Novel [6 + 2] cycloaddition of fulvenes with alkenes: a facile synthesis of the anislactone and hirsutane framework

[reaction: see text] In contrast to the Diels-Alder reaction of fulvenes and various alkenes, 6-aminofulvenes react with maleic anhydride (or maleimide) to give [6 + 2] cycloaddition adducts, constituting an efficient and novel route to pentaleno[1,2-c]furan, pentaleno[1,2-c]pyrrole, and cyclopenta[a]pentalene skeleton.     

Reaction of ketones with lithium hexamethyldisilazide: competitive enolizations and 1,2-additions

Reaction of 2-methylcyclohexanone with lithium hexamethyldisilazide (LiHMDS, TMS(2)NLi) displays highly solvent-dependent chemoselectivity. LiHMDS in THF/toluene effect enolization. Rate studies using in situ IR spectroscopy are consistent with a THF concentration-dependent monomer-based pathway. LiHMDS in pyrrolidine/toluene affords exclusively 1,2-addition of the pyrrolidine fragment to form an alpha-amino alkoxide-LiHMDS mixed dimer shown to be a pair of conformers by using (6)Li, (15)N, and (13)C NMR spectroscopies. Rate studies are consistent with a monomer-based transition structure [(TMS(2)NLi)(ketone)(pyrrolidine)(3)](). The partitioning between enolization and 1,2-addition is kinetically controlled.     

The regiospecific acylation of fulvenes

1-Acylated fulvenes were the only monoketones formed by treatment of fulvenes with methyl iodide, carbon monoxide, catalytic quantities of benzyltriethylammonium chloride and dicobalt octacarbonyl, in a two-phase system [5N NaOH/C₆H₆].     

Proliferative and antiproliferative effects in substituted titanocene anticancer drugs

Substituted titanocenes like ansa-titanocenes, diarylmethyl-substituted and benzyl-substituted titanocenes, are known for their cytotoxic potential and they can be synthesised using 6-arylfulvenes. Nevertheless, in the case of using 6-(4-morpholin-4yl-phenyl) fulvene (5a) or 6-{[bis-(2-methoxyethyl)amino]phenyl} fulvene (5b) the synthetic possibilities seem to be limited, but the morpholino and the bis-(2-methoxyethyl)amino substituent are in terms of an improved water solubility and drug availability in the cell very interesting groups. The corresponding benzaldehydes, which are the starting material for the synthesis of these fulvenes, were not commercially available and therefore, a modified synthetic approach had to be introduced. Nevertheless, the reactivity of the obtained fulvenes was unexpected and only the ansa-titanocene bis-[{[bis-(2-methoxyethyl)amino]phenyl}cyclopentadienyl] titanium(IV) dichloride (6b) and the benzyl-substituted titanocene [1,2-di(cyclopentadienyl)-1,2-di(4-morpholin-4yl-phenyl)-ethanediyl] titanium dichloride (8a) could be obtained and characterised. When the benzyl-substituted titanocene (8a) was tested against pig kidney cells (LLC-PK) an anti-proliferative effect, resulting in an IC₅₀ value of 25 μM, was observed. This IC₅₀ value is in the lower range of the cytotoxicities evaluated for titanocenes up to now. The ansa-titanocene (6b) showed surprisingly, when tested on the same cell line, a proliferative effect.     

A frontier molecular orbital treatment of fulvene cycloadditions : Molecular orbital calculations and photoelectron spectra of substituted fulvenes

MO calculations have been carried out on substituted fulvenes by several semiempirical methods. The results of these calculations are compared with those by other methods, and with photoelectron spectroscopic data obtained here for several substituted fulvenes. Predictions about the periselectivity ([6+4] or [4+2]) of fulvene cycloadditions with dienes, 1,3-dipoles, and ketenes are made and compared with experimental data, where available.     

Synthese von Fulvenen über 1-Chloralkyl-acetate

Synthesis of fulvenes via 1-chloroaklyl-acetates The synthesis of fulvenes (5) via l-chloroalkyl acetates (3) is extended to 6-alkyl-fulvenes with branched side-chains, to 6-phenylfulvene (5f) and 6-(2-furyl)fulvene (5g) , as well as to 6-vinylfulvenes ( 5h and 5i ) containing chlorine and acetoxy-substituents in ω-position. The reaction is carried out at low temperature under water-free conditions. The purification of the reaction products is simple. - An improved procedure for the preparation of pure fulvene ( 5a , R=R′=H) is reported.     

A highly enantioselective approach towards 2-substituted 3-bromopyrrolidines

A facile and highly enantioselective approach towards 2-substituted 3-bromopyrrolidines has been developed. The process involves an amino-thiocarbamate catalyzed bromoaminocyclization of 1,2-disubstituted olefinic amides. The pyrrolidine products could readily be converted into other useful building blocks including a dihydropyrrole and a 2-substituted pyrrolidine.     

取代环戊二烯基锂芳酰化的研究

本文研究了由616-二烷基富烯与有机锂所制得取代环戊二烯基锂和芳酰氯的反应,合成了二十个未见文献报道的新富烯类化合物,并通过^1HNMR、IR和元素分析确定了它们的结构.     

First Total Synthesis of Hyacinthacine A6 from the Protected Derivative of Polyhydroxylated Pyrrolidine

（1S、2R、3R、5R、7aR）-1,2-Dihydroxy-3-hydroxy methyl-5-methylpyrrolizidine（hyacinthacine A6, I） was synthesized by Wittig＇s methodology via the reaction of aldehyde 6, prepared from the partially protected derivative of polyhydroxylated pyrrolidine, with appropriated ylides, followed by cyclization through the intemal reductive amination process of the resulting a,B-unsaturated ketone 7, and total deprotection.     

Highly enantioselective catalytic [6+3] cycloadditions of azomethine ylides

Under control: Highly functionalized chiral annulated piperidines with eight stereocenters are efficiently obtained by means of a highly enantioselective one-pot [6+3]/[4+2] sequence. This sequence included the first enantioselective [6+3] cycloaddition of azomethine ylides with fulvenes.     

6-羟基富烯及环戊二烯并[d]哒嗪的合成

本文以6, 6-二烷基富烯与烯丙基格氏试剂反应所得的取代环戊二烯基负离子与芳酰氯反应, 合成了5个新的6-羟基富烯化合物(1-5)。用此化合物与肼反应, 合成了5个新的环戊二烯并[d]哒嗪化合物(6-10)。通过^1H NMR、IR及元素分析确定了它们的结构。     

Formal [6+3] cycloaddition of fulvenes with 2H-azirine: a facile approach to the [2]pyrindines system

2H-Azirine reacts with fulvenes to give either alkylated fulvene azirines (ultrasound) or the formal [6+3] cycloaddition adducts (Lewis acid). The later constitutes an efficient and novel route to [2]pyrindines.     

Eine neue Fulvensynthese. 4. Mitteilung

Fulvenes are prepared by condensation of sodium cyclopentadienide with x-acetoxy-x-chloro-hydrocarbon derivatives, followed by elimination of acetic acid with triethylamine. The yields are approximately 60% for 6-alkylfulvenes and similar to those of the classical synthesis for 6, 6-polymethylenefulvenes. The reaction is carried out at low temperatures and under water-free conditions. The purification of the fulvenes is simple.     

The synthesis of diphenyltrideca-, -pentadeca-, -heptadeca-, and -nonadecafulvene derivatives

Title fulvenes were synthesized through the reaction of the large-membered annulenones with diphenylketene, and examination of ¹H-NMR spectra suggests that the fulvenes are atropic.     

Influence of excited state aromaticity in the lowest excited singlet states of fulvene derivatives

The absorption spectra and excited state dipole moments of four differently substituted fulvenes have been investigated both experimentally and computationally. The results reveal that the excited state dipole moment of fulvenes reverses in the first excited singlet state when compared to the ground state. The oppositely polarized electron density distributions, which dominate the ground state and the first excited singlet state of fulvenes, respectively, reflect the reversed π-electron counting rules for aromaticity in the two states (4n + 2 vs. 4n, respectively). The results show that substituents indeed influence the polarity of fulvenes in the two states, however, cooperative interactions between the substituents and the fulvene moiety are most pronounced in the ground state.     

Demonstration of the facile reversibility of fulvene formation

Cleavage of fulvenes under mild conditions and interchange between electron-deficient fulvenes and their constituent cyclopentadienes and imines is demonstrated for the first time. A series of cyclopentadienes and imines are investigated to probe the dependence of fulvene equilibration on structure. The exchange of one fulvene for another is demonstrated in the first reported example of transfulvenation. Finally, the metathesis of two fulvenes to generate all four possible cross products is shown.     

Stable fulvenes of the furan series

Relatively stable fulvenes were obtained by the reaction of cyclopentadiene with furan compounds containing unconjugated carbonyl groups.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 738–739, June, 1972.     

Pyrimidine derivatives. VII. Nucleophilic reactions of 5-bromo-1-(bromoalkyl)-6-bromomethyl-2,4(1H,3H)-pyrimidinediones

The reactions of 1-(bromoalkyl)-5-bromo-6-bromomethyl-3-methyl-2,4(1H,3H)-pyrimidinedione (1) with several nucleophiles were examined as follows: by reaction with sodium methoxide, 6-(bismethoxy)methyl-5-debrominated derivatives 2, 3 , and 4 were prepared; the corresponding di-substituted compounds (side chains in 1-and 6-positions) 5, 6, 7 , and 9 were obtained by treatment with silver nitrate, silver acetate, potassium thiocyanate, and potassium thioacetate; the reaction with thioacetamide and iso-butylamine gave bicyclic compounds [1,4]thiazino[4,3-c]- 11 , pyrazino[1,2-c]- 12 , and [1,4]diazepino[1,2-c]pyrimidinedione 13 , respectively; pyrrolidine, morpholine, and sodium azide afforded the corresponding 6-substituted compounds 14, 15 , and 16 .     

1－芳酰基－3－烷基－6－羟基－6－芳基富烯的合成

１－芳酰基－３－烷基－６－羟基－６－芳基富烯的合成焦纶基,董育斌,马玉道（山东大学应用化学研究所,济南,２５０１００）关键词富烯,二茂铁,芳酰化,合成前文［１］曾报道过甲基锂、苯基锂与６,６－二烷基富烯加成物的芳酰化。为进一步探讨取代环戊二烯负离子的...     

Reactivity of a kinetically stabilized 1,3,6-triphosphafulvene toward some nucleophiles

A kinetically stabilized 1,3,6-triphosphafulvene displayed regioselective reactivity toward nucleophiles at the external phosphorus atom (position 6) to afford the corresponding phosphinodiphospholide anions, which gave phosphinodiphospholes after quenching with electrophiles, as well as being readily reduced by sodium naphthalenide suggesting properties similar to fulvenes.