Tri(1-cyclohepta-2,4,6-trienyl)phosphan,P(C7H7)3 und Tetra(1-cyclohepta-2,4,6-trienyl)phosphonium-tetrafluoroborat, [P(C7H7)4]BF4

Tri(1-cyclohepta-2,4,6-trienyl)phosphane, P(C₇H₇)₃, and Tetra(1-cyclohepta-2,4,6-trienyl)phosphonium Tetrafluoroborate, [P(C₇H₇)₄]BF₄ The reaction of tris(trimethylsilyl)phosphane, P(SiMe₃)₃, with tropylium bromide, C₇H₇⁺Br^?, in polar solvents such as dichloromethane or tetrahydrofuran gives P(C₇H₇)₃ ( 1 ) and [P(C₇H₇)₄]Br ( 2a ). According to the X-ray crystallographic structure determinations, all 1-cyclohepta-2,4,6-trienyl substituents are present in the boat conformation in both P(C₇H₇)₃ ( 1 ) and the phosphonium salt, [P(C₇H₇)₄]BF₄ ( 2b ). The boat-shaped C₇H₇ rings are significantly more flattened if the phosphorus occupies the axial rather than the equatorial position at the ring substituent. Addition of a chalcogen to the lone pair at the central phosphorus atom of 1 leads to the chalcogena-phosphoranes EP(C₇H₇)₃ (E = O ( 3a ), S ( 3b ), Se ( 3c )). The new 1-cyclohepta-2,4,6-trienyl-phosphorus compounds 1, 2 b and 3a–c were characterized by their ¹H, ¹³C, and ³¹P NMR spectra in C₆D₆ solution.     

(Perhalogenmethylthio)heterocyclen. XVIII . Synthese und eigenschaften von halogenierten (perhalogenmethylthio)pyrrolen

(Trifluoromethyltho)pyrroles 1-5 and (chlorodifluoromethylthio)pyrroles 6 were chlorinated by sulfuryl chloride, sulfuryl chloride/silicon dioxide, sulfuryl chloride/disulfur dichloried/aluminium trichloried to give the corresponding chloropyrroles 1a-d , 2a,b , 3a,b , 4a , 5a , and 6a-c Bromination with bromine or iodination with iodine/potassium iodide of 2, 3, 4 , and 6 yielded the derivatives 2c,d, 3c,d, 4b, 6d , and 2e, 3e, f, 4c , 6e respectively. Mixed halogenated pyrroles 3g and h were obtained from 3a and bromne or 3a and iodine/potassium iodide. During some chlorination reactions 7, 8 , and 9 were fromed in low yield asbyproducts. The ¹H-nmr, ¹⁹F-nmr and ir spectroscopic data are presented.     

HPLC and 1H-NMR Studies of Alkaline Hydrolysis of Some 7-(Oxyiminoacyl)cephalosporins

Alkaline hydrolysis (pH 10.5) of the three 7-(oxyiminoacyl)cephalosporins 1a–c (cefuroxime, ceftazidime, and ceftriaxone) was studied at 37° using HPLC and ¹H-NMR techniques. The 7-epicephalosporin 2 , the 3-methylidene compound 3 , and the 6-epimer 4 of the 3-methylidene compound 3 were identified for each cephalosporin as the major degradation products under the conditions used; ceftazidime ( 1b ) yielded also the Δ²-isomer 5b (Scheme 1). A kinetic scheme was developed to account for the production of these compounds, and the different kinetic constants involved in the process were calculated. The experimental results show that the presence of a pyridinio group at position C–C(3) favours the appearance of the Δ²-isomer, which was detected mainly in cephalosporins bearing an ester function at C(4). The presence of an oxyimino group at C? CONH? C(7) facilitates epimerization at C(7) (→ 2 ), whereas that of an electron-withdrawing group at C? C(3) results in a increased formation constant for the 3-methylidene compound 3 . The 3-methylidene compounds 3a–c produced by the three cephalosporins on cleavage of the β-lactam ring all underwent epimerization at C(6) to yield the corresponding 6-epimer 4 .     

Synthesis,cytotoxic, and carbonic anhydrase inhibitory effects of new 2-(3-(4-methoxyphenyl)-5-(aryl)-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazole derivatives

2-(3-[4-Methoxyphenyl]-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazoles ( 1b-7b ) were synthesized for the first time except 1b , and spectral methods such as ¹H NMR, ¹³C NMR and HRMS were utilized to illuminate the chemical structures of the synthesized compounds. Phenyl ( 1b ), 2-methoxyphenyl ( 2b ), 4-methoxyphenyl ( 3b ), 4-methoxy-3-hydroxyphenyl ( 4b ), 2,5-dimethoxyphenyl ( 5b ), 3,4,5-trimethoxyphenyl ( 6b ), or thiophene-2-yl ( 7b ) was used as a aryl part. The inhibitory effects of the compounds were evaluated toward human carbonic anhydrase I and II enzymes (hCA I and hCA II). In vitro cytotoxic effects of the compounds against human oral squamous carcinomas and human normal oral cells were carried out via MTT. The compounds ( 1b-7b ) had Ki values of 36.87 ± 11.62-66.24 ± 2.99 μM (hCA I) and 22.66 ± 1.41-89.95 ± 6.25 μM (hCA II). Compounds 1b (Ki = 36.87 ± 11.62 μM) toward hCA I, 6b (Ki = 22.66 ± 1.41 μM) toward hCA II had significant enzyme inhibitory potency. Compound 6b had the highest tumor selectivity (TS = 29.3) and potency selectivity expression (PSE = 272.3) values. Therefore, compounds 1b and 6b with CAs inhibition effect and compound 6b with the cytotoxicity may be forwarded to further studies as potent compounds.     

Synthesis of 32‐phenyl‐substituted methyl E/Z‐pyropheophorbide‐a's from methyl E/Z‐pyropehophorbide‐a 131‐ketoximes

Methyl E/Z‐pyropheophorbide‐a 13¹‐ketoximes 2a,b and their O‐acetyl derivatives 3a,b were oxidized with osmium(VIII) oxide to give aldehydes 4a,b and 5a,b , respectively. The Wittig reactions of the aldehyde chlorines 4a,b and 5a,b with benzyltriphenylphosphonium chloride were performed to form the corresponding methyl (3¹E/Z,13¹E/Z)‐3²‐phenylpyropheophorbide‐a 13¹‐ketoximes 6aa‐bb and their O‐acetyl derivatives 7aa‐bb ; hydrolysis of these ketoximes 6aa,ba and 6ab,bb in formic acid produced methyl (E/Z)‐3²‐phenylpyropheophorbide‐a's 8a,b .     

Synthesis of 1-(1,1-dimethylethyl)-1H-pyrazole-4-carboxylate ester derivatives

Attempts to prepare ethyl 5-cyano-1-(1,1-dimethylethyl)-1H-pyrazole-4-carboxylate ( 7 ) by the reaction of the corresponding 5-chloro derivative 1b with cyanide ion were unsuccessful. The chloro ester was synthesized from the corresponding amino ester la utilizing nonaqueous diazotization with nitrosyl chloride. An alternate process was developed which allowed the preparation of 7 from the corresponding 5-methyl ester 3 in four steps. The structure of the N-methylamide 8 synthesized from 7 was confirmed by X-ray diffraction analysis.     

Syntheses with nitriles. 62. 3,5-Dicyanopyridine derivatives by vilsmeier formylation of malononitrile and tetracyanopropenides

Reaction of malononitrile with dimethylformamide and phosphorus oxychloride gave (dimethylamino-methylene)malononitrile ( 1 ), 4-chloro-7-methyl-5,7-diaza-1,3,5-octatriene-1,1,3-tricarbonitrile ( 3a ) and the pyridine 2 . Compounds 3a and 3b as well as the triaza-derivative 3c may also be obtained by treatment of tetracyanopropenides 4a-c with dimethylformamide and phosphorus oxychloride. Ring closures were achieved by heating 3 under alkaline or acidic conditions. Substitution of chlorine in 3a with aromatic amines provided 1-aryl-1,2-dihydro-2-imino-3,5-pyridinedicarbonitriles 7 . Hydrolysis of 7 gave the 2-oxo-derivatives 8 .     

(1+1) Resonance‐Enhanced Multiphoton Ionization and Photodissociation Study of CS2 via the 1B2 State

(1+1) resonance‐enhanced multiphoton ionization (REMPI) spectra of CS₂ and molecular dissociation dynamics are investigated using a time‐of‐flight mass spectrometer equipped with velocity imaging detection. The REMPI spectra via a linear‐bent →¹B₂( ) transition are acquired in the wavelength range of 208–217 nm. Each ro‐vibrational band profile of the ¹B₂( ) state is deconvoluted to yield the corresponding predissociative lifetime from 0.3 to 3 ps. Upon excitation at 210.25 and 212.54 nm, the resulting images of S⁺ and CS⁺ fragments are analyzed to give individual translational energy distributions, which are resolved into two components corresponding to the CS+S(³P) and CS+S(¹D) channels. The product branching ratios of S(³P)/S(¹D) are evaluated to be 5.7±1.0 and 9.6±2.5 at 210.25 and 212.54 nm, respectively. Despite the difficulty avoiding the effect of multiphoton absorption, the molecular dissociation channel is verified to prevail over the dissociative ionization channel of CS₂. The anisotropy parameters for the triplet and singlet channels are determined to be ～0.8 and 1.1–1.3, respectively, suggesting that the predissociative state should have a bent configuration with a short lifetime.     

Synthesis of Bis{(S‐methyl)azolespoly(ethylene oxide)} from 3,6‐dioxa‐1,8‐octanedithiol

Bis(1,3,4‐oxadiazoles) 4 , 5 and bis(1,2,4‐triazoles) 6a , 6b have been prepared from 3,6‐dioxa‐1,8‐octanedithiol 1 through a multistep reaction sequence. Compound 4 reacted with the appropriate alkyl halide in the presence of potassium carbonate in refluxing acetone to give the corresponding bis(S‐alkylated‐1,3,4‐oxadiazoles) 7a , 7b . The title compound 8 was prepared by condensing 4 with benzoyl bromide in the presence of triethylamine. Further, 6,9‐dioxa‐3,12‐dithiotetradecanedihydrazide 3 was converted to bis{N′‐(phenylaminocarbonyl) hydrazides} and bis{N′‐(phenylaminocarbonothioyl)hydrazides} 9a , 9b using phenylisocyanate and phenylthioisocyanate, respectively, which underwent cyclization in alkaline medium to produce 6,9‐dioxa‐3,12‐dithiotetradecane bis(4‐phenyl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐one) and their 3‐thio analogs 10a , 10b . The new compounds 4 , 5 , 6 , 7 , 8 , 9 , 10 were characterized by their IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analyses.     

Novel 5,6-bis-(4-substitutedphenyl)-2H(3)-pyridazinones: Synthesis and reactions

A series of 5,6-bis(4-substitutedphenyl)-2H(3)-pyridazinones 2a–f have been synthesized from the condensation of the corresponding benzil monohydrazones 1 either with ethyl cyanoacetate or diethyl malonate in ethanol. The synthesized pyridazinones were converted to the corresponding 3-chloro derivatives 3a–f by the action of phosphoryl chloride. Reaction of the latter halogenated pyridazines with various aromatic amines led to the formation of new 3-aminoaryl pyridazines (4) in moderate yield. The structures of all new compounds 2b,c,e,f, 3b–e, 4 were fully identified by the analysis of their ¹H and ¹³C NMR and mass spectra. Some of these synthetic heterocyclic compounds were screened for their antimicrobial activities but they were almost negative.     

Platinum(II) and Palladium(II) Halides and Pseudohalides with the Ligand Tri(1‐cyclohepta‐2, 4, 6‐trienyl)phosphane. X‐Ray Structural Analysis of [P(C7H7)2(η2‐C7H7)]PtI2

Tri(1‐cyclohepta‐2, 4, 6‐trienyl)phosphane, P(C₇H₇)₃ ( 1 ) ([P] when coordinated to a metal) stabilizes platinum(II) ( 2 ) and palladium(II) dihalides ( 3 ) as [P]MX₂ with X = Cl ( a ), Br ( b ) and I ( c ). The phosphane coordinates to the metal as a chelate ligand via both phosphorus and the central η²‐C=C bond of one of the cyclohepta‐2, 4, 6‐trienyl rings. The complexes were prepared by various routes, mainly by the reaction of (cod)MCl₂ (cod = cycloocta‐1, 5‐diene) with 1 to give the chlorides 2a and 3a , which then could be converted into the bromides 2b , 3b or the iodides 2c , 3c by reaction with NaBr or NaI, respectively. The molecular structure of 2c was determined by X‐ray analysis. Treatment of 2a and 3a with sodium or potassium salts of several pseudohalides afforded the complexes [P]MX₂ 2d (NCO/NCO), 2e₁ (NCS/SCN), 2e₁' (SCN/NCS), 2f₂ (SeCN/SeCN), 3f₁ (NCSe/SeCN), 2g and 3g (X = N₃). Attempts failed to synthesize the cyanides 2h and 3h by the same route. By using an excess of trimethylsilyl cyanide in the reaction with 2a in THF solution, the complex trans‐{[(C₇H₇)₃P]₂Pt(CN)₂} ( 4h ) was obtained instead of 2h . The analogous complexes trans‐{[(C₇H₇)₃P]₂MX₂} with M = Pt ( 4 ) and Pd ( 5 ) for X = Cl ( a ), Br ( b ), I ( c ) could be prepared from the reaction of the corresponding tetrahalogenometallates and 1 (in the case of 5c from PdI₂ and 1 ). In contrast to 4h , the complexes 4a‐c and 5a‐c were found to be labile in solution with respect to partial loss of the phosphane 1 and rearrangement into 2a‐c and 3a‐c , respectively. All compounds were characterized by IR spectroscopy and by multinuclear magnetic resonance spectroscopy (¹H, ¹³C, ³¹P, ⁷⁷Se and ¹⁹⁵Pt NMR). The ligand [P] in 2 and 3 is fluxional with regard to coordination of the C₇H₇ rings to the metal.     

The Environmentally Friendly Energetic Salt (ATZ)(TNPG) Based on 4‐Amino‐1, 2, 4‐triazole (ATZ) and Trinitrophloroglucinol (TNPG)

The environmentally friendly energetic salt (ATZ)(TNPG) (ATZ = 4‐amino‐1, 2, 4‐triazole, TNPG = trinitrophloroglucinol) was synthesized and characterized by elemental analysis and FT‐IR spectroscopy. The crystal structure was determined by X‐ray single crystal diffraction. It crystallizes in monoclinic space group P2₁/c and its crystal density is 1.832 g · cm^–3. Thermal decomposition mechanisms were investigated through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In addition, the experimental data showed that the energy of combustion was approximately equal to the energies of combustion of RDX (1, 3, 5‐trinitro‐1, 3, 5‐triazacyclohexane) and HMX (1, 3, 5, 7‐tetranitro‐1, 3, 5, 7‐tetraazocane). The non‐isothermal kinetics parameters were also studied by applying Kissinger's, Ozawa's, and Starink's methods. Determination of the sensitivities revealed higher sensitivities of (ATZ)(TNPG) as compared to (ATZ)(PA) (PA = picrate).     

Synthesis,characterization and mesomorphic properties of Ag(I) and Pd(II) complexes containing the pyridyl and tetrazoyl rings: crystal structure of [C30H46N10Ag ClO4]

The synthesis of new monodentate heterocyclic ligands 5-(4-pyridyl)-2-alkyltetrazole (L¹a,b) and 4-[5-(2-alkyltetrazole)]aryl-4'-pyridinecarboxylate (L²a,b,c) containing two or three aromatic or heterocyclic rings (tetrazole, pyridine and benzene) and preparation of their corresponding silver(I) and palladium(II) complexes (Ia,b,c and IIa,b,c) are described. The thermal behaviour of the ligands and complexes was characterized by polarizing optical microscopy. The ligands and the complexes Ia,b,c and IIc showed no liquid crystalline phase. The complexes IIa,b showed mesomorphic behaviour, exhibiting smectic A enantiotropic mesomorphism X-ray diffraction measurements for complex Ia showed monodentate coordination of N-pyridine, and no coordination on the nitrogen atoms of the tetrazole ring.     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Synthesis and Characterization of Novel Methyl (3)5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates

Series of methyl 3- and 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates were developed and regioselectively synthesized as novel heterocyclic amino acids in their N-Boc protected ester form for achiral and chiral building blocks. In the first stage of the synthesis, piperidine-4-carboxylic and (R)- and (S)-piperidine-3-carboxylic acids were converted to the corresponding β-keto esters, which were then treated with N,N-dimethylformamide dimethyl acetal. The subsequent reaction of β-enamine diketones with various N-mono-substituted hydrazines afforded the target 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates as major products, and tautomeric NH-pyrazoles prepared from hydrazine hydrate were further N-alkylated with alkyl halides to give 3-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates. The structures of the novel heterocyclic compounds were confirmed by ¹H-, ¹³C-, and ¹⁵N-NMR spectroscopy and HRMS investigation.     

Copper(II)-Mediated Iodination of 1-Nitroso-2-naphthol

The 3-Iodo-1-nitrosonaphthalene-2-ol (I-NON) was obtained by the copper(II)-mediated iodination of 1-nitroso-2-naphthol (NON). The suitable reactants and optimized reaction conditions, providing 94% NMR yield of I-NON, included the usage of Cu(OAc)₂·H₂O and 1:2:8 Cu^II/NON/I₂ molar ratio between the reactants. The obtained I-NON was characterized by elemental analyses (C, H, N), high-resolution ESI⁺-MS, ¹H and ¹³C{¹H} NMR, FTIR, UV-vis spectroscopy, TGA, and X-ray crystallography (XRD). The copper(II) complexes bearing deprotonated I-NON were prepared as follows: cis-[Cu(I-NON–H)(I-NON)](I₃) (1) was obtained by the reaction between Cu(NON-H)₂ and I₂ in CHCl₃/MeOH, while trans-[Cu(I-NON–H)₂] (2) was synthesized from I-NON and Cu(OAc)₂ in MeOH. Crystals of trans-[Cu(I-NON–H)₂(THF)₂] (3) and trans-[Cu(I-NON–H)₂(Py)₂] (4) were precipitated from solutions of 2 in CHCl₃/THF and Py/CHCl₃/MeOH mixtures, respectively. The structures of 1 and 3–4 were additionally verified by X-ray crystallography. The characteristic feature of the structures of 1 and 3 is the presence of intermolecular halogen bonds with the involvement of the iodine center of the metal-bound deprotonated I-NON. The nature of the I···I and I···O contacts in the structures of 1 and 3, correspondingly, were studied theoretically at the DFT (PBE0-D3BJ) level using the QTAIM, ESP, ELF, NBO, and IGM methods.     

Synthese von 4(5)-acyl-5(4)-alkylimidazolen aus symmetrischen 1,3-dicarbonylverbindungen

Synthesis of 4(5)-Acyl-5(4)-alkylimidazoles from Symmetrical 1,3-Diones A new synthesis of 4(5)-acyl-5(4)-alkylimidazoles 1 is described. The symmetrical 1,3-diones 5a and 5b were reacted with N₂O₄ to give the nitro compounds 7a and 7b , respectively; 5c was treated with NaNO₂ to give the nitroso compound 7c (Scheme 2). Hydrogenation of 7a , 7b and 7c over Pd/C in acetic acid/acetic formic anhydride yielded the formamides 9a , 9b and 9c , whose cyclization in formamide/formic acid afforded the 4(5)-acyl-5(4)-alkylimidazoles 1a, 1b and 1c , respectively. Oxazoles 11a and 11b were obtained from the corresponding formamides 9a and 9b with methanesulfonic acid/P₂O₅.     

Oxidation Reactivity of Bis(μ‐oxo) Dinickel(III) Complexes: Arene Hydroxylation of the Supporting Ligand

In the nick(el) of time : Bis(μ‐oxo) dinickel(III) complexes 2 (see scheme), generated in the reaction of 1 with H₂O₂, are capable of hydroxylating the xylyl linker of the supporting ligand to give 3 . Kinetic studies reveal that hydroxylation proceeds by electrophilic aromatic substitution. The lower reactivity than the corresponding μ‐η²:η²‐peroxo dicopper(II) complexes can be attributed to unfavorable entropy effects.

     

Stereospezifische carbonyl(z)oxiranierung von benzaldehyd mit iodo-triphenylsilyl- und iodo-triphenylgermyl-methyllithium (1)

The reagents Ph₃M-CH(I)Li (M = Si, Ge) react with benzaldehyde via anionic benzaldehyde adducts stereospecifically to give (Z)-1-phenyl-2-triphenylsilyl- (7a) or (Z)-1-phenyl-2-triphenylgermyl-oxirane (7b), respectively. By protolysis of the anionic benzaldehyde adducts at ?65°C corresponding iodohydrins (5a,5b) have been obtained.     

Kurze Totalsynthesen von (±)-Sativen und (±)-cis-Sativendiol

Short Total Syntheses of (±)-Sativene and (±)-cis-Sativenediol Our approach to (±)-sativene (7) and (±)-cis-sdtivenediol (9) involves: (a) reaction of 3-methylbutanoyl chloride with Et₃N/cyclopentadiene to give the endo-isopropyl-ketone 1 (here improved to 71%), (b) NBS bromination of 1 to a 5:1 mixture (87%) of the bromo-ketones 2 and 3 , (c) NFD-reaction sequence initiated by the attack of 1,2-butadienyl titanate (complex of 15 , obtained from 2-butine) on 2/3 to afford 52% of the brexenone derivative 4 (along with 8% of its epimer 16 ), (d) addition of dibromomethane to 4 forming 63% of the diene-alcohol 5 (along with 13% of the diene-carbaldehyde 38 ), and (e) carbenoid ring-expansion with MeLi applied to 5 resulting in 41% the diene-ketone 6 (along with 15% of a 1:3 mixture of the diene-ketones 32 and 33 ). Wolff-Kishner reduction of 6 led to 81% of (±)-sativene (7), when enough O₂ was present, but to 97% of the diene 8 in the strict absence of O₂. (±)-cis-Sativenediol (9) was obrained (86%) by OsO₄ hydroxylation of 8 . The brexenone derivatives 4 and 16 (6:1, 50%) were also produced when the NFD-reaction sequence was applied to the isomeric bromo-ketone mixture 13/13 (1:3). The latter was obtained by NBS bromination of 10 , which in turn was available by base epimerization of 1 , followed by destructive removal of unreacted 1 by repeated gas-flow thermolysis. An analogous (less convenient) route to (±)-sativene (7) passed through a series of dihydro compounds (the ene series) it started with the methylidene-ketone 36 , which was the product (97%) of a partial hydrogenation of 4 . Addition of dibromomethane to 36 led t 62% of the methylidene-alcohol 39 (along with a little tetracyclic ether 40 ). Carbenoid ring expansion of 39 with MeLi afforded ca. 42% of the methylidene-ketone 41 (along with 7% of the methylidene-ketone 43 or, under slightly different condition, along with 9% of the methylidene-ketone 42 and 10% of the methylidene-carabaldehyde 44 ). The methylidene-alcohol 39 and the methylidene-ketone 43 were also obtained by partial hydrogenation of 5 and 33 , respectively. Wolff-Kisher reduction converted 41 into (±)-sativene ( 7 99%); the same conditons applied to 42 afforded only ca. 8% 7 (along with three other hydrocarbons, one of them (ca. 21%) probably being (±)-copacamphene (45)). In the diene series, the two succeeding reactions ( 4→5 and 5→6 ) competed with the same side reaction, a rearrangement leading to the brendene-aldehyde 38. In the ene series, the corresponding dihydro-by-product 44 was found in the reacton 39→41 , but not during 36→39. These side reactons could largely be suppressed by keeping the reaction temperature low. An explanation is proposed.