Fast ring opening of unstable mesoionic 1,3-dioxolylium-4-olates to acyloxyketenes: formation of [2+2] cycloadducts of acyloxyketene with several ketenophiles

Fast ring opening of mesoionic 1,3-dioxolylium-4-olate 5, generated by Rh₂(OAc)₄-catalyzed decomposition of a phenyldiazoacetic anhydride 6, to an acyloxyketene 10 was demonstrated by trapping the ketene 10. Rh₂(OAc)₄-catalyzed decomposition of p-nitrophenyldiazoacetic p-chlorobenzoic anhydride 6a in the presence of ketenophiles such as dihydrofuran, carbodiimides, and imines did not give 1,3-dipolar cycloadducts with the 1,3-dioxolylium-4-olates 5a, but their [2+2]-cycloadducts with the acyloxyketene 10a. PM3 calculation of heats of formation of a 1,3-dioxolylium-4-olate 5 and an acyloxyketene 10 indicates that the acyloxyketene 10 is 9 kcal/mol more stable than the 1,3-dioxolylium-4-olates 5.     

(Fluorosilyl)ethylenediamines and fluorosilyl-1,3-diaza-2-silacyclopentanes

This paper presents the chemistry of ethylenediamines and fluorosilanes. The synthesis of thermally stable monosilyl (1-5)- and bis(fluorosilyl)ethylenediamines (6) is described. Starting with the dilithium salt of ethylenediamine and F₂Si(CMe₃)₂ the five-membered 1,3-diaza-2-silacyclopentane (8) is obtained. The reaction of tetra- and trifluorosilanes with dilithiated bis(silyl)ethylenediamines leads to the formation of 1,3-diaza-2-fluorosilylsilacyclopentanes (9-14). Fluorosilanes substitute 8 in 1 and 3 positions (15-28). A fluorosilyl-bridged five-membered ring (29) is isolated in the reaction of 1-trimethylsilyl-1,3-diaza-2-silacyclopentane, BuLi and MeSiF₃. In the synthesis of N-fluorosilyl-1,3-diaza-2-silacyclopentanes constitutional isomers were formed (30-33). Quantum-chemical calculations support the isomerisation mechanism. An iminosilane with an SiN double bond is the intermediate product of the rearrangement process.Crystal structures of 7, 13, 20 and 23 are reported.     

Regio- and stereoselective reactions of a rhodanine derivative with optically active 2-methyl- and 2-phenyloxirane

The reaction of a rhodanine derivative (=(Z)-5-benzylidene-3-phenyl-2-thioxo-1,3-thiazolidin-4-one; 1) with (S)-2-methyloxirane (2) in the presence of SiO₂ in dry CH₂Cl₂ for 10 days led to two diastereoisomeric spirocyclic 1,3-oxathiolanes 3 and 4 with the Me group at C(2) (Scheme 2). The analogous reaction of 1 with (R)-2-phenyloxirane (5) afforded also two diastereoisomeric spirocyclic 1,3-oxathiolanes 6 and 7 bearing the Ph group at C(3) (Scheme 3). The structures of 3, 4, 6, and 7 were confirmed by X-ray crystallography (Figs. 1 and 2). These results show that oxiranes react selectively with the thiocarbonyl group (CS) in 1. Furthermore, the nucleophilic attack of the thiocarbonyl S-atom at the SiO₂-activated oxirane ring proceeds with high regio- and stereoselectivity via an S_N2-type mechanism.     

[4+2] Cycloaddition reactions of 4-sulfur-substituted 2-pyridones with electron-deficient dienophiles

[4+2] Cycloaddition reactions of 4-(phenylthio)-1-tosyl-2-pyridone (6a) and 4-(phenylsulfonyl)-1-tosyl-2-pyridone (6b) with electron-deficient dienophiles 7 (N-methylmaleimide, N-phenylmaleimide, and methyl acrylate) gave new isoquinuclidine products 8-10. The N-tosyl group of 6a and 6b was also efficiently converted to N-alkyl derivatives 6c-f, which showed different stereoselectivity toward reactions with dienophiles 7. Several other dienophiles 15 (dimethyl acetylenedicarboxylate, methyl vinyl ketone, ethyl vinyl ether, and methyl methacrylate) were found not to react with 6a or 6b, but led to the formation of tosyl migration products 4-(phenylthio)-O-tosyl-pyridinol (16a) and 4-(phenylsulfonyl)-O-tosyl-2-pyridinol (16b), respectively. The reactivity, regioselectivity, and stereoselectivity of the cycloaddition reactions were also compared with semi-empirical calculations.     

Palladium complexes of N-aryl-2-pyridylamines

Palladium complexes of N-phenyl-2-pyridylamine (4) and dipyridylamine substrates (7, 11) have been studied. Due to the coordination ability of the pyridine-nitrogen atoms, the pyridyl substrates, 4, 7, 11 were subjected to Pd(OAc)₂ complexations and a number of N-aryl-2-pyridylamine Pd complexes (13-17) were isolated and characterised, in particular by NMR and ESI-MS. A new method for the preparation of the acetato-bridged six-membered ring palladacycle complex (13) of 4 is reported. The dipyridyl amines 7, 11 formed cis/trans bis-dentate acetato-bridged dimeric Pd₂Lig₂(OAc)₂ (14a,b/16a,b) and Pd₃Lig₂(OAc)₄ complexes (15a,b/17a,b). The N-aryl-2-pyridylamine substrates (4, 7, 11) were prepared by oxidative nucleophilic substitution, by 1,3-cycloaddition reaction or by Buchwald amination.     

[3+2] Cycloaddition-mediated synthesis of 3-methylsulfanyl-pyrrolidine-3-carboxylic acid methyl ester

1,3-Dipolar cycloaddition reactions are fundamental processes in organic chemistry. Herein we report [3+2] annulation of thiomethylacrylate 2 and azomethine ylide precursor 3 towards the synthesis of novel 3-methylsulfanyl-pyrrolidine 5. Alternatively, we have also explored the alkylation of 7 with dimethyldisulfide/LDA for the introduction of thiomethyl group towards the synthesis of 5 in moderate to good yields. Efficacy of these two routes under various conditions/catalysts for the synthesis of 5 is presented.     

Reactions of P4S10 and pyPS2Cl with N,N′-diphenylurea and N,N′-diphenylthiourea

The reaction of P₄S₁₀ (1) with N,N′-diphenylurea (PhNH)₂CO (2) results in new heterocyclic compounds: the pyridinium salt of 1,3-diphenyl-2-sulfido-2-thioxo-1,3-diaza-2λ⁵-phosphetidine (3) (with a P–N–C–N cycle) and the pyridinium salt of 1,4-diphenyl-2,5-disulfido-2,5-dithioxo-1,4-dithiadiaza-2λ⁵,5λ⁵-diphosphinane (4), containing the (P–S–N)₂ cycle and the cyclic thiophosphates [pyH]₂[P₂S₈] (5), [pyH]₂[P₂S₇] (6) and [pyH]₃[P₃S₉] (7). A similar reaction, but carried out with N,N′-diphenylthiourea (PhNH)₂CS (8), leads to the formation of 4 and 6. pyPS₂Cl (9), used as an alternative starting material, also yields compounds 3, 4, 5, and further [pyH][PS₂Cl₂] (10) and S₈ after reaction with 2. Compound 3 reacts with Pd(CH₃COO)₂, with the formation of the complex [Pd(Ph₂N₂COPS₂)₂] (11). The crystal structures of 3 and 7 were determined by single-crystal X-ray diffraction.     

Cycloaddition of methyl 2-(2,6-dichorophenyl)-2H-azirine-3-carboxylate to electron-rich 2-azadienes

tert-Butyldimethylsililoxy-2-aza-1,3-butadienes react with 2H-azirine 3 leading to Diels-Alder cycloadducts in moderate yields. The reactions are endo- and regioselective with the azirine being added by its less hindered face. There is only one product in the case of 1b, 4b. There are two isomers (4 and 5) from 1a, 1c and 1d. A different result was obtained with the diene 1e. Diene 1e formed products 4e and 8. Some of compounds 4 and 5 have been hydrolysed leading to functionalised aziridines 7. Compound 8 gave aziridine 9.     

1,4-Cycloaddition of pyrazole with mesityl oxide; solid-state structure of bicyclic [C6H5Me3N2(OH)]Cl

The synthesis of bicyclic 6-hydroxy-6,8,8-dimethyl-5-aza-1-azonia-bicyclo[3.3.0]octa-1,3-diene chloride, [C₆H₅Me₃N₂(OH)]Cl, (5) by the HCl-catalyzed 1,4-cycloaddition of pyrazole (1) with mesityl oxide (4) is described. A proposed mechanism for the formation of 5 will be given.     

Coordination compounds of N,N′-olefin functionalized imidazolin-2-ylidenes

N-Heterocyclic carbene ligands (NHC) were metalated with Pd(OAc)₂ or [Ni(CH₃CN)₆](BF₄)₂ by in situ deprotonation of imidazolium salts to give the N-olefin functionalized biscarbene complexes [MX₂(NHC)₂] 3-7 (3: M = Pd, X = Br, NHC = 1,3-di(3-butenyl)imidazolin-2-ylidene; 4: M = Pd, X = Br, NHC = 1,3-di(4-pentenyl)imidazolin-2-ylidene; 5: M = Pd, X = I, NHC = 1,3-diallylimidazolin-2-ylidene; 6: M = Ni, X = I, NHC = 1,3-diallylimidazolin-2-ylidene; 7: M = Ni, X = I, NHC = 1-methyl-3-allylimidazolin-2-ylidene). Molecular structure determinations for 4-7 revealed that square-planar complexes with cis (5) or trans (4, 6, 7) coordination geometry at the metal center had been obtained. Reaction of nickelocene with imidazolium bromides afforded the η⁵-cyclopentadienyl (η⁵-Cp) monocarbene nickel complexes [NiBr(η⁵-Cp)(NHC)] 8 and 9 (8: NHC = 1-methyl-3-allylimidazolin-2-ylidene; 9: NHC = 1,3-diallylimidazolin-2-ylidene). The bromine abstraction in complexes 8 and 9 with silver tetrafluoroborate gave complexes [NiBr(η⁵-Cp)(η³-NHC)] 10 and 11. The X-ray structure analysis of 10 and 11 showed a trigonal-pyramidal coordination geometry at the nickel(II) center and coordination of one N-allyl substituent.     

Utilisation of 1,3-dialkylimidazolium-2-carboxylates as CO2-carriers in the presence of Na and K: application in the synthesis of carboxylates, monomethylcarbonate anions and halogen-free ionic liquids

1,3-Dialkylimidazolium-2-carboxylate compounds have recently been fully characterised. Here we describe the utilisation of 1,3-dimethyl (1a) and 1-butyl-3-methyl-imidazolium-2-carboxylate (1b) in a carboxylation reaction with transfer of the CO₂ moiety to benzoylacetone and methanol for the synthesis, in high yield, of benzoylacetate and monoalkylcarbonate anions, respectively. Conversely, when compounds 1a and b are reacted with carbonylic substrates lacking C-H active bonds, a product resulting from nucleophilic attack of the 1,3-dialkylimidazol-2-ylidene species on the carbonyl moiety is obtained. The reported reactions can find applications in organic synthesis and in the synthesis of halogen-free ionic liquids.     

Synthesis of polyfunctionalized furans from 3-acetyl-1-aryl-2-pentene-1,4-diones

The BF₃-catalyzed cyclization of 3-acetyl-1-aryl-2-pentene-1,4-diones 1a-e in the presence of water in boiling tetrahydrofuran gave bis(3-acetyl-5-aryl-2-furyl)methanes 2a-e in 26-79% yields along with a small amount of 3-acetyl-5-aryl-2-methylfurans 3a-e. The exact structure of 2a was determined by X-ray crystallography. The use of a half volume of the solvent for the reaction of 1a resulted in the formation of 2,4-bis(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-phenylfuran (4) together with 2a and 3a. A similar reaction of 1a was carried out in the presence of 3-acetyl-5-(4-methylphenyl)-2-methylfuran (3d) to afford 4-(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-(4-methylphenyl)-2-methylfuran (5) in 49% yield. The BF₃-catalyzed reaction of 1a with 2,4-pentanedione in dry tetrahydrofuran at 23°C gave 3-(3-acetyl-5-phenyl-2-furfuryl)-4-hydroxy-3-penten-2-one (6a) and 3-(3-acetyl-2-methyl-4-phenyl-5-furyl)-4-hydroxy-3-penten-2-one (7a) in 66 and 24% yields, respectively. The product distribution depended on the reaction temperature. A similar reaction of 1b-e also yielded the corresponding trisubstituted furans 6b-e and tetrasubstituted furans 7b-e in good yields. These results suggested the presence of the furfuryl carbocation intermediate A during the reaction. The one-pot synthesis of 6a and 7a was also achieved by a similar reaction using phenylglyoxal. The deoxygenation of 1a with triphenylphosphine gave 3a in 88% yield, while 1a was treated with concentrated hydrochloric acid to yield 3-acetyl-2-chloromethyl-5-phenylfuran (8) which was quantitatively transformed in ethanol into 3-acetyl-2-ethoxymethyl-5-phenylfuran (9) and in water into 3-acetyl-5-phenylfurfuryl alcohol (10), respectively. In addition, the Diels-Alder reaction of cyclopantadiene with 1a gave the corresponding [4+2] cycloaddition products 11 and 12.     

A convenient one-pot synthesis of 2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives and their further transformations

The trifluoromethyl containing heterocycles, 2-hydroxy-4-aryl-3-(thien-2-oyl)-2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives 4, were synthesized via a one-pot three-component reaction of aldehyde 1 with 1,3-cyclohexanedione 2 and 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione 3 in the presence of a catalytic amount of Et₃N. The effect of bases and solvents on the reaction efficiency and yield was briefly investigated. Treatment of 4 with an excess amount of NH₄OAc in ethanol afforded 2-trifluoromethyl-1H-quinolin-5-one derivatives 5. Refluxing of 4 with TsOH in CHCl₃ gave the corresponding dehydrated products 8.     

Solid-state and solution photocycloadditions of 4-acyloxy-2-pyrones with maleimide

Solid-state photosensitized reactions of 4-acyloxy-2-pyrones (1b,c) with maleimide (2) afforded endo-endo double-[4+2] cycloadducts (3b,c) with high stereoselectivity. Sensitized photoreactions of 1a-d with 2 in solution gave exo-endo double-[4+2] cycloadducts (4a-d). 2-Pyrones 1a-d were photolyzed to give carboxylic acids (5a-d) via their valence isomerization in the solid state and in solution. Such kinds of photoreaction of the 4-acyloxy-2-pyrones were dramatically different from regio- and stereoselective [2+2] cycloadditions of 4-alkyloxy-2-pyrones. The photoreaction mechanisms of 1 with 2 and 1 itself were analyzed by powder X-ray diffraction analysis and MO calculations.     

A biomimetic total synthesis of (+)-intricarene

An asymmetric synthesis of the furanocembrane (−)-bipinnatin J (3a) found in gorgonian corals is described. Treatment of 3a with VO(acac)₂-^tBuOOH, followed by acetylation, gave acetoxypyranone 15. When 15 was heated in the presence of DBU, it underwent a transannular oxidopyrylium-alkene [5+2] cycloaddition producing the polycyclic diterpene (+)-intricarene 1, isolated from the coral Pseudopterogorgia kallos. The total synthesis of intricarene 1 mimics its most likely biosynthesis via oxidation of bipinnatin J (3a) in vivo.     

One-pot synthesis of macrocyclic compounds possessing two cyclobutane rings by sequential inter- and intramolecular [2+2] photocycloaddition reactions

Sensitized photocycloaddition reactions of 6,6′-dimethyl-4,4′-[1,3-bis(methylenoxy)phenylene]-di-2-pyrone (1) with electron-poor α,ω-diolefins such as ethylene diacrylate (2a) and polyoxyethylene dimethacrylates (2b-d) afforded site- and stereoselective macrocyclic dioxatetralactones (3a-d) and (4b) having 18- to 25-membered rings across the C5-C6 and C5′-C6′ double bonds, or C5-C6 and C3′-C4′ double bonds in 1, respectively. Similar photoreactions of 1 with electron-rich α,ω-diolefins such as poly(ethylene glycol)divinyl ether (2e and 2f) afforded crown ether-type macrocyclic compounds (5e and 5f) having 18- and 21-membered rings across the C3-C4 and C3′-C4′ double bonds in 1, respectively. The stereochemical features of 3b, 5e-xx, and 5e-nn were determined by the X-ray crystal analysis. The reaction mechanism was inferred by MO methods.     

Synthesis of potassium 2,3,4-trihydroxy-2-methylbutanoate: a leaf-closing substance of Leucaena leucocephalam

Starting from citraconic anhydride (2), a six step synthesis of leaf closing substance (±)-erythro potassium 2,3,4-trihydroxy-2-methyl-butanoate (1) has been described with 29% overall yield via diesterification, OsO₄-dihydroxylation, acetonide protection, regioselective mono hydrolysis of unhindered ester moiety, borane-dimethylsulfide induced chemoselective reduction of carboxylic group and hydrolysis pathway. Surprisingly, the sodium borohydride reduction of monoester 5 and lithium borohydride reduction of 11 furnished the undesired regioisomer 7.     

Regioselective Baeyer-Villiger lactonization of 2-substituted pyrrolidin-4-one. Synthesis of statine

Nine 2-substituted pyrrolidin-4-ones 4a-i were obtained via a series of functional group transformation of known prolinol 5 by facile six kinds of methodologies. The target structure of 1,3-amino alcohols 2a-i was constructed in the regioselective Baeyer-Villiger lactonization of ketones 4a-i and reduction of the resulting 4-substituted tetrahydro-1,3-oxazin-6-ones 3a-i. A new and straightforward synthesis of (3S,4S)-statine (6) has been established starting from trans-(2S,4R)-4-hydroxyproline (1).     

Highly stereoselective synthesis of novel trans-thiophenylene-silylene-vinylene-arylene molecular and macromolecular compounds

Novel stereoregular molecular compounds 8-13 containing thiophenylene-silylene-vinylene-phenylene units have been synthesised via highly effective silylative coupling of styrene and 1,4-divinylbenzene (7) with respective vinylsilylthiophenes (3, 4) and bis(vinylsilyl)thiophenes (5, 6) catalyzed by RuHClCO(PCy₃)₂. Respective copolymers (14, 15) were produced via silylative copolycondensation of 5 and 6 with 7. All products were isolated and characterised by NMR, MS, HRMS and two of them 10 and 11 by X-ray method. Catalytic study as well as stoichiometric reactions of Ru-H (1) with 2-(vinylsilyl)thiophene (3) and Ru-Si (16) with styrene confirmed the mechanism of the silylative coupling olefins with vinylsilicon compounds.     

[4+2] Cycloaddition of 1-phosphono-1,3-butadiene with azo- and nitroso-heterodienophiles

Under microwave activation, diethyl 1-phosphono-1,3-butadiene (1) reacted with t-butyl azodicarboxylate (2) and o-nitrosotoluene (5) to furnish quantitatively [4+2] cycloadducts, 3-phosphono-3,6-dihydro-1,2-pyridazine (3) and 6-phosphono-3,6-dihydro-1,2-oxazine (6), respectively. Selective oxidation and/or reduction of 6 led to functionalized δ-aminophosphonic derivatives in cyclic (7, 8) and aliphatic series (9, 10). Intermediate 10 may be cyclized into 2-phosphono-2,5-dihydro-1-pyrrole (12).