Generation and Trapping of Triafulvene

Substituted methylidenecyclopropanes 12a – d , being easily available from 1,1-dibromo-2-(phenylthio)-cyclopropane ( 9a ), are attractive precursors of triafulvene (2-methylidene-1-cyclopropene; 1 ). Both the sulfoxide 12b and the sulfone 12c react with an excess of alkoxides (t-BuOK and NaOMe) to give 12e and 12f , respectively, while the sulfinyl group of 12b may be replaced by the PhCH₂S substituent in the presence of PhCH₂SH/t-BuOK. These reactions (Scheme 4) may be explained by assuming 1 as a reactive intermediate, although an alternative sequence including carbene 20 (Scheme 6) is not completely ruled out. D -labelling experiments (Scheme 5) do not give conclusive evidence due to D scrambling, but deprotonation/methylation sequences show that H? C(2) of 12a – c is the most acidic proton. Final evidence for 1 results from the reaction of 12d with cyclopentadienide (Scheme 7): the reaction of 1 with cyclopentadiene produces the expected [4 + 2]-cycloaddition product 23 , while some mechanistic insight results from the sequence 12d → 24 → 25 .     

Studies on t-BuOK-catalyzed Michael addition of 1,2-allenic ketones with 2-substituted diethyl malonates: highly selective synthesis of β,γ-unsaturated enones

In this paper, we have demonstrated a facile nucleophilic addition of 2-substituted diethyl malonate to various substituted 1,2-allenic ketones to afford β,γ-unsaturated enones using a catalytic amount of t-BuOK as the base. The reaction usually completes within 10 min in acetone at room temperature. The stereoselectivity of the reaction with γ-substituted allenic ketones is very high affording the β,γ-unsaturated E-enones.     

Highly efficient total synthesis of Δ-PGJ2, 15-deoxy-Δ-PGJ2, and their analogues

Palladium-catalyzed reaction of TBS ether of 4-cyclopentene-1,3-diol monoacetate (>95% ee) with an anion derived from methyl malonate and a base such as t-BuOK and LDA proceeded highly efficiently and reproducibly. The product obtained in >90% isolated yield was transformed in five steps into the key cyclopentenone possessing the α-chain at the γ position. Aldol reaction of this enone with the ω-chain aldehyde afforded the aldol adduct, and exposure of the derived mesylate to Al₂O₃ furnished the cross-conjugated dienone of the full structure. Finally, functional group manipulation furnished Δ¹²-PGJ₂ efficiently. Similarly, 15-deoxy-Δ^12,14-PGJ₂, 5,6-acetylene analogues, and a 5,6-dihydro analogue were synthesized.     

Preparation of Polymer-Supported Chiral 1,2-Diamine as an Efficient Ligand for Asymmetric Hydrogenation Catalyst

An enantiopure 1,2-diamine having two phenolic hydroxy groups was synthesized, and attached to chloromethylated poly(styrene) through a benzyl ether linkage. The polymer-supported Ru precatalysts were prepared from the polymeric chiral 1,2-diamine and RuCl₂/BINAP complex. In the presence of t-BuOK the polymeric catalyst system worked well in asymmetric hydrogenation of aromatic ketones in a mixed solvent of 2-propanol and DMF. The insoluble polymeric catalyst was readily separated from the reaction mixture and reused at least several times without loss of the catalytic activity.     

New Syntheses of Di-π-Substituted Heptalenes

To study the effect of double-bond shifts (DBS) in different type of heptalenes linked to extended π-systems, several di-π-substituted heptalenes were synthesized. 6-[(E)-Styryl]heptalene-dicarboxylate 4 was smoothly converted to 1-(chloromethyl)heptalene-dicarboxylate 5 by treatment with t-BuOK and C₂Cl₆ in THF at −78°. The one-pot reaction of 5 and P(OEt)₃ in the presence of NaI, followed by Wittig-Horner reaction, afforded the 1,6-di-π-substituted heptalene 6 . The reaction of 6-[(1E,3E)-4-phenylbuta-1,3-dienyl]heptalenes 7 or 15 with t-BuOK and benzaldehyde in THF led to the formation of the 1,6-di-π-substituted heptalenes 13 or 16 , together with transesterification products 14 or 17 . The transformation of the MeOCO group at C(4) of 6-[(E)-styryl]heptalene-dicarboxylate 4 to a phenylbuta-1,3-dienyl substituent afforded the 4,6-di-π-substituted heptalene 21a , which is in thermal equilibrium with its DBS isomer 21b in solution. Oxidation of heptalene 22 with SeO₂ in dioxane gave carbaldehyde 23 , which was then subjected to a Wittig reaction to give the 6,9-di-π-substituted heptalene-dicarboxylate 24 .     

Studies on the Synthetic Usefulness of the Nitro Function. Part I. A Novel Cyclopentenone Ring Annelation

A novel cyclopentenone ring annelation reaction is described. The treatment of the nitro compound 13 with aqueous sodium hydroxide in the presence of a phase-transfer catalyst furnished 14a in one step. Similar treatment of 7 led to 8 , the reaction of which with t-BuOK afforded 9a without purification in high yield.     

Synthesis of 4- and 6-substituted nitroindoles

Enolizable ketones react with m-nitroaniline in the presence of strong base such as t-BuOK to give 4- and 6-substituted nitroindoles. The reaction proceeds via oxidative nucleophilic substitution of hydrogen in m-nitroaniline with enolate anions in positions ortho to the amino group giving anionic σ^H adducts that are additionally stabilized by intramolecular interaction between the amino and the carbonyl group. Spontaneous oxidation of the σ^H adducts followed by the Bayer type condensation of the produced ortho-aminonitrobenzyl ketones gives 4- and 6-substituted nitroindoles. The scope of this reaction and its basic mechanistic features are discussed.     

Oxaphospholes and Bisphospholes from Phosphinophosphonates and α,β‐Unsaturated Ketones

The reaction of a {W(CO)₅}‐stabilized phosphinophosphonate 1 , (CO)₅WPH(Ph)? P(O)(OEt)₂, with ethynyl‐ ( 2 a – f ) and diethynylketones ( 7 – 11 , 18 , and 19 ) in the presence of lithium diisopropylamide (LDA) is examined. Lithiated 1 undergoes nucleophilic attack in the Michael position of the acetylenic ketones, as long as this position is not sterically encumbered by bulky (iPr)₃Si substituents. Reaction of all other monoacetylenic ketones with lithiated 1 results in the formation of 2,5‐dihydro‐1,2‐oxaphospholes 3 and 4 . When diacetylenic ketones are employed in the reaction, two very different product types can be isolated. If at least one (Me)₃Si or (Et)₃Si acetylene terminus is present, as in 7 , 8 , and 19 , an anionic oxaphosphole intermediate can react further with a second equivalent of ketone to give cumulene‐decorated oxaphospholes 14 , 15 , 24 , and 25 . Diacetylenic ketones 10 and 11 , with two aromatic acetylene substituents, react with lithitated 1 to form exclusively ethenyl‐bridged bisphospholes 16 and 17 . Mechanisms that rationalize the formation of all heterocycles are presented and are supported by DFT calculations. Computational studies suggest that thermodynamic, as well as kinetic, considerations dictate the observed reactivity. The calculated reaction pathways reveal a number of almost isoenergetic intermediates that follow after ring opening of the initially formed oxadiphosphetane. Bisphosphole formation through a carbene intermediate G is greatly favored in the presence of phenyl substituents, whereas the formation of cumulene‐decorated oxaphospholes is more exothermic for the trimethylsilyl‐containing substrates. The pathway to the latter compounds contains a 1,3‐shift of the group that stems from the acetylene terminus of the ketone substrates. For silyl substituents, the 1,3‐shift proceeds along a smooth potential energy surface through a transition state that is characterized by a pentacoordinated silicon center. In contrast, a high‐lying transition state TS(E′–F′)_R=Ph of 37 kcal mol^?1 is found when the substituent is a phenyl group, thus explaining the experimental observation that aryl‐terminated diethynylketones 10 and 11 exclusively form bisphospholes 16 and 17 .     

Efficient ruthenium-catalyzed α-alkylation of ketones using pyridyl methanols

By employing an easily available [Ru(p-cymene)Cl₂]₂/Xantphos/t-BuOK catalyst system, the α-alkylation of ketones was demonstrated by using pyridyl methanol as the alkylating reagents. The synthetic protocol allows synthesizing a wide range of α-pyridyl methylated ketones in reasonable to excellent isolated yields with high atom-efficiency. The transformation is operationally simple, the substrate scope is wide, and the starting materials are readily-available. There is no need for addition of alkenes as the hydrogen receptors or the use of stoichiometric amount of base.     

A novel electrochemical conversion of CO2 with aryl hydrazines and paraformaldehyde into 1,3,4-oxadiazol-2(3H)-one derivatives in one step

Using CO₂ to replace phosgene or CO as the C1 synthon, we successfully achieved the one-pot electrochemical synthesis of 1,3,4-oxadiazol-2(3H)-one derivatives via a three-component coupling reaction of CO₂ with aryl hydrazines and paraformaldehyde in an undivided cell. With NaI as the electro-catalyst and t-BuOK as the base, this electrochemical process could be smoothly performed to afford the target products in good to high yields at room temperature.     

Tricarbonyl-chromium complexes of benzannelated cycloproparenes

Reaction of 1H-cyclopropa [b]naphthalene ( 1a ) or 1H-cyclopropa[b]anthracene ( 10a ) with tris(acetonitrile)tricarbonylchromium affords cyclobutanaphthalenone and cyclobutaanthracenone 2 and 11 , respectively. In contrast, the bis-silylated Cycloproparenes 1b and 10b undergo complexation at the terminal benzene ring and lead to the arene-tricarbonylchromium complexes 4b and 12 , respectively. Desifylation of 4b to 4a is effected by t-BuOK.     

The Influence of solvent and crown polyethers on the nucleophilic reactivity of potassium tert-Butylperoxide,potassium tert-Butoxide,and some other oxygen bases

The rates of reaction of t-BuOOK, t-BuOK, n-BuOOK, and p-MeC₆H₄OKwith p-nitrophenyl diphenylphosphinate 1 and with p-nitrophenyl benzoate 2 have been measured in toluene both in the absence and in the presence of crown polyether dicyclohexyl-18-crown-6 3a . The rates of nucleophilic displacementon 1 by HOO^?, t-BuOO^?, and some “nonalpha” oxyanions in water have also been determined. Solvent transfer from water to toluene results in increasing the nucleophilic reactivity of the t-butyl hydroperoxide anion. Rate ratios Q_Qa are given which allow one to estimate the enhanced reactivity of t-BuOO^? (an α-nucleophile) compared to oxygen nucleophiles of comparable base strength toward 1 and 2 . These are for substrate 1 , Q_α (water) ? 6.5 and Q_α (toluene) ? 2.7; for substrate 2 , Q_α (water) ? 5.5 and Q_α (toluene) ? 5. The hypothesis is advanced that solvation is not a major factor in determining the α-effect of the t-butylhydroperoxide anion.     

Synthesis and photophysical properties of benzo[c]thiophene,p-phenylene-, triphenylamine-, and pyrene-based vinylenes

An efficient synthesis of benzo[c]thiophenyl/p-phenylenyl/pyrenyl phosphonate esters has been achieved using ZnBr₂-catalyzed Michaelis–Arbuzov reaction of corresponding benzyl alcohol/bromides at room temperature. Horner–Wadsworth–Emmons reaction of the phosphonate esters with aryl/heteroaryl aldehydes in the presence of t-BuOK furnished the vinylenes in good yields. The absorption and emission characteristics of the synthesized vinylenes were also reported.     

Synthesis of Tricyclic (λ5)-Phosphoranes; unusual N-demethylation/N-alkylation reactions during the oxidative addition of hexafluoroacetone and tetrachloro-ortho-benzoquinone to benzodiaza-λ3-phosphorinones. Single crystal X-ray diffraction studies of various products

The reaction of methylisatoic acid anhydride 1 with benzylamines led to the N-benzyl-N′-methylanthranilamide derivatives 2 – 4 . Their reaction with phosphorus trichloride furnished the 2-chloro-1-halobenzyl/benzyl-3-methyl-4(1 H)-1,3,2-benzodiazaphosphorin-4-ones 5 – 7 which, upon reaction with bis-(2-chloroethyl)ammonium chloride/triethylamine, were converted into the P-bis-(2-chloroethyl)amino-1-halobenzyl/benzyl-3-methyl-4(1 H)-1,3,2-benzodiazaphosphorin-4-ones 8 – 10 and 12 . With 2-chloroethylammonium chloride/triethyl-amine the P? NHCH₂CH₂Cl-substituted compound 11 was obtained from the P^IIICl-species 6 . The reaction of 8 – 10 and 12 with hexafluoroacetone (HFA) took an unusual course: apart from the oxidative addition of HFA and formation of the perfluoropinacolyl ring system, one of the two CH₂CH₂Cl groups was found to alkylate the CH₃N atom with formation of a five-membered (diazaphospholane) ring in the tricyclic phosphoranes 13 – 16 . The reaction of 11 with HFA also produced a spirophosphorane 17 which involved a λ⁵-oxazaphosphetidine ring system. In the reaction of 8, 10 and 12 with tetrachloro-o-benzoquinone, an oxidative addition reaction with concomitant N-alkylation and formation of the tricyclic phosphoranes 18 – 20 was found to take place. Single crystal X-ray structure determinations are described for the phosphoranes 13, 14 and 16 , and for the precursor compound 9 . The following features are common to the isostructural compounds 13 and 16 and the diethyl ether hemisolvate of 14 : the (λ⁵)-spiro phosphorus atom lies out of the plane of the other atoms of the rings to which it is common, and the dioxaphospholane rings display a twist conformation. In the λ³P-compound 9 the phosphorus atom also lies out of the plane of the other ring atoms.     

Generation and Trapping of Cyclopropenes from 2-Alkoxy-1,1-dichlorocyclopropanes

In presence of crown ether, 2-alkoxy-1,1-dichlorocyclopropanes react with t-BuOK/THF preferentially via ring opening to 2-chloroalk-2-en-1-ones and alkynones or to chlorocyclopropenes. The latter may be intercepted with 1,3-diphenylisobenzofuran, but in the absence of trapping agent, the rearrangement to vinylcarbenes does not occur.     

Intramolecular Diels-Alder Reaction of Furans with Allenyl Ethers Followed by Phenylthio and Trialkylsilyl Groups Rearrangement

A new reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by phenylthio group rearrangement was discovered. Treatment of the propargyl ethers 2a-c with t-BuOK in t-BuOH at 85 ° C gave the phenylthio group rearrangement products 5a-c and 6a-c . A reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by trialkylsilyl group rearrangement is also demonstrated.     

Large Amplitude Motions in Fruit Flavors: The Case of Alkyl Butyrates

To accurately characterize the large amplitude motions and soft degrees of freedom of isolated molecules, sampling their conformational landscape by molecular mechanics and quantum chemical calculations may provide a valuable insight into the structure and dynamics. However, the resulting models need to be validated by a reliable experimental counterpart. For ethyl pentanoates, which belong to the family of fruit esters, benchmark calculations at different levels of theory showed that the C−C bond in proximity to the ester carbonyl group exhibits a large amplitude motion that is extremely sensitive to the choice of quantum chemical method and basis set. In such cases, insights from high-resolution molecular jet techniques are ideal to accurately identify and characterize soft degrees of freedom. Here, we report on the most abundant conformer of ethyl 2-ethyl butyrate using Fourier-transform microwave spectroscopy. We show that – unlike other structurally related pentanoates for which gas-phase and crystallographic data is available – ethyl 2-ethyl butyrate possesses a C_s symmetry plane under molecular jet conditions.     

Ruthenium(II) <Emphasis Type="Italic">N</Emphasis>-heterocyclic Carbene Complexes in the Transfer Hydrogenation of Ketones

Six ruthenium-N-heterocyclic carbene complexes (2–7) have been prepared and the new compounds characterized by C, H, N analyses, ¹H-n.m.r. and ¹³C-n.m.r. The reduction of ketones to alcohols via transfer hydrogenation was achieved with catalytic amounts of complexes (2–7) in the presence of t-BuOK.     

An efficient synthesis of enantiopure (+)- and (−)-3-exo-amino-7,7-dimethoxynorbornan-2-exo-ols

We describe the synthesis of new amino alcohols (+)- and (−)-3-exo-amino-7,7-dimethoxynorbonan-2-exo-ols. The (+)- or (−)-7,7-dimethoxy-1,4,5,6-tetrachlorobicyclo[2.2.1]hept-5-en-2-endo-ol, obtained from the enzyme catalysed transesterification of the racemate, was reduced and dechlorinated (Na/NH₃; ethanol), followed by pyridinium chlorochromate oxidation of the resultant alcohols to the corresponding ketones. After treatment with t-BuOK/BuONO, in a nitrosation reaction, α-keto oximes were obtained. Reduction over two steps with NaBH₄ and NaBH₄/NiCl₂·6H₂O followed by in situ acetylation furnished the corresponding acetamido esters, which were hydrolysed with CH₃OH/Na to produce the enantiopure amino alcohols in good yields.     

Photo-CIDNP. Investigation of β,γ-Unsaturated Ketones: Evidence for Temperature-dependent S1 vs. T2 Reactivities of Cyclopent-2-enyl Methyl Ketones

On ultraviolet irradiation of the cyclopent-2-enyl methyl ketones 1a – c at ?54° ? t ? 139°, photo-CIDNP. effects of the starting ketones, the 1,3-acetyl shifted isomers (2) , and radical disproportionation and combination products (4 – 7) were observed. These effects show a unique dependence of the polarization phase on temperature which is a novel feature in photo-CIDNP. studies. The results of the investigation, which also included experiments using triplet quenchers, triplet sensitizers and radical scavengers, are rationalized in terms of Schemes 2 and 3. α-Cleavage is a major excited-state reaction of 1a – c on direct irradiation. Temperature-activated α-cleavage (k(t)) to the radical pair R · · R ′¹ and intersystem crossing (k_isc) to the T₂ state are among the competing S₁ deactivation processes. The T₂ state in turn cleaves (k) to R · · R ′³ A ‘low-temperature range’ with k_isc ? k(t) and a ‘high-temperature range’ with k(t) ? k_isc exhibiting preferential reactivity from the T₂ and S₁ states, respectively, can be defined for all three β,γ-unsaturated ketones 1a – c .