Synthese eines cyclischen Depsipeptides mittels Amidcyclisierung

Synthesis of a Cyclic Depsipeptide via an Amide Cyclization The synthesis of (S)-Pms-(R)-Pro-(S)-Ala-Aib-N(CH₃)₂ ( 12 ) has been achieved according to Scheme 3. For the formation of fragment 11 , the reaction of Z-alanine (Z = benzyloxycarbonyl) and 3-dimethylamino-2,2-dimethyl-2-azirine ( 1 ) has been used, whereby 1 serves as an aminoisobutyric-acid dimethylamide (aib-N(CH₃)₂) equivalent. Treatment of a suspension of 12 in toluene with HCl gas at 100° led to the cyclic depsipeptide 13 in 72% yield (Scheme 4). In presence of water, the acid 14 was isolated as the sole product. A mechanism for the formation of 13 and 14 via an oxazolinone intermediate, is postulated in Scheme 4.     

Umsetzung von 3-Amino-2H-azirinen mit Salicylohydrazid

Reaction of 3-Amino-2H-azirines with Salicylohydrazide 3-Amino-2H-azirines 1a–g react with salicylohydrazide ( 7 ) in MeCN at 80° to give 2H, 5H-1,2,4-triazines 10 , 1,3,4-oxadiazoles 12 and, in the case of 1d , 1,2,4-triazin-6-one 11a (Scheme 3). The precursor of these heterocycles, the amidrazone of type 9 , except for 9c and 9g , which could not be isolated, has been found as the main product after reaction of 1 and 7 in MeCN at room temperature. 3-(N-Methyl-N-phenylamino)-2-phenyl-2H-azirin ( 1g ) reacts with 7 to give mainly the aromatic triazines 15b₁ and 15b₂ . In this case, two unexpected by-products, 16 and salicylamide ( 17 ), occurred, probably by disproportionation of a 1:1 adduct from 1g and 7 (Scheme 8). Oxidation of 10f with DDQ leads to the triazine 15a . The structure of 10c, 11a, 12c, 13 (by-product in the reaction of 1b and 7 ), the N′-phenylureido derivative 14 of 9d (Scheme 4) as well as 15b₂ has been established by X-ray crystallography. The ratio of 10/12 as a function of substitution pattern in 1 and solvent has been investigated (Tables 1, 3, 4, and 7). A mechanism for the formation of 10 and 12 is proposed in Scheme 7.     

Synthese einer Calicen-Vorstufe für Retro-Diels-Alder-Reaktionen

Synthesis of a Calicene Precursor for Retro-Diels-Alder Reactions In view of retro-Diels-Alder reactions (RDA reactions), the calicene precursor 9 has been synthesized in a comparably simple four-step synthesis by dibromocarbene addition at dibenzobarrelene ( 10 → 11 , 44%), halogenlithium exchange followed by reaction with cyclopentenone ( 11→12 , 91%) and H₂O as well as HBr elimination ( 12→14→9 , 43%) (Scheme 5). First experiments with respect to the thermal behavior of 9 show that, although RDA reaction seems to be relatively easily occurring according to the results of ‘Curie-Point’ pyrolysis, only anthracene and no calicene 2 has been detected so far.     

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.     

A Novel Route for the Synthesis of Deoxy Fluoro Sugars and Nucleosides

The reaction of (diethylamino)sulfur trifluoride (DAST) with methyl 5-O-benzoyl-β-D -xylofuranoside ( 1 ) followed by column chromatography afforded the riboside 2 (62%) and the ribo-epoxide 3 (18%) (Scheme 1). Under similar reaction conditions, the α-D -anomer 4 gave the riboside 5 and the difluoride 6 in 60 and 9% yield, respectively. Treatment of the β-D -xyloside 10 with DAST gave, after chromatographic purification, the riboside 11 as the principal product (48%; Scheme 2). These results suggest that the C(3)−O−SF₂NEt₂ derivatives were initially formed in the case of the xylosides studied. The distinctive feature of the reaction of DAST with the β-D -arabinoside 12 consists in the formation of a 3- or 5-benzylideneoxoniumyl-substituted intermediate on one of the consecutive transformations, which finally give rise to the inversion of the configuration at C(3) affording the xylosides 17 (18%) and 18 (55%); the lyxoside 14 was also isolated from the reaction mixture in a yield of 25% (Scheme 3). In the presence of the non-participating 5-O-trityl group, i.e., from the reaction products of 21 with DAST, the compounds 23 and 24 were isolated in 16 and 52% yield, respectively (Scheme 4). It may be thus reasonable to conclude that, in the case of the β-D -arabinosides 12 and 21 , the principal route of the reaction is the formation of the intermediate C(2)−O−SF₂NEt₂ derivative. Unlike 21 , the α-D -arabinoside 26 was converted to the lyxo-epoxide 25 (53%) and the lyxoside 27 (14%), which implies the intermediate formation of the C(3)−O−SF₂NEt₂ derivative (Scheme 5).     

Reactions of Stable α‐Chlorosulfanyl Chlorides with CS‐Functionalized Compounds

The smooth reaction of 3‐chloro‐3‐(chlorosulfanyl)‐2,2,4,4‐tetramethylcyclobutanone ( 3 ) with 3,4,5‐trisubstituted 2,3‐dihydro‐1H‐imidazole‐2‐thiones 8 and 2‐thiouracil ( 10 ) in CH₂Cl₂/Et₃N at room temperature yielded the corresponding disulfanes 9 and 11 (Scheme 2), respectively, via a nucleophilic substitution of Cl^? of the sulfanyl chloride by the S‐atom of the heterocyclic thione. The analogous reaction of 3‐cyclohexyl‐2,3‐dihydro‐4,5‐diphenyl‐1H‐imidazole‐2‐thione ( 8b ) and 10 with the chlorodisulfanyl derivative 16 led to the corresponding trisulfanes 17 and 18 (Scheme 4), respectively. On the other hand, the reaction of 3 and 4,4‐dimethyl‐2‐phenyl‐1,3‐thiazole‐5(4H)‐thione ( 12 ) in CH₂Cl₂ gave only 4,4‐dimethyl‐2‐phenyl‐1,3‐thiazol‐5(4H)‐one ( 13 ) and the trithioorthoester derivative 14 , a bis‐disulfane, in low yield (Scheme 3). At ?78°, only bis(1‐chloro‐2,2,4,4‐tetramethyl‐3‐oxocyclobutyl)polysulfanes 15 were formed. Even at ?78°, a 1 : 2 mixture of 12 and 16 in CH₂Cl₂ reacted to give 13 and the symmetrical pentasulfane 19 in good yield (Scheme 5). The structures of 11, 14, 17 , and 18 have been established by X‐ray crystallography.     

A convenient synthesis of 2-amino-4H-1,3,4-oxadiazino[5,6-b]-quinoxaline derivatives

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5 with a 2-fold molar amount of ethyl chloroglyoxalate gave ethyl 8-chloro-4-methyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline-2-carboxylate 6 , whose reaction with hydrazine hydrate afforded the C₂-hydrazinocarbonyl derivative 7 . The reaction of compound 7 with nitrous acid provided the C₂-acylazide derivative 8 , which was converted into the C₂-amino 9 , C₂-carbamate 11a-c, 12a,b , and C₂-ureido 13a-c, 14 derivatives. The mass spectral fragmentation patterns were examined for compounds 10–14 , wherein the molecular ion peak did not appear in the mass spectra of compounds 10c, 11a-c, 12a,b, 13c , and 14.     

Kinetics of the reactions of CCl3 with O and O2 and of CCl3O2 with NO at 295 K

The reactions of CCl₃ with O(³P) and O₂ and those of CCl₃O₂ with NO have been studied at 295 K using discharge flow methods with helium as the bath gas. The rate coefficient for the reaction of CCl₃ with O was found to be (4.2 ± 0.6) × 10^?11 cm³/s and that for CCl₃O₂ with NO was (18.6 ± 2.8) × 10^?12 cm³/s with both coefficients independent of [He]. For reaction between CCl₃ and O₂ the rate coefficient was found to increase from 1.51 7times; 10^?14 cm³/s to 7.88 × 10^?14 cm³/s as the [He] increased from 3.5 × 10¹⁶ cm^?3 to 2.7 × 10¹⁷ cm^?3. There was no evidence for a direct two-body reaction, and it is concluded that the only product of this reaction is CCl₃O₂. Examination of these results for CCl₃ + O₂ in terms of current simplified falloff treatment suggests that the high-pressure limit for this reaction is ～ 2.5 × 10^?12 cm³/s, which may be compared with a direct measurement of the high-pressure limit of 5 × 10^?12 cm³/s. A value of (5.8 ± 0.6) × 10^?31 cm⁶/s has been obtained for k₀, the coefficient in the low-pressure region. This value is compared with corresponding values found earlier for the (CH₃, O₂) and (CF₃, O₂) systems and with estimates based on unimolecular rate theory.     

Reaction of Optically Active Oxiranes with Thiofenchone and 1‐Methylpyrrolidine‐2‐thione: Formation of 1,3‐Oxathiolanes and Thiiranes

The SnCl₄‐catalyzed reaction of (?)‐thiofenchone (=1,3,3‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 10 ) with (R)‐2‐phenyloxirane ((R)‐ 11 ) in anhydrous CH₂Cl₂ at ?60° led to two spirocyclic, stereoisomeric 4‐phenyl‐1,3‐oxathiolanes 12 and 13 via a regioselective ring enlargement, in accordance with previously reported reactions of oxiranes with thioketones (Scheme 3). The structure and configuration of the major isomer 12 were determined by X‐ray crystallography. On the other hand, the reaction of 1‐methylpyrrolidine‐2‐thione ( 14a ) with (R)‐ 11 yielded stereoselectively (S)‐2‐phenylthiirane ((S)‐ 15 ) in 56% yield and 87–93% ee, together with 1‐methylpyrrolidin‐2‐one ( 14b ). This transformation occurs via an S_N2‐type attack of the S‐atom at C(2) of the aryl‐substituted oxirane and, therefore, with inversion of the configuration (Scheme 4). The analogous reaction of 14a with (R)‐2‐{[(triphenylmethyl)oxy]methyl}oxirane ((R)‐ 16b ) led to the corresponding (R)‐configured thiirane (R)‐ 17b (Scheme 5); its structure and configuration were also determined by X‐ray crystallography. A mechanism via initial ring opening by attack at C(3) of the alkyl‐substituted oxirane, with retention of the configuration, and subsequent decomposition of the formed 1,3‐oxathiolane with inversion of the configuration is proposed (Scheme 5).     

New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven-membered ring

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde ( 1 ) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde ( 2 ) as well as dihydrolactaroviolin ( 3 ) yielded with 4a the corresponding styrylazulenes 6 and 7 , respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9 , respectively (cf. Scheme 1). The reaction of 4,6,8-trimethylazulene ( 10 ) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b . 4,6,8-Trimethylazulene-2-carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH₄) and dehydrogenation (MnO₂) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b , respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene ( 21 ) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me₂N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4-NO₂C₆H₄CH=NC₆H₅ ( 22e ) in DMF yielded no corresponding styrylazulene derivative 23e . Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene ( 27 ) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene ( 10 ) and benzanil ( 22a ) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).     

Thermal and Ru-catalyzed Reactions of Styryl-Substituted Azulenes with Dimethyl Acetylenedicarboxylate

The thermal reaction of 1-[(E)-styrl]azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin at 190–200° does not lead to the formation fo the corresponding heptalene-1,2-dicarboxylates (Scheme 2). Main products are the corresponding azulene-1,2-dicarboxylates (see 4 and 9 ), accompanied by the benzanellated azulenes trans- 10a and trans- 11 , respectively. The latter compounds are formed by a Diels-Alder reaction of the starting azulenes and ADM, followed by an ene reaction with ADM (cf. Scheme 3). The [RuH₂(PPh₃)₄]-catalyzed reaction of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes (R=H, MeO, Cl; Scheme 4) with ADM in MeCN at 110° yields again the azulene-1,2-dicarboxylates as main products. However, in this case, the corresponding heptalene-1,2-dicarboxylates are also formed in small amounts (3–5%; Scheme 4). The benzanellated azulenes trans- 10a and trans- 10b are also found in small amounts (2–3%) in the reaction mixture. ADM Addition products at C(3) of the azulene ring as well as at C(2) of the styryl moiety are also observed in minor amounts (1–3%). Similar results are obtained in the [RuH₂(PPh₃)₄]-catalyzed reaction of 3-[(E)-styryl]guaiazulene ((E)- 8 ; Scheme 5) with ADM in MeCN. However, in this case, no heptalene formation is observed, and the amount of the ADM-addition products at C(2) of the styryl group is remarkably increased (29%). That the substitutent pattern at the seven-membered ring of (E)- 8 is not responsible for the failure of heptalene formation is demonstrated by the Ru-catalyzed reaction of 7-isopropyl-4-methyl-1-[(E)-styryl]azulene ((E)- 23 ; Scheme 11) with ADM in MeCN, yielding the corresponding heptalene-1,2-dicarboxylate (E)- 26 (10%). Again, the main product is the corresponding azulene-1,2-dicarboxylate 25 (20%). Reaction of 4,6,8-trimethyl-2-[(E)-styryl]azulene ((E)- 27 ; Scheme 12) and ADM yields the heptalene-dicarboxylates (E)- 30A / B , purely thermally in decalin (28%) as well as Ru-catalyzed in MeCN (40%). Whereas only small amounts of the azulene-1,2-dicarboxylate 8 (1 and 5%, respectively) are formed, the corresponding benzanellated azulene trans- 29 ist found to be the second main product (21 and 10%, respectively) under both reaction conditions. The thermal reaction yields also the benzanellated azulene 28 which is not found in the catalyzed variant of the reaction. Heptalene-1,2-dicarboxylates are also formed from 4-[(E)-styryl]azulenes (e.g. (E)- 33 and (E)- 34 ; Scheme 14) and ADM at 180–190° in decalin and at 110° in MeCN by [RuH₂(PPh₃)₄] catalysis. The yields (30%) are much better in the catalyzed reaction. The formation of by-products (e.g. 39–41 ; Scheme 14) in small amounts (0.5–5%) in the Ru-catalyzed reactions allows to understand better the reactivity of zwitterions (e.g. 42 ) and their triyclic follow-up products (e.g. 43 ) built from azulenes and ADM (cf. Scheme 15).     

Electrocrystallization of Tetra‐ and Hexa‐coordinated Silver(II) Compounds Based on 4,4′‐Dimethyl‐2,2′‐Bipyridine Ligand – Single Crystal Structures and Magnetic Studies

In this paper we report on the potential dependent electrocrystallization of [Ag(4,4′‐dimethyl‐2,2′‐bipyridine)₂(NO₃)₂] ( 1 ) and Ag(4,4′‐dimethyl‐2,2′‐bipyridine)(NO₃)₂ ( 2 ) from the same electrolytic bath. Thus it has been shown for the first time that the coordination number of silver ion to ligands can be tuned by the electrocrystallization potential. The single crystal structure analysis [ 1 : C2/c, a = 18.6308(15), b = 14.5708(12), c = 11.5867(10) Å, β = 126.5910(10)°, Z = 4, R = 3.9 %] [ 2 : P2₁/c, a = 8.5865(11) b = 11.0157(14) c = 16.4554(10) Å, β = 111.102(10), Z = 4 , R = 3.5 %] show divalent silver to be in an approximately square planar surrounding. Both complexes are paramagnetic following Curie's law with magnetic moments of 1.86 μ_B and 1.72 μ_B respectively.     

‘Three-Component Reaction’ with aromatic thioketones,phenyl azide,and dimethyl fumarate

The reaction of thiobenzophenone (= diphenylmethanethione; 8a ) or 9H-fluorene-9-thione ( 8b ) and methyl fumarate ( 9 ) in excess PhN₃ at 80° yields a mixture of diastereoisomeric thiiranes 10 and 11 (Scheme 1). A mechanism involving the initial formation of 1-phenyl-4, 5-dihydro-1H-1, 2, 3-triazole-4, 5-dicarboxylate 12 by 1, 3-dipolar cycloaddition of PhN₃ and 9 is proposed in Scheme 2. The diazo compound 13 , which is in equilibrium with 12 , undergoes a further 1, 3-dipolar cycloaddition with thioketones 8 to give 2, 5-dihydro-1, 3, 4-thiadiazoles 14 . Elimination of N₂ yields the thiocarbonyl ylide 15 which cyclizes to the corresponding thiirane. Desulfurization of the thiiranes 10 and 11 with hexamethylphosphorous triamide leads to the olefinic compounds 16 (Scheme 3). The crystal structures of 10a , 11a , and 16b were determined.     

Synthesis and Reactions of New Dithiolopyrroles

The title compounds were prepared starting from pyrrolinone 4 . Nucleophilic‐displacement and ring‐closure reactions yielded the dithiolopyrrole 5a , which formed salts with electrophiles ( 7, 8 ) as well as with bases. The crystal structure of 5a was determined. Oxidation of the dithioles 5a and 6a led to S(2)‐oxides ( 10a, 11a ) and the corresponding S(2)‐dioxides ( 10b, 11b ) depending on reaction conditions. The thiosulfinate 10a was converted by a ring‐opening/ring‐closure reaction sequence to the bicyclic sulfinamide 12 . The oxidative addition reactions of [Pt(η²‐C₂H₄) (PPh₃)₂] ( 14 ) with the disulfides 5a and 13 led to the dithiolatoplatinum(II) complexes 15 and 16 , respectively. Complex 16 was characterized structurally. The sulfenato‐thiolato complex 17 was synthesized via reaction of 14 with the thiosulfinate 10a . The thiosulfonato Pt^II complex 18 was prepared by an oxidative insertion of Pt⁰ into the C? S bond of the corresponding thiosulfonate 10b . Furthermore, complex 18 was characterized by single‐crystal X‐ray‐diffraction studies.     

The Diastereoselective Formation of 1,2,4-Trioxanes and 1,3-Dioxolanes by the reaction of endoperoxides with chiral cyclohexanones

1,4-Diphenyl-2,3-dioxabicyclo[2.2.1]hept-5-ene ( 2 ), on treatment with a catalytic amount of trimethylsilyl trifluoromethanesulfonate (Me₃SiOTf) in CH₂Cl₂ at ?78°, reacts with excess (?)-menthone ( 10 ) to give (1S,2S,4′aS,5R,7′aS)-4′a,7′a-dihydro-2-isopropyl-5-methyl-6′,7′-diphenylspiro[cyclohexane-1,3′-[7′H]cyclopenta-[1,2,4]trioxine] ( 11 ) and its (1R,2S,4′aR,5R,7′aR)-diastereoisomer 12 in a 1:1 ratio and in 21% yield. Repeating the reaction with 1.1 equiv. of Me₃SiOTf with respect to 2 affords 11 , 12 , and (1S,2S,3′a.R,5R,6′aS)-3′a,6′a-dihydro-2-isopropyl-5-methyl-3′a-phenoxy-5′-phenylspiro[cyclohexane-l,2′-[4′H]cyclopenta[1,3]dioxole] ( 13 ) together with its(1R,2S,3′aS,5R,6′aR)-diastereoisomer 14 in a ratio of 3:3:3:1 and in 56% yield. (+)-Nopinone( 15 ) in excess reacts with 2 in the presence of 1.1 equiv. of Me₃SiOTf to give a pair of 1,2,4-trioxanes ( 16 and 17 ) analogous to 11 and 12 , and a pair of 1,3-dioxolanes ( 18 and 19 ) analogous to 13 and 14 , in a ratio of 8:2:3:3 and in 85% yield. (?)-Carvone and racemic 2-(tert-butyl)cyclohexanone under the same conditions behave like 15 and deliver pairs of diastereoisomeric trioxanes and dioxolanes. In general, catalytic amounts of Me₃SiOTf give rise to trioxanes, whereas 1.5 equiv. overwhelmingly engender dioxolanes. Adamantan-2-one combines with 2 giving only (4′aRS,7′aRS)-4′a,7′a-dihydro-6′.7′a-diphenylspiro[adamantane-2,3′-[7′H]cyclopenta[1,2,4]trioxine] in 98% yield regardless of the amount of Me3SiOTf used. The reaction of 1,4-dipheny 1-2,3-dioxabicyclo[2.2.2]oct-5-ene ( 32 ) with 10 and 1.1 equiv. of Me3SiOTf produces only the pair of trioxanes 33 and 34 homologous to 11 and 12 . Treatment of the (S,S)-diastereoisomer 33 with Zn and AcOH furnishes (1S,2S)-1,4-diphenylcyclohex-3-ene-1,2-diol. The crystal structures of 11 – 13 and 16 are obtained by X-ray analysis. The reaction courses of 10 and the other chiral cyclohexanones with prochiral endoperoxides 2 and 32 to give trioxanes are rationalized in terms of the respective enantiomeric silylperoxy cations which are completely differentiated by the si and re faces of the ketone function. The origin of the 1,3-dioxolanes is ascribed to 1,2 rearrangement of the corresponding trioxanes, which occurs with retention of configuration of the angular substituent.     

Probing the Metal Composition of Ternary 12–12′‐16 Nanoclusters via Electrospray Ionization Mass Spectrometry

The reaction of [(3,5‐Me₂–C₅H₃N)₂Zn(SeSiMe₃)₂] with a solution of Cd(OAc)₂, Se(Ph)SiMe₃ and PPr₃ at low temperature was used to prepare single crystals of ternary group 12–12′‐16 nanoclusters with the composition [Zn_1.8Cd_8.2Se₄(SePh)₁₂(PPr₃)₄]. A ligand exchange reaction using Na[SePh] was performed to displace the neutral PPr₃ ligands. The resulting clusters were probed using electrospray ionization mass spectrometry to determine the number of zinc and cadmium atoms in the cluster and compared to the all cadmium cluster [Cd₁₀Se₄(SePh)₁₂(PPr₃)₄]. The dianionic clusters [Zn_xCd_10–xSe₄(SePh)₁₄]^2– where x = 0, 1, 2 were assigned in the mass spectra, revealing that the clusters exhibit elemental distributions that are quite narrow in these experiments.     

Ferrocenyl,Alkyl, and Aryl‐Pyrido[2,3‐d]Pyrimidines as Vasorelaxant of Smooth Muscle of Rat Aorta via cAMP Conservation Through Phosphodiesterase Inhibition

New pyrido[2,3‐d]pyrimidines 11 , 12 , 13 , and 21 have been synthesized. The vasorelaxant effect on smooth muscle isolated from rat aorta, via PDEs inhibition, of these compounds along with other pyrido[2,3‐d]pyrimidines 14 , 15 , 16 , 17 , 18 , 19 , 20 reported earlier by our group, has also been determined. These pyrido[2,3‐d]pyrimidines 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 were synthesized by the reaction of ferrocenyl‐ethynyl ketones ( 1 , 2 , 3 , 4 ) or α‐alkynyl ketones ( 5 , 6 , 7 , 8 , 9 , 10 ) with 6‐amino‐1,3‐dimethyluracil using [Ni(CN)₄]^?4 as an active catalytic species, formed in situ in a Ni(CN)₂/NaOH/H₂O/CO/KCN aqueous system. Evaluation of the vasorelaxant effect of compounds 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 demonstrated that all compounds relax the tissue in a concentration‐dependent manner. The structural changes do not alter the effectiveness; however, there are differences related to potency expressed as EC₅₀. Compounds 12 (7‐ferrocenyl‐1,3‐dimethyl‐5‐(m‐tolyl)‐pyrido[2,3‐d]pyrimidine) and 13 (7‐ferrocenyl‐1,3‐dipropyl‐5‐(4‐metoxyphenyl)‐pyrido[2,3‐d]pyrimidine) were the most potent compounds, even more than rolipram, reference drug; the EC₅₀ was 0.41 ± 0.02 μM and 0.81 ± 0.11 μM for 12 and 13 , correspondingly. The EC₅₀ of compounds 15 (7‐ferrocenyl‐1,3‐dimethyl‐5‐phenyl‐pyrido[2,3‐d]pyrimidine), 14 (7‐ferrocenyl‐5‐(3,5‐dimethoxyphenyl)‐1,3‐dimethylpyrido[2,3‐d]pyrimidine), and 19 (5‐n‐butyl‐7‐ethyl‐1,3‐dimethylpyrido[2,3‐d]pyrimidine) was similar to EC₅₀ of rolipram. Compounds 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 significantly induce concentration‐dependent vasorelaxation in endothelium‐intact aortic rings. In addition, the relaxation responses to each compound in either endothelium‐intact or endothelium denuded aortic rings were comparable, suggesting that removal of the functional endothelium has no significant influence on its intrinsic vasorelaxant activity. In vitro capability of conserving cyclic‐AMP or cyclic‐GMP (adenosine and guanosine 3′, 5′‐cyclic monophosphate) via PDE inhibition for compounds 12 , 13 , 14 , 15 and 19 was evaluated. Compounds 15 and 19 show the highest percent inhibition effect (94.83% and 83.98%, respectively) for the decomposition of c‐AMP. Docking studies showed that the compound 15 was selective for the inhibition of PDE‐4.     

Time‐Resolved Assembly of Cluster‐in‐Cluster {Ag12}‐in‐{W76} Polyoxometalates under Supramolecular Control

We report the time‐resolved supramolecular assembly of a series of nanoscale polyoxometalate clusters (from the same one‐pot reaction) of the form: [H_(10+m)Ag₁₈Cl(Te₃W₃₈O₁₃₄)₂]_n, where n=1 and m=0 for compound 1 (after 4 days), n=2 and m=3 for compound 2 (after 10 days), and n=∞ and m=5 for compound 3 (after 14 days). The reaction is based upon the self‐organization of two {Te₃W₃₈} units around a single chloride template and the formation of a {Ag₁₂} cluster, giving a {Ag₁₂}‐in‐{W₇₆} cluster‐in‐cluster in compound 1 , which further aggregates to cluster compounds 2 and 3 by supramolecular Ag‐POM interactions. The proposed mechanism for the formation of the clusters has been studied by ESI‐MS. Further, control experiments demonstrate the crucial role that TeO₃^2?, Cl^?, and Ag⁺ play in the self‐assembly of compounds 1 – 3 .     

Ring Enlargement and Sulfur‐Transfer Processes in SiO2‐Catalyzed Reactions of Thiocarbonyl Compounds with Optically Active Oxiranes

The reactions of 1,3‐dioxolane‐2‐thione ( 3 ) with (S)‐2‐methyloxirane ((S)‐ 1 ) and with (R)‐2‐phenyloxirane ((R)‐ 2 ) in the presence of SiO₂ in anhydrous dichloroalkanes led to the optically active spirocyclic 1,3‐oxathiolanes 8 with Me at C(7) and 9 with Ph at C(8), respectively (Schemes 2 and 3). The analogous reaction of 1,3‐dimethylimidazolidine‐2‐thione ( 4a ) with (R)‐ 2 yielded stereoselectively (S)‐2‐phenylthiirane ((S)‐ 10 ) in 83% yield and 97% ee together with 1,3‐dimethylimidazolidin‐2‐one ( 11a ). In the cases of 3‐phenyloxazolidine‐2‐thione ( 4b ) and 3‐phenylthiazolidine‐2‐thione ( 4c ), the reaction with (RS)‐ 2 yielded the racemic thiirane (RS)‐ 10 , and the corresponding carbonyl compounds 11b and 11c (Scheme 4 and Table 1). The analogous reaction of 4a with 1,2‐epoxycyclohexane (= 7‐oxabicyclo[4.1.0]heptane; 7 ) afforded thiirane 12 and the corresponding carbonyl compound 11a (Scheme 5). On the other hand, the BF₃‐catalyzed reaction of imidazolidine‐2‐thione ( 5 ) with (RS)‐ 2 yielded the imidazolidine‐2‐thione derivative 13 almost quantitatively (Scheme 6). In a refluxing xylene solution, 1,3‐diacetylimidazolidine‐2‐thione ( 6 ) and (RS)‐ 2 reacted to give two imidazolidine‐2‐thione derivatives, 13 and 14 (Scheme 7). The structures of 13 and 14 were established by X‐ray crystallography (Fig.).