Synthesis and reactions of a new 1,1-disubstituted cyclopentadiene

The synthesis and several synthetic transformations of methyl 1-benzylcyclopenta-2


Introduction
For several years, we have been working on the generation, trapping and dimerization of highly pyramidalized alkenes containing the skeleton of tricyclo[3.3.0.0 3,7 ]oct-1(5)-ene, as very reactive species for the fast elaboration of complex polycyclic compounds. 1These pyramidalized alkenes are usually generated by deiodination of double bridgehead 1,2-diiodo precursors with molten sodium in boiling 1,4-dioxane or t-BuLi in THF.In connection with this work, we planned the preparation of a conveniently functionalized 1,1-disubstituted cyclopenta-2,4-diene, to study different model transformations, specially a simple introduction of a 1,2-diiodoethylene functionality.

Results and Discussions
In this study, we chose methyl 1-benzylcyclopenta-2,4-diene-1-carboxylate 5 as the 1,1disubstituted cyclopenta-2,4-diene, whose ester function opens the way for different transformations, apart from those derived from the presence of the diene substructure.Diene 5 was obtained as shown in Scheme 1 from methyl 1-benzyl-2-oxocyclopentanecarboxylate 1. 2 Following a procedure described for a related case, 3 keto ester 1 was reacted with trimethylsilyl triflate to give the corresponding silylated enol ether 2, which was directly oxidized by bubbling oxygen through a vigorously stirred DMSO solution in the presence of Pd(OAc) 2 as the catalyst to give the known 4 enone 3 in 82% yield of chromatographed product.NaBH 4 reduction of 3 in the presence of CeCl 3 •7H 2 O following the Luche procedure, 3,5 gave the known 4 allylic alcohol 4, which was subjected as such to acid catalyzed dehydration to give cyclopentadiene 5 in 66% yield of chromatographed product (Scheme 1).Diene 5 is a relatively stable compound that slowly dimerizes at room temperature to give after 4 months a unique stereoisomeric dimer 6 in 58% yield (Scheme 2), still remaining some diene 5.The structure and relative configuration of this dimer were fully established through NMR data: 1 H/ 1 H homocorrelation (COSY and NOESY) and 1 H/ 13 C heterocorrelation experiments ( 1 H/ 13 C gHSQC and gHMBC sequences).Formation of this stereoisomer requires approaching of both components from the side of the less bulky methoxycarbonyl substituent.The stereochemistry of 6 coincides with that established by other means for the dimer obtained from a related compound, methyl 1-methylcyclopenta-2,4-diene-1-carboxylate. 6iene 5 participated without problems in standard Diels-Alder reactions.Thus, reaction of crude diene 5 with maleic anhydride or cis-1,2-bis-(phenylsulfonyl)ethylene 7 gave the corresponding endo-adducts 7 and 8, respectively (Scheme 2).In both cases, only endo-adducts derived from the addition of the dienophile to the diene from the side of the less bulky methoxycarbonyl group were detected.Formation of the exo-adducts must be disfavored by the steric interaction among the 7-syn substituent and the 2-exo and 3-exo substituents.This type of interaction must be the responsible for the fact that no reaction took place among diene 5 and trans-1,2-bis-(phenylsulfonyl)ethylene, after 60 h in refluxing toluene.In the corresponding adduct, one of the phenylsulfonyl groups will be in an exo-position, thus being very close to the syn-substituent at position 7.
Cis-1,2-Bis(phenylsulfonyl)ethylene has been used as an acetylene equivalent in Diels-Alder reactions, 7 when combined with the reductive desulfonylation of the cycloadduct with 2% sodium amalgam.This reduction is usually performed in MeOH in the presence of monosodium phosphate.When we reacted adduct 8 with 2% sodium amalgam under the above conditions, we could isolate slightly impure cyclopropanated compound 11 and a mixture of 11 and the expected diene 10 in low yields.Since compound 11 contains two hydrogen atoms more than diene 10, we considered that these hydrogen atoms must come from the protic medium.When the above reaction was carried out in an aprotic solvent (1,4-dioxane) in the absence of any hydrogen source, diene 10 was isolated in 53% yield (Scheme 2).Diene 10 could not be obtained from anhydride 7 by hydrolysis followed by reaction with Pb(OAc) 4 , anhydride 7 being the only product recovered in the last reaction.For the preparation of compound 12 we first synthesized the novel (2-iodoethynyl)-(phenyl)iodonium triflate 14, by using a procedure similar to that used for the preparation of [(2-trimethylsilyl)ethynyl](phenyl)iodonium triflate. 8Thus, iodination of (trimethylsilyl)acetylene 15 by reaction with n-BuLi and iodine in THF, as described, 9 gave 1-iodo-2-(trimethylsilyl)acetylene 16.Reaction of compound 16 with iodosobenzene diacetate (IBDA) and triflic acid gave the crude iodonium triflate 14, as light brown solid containing some acetic acid (Scheme 3).After crystallization from MeCN/CH 2 Cl 2 1:3, triflate 14 was obtained in 46% yield, as white solid, quite stable in a dry argon atmosphere at 5 ºC.This procedure is more simple than that described for the preparation of (2-chloroethynyl)(phenyl)iodonium triflate, 10 which implies reaction of (2-chloroethynyl)tributylstannane with (cyano)(phenyl)iodonium triflate, both not commercially available.
Reaction of crude diene 5 with the triflate 14 in MeCN at room temperature for 20 h gave the expected Diels-Alder adduct 9 in 79% yield.Reaction of 9 with NaI/CuI in MeCN, following the procedure described by Stang et al. 11 in related cases, gave diiodide 12 in 46% yield (Scheme 2).The stereochemistry of both compounds was clearly established as for 6 on the basis of the different NMR data, especially the 1 H/ 1 H NOESY experiments, thus showing that the addition of triflate 14 to the diene 5 had taken place, as in the precedent cases, by the less hindered methoxycarbonyl face.Worthy of note, reaction of the iodonium triflate 9 with aqueous sodium hydroxide gave a mixture of the volatile iodobenzene (traces), diiodide 12 (35%) and iodoketone 13 (23%).These facts suggest competition of the nucleophilic attack of the hydroxide ion to the ipso phenyl and the 2-norbornadiene positions.The enol, initially formed by substitution of the phenyliodonium group by hydroxide, would then tautomerize to the more stable 3-endoiodoketone 13.
1,2-Diiodoethylene derivatives related to 12 have been prepared through Diels-Alder reactions using bis[phenyl[[(trifluoromethyl)sulfonyl]oxy]iodo]acetylene 12 as the dienophile, followed by reaction of the adducts with NaI/CuI. 11However, this dienophile is much less stable and more difficult to prepare than 14.

Conclusions
In conclusion we have prepared methyl 1-benzylcyclopenta-2,4-diene-1-carboxylate and studied its Diels-Alder reactions with maleic anhydride, cis-1,2-bis(phenylsulfonyl)ethylene and (2iodoethynyl)(phenyl)iodonium triflate, and further transformations of the obtained adducts.Of special interest is the adduct with the above iodonium triflate, that has been transformed into methyl 1-benzyl-2,3-diiodonorbornadiene-7-carboxylate.Work is in progress to apply the described methodologies for the preparation of more complex polycyclic compounds.

Experimental Section
General.Melting points were determined with a MFB 595010 M Gallenkamp melting point apparatus. 1H NMR spectra were recorded on Varian Gemini-300 (300 MHz), Varian Mercury-400 (400 MHz), or Varian VXR-500 (500 MHz) spectrometers. 13C NMR spectra were recorded on Varian Mercury-400 (100.6 MHz), or Varian VXR-500 (125.8MHz) spectrometers.The 1 H/ 1 H homocorrelation spectra (COSY and NOESY) and the one bond and long range 1 H/ 13 C heterocorrelation spectra (gHSQC and gHMBC, respectively) were performed on a Varian VXR-500 spectrometer.Chemical shifts are given in δ scale and the coupling constants in Hz.IR spectra were registered on a FTIR Perkin−Elmer Spectrum RX1 spectrometer usually with the attenuated total reflectance (ATR) technique.High resolution MS spectra were performed in a LC/MSD-TOF spectrometer at the Serveis Científico-Tècnics of the University of Barcelona.The elemental analyses were determined in a Carlo Erba model 1106 equipment at the IIQAB (CSIC) of Barcelona, Spain.For the column chromatography, silica gel 60 AC (35-70 µM, SDS, ref. 2000027) was used.Thin-layer chromatography (TLC) was performed on aluminum-backed sheets with silica gel 60 F 254 (Merck, ref. 1.05554) and spots were visualized with UV light, a 1% aqueous solution of KMnO 4 or by placing the sheets in an iodine atmosphere.