Synthesis and structure of some cis-and trans-myrtanylstannanes

Enantiomerically pure cis- and trans-myrtanylstannanes cis-MyrSnPh₃ (1), trans-MyrSnPh₃ (2), cis-MyrSnPh₂Cl (3), trans-MyrSnPh₂Cl (4), cis-MyrSnPhCl₂ (5), trans-MyrSnPhCl₂ (6), cis-MyrSnCl₃ (7), trans-MyrSnCl₃ (8) were synthesized and fully characterized by ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy. The molecular structures of 1, 3, 6, 7, and [trans-MyrSn(OH)Cl₂ · H₂O]₂ (8a) a hydrolysis product of 8, were determined by X-ray crystallography.     

The first asymmetric synthesis of all four isomers of cis- and trans-3,4-dihydroxy-3,4-dihydromollugin

Asymmetric synthesis of all the four stereoisomers of cis-3,4-dihydroxy-3,4-dihydromollugins 4 and 6 and trans-3,4-dihydroxy-3,4-dihydromollugins 5 and 7 was achieved. The O-methoxymethyl mollugin derivatives were dihydroxylated to (−)- and (+)-cis-3,4-dihydroxy-3,4-dihydromollugin derivatives using both AD-mix-α and AD-mix-β. Deprotection of the MOM-ethers of cis-dihydroxy compounds resulted in the targeted stereoisomers (−)-(3R,4R)-cis-3,4-dihydroxy-3,4-dihydromollugin 4, (−)-(3R,4S)-trans-3,4-dihydroxy-3,4-dihydromollugin 5, (+)-(3S,4S)-cis-3,4-dihydroxy-3,4-dihydromollugin 6 and (+)-(3S,4R)-trans-3,4-dihydroxy-3,4-dihydromollugin 7. These routes were paved with difficulties, for example, incompatibility of the substrates with AD-mixes, the unexpected formation of trans-dihydroxy compounds and failures in deprotection protocols.     

Montamine, a unique dimeric indole alkaloid, from the seeds of Centaurea montana (Asteraceae), and its in vitro cytotoxic activity against the CaCo2 colon cancer cells

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea montana afforded a flavanone, montanoside (4), six epoxylignans, berchemol (7), berchemol 4′-O-β-d-glucoside (5), pinoresinol (10), pinoresinol 4-O-β-d-glucoside (8), pinoresinol 4,4′-di-O-β-d-glucoside (6), pinoresinol 4-O-apiose-(1→2)-β-d-glucoside (9), two quinic acid derivatives, trans-3-O-p-coumaroylquinic acid (1), cis-3-O-p-coumaroylquinic acid (2), and eight indole alkaloids, tryptamine (3), N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (11), cis-N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (12), centcyamine (16), cis-centcyamine (17), moschamine (13), cis-moschamine (14) and a dimeric indole alkaloid, montamine (15). While the structures of two new compounds, montanoside (4) and montamine (15), were established unequivocally by UV, IR, MS and a series of 1D and 2D NMR analyses, all known compounds were identified by comparison of their spectroscopic data with literature data. The antioxidant properties of these compounds were assessed by the DPPH assay, and their toxicity towards brine shrimps and cytotoxicity against CaCo-2 colon cancer cells were evaluated by the brine shrimp lethality and the MTT cytotoxicity assays, respectively. The novel dimer, montamine (15), showed significant in vitro anticolon cancer activity (IC₅₀=43.9 μM) while that of the monomer, moschamine (13), was of a moderate level (IC₅₀=81.0 μM).     

Stereochemical substituent effects: investigation of the cyano, amide and carboxylate group

Three pairs of diastereomeric piperidines, cis- and trans-2-methylpiperidine-3-carboxylate (6a and 6b), cis- and trans-2-methylpiperidine-3-carboxylamide (9a and 9b) and cis- and trans-2-methyl-3-cyanopiperidine (11a and 11b), were synthesised for the purpose of investigating the effect of the axial versus equatorial carboxylate, carboxamide and cyano group on piperidine base strength. The pK_a values of the six compounds were determined to be 11.0 (6a), 10.4 (6b), 9.5 (9a), 9.3 (9b), 7.8 (11a) and 8.0 (11b). This shows that the strong electron-withdrawing effect of the cyano group and the effect of the amide group are relatively independent of spacial orientation. The carboxylate, on the other hand is considerably less electron-withdrawing when axial.     

Synthesis, coordination studies and redox properties of a novel ditertiary phosphine bearing two ferrocenyl groups

The new ferrocenyl substituted ditertiary phosphine {FcCH₂N(CH₂PPh₂)CH₂}₂ [Fc = (η⁵-C₅H₄)Fe(η⁵-C₅H₅)] (1) was prepared, in 72% yield, by Mannich based condensation of the known bis secondary amine {FcCH₂N(H)CH₂}₂ with 2 equiv. of Ph₂PCH₂OH in CH₃OH. Phosphine 1 readily coordinates to various transition-metal centres including Mo⁰, Ru^II, Rh^I, Pd^II, Pt^II and Au^I to afford the heterometallic complexes {RuCl₂(p-cym)}₂(1) (2), (AuCl)₂(1) (3), cis-PtCl₂(1) (4), cis-PdCl₂(1) (5), cis-Mo(CO)₄(1) (6), trans,trans-{Pd(CH₃)Cl(1)}₂ (7) and trans,trans-{Rh(CO)Cl(1)}₂ (8). In complexes 2, 3, 7 and 8 ligand 1 displays a P,P′-bridging mode whilst for 4-6 a P,P′-chelating mode is observed. All new compounds have been fully characterised by spectroscopic and analytical methods. Furthermore the structures of 1, 2 · 2CH₂Cl₂, 3 · CH₂Cl₂, 4 · CH₂Cl₂, 6 · 0.5CHCl₃ and 8 have been elucidated by single crystal X-ray crystallography. Electrochemical measurements have been undertaken, and their redox chemistry discussed, on both noncomplexed ligand 1 and representative compounds containing this new ditertiary phosphine.     

N-Arylmethyl-7-azabicyclo[2.2.1]heptane derivatives: synthesis and reaction mechanisms

N-Arylmethyl-7-azabicyclo[2.2.1]heptane (I) derivatives have been synthesized by deprotection of N-protected, N-(arylmethyl)cyclohex-3-enamines, bromination of the resulting secondary cyclohex-3-enamines, followed by base-promoted cyclization (route a), or by bromination of N-protected, N-(arylmethyl)cyclohex-3-enamines followed by deprotection and base-mediated cyclization (route b). In these protocols we have observed that the bromination of the key intermediates (12, 13, and 19) is stereoselective leading to major trans-3-cis-4-dibromides (14, 17, and 20), whose mild base-mediated heterocyclization (on compound 14), or the two-step acid hydrolysis plus base-promoted cyclization (on compounds 17 and 20), gave products 6 and 7 in good yield. A mechanistic investigation using DFT has been carried out to explain the results observed in this work.     

Preparation of phosphinoferrocene carboxamides from isocyanates. Synthesis and structural characterisation of palladium(II) and platinum(II) complexes with 1′-(diphenylphosphino)-1-(N-phenylcarbamoyl)ferrocene

The reaction of in situ generated 1′-(diphenylphosphino)-1-lithioferrocene with isocyanates RNCO affords the respective phosphino-carboxamides Ph₂PfcCONHR (fc = ferrocene-1,1′-diyl, R = cyclohexyl (2), and Ph (3)) in moderate yields. The coordination behaviour of 3 chosen as a representative was studied in palladium(II) and platinum(II) complexes. Depending on the metal precursor and the reaction conditions, the following compounds featuring this ligand as a P-monodentate or an O,P-chelating donor were isolated and characterised by spectroscopic methods (IR, multinuclear NMR and electrospray ionisation MS): trans-[PdCl₂(3-κP)₂] (5), trans-[PtCl₂(3-κP)₂] (6), cis-[PtCl₂(3-κP)₂] (7), [SP-4-4]-[(L^NC)PdCl(3-κP)] (8; L^NC = 2-[(dimethylamino-κN)methyl]phenyl-κC¹), and [SP-4-3]-[(L^NC)PdCl(3-κ²O,P)]SbF₆ (9). Besides, the crystal structures of a phosphine oxide resulting by oxidation of 2, viz Ph₂P(O)fcCONHCy (4), and of complexes 5·2Et₂O and 9 have been determined by single-crystal X-ray diffraction analysis.     

Synthesis, characterization, and C-H activation reactions of novel organometallic O-donor ligated Rh(III) complexes

The synthesis and characterization of the O-donor ligated, air and water stable organometallic complexes trans- (2), and cis-(hfac-O,O)₂Rh(CH₃)(py) (3), trans-(hfac-O,O)₂Rh(C₆H₅)(py) (4), cis-(hfac-O,O)₂Rh(C₆H₅)(py) (5), and cis-(hfac-O,O)₂Rh(Mes)(py) (6) (where hfac-O,O = κ²-O,O-1,1,1,5,5,5-hexafluoroacetylacetonato) are reported. These compounds are analogues to the O-donor iridium complexes that are active catalysts for the hydroarylation and C-H activation reactions as well as the bis-acetylacetonato rhodium complexes, which we recently reported. The trans-complex 2 undergoes a quantitative trans to cis isomerization in cyclohexane to form 3, which activates C-H bonds in both benzene and mesitylene to form compounds 5 and 6, respectively. All of these compounds are air and water stable and do not lead to decomposition products. Complex 5 promotes hydroarylation of styrene by benzene to generate dihydrostilbene.     

Synthesis and structural characterisation of rhodium hydride complexes bearing N-heterocyclic carbene ligands

Addition of excesses of N-heterocyclic carbenes (NHCs) IEt₂Me₂, IⁱPr₂Me₂ or ICy (IEt₂Me₂ = 1,3-diethyl-4,5-dimethylimidazol-2-ylidene; IⁱPr₂Me₂ = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene; ICy = 1,3-dicyclohexylimidazol-2-ylidene) to [HRh(PPh₃)₄] (1) affords an isomeric mixture of [HRh(NHC)(PPh₃)₂] (NHC = IEt₂Me₂ (cis-/trans-2), IⁱPr₂Me₂ (cis-/trans-3), ICy (cis-/trans-4) and [HRh(NHC)₂(PPh₃)] (IEt₂Me₂(cis-/trans-5), IⁱPr₂Me₂ (cis-/trans-6), ICy (cis-/trans-7)). Thermolysis of 1 with the aryl substituted NHC, 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene (IMesH₂), affords the bridging hydrido phosphido dimer, [{(PPh₃)₂Rh}₂(μ-H)(μ-PPh₂)] (8), which is also the reaction product formed in the absence of carbene. When the rhodium precursor was changed from 1 to [HRh(CO)(PPh₃)₃] (9) and treated with either IMes (=1,3-dimesitylimidazol-2-ylidene) or ICy, the bis-NHC complexes trans-[HRh(CO)(IMes)₂] (10) and trans-[HRh(CO)(ICy)₂] (11) were formed. In contrast, the reaction of 9 with IⁱPr₂Me₂ gave [HRh(CO)(IⁱPr₂Me₂)₂] (cis-/trans-12) and the unusual unsymmetrical dimer, [(PPh₃)₂Rh(μ-CO)₂Rh(IⁱPr₂Me₂)₂] (13). The complexes trans-3, 8, 10 and 13 have been structurally characterised.     

The reaction of manganese carbonyl with tert-butylisocyanide: Synthesis and characterization of cis- and trans-[Mn(BuNC)4(CN)(CO)]

The reaction of Mn₂(CO)₁₀ with tert-butyl isocyanide in the presence of 10 bar of carbon monoxide leads to the formation of cis- and trans-[Mn(^tBuNC)₄(CN)(CO)], 1a and 1b, in good yields together with [Mn(^tBuNC)₆]CN (2), as a minor product. Nevertheless, the reaction pathway highly depends on the reaction conditions. An interesting side-product is obtained, if chloroform is used during the workup procedure. Compound 3 is composed of cationic [Mn(^tBuNC)₅(CO)] units as well as dinuclear anionic [Mn(^tBuNC)₄(CO)(μ-CN)MnCl₃] moieties. If no additional CO pressure is applied to the system, the organic product N,N′-di-tert-butyl-3,5-bis-tert-butylimino-4-phenyl-cyclopent-1-ene-1,2-diamine (4), is formed in considerable amount. Compound 4 most probably is produced via a double benzylic C-H activation of the solvent toluene and the oligomerization of four isocyanide moieties. The reaction of 1b with Co(NO₃)₂ leads to the isolation of the trinuclear cyanide bridged coordination compound {[Mn(^tBuNC)₄) (CO) (μ-CN)]₂Co(NO₃)₂}, 5, in which the cobalt atoms are tetrahedrally surrounded by the two cyanide ligands and the η¹-coordinated nitro groups. In contrast to the reaction of 1b, treatment of the dicyano complexes cis- or trans-[Ru(^tBuNC)₄(CN)₂] with Co(NO₃)₂ results in the formation of the coordination polymers {[Ru(^tBuNC)₄(CN)₂]Co(NO₃)₂}_n, 7 (trans) and 9 (cis). All new compounds are characterized by X-ray diffraction experiments.     

Comparative studies for selective deprotection of the N-arylideneamino moiety from heterocyclic amides: kinetic and theoretical studies. Part 2

4-Benzylideneamino-1,2,4-triazine-3,5(2H,4H)-diones (2-5), 6-styryl-1,2,4-triazine-3,5(2H,4H)-dione (6), and 6-styryl-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one (7) were synthesized and pyrolyzed in the gas phase. The kinetic effect of changing the substituent on the triazine ring from hydrogen to methyl, phenyl, and styryl was measured. Analyses of the pyrolyzates of 2-5 showed the elimination products to be benzonitrile and the triazine fragment, while the pyrolyzates of 6 and 7 reveal the formation of cis- and trans-cinnamonitriles. Theoretical study of the pyrolysis reactions of 2-5 using an ab initio SCF method was investigated.     

Synthesis of fluorinated trithioether compounds: X-ray structures of 1,3,5-(CH2SRf)3-2,4,6-(CH3)3C6, Rf = C6F5, 4-HC6F4, or 2-FC6H4

A series of three new trithioether compounds containing fluorinated phenyl moieties, 1,3,5-(CH₂SR_f)₃-2,4,6-(CH₃)₃C₆, R_f = C₆F₅ (1), 4-HC₆F₄ (2), or 2-FC₆H₄ (3), were prepared by treatment of 1,3,5-(CH₂Br)₃-2,4,6-(CH₃)₃C₆ with the corresponding Pb(SC₆F₅)₂ or NaSR_f. The new structures were verified by elemental analyses, IR, ¹H NMR, ¹⁹F NMR spectroscopies, and mass spectra. The single crystal X-ray diffraction studies of 1-3 show a similar cis,trans,trans-conformation for the three fluorophenylthiomethyl groups attached to the central benzene ring with all dihedral angles between planes of central ring and external rings close to 0°, giving flat molecules. Comparing, 1-3 with closely related tripodal molecules built-up on 2,4,6-trimethylbenzene, arrangement of one SR group respect to others seems to be defined by the nature of the R substituent. Then in the case of 1-3, a parallel arrangement of rings is favored over an orthogonal one, which would bring the ortho-F atoms close to H atoms of the methylene groups.     

Syntheses, structures and ligand conformations of Cu(II), Co(II) and Ag(I) complexes containing the phosphinic amide ligands

The syntheses, structures and ligand conformations of the complexes trans-Cu(L1)₂(ClO₄)₂, (L1 = N-(2-pyrimidinyl)-P,P-diphenyl-phosphinic amide), 1, [trans-Co(L1)₂(CH₃OH)₂](ClO₄)₂·O(C₂H₅)₂, 2, [trans-Co(L2)₂(H₂O)₂](ClO₄)₂·2CH₃OH, (L2 = N-(2-pyridinyl)-P,P-diphenyl-phosphinic amide), 3, [cis-Co(L2)₂(NO₃)](NO₃), 4, and [Ag(L3)(NO₃)(CH₃CN)]_∞, (L3 = N-(6-methyl-2-pyridinyl)-P,P-diphenyl-phosphinic amide), 5, are reported. The L1 and L2 ligands in the monomeric complexes 1-4 chelate the metal centers through the pyrimidyl/pyridyl nitrogen atoms and the phosphinic amide oxygen atoms, whereas the L3 ligands in complex 5 bridge the metal centers, forming a 1-D zigzag chain. The chelating L2 ligands in complexes 3 and 4 adopt cis conformations and the bridging L3 ligand in complex 5 adopts a trans conformation, respectively.     

Silicon-carbon unsaturated compounds. 73. Photolysis of cis- and trans-1,2-dimethyl-1,2-diphenyl-1,2-disilacyclohexane in the presence of tert-butyl alcohol and acetone

Irradiation of cis-1,2-dimethyl-1,2-diphenyl-1,2-disilacyclohexane (1a) in the presence of tert-butyl alcohol in hexane with a low-pressure mercury lamp bearing a Vycor filter proceeded with high stereospecificity to give cis-2,3-benzo-1-tert-butoxy-1,4-dimethyl-4-phenyl-1,4-disilacyclooct-2-ene (2a), in 33% isolated yield, together with a 15% yield of 1-[(tert-butoxy)methylphenylsilyl]-4-(methylphenylsilyl)butane (3). The photolysis of trans-1,2-dimethyl-1,2-diphenyl-1,2-disilacyclohexane (1b) with tert-butyl alcohol under the same conditions gave stereospecifically trans-2,3-benzo-1-tert-butoxy-1,4-dimethyl-4-phenyl-1,4-disilacyclooct-2-ene (2b) in 41% isolated yield, along with a 12% yield of 3. Similar photolysis of 1a and 1b with tert-butyl alcohol-d₁ produced 2a and 2b, respectively, in addition to 1-[(tert-butoxy)(monodeuteriomethyl)(phenyl)silyl]-4-(methylphenylsilyl)butane. When 1a and 1b were photolyzed with acetone in a hexane solution, cis- and trans-2,3-benzo-1-isopropoxy-1,4-dimethyl-4-phenyl-1,4-disilacyclooct-2-ene (4a and 4b) were obtained in 25% and 23% isolated yield. In both photolyses, 1-(hydroxymethylphenylsilyl)-4-(methylphenylsilyl)butane (5) was also isolated in 4% and 5% yield, respectively. The photolysis of 1a with acetone-d₆ under the same conditions gave 4a-d₆ and 5-d₁ in 18% and 4% yields.     

Alkaline hydrolysis of N-bromoiminothianthrene derivatives

5-(N-Bromo)iminothianthrene (2) and 5-(N-bromo)iminothianthrene 10-oxide (5) and 10,10-dioxide (8) were prepared and their alkaline hydrolyses were studied. The compound 2 and cis-5-(N-bromo)iminothianthrene 10-oxide (cis-5) afforded the corresponding sulfoximine exclusively. While, unexpectedly, both trans-5-(N-bromo)iminothianthrene 10-oxide (trans-5) and 8 afforded mainly de-brominated products, trans-5-iminothianthrene 10-oxide (trans-4) and 5-iminothianthrene 10,10-dioxide (7), respectively. In these cases, 5-iminothianthrene 5,10-dioxide (6) (Z- and E-mixture) and 5-iminothianthrene 5,10,10-trioxide (9) and further de-iminated products were also formed respectively as minor products. The stereochemical considerations on the S_N reactions are described in view of the steric effect and ‘flip-flap’ motion of the thianthrene framework.     

An improved synthesis of ethyl cis-5-iodo-trans-2-methylcyclohexanecarboxylate, a potent attractant for the Mediterranean fruit fly

Both racemic ethyl 5-iodo-2-methylcyclohexanecarboxylate (1), known as Mediterranean fruit fly attractant ceralure B₁, and its (−)-(1R,2R,5R) enantiomer 1a were conveniently synthesized from commercially available racemic trans-6-methyl-3-cyclohexenecarboxylic acid 2 or its (1R,6R) enantiomer 2a. Key steps included an asymmetric Diels-Alder reaction using a sultam auxiliary and cyclization of the unwanted trans-5-iodo-trans-2-methylcyclohexanecarboxylic acid (8) to the intermediate lactone 7 (or 8a to 7a). The new method may circumvent chromatographic separations and seems amenable to scale-up.     

Ferrocenylpyrazole—A versatile building block for hydrogen-bonded organometallic supramolecular assemblies

The crystal architectures of 5-ferrocenylpyrazole (1) and its metal complexes were investigated. Compound 1 can form non-solvated and chloroform-solvated crystals. In both cases, 1 forms a zigzag one-dimensional architecture via NH?N hydrogen bonds. The hydrogen bond exhibits a twofold disorder, which was shown to be static by solid-state ¹³C NMR. In the solvated crystal, the chloroform is released at 415 K, associated with melting of the crystal. The reaction of 1 with metal salts provided metal-centered ferrocenyl clusters [Zn(NO₃)₂(1)₄] (4), [Co(NO₃)₂(1)₄] (5), [CoCl₂(1)₄] (6), [Zn(NCS)₂(1)₂] (7), cis-[Pt(NH₃)₂(1)₂](PF₆)₂ (8), and trans-[Pt(NH₃)₂(1)₄](PF₆)₂ (9). In all of these complexes, 1 acts as a monodentate ligand. In 4, 5, and 7, the multinuclear units are joined via hydrogen bonds to form supramolecular chains. Two polymorphs were found for the crystals of 4. Both are composed of the same hydrogen-bonded chains, but their arrangements are different. 5-Ferrocenyl-1-tritylpyrazole (2) and 4-ferrocenyl-1-methylpyrazole (3) were also crystallographically characterized.     

New diastereomeric bis-sesquiterpenes from Hainan marine sponges Axinyssa variabilis and Lipastrotethya ana

Three unprecedented diastereoisomeric dimers, cis-dimer A (1), cis-dimer B (2) and trans-dimer C (3), exhibiting a bis-bisabolene skeleton, and a new sesquiterpene, dehydrotheonelline (4), their potential precursor, have been isolated from the South China Sea sponges Axinyssa variabilis and Lipastrotethya ana, along with known related sesquiterpenes. The structure of the novel molecules has been determined by extensive NMR spectral analysis.     

Synthesis, crystal structure, and chirality of divalent lanthanide reagents containing tri- and tetraglyme

Six new divalent lanthanide complexes using triglyme (trigly) and tetraglyme (tetgly) as achiral ligands have been prepared, using a facile synthetic method, in search for enantioselective solid-state reagents. The crystal structures of cis-[SmI₂(trigly)thf] (1), trans-[YbI₂(trigly)thf] (2), trans-[SmI₂(trigly)dme] (3), trans-[YbI₂(tetgly)] (4), trans-[EuI₂(tetgly)thf] (5), and [Sm(tetgly)₂][SmI₃(tetgly)]I (6) have been determined. All complexes, except 5, are chiral. The 10-coordinate cation in 6 displays a helical chirality since the two tetraglyme ligands are wrapped around the samarium ion. Since trans-[YbI₂(tetgly)] (4), which has a chiral arrangement of terminal methyl groups, crystallizes as a conglomerate, preferential crystallization and consequent enantioselective reduction of acetophenone was attempted, but resulted in racemic products, possibly on account of racemic twinning in 4.     

Aminobis(phenolate)s of imidomolybdenum(VI) and -tungsten(VI)

The reactions of trans-[MoO(ONO^Me)Cl₂] 1 (ONO^Me = methylamino-N,N-bis(2-methylene-4,6-dimethylphenolate) dianion) and trans-[MoO(ONO^tBu)Cl₂] 2 (ONO^tBu = methylamino-N,N-bis(2-methylene-4-methyl-6-tert-butylphenolate) dianion) with PhNCO afforded new imido molybdenum complexes trans-[Mo(NPh)(ONO^Me)Cl₂] 3 and trans-[Mo(NPh)(ONO^tBu)Cl₂] 4, respectively. As analogous oxotungsten starting materials did not show similar reactivity, corresponding imido tungsten complexes were prepared by the reaction between [W(NPh)Cl₄] with aminobis(phenol)s. These reactions yielded cis- and trans-isomers of dichloro complexes [W(NPh)(ONO^Me)Cl₂] 5 and [W(NPh)(ONO^tBu)Cl₂] 6, respectively. The molecular structures of 4, cis-6 and trans-6 were verified by X-ray crystallography. Organosubstituted imido tungsten(VI) complex cis-[W(NPh)(ONO^tBu)Me₂] 7 was prepared by the transmetallation reaction of 6 (either cis or trans isomer) with methyl magnesium iodide.