrahydro-1,5-naphthyridine derivatives 3 with regio- and stereoselective control of three stereocenters through a [4+2] cycloaddition process via endo transition states. However, when aldimine 1a was used in the reaction with strained olefins, such as norbornene or dicyclopentadiene, the corresponding [4+2] and [2+2] cycloadducts were obtained, through exclusive exo π-facial stereoselective cycloaddition. The addition of a second strained C=C bond in the olefin, such as norbornadiene, increased the multifunctional character of the olefin and a mixture of the corresponding exo [4+2] 11a and exo [2+2] 12a cycloadducts, as well as the corresponding HOMO cycloadduct 13a, was obtained. Reaction between norbornadiene and aldimines derived from p-nitro- and o,p-dinitroanilines and ethyl glyoxalate gave exo [4+2] cycloadducts 11b,c, HOMO cycloadducts 13b,c and α-amino γ-lactones 15b,c. A mechanistic explanation for the formation of the new products is suggested.

A AuI-catalyzed intramolecular cyclization reaction of 2-alkenylphenyl carbonyl compounds to afford a variety of indene, indenol, and indanone ring systems was developed. In this process, AuI serves to activate the carbonyl group of β-keto esters, aldehydes, and ketones, preferentially exhibiting oxophilicity in the presence of C–C multiple bonds. Furthermore, β-keto esters could participate as the electrophilic partner in reactions with carbon nucleophile such as alkenes.

Oxidative isomerization of vinylidenecyclopropanes 1 produces dimethylenecyclopropane aldehydes 2 in moderate to good yields using tetrapropylammonium perruthenate (TPAP)/4-methylmorpholine N-oxide (NMO) as a catalytic system and the obtained dimethylenecyclopropanes 3 can be transformed to indene derivatives smoothly in the presence of Bronsted acid (HOTf). The scope and limitations as well as the plausible mechanisms have been discussed.

A novel cascade combination reaction catalyzed by a single palladium source for the synthesis of various indene derivatives is reported. The approach involved sequential Sonogashira/carbopalladative cyclization/Suzuki coupling reactions by using three readily available components, such as homopropargyl alcohol, aryl iodides or aryl bromides, and arylboronic acids. The overall domino reaction yields were up to 70 %.

A combined theoretical and experimental study of a Povarov-type cycloaddition reaction suggests an asynchronous concerted process that is favored by double Lewis acid activation with BF 3· Et 2 O; endo selectivity was observed in the reactions between N-(3-pyridyl)aldimines and styrene, cyclopentadiene, or indene, and substituted tetrahydro-1,5-naphthyridine derivatives were obtained in a regio- and stereoselective fashion.

A new reaction setup for kinetic enzymatic resolution was established and is demonstrated for the case of the hydrolase-catalysed conversion of methyl 2,3-dihydro-1H-indene-1-carboxylate (1) in conjunction with a base-catalysed racemisation. The system allows controlled racemisation, resulting in efficient dynamic kinetic resolution (DKR) of the title compound. Short reaction times and high enantioselectivities were obtained with CAL-B and TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene). Compound (R)-1 (ee 95 %) served as a starting material in a domino reaction that led to the biaryl indanyl ketone (R)-8, a lead compound for novel inhibitors of peptidyl-prolyl-cis/trans-isomerases, in 94 % ee. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Chiral N-(diethoxymethyl)oxazolidinones, prepared from the corresponding oxazolidinones by heating in triethyl orthoformate can he used as organozinc carbenoid precursors for the direct enantioselective amidocyclopropanation of alkenes. The reaction is successful with it wide range of oxazolidinones and alkenes and proceeds with moderate to excellent, yield and stereoselectivity. In most cases the trans/exo amido-cyclopropane product is favoured, although certain cyclic alkenes such is indene favour the formation of the endo cyclopropane. The products can be readily elaborated to produce cyclopropylamino alcohols and amino acids. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Highly substituted indene and naphthalene derivatives have been readily prepared in good-to-high yields by a palladium-catalyzed domino reaction. This domino reaction involves a Heck carbopalladation/cyclization/coupling process. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The bromofluorocarbene adduct rac-1 of indene, possessing the fluorine atom at the endo position, is a useful substrate for the generation of the isonaphthalene 4 by the Doering–Moore–Skattebol reaction. By resolution of rac-1, an enantiomerically pure precursor of a six-membered cyclic allene was obtained for the first time. The treatment of (+)- or (–)-1, dissolved in 2,5-dimethyl-, 2-tert-butyl-5-methyl-, or 2,5-bis(tert-butyl)furan, with methyllithium gave rise to the [4+2] cycloadducts 6 of 4 to the furans. It was shown by means of HPLC on Chiralcel OD that the formation of 6 proceeded with about 40 % ee, and that this value was independent of the type and concentration of the furan, and the reaction temperature. The absolute configurations of the enantiomers 1, as well as those of the enantiomers 6, were determined by simulation of the CD spectra by quantum chemical methods and by the comparison of them with the experimental spectra. In the case of (+)-1, the reliability of this procedure was checked by X-ray crystal structure analysis. On the basis of these results, a model is proposed for the steric course of the reaction sequence, leading from a pure enantiomer 1 to the 70:30 mixtures of the product enantiomers 6. The use of indene as trapping reagent for 4 furnished the [2+2] cycloadduct 15. For the preparation of rac-15, the particularly simple one-pot procedure was employed, in which indene, tetrabromomethane, and methyllithium were combined and in which the dibromocarbene adduct 2 of indene serves as precursor of 4. Compound 2 could not be isolated, but was characterised by low-temperature 1H NMR spectra. The conversion of (+)- or (–)-1 into 4 in the presence of indene afforded 15 only with a very low enantioselectivity. The constitutions and the relative configurations of 15 as well as the compounds 8 and 16, which resulted from thermolysis of the cycloadducts 6b and 15, respectively, were elucidated by X-ray crystal diffraction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Alkenyloxy-substituted aryl bridgeheads have been connected to 2,9-dichloro-1,10-phenanthroline (11) either by Suzuki coupling or by nucleophilic aromatic substitution. The resulting di- or tetraalkenes 12 or 17 have been cyclized by ring-closing metathesis to give concave 1,10-phenanthrolines 14 and 19, differing from other concave 1,10-phenanthrolines 1 in their geometries. The influence of the shapes of these ligands and those of the related concave 1,10-phenanthrolines 1a–f and 2 on the stereochemistry of the copper(I)-catalyzed cyclopropanation of indene (3) and styrene (4) has been investigated, identifying factors that favour the formation of thermodynamically less stable syn-cyclopropanes 6 and 7. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The acidity of the parent 1H-benz[f]indene (1a), 1H-benz[e]indene (2a), 1H-benz[fg]acenaphthylene (3a) and 1H-cyclopenta[l]phenanthrene (4a) and of their polycyano derivatives is examined in the gas phase and in DMSO by the DFT-B3LYP methods. It is shown that the parent hydrocarbons exhibit modest acidities, whereas a dramatic increase in acidity is observed upon multiple cyanation leading to hyperstrong neutral organic superacids. It is found that polycyano derivatives undergo prototropic tautomerism with a consequence that the most stable tautomer contains a ketene imine C=C=NH functionality. The origin of their highly pronounced acidity is identified as a very strong anionic resonance effect efficiently assisted by a large number of CN groups in a concerted manner. It is stressed that the polycyanated anions are very stable and have a highly dispersed negative charge, which should lead to a low nucleophilicity and weak coordinating properties, thus making them potentially very useful in academic research and technological applications. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Azulene has been shown to react with pyrrole and a series of aromatic aldehydes in the presence of boron trifluoride etherate to give meso-tetraarylazuliporphyrins 6. Good yields of azuliporphyrins were obtained for benzaldehyde, 4-chlorobenzaldehyde, 4-bromobenzaldehyde, and 4-iodobenzaldehyde, and under dilute conditions p-tolualdehyde gave respectable yields. In each case, substantial amounts of meso-tetraarylporphyrins were also formed and a minor fraction of carbaporphyrin by-products could be detected, but otherwise no other macrocyclic products could be identified. 4-Nitrobenzaldehyde gave relatively poor yields of the corresponding azuliporphyrin, while p-anisaldehyde only gave trace amounts of product. Pentafluorobenzaldehyde gave variable results, although in this case a large number of additional by-products were identified including N-fused pentaphyrin, hexaphyrin, and higher order porphyrinoids, but no expanded azulene-containing macrocycles could be detected. Azuliporphyrins undergo reversible nucleophilic substitution on the seven-membered ring with pyrrolidine, benzenethiol, hydrazine, or benzylamine to give carbaporphyrin adducts. This property appears to facilitate an oxidative ring contraction of azuliporphyrins 6 with tert-butyl hydroperoxide in the presence of potassium hydroxide to produce mixtures of benzocarbaporphyrins 19 and 20. Tetraaryl-benzocarbaporphyrins exhibit slightly reduced diatropic ring currents compared to their meso-unsubstituted counterparts, although their UV/Vis spectra are very porphyrin-like and exhibit strong Soret bands near 450 nm. The benzocarbaporphyrins undergo reversible protonation to give monocationic and dicationic species. The latter involves C-protonation to generate an internal CH2 within the macrocyclic cavity. X-ray crystallography of tetraphenylbenzocarbaporphyrin 19a confirms that the preferred tautomer has the two NHs on either side of the indene subunit, in agreement with previous theoretical and spectroscopic studies. In addition, the presence of phenyl substituents at the 5,20-positions was found to tilt the indene moiety substantially by 27.4(1)° relative to the [18]annulene substructure. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

[2.2]Paracyclophane-1,9-diene (1) is readily deprotonated at its vinylic positions with BuLi to give the monolithium derivative 2 and – in the presence of TMEDA – even the 1,9-/1,10-dilithium derivatives 1,9-/1,10-6. Reaction of 2 with a variety of electrophiles including benzaldehyde and ethyl formate led to bridge-substituted derivatives 3a–d (71-89% yields) and 4, 5 (95 and 91%, respectively). Electrophilic substitution of 1,9-/1,10-6 with benzaldehyde gave the bis(vinylbenzyl) alcohols 1,9-/1,10-8 in 39% yield. The vinylbenzyl alcohols 5 and 1,9-/1,10-8 underwent cyclization upon treatment with zinc(II) chloride in 1,2-dichloroethane to give the indene-annelated [2.2]paracyclophane 9 (72%) and the bis(indene)-annelated compounds syn-11 and anti-11 (39%, ratio 19:1). Both 9 and syn-11, when treated with FeCl2•(THF)2 after deprotonation with methyllithium in the presence of excess lithium cyclopentadienide gave mixed-ligand ferrocene-type complexes 12 (63%) and syn-/anti-16 (46%). The bis(indeno[2.2]paracyclophane-9-ene) complex 13 was obtained from deprotonated 9 in 61% yield and characterized by an X-ray crystal structure analysis.

o-Bromostyrenes 2-Br react with various alkenes in the presence of palladium catalysts to give either substituted indene 6 or o-diethenylbenzene derivatives 3, depending on the reaction conditions. Under oxidative conditions the latter can be cyclized to indene derivatives as well.