Functionalization of the methylene groups of p-tert-butylcalix[4]arene: S-C,N-C,and C-C bond formation

Reaction of the calixarene derivative 7 with two exocyclic double bonds with carbon-, nitrogen-, oxygen-, or sulfur-containing nucleophiles afforded bis(spirodienone) derivatives substituted at two opposite methylene groups in a trans fashion. LiAlH(4) reduction of the bis(spirodienone) derivatives with two methylenes functionalized by thiomethoxy, diethyl malonate, or anilino substituents yielded trans methylene-substituted calix[4]arenes. Upon standing in solution, the calixarene derivative incorporating SMe groups on the bridges underwent trans right harpoon over left harpoon cis isomerization. An equilibration study performed on this calixarene derivative (tetrachloroethane-d(2), 430 K) indicated that the cis isomer is the form of lower free energy.     

Spirodienone route for the stereoselective methylene functionalization of p-tert-butylcalix[4]arene.

A new method for the regio- and stereoselective functionalization of two distal methylene groups of p-tert-butylcalixarene (1a) is described. Reaction of the meso bis(spirodienone) calixarene derivative 2a with bromine afforded the tetrabrominated product 3a derived from exo 1,4-additions of bromine to the diene subunits. A phase-transfer-catalyzed reaction of 3a with aqueous NaOH/CH2Cl2 yielded the exo bis(epoxide) calixarene derivative 4. Heating 3a in a vacuum eliminated two molecules of HBr and afforded a product (5b) that retained the C(i) symmetry of the starting material. X-ray analysis indicated that the calixarene derivative 5b possesses two exocyclic double bonds of E configuration. Calixarene 5b undergoes reaction with nucleophiles at the exocyclic double bonds, with concomitant bond shifts and expulsion of the bromine atoms. Selective trans monodeuteration of two methylene groups of 1 was achieved by reaction of 5b with NaBD4 followed by aromatization of the labeled spirodienol derivative. Reaction of 5b with RONa/ROH (R = Me, Et) afforded the methylene-substituted bis(spirodienone) derivatives 9a and 9b possessing two trans alkoxy groups. X-ray crystallography of 9b indicated that the two trans substituents are located at pseudoequatorial positions of the methylene groups. LiAlH4 reduction of the substituted bis(spirodienone) derivatives afforded calix[4]arenes incorporating trans alkoxy groups at two distal methylene positions.     

Extraannular fluorinated calixarenes: regiospecificity of the deoxofluorination reactions of bis(spirodienol) derivatives

A new route for the partial displacement of OH groups of p-tert-butylcalixarene via spirodienol derivatives is described. NaBH(4) reduction of the bis(spirodienone) calixarene derivatives 2a-2c afforded the corresponding bis(spirodienols) 3a-3c in stereospecific fashion. (1)H NMR NOESY spectroscopy indicated that in the case of 2a, the reaction proceeds by attack at the exo face of the two carbonyls (the face located anti to the spiro C-O bond). The spirodienols readily revert to p-tert-butylcalix[4]arene when heated. The reaction of 3a with the deoxofluorinating agent DAST (Et(2)NSF(3)) afforded a mixture of extraannular substituted calixarenes possessing one or two fluoro-substituted dehydroxylated rings. The bisfluorinated calixarene 6a adopts in the crystal a conformation (1,3-alternate) similar to that adopted in solution by the di-dehydroxylated calixarene 6b. An experiment conducted with a selectively deuterated spirodienol derivative indicated that the deoxofluorination reaction involves regiospecific nucleophilic attack at the gamma position of the pentadienol subunit.     

A "classical" tetrahydroxycalix[4]arene adopting the 1,2-alternate conformation

The first example of a "classical" tetrahydroxycalixarene, which adopts the 1,2-alternate conformation both in solution and in the crystal, is described. Calixarene derivatives with two distal methylene groups substituted in a trans fashion by phenyl (5a) or mesityl (5b) groups were synthesized via addition of PhMgBr/CuCN or MesMgBr/CuCN to the bis(spirodiene) derivative 3. Whereas the phenyl-substituted calixarene derivative 5a adopts the usual "cone" conformation, solution NMR data and X-ray crystallography indicate that the more crowded mesityl derivative 5b adopts a 1,2-alternate conformation with the two mesityl groups located at isoclinal positions of the macrocycle.     

Intramolecular AR--O--AR bond formation in calixarenes

The formal dehydration of two vicinal phenol moieties of p-tert-butylcalix[6]arene was achieved in two steps by mild oxidation of the calixarene followed by treatment of the resulting monospirodienone derivative (9c) with an ionic hydrogenation mixture (Et(3)SiH/CF(3)COOH). Reaction of 9c yielded the unsubstituted xanthenocalix[6]arene 11d, while treatment of the monospirodienone derivative of a spherand-type calixarene (13) with Et(3)SiH/CF(3)COOH afforded the dibenzofuran derivative 15. The formation of the latter product indicates that, at least for 13, the rings forming the Ar--O--Ar bond in the product are not those connected by the spiro bond in the starting material. Methylation of the phenolic hydroxyl groups of 11d with methyl p-toluenesulfonate/K(2)CO(3) or dimethyl sulfate/base afforded its dimethyl and tetramethyl ether derivatives. The parent xanthone calix[6]arene derivative 17b was prepared by O-methylation of the phenol groups followed by CrO(3) oxidation of the xanthene methylene group and deprotection of the OH groups. McMurry coupling of calixanthone 17a afforded the dixanthylene 18. Calixarenes 11d and 15 (which possess a xanthene and dibenzofuran group, respectively) were structurally characterized by X-ray crystallography.     

An Exploratory Study of Silylated Amino Boronic Ester Chemistry

Diisopropyl [bis(trimethylsilylamino)methyl]-boronate, the analogous pinacol boronic ester ( 3 ), andpinacol [(2,2,5,5-tetramethyl-2,5,1-disilazol-1-yl)-methyl]boronate ( 8 ) were prepared from the corresponding (bromomethyl)boronic ester 1 or 2 and silylated lithium amide. Reaction of 3 or 8 with (dichloromethyl)lithium yielded the corresponding [1-chloro-2-(silylated amino)ethyl]boronate 4 or 9 . Further transformations of 4 to methylthio derivative 5 and dimethylamino derivative 7 as well as conversion of 5 to ureido derivatives 6 are described. (S,S)-1,2-Dicyclohexylethanediol [1-chloro-2-(trityloxy)-ethyl]boronate ( 13 ) has been converted to bis(tri-methylsilyl)amino derivative 14 and formamido derivative 15 as well as to N-benzyl analogs 18 and 19 . Attempted chain extensions of 14, silylated 15, or 19 with (dichloromethyl)lithium indicated that the alkyl migration from boron to carbon is slow and incomplete. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8: 487–494, 1997     

Highly selective addition of chiral,sulfonimidoyl substituted bis(allyl)titanium complexes to N-sulfonyl alpha-imino esters: asymmetric synthesis of gamma,delta-unsaturated alpha-amino acids bearing a chiral,electron-withdrawing nucleofuge at the delta-position

Selective addition of the chiral, sulfonimidoyl substituted bis(allyl)titanium complexes 5a-d, which are configurationally labile in regard to the Calpha-atoms, to N-toluenesulfonyl (Ts)-, N-2-trimethylsilylethanesulfonyl (SES)-, and N-tert-butylsulfonyl (Bus) alpha-imino ester (9a-c) in the presence of Ti(OiPr)(4) and ClTi(OiPr)(3) afforded with high regio- and diastereoselectivities in good yields the (syn, E)-configured beta-alkyl-gamma,delta-unsaturated alpha-amino acid derivatives 2a-g, which carry a chiral, electron-withdrawing nucleofuge at the delta-position and a cyclohexyl, an isopropyl, a phenyl, and a methyl group at the beta-position. Addition of the cyclic bis(allyl)titanium complex 14 to N-Bus alpha-imino ester 9c afforded with similar high regio- and diastereoselectivities the (E)- and (Z)-configured amino acid derivatives (E)-8 and (Z)-8. Reaction of complexes 5a-d with alpha-imino esters 9a-c in the presence of Ti(OiPr)(4) occurs stepwise to give first the mono(allyl)titanium complexes containing 2a-g as ligands, which react in the presence of ClTi(OiPr)(3) with a second molecule of 9a-c with formation of two molecules of 2a-g. Formation of (S,R,E)-configured homoallylic amines 2a-g entails Si,Re,E processes of alpha-imino esters 9a-c with the (R,R)-configured bis(allyl)titanium complexes (R,R)-5a-d and (R)-configured mono(allyl)titanium complexes (R)-17a-d, both of which are most likely in rapid equilibrium with their (S,S)-diastereomers and (S)-diastereomers, respectively. Interestingly, in the reaction of 5a-d with aldehydes, the (S,S)-configured complexes (S,S)-5a-d are the ones which react faster. Reaction of the N-titanated amino acid derivatives Ti-2a and Ti-2b with N-Ts alpha-imino ester 9a led to the highly diastereoselective formation of imidazolidinones 15a and 15b, respectively. Cleavage of the sulfonamide group of the N-Bus amino acid derivative 2d with CF(3)SO(3)H gave quantitatively the sulfonimidoyl functionalized amino acid H-2d. A Ni-catalyzed cross-coupling reaction of the amino acid derivative 2e with ZnPh(2) led to a substitution of the sulfonimidoyl group by a phenyl group and furnished the enantiomerically pure protected alpha-amino acid Bus-1. Two new N-sulfonyl alpha-imino esters, the SES and the Bus alpha-imino esters 9b and 9c, respectively, have been synthesized from the corresponding sulfonamides by the Kresze method in medium to good yields. The N-SES alpha-imino ester 9b and the N-Bus alpha-imino ester 9c should find many synthetic applications, in particular, in cases where the N-Ts alpha-imino ester 9a had been used before.     

Synthesis of porphyrins bearing uracyl groups and their assembly induced by melamine derivatives

Self‐assembled porphyrins via noncovalent bonding have attracted wide‐ranging researchers in material science. We reported herein the synthesis of the tetraphenyl porphyrin derivatives bearing uracyl groups as acceptor–donor–acceptor (ADA) type hydrogen bonding units, through the condensation of 5,10‐ or 5,15‐bis (3‐amino‐4‐ethylhexylphenyl) porphyrin derivatives with 6‐carboxyuracyl derivatives. When two porphyrins having uracyl groups at the different substituted positions were respectively mixed with a melamine derivative in benzene, ¹H NMR spectra showed that the 5,15 substituted uracyl porphyrin formed a hydrogen‐bonded suprastructure with the melamine derivative as a complementary molecule to the uracyl moiety, although the other 5,10‐substituted uracylporphyrin could not form such a structure. The SEM observation indicated that the mixture with the 5,15‐substituted uracyl porphyrin and the melamine with long alkyl chains formed a sheet‐like structure. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis of Flavin–Calix[4]arene Conjugate Derivatives

The synthesis of two new flavin substituted calix[4]arene derivatives, 9 and 10 , is described. The first flavin substituted calix[4]arene derivative 9 was synthesized by the reaction of 3‐methylalloxazine ( 5 ) with 25,27‐bis(3‐bromopropoxy)‐26,28‐dihydroxy‐5,11,17,23‐tetra(tert‐butyl)calix[4]arene ( 4 ) in high yield (92%). The other derivative 10 was prepared from 3‐methylalloxazine‐1‐acetic acid ( 7 ) and 25,27‐bis(3‐cyanopropoxy)calix[4]arene ( 3 ). All new compounds were characterized by a combination of FT‐IR and ¹H‐NMR spectroscopy, and elemental‐analysis techniques.     

Synthesis of alkyl or aryl pyridazinyl ethers

This paper presents the synthesis of some alkyl or aryl pyridazinyl ethers from 2‐alkyl‐4‐halo‐5‐hydroxy‐and 2‐alkyl‐4,5‐dichloropyridazin‐3(2H)‐ones or 3,6‐dichloropyridazine. Reaction of 2‐alkyl‐4‐halo‐5‐hydroxypyridazin‐3(2H)‐ones 1 with 1,2‐dibromoethane or 1,3‐dibromopropane gave the corresponding monopyridazin‐5‐yl ethers 2 and α,ω‐[di(pyridazin‐5‐oxy)]alkanes 3 . Treatment of 4 with 4‐substituted‐phenol afforded 5‐(4‐substituted‐phenoxy)‐2‐(4‐substituted‐phenoxymethyl) derivatives 5 . Reaction of 2‐alkyl‐4,5‐dichloro derivatives 7 with 1 gave the corresponding di(pyridazin‐5‐yl) ethers 8 in good yields. Compound 10 was reacted with catechol to give monopyridazin‐3‐yl ether 11 and/or di(pyridazin‐3‐yl) ether 12 . Also we described the results for the reaction of 2‐alkyl‐4‐chloro‐5‐(4‐substituted‐phenoxy)pyridazin‐3(2H)‐ones with nucleophiles.     

Synthesis of 2-S-dioxo isosteres of purine and pyrimidine nucleosides. I. Alkyl and glycosyl derivatives of 3,5-diamino-4H-1,2,6-thiadiazine 1,1-dioxide

Preparation of alkyl and glycosyl derivatives of 3,5-diamino-4H-1,2,6-thiadiazine 1,1-dioxide (1) is described. Reaction of 1 with dimethyl sulfate gave the 4-methyl and 2,4-dimethyl derivatives. With benzyl chloride and allyl bromide C-4 substituted compounds were obtained. Reaction of the disilyl derivative of 1 with either 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide or 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose in the presence of Friedel-Crafts catalysts afforded the α and β anomers of the N-2 nucleoside and the β-O-glucoside. When the reaction was performed with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose, a β-C-glycoside and the α and β anomers of the N-2 nucleoside were obtained. The structure of the corresponding nucleosides were elucidated by ¹H nmr and uv by comparing the latter with those of the alkyl derivatives.     

Synthesis and photochemical reaction of novel p-alkylcalix[n]arene derivatives containing cationically polymerizable groups

New photoreactive p-methylcalix[6]arene (MCA) derivatives containing cationically polymerizable groups such as propargyl ether (calixarene 1), allyl ether (calixarene 2), and ethoxy vinyl ether (calixarene 3) groups were synthesized with 80, 74, and 84% yields by the substitution reaction of MCA with propargyl bromide, allyl bromide, and 2-chloroethyl vinyl ether (CEVE), respectively, in the presence of either potassium hydroxide or sodium hydride by using tetrabutylammonium bromide (TBAB) as a phase transfer catalyst (PTC). The p-tert-butylcalix[8]arene (BCA) derivative containing ethoxy vinyl ether groups (calixarene 4) was also synthesized in 83% yield by the substitution reaction of BCA with CEVE by using sodium hydride as a base and TBAB as a PTC. The MCA derivative containing 1-propenyl ether groups (calixarene 5) was synthesized in 80% yield by the isomerization of calixarene 2, which contained allyl ether groups, by using potassium tert-buthoxide as a catalyst. The photochemical reactions of carixarene 1, 3, 4, 5, and 6 were examined with certain photoacid generators in the film state. In this reaction system, calixarene 3 containing ethoxy vinyl ether groups showed the highest photochemical reactivity when bis-[4-(diphenylsulfonio)phenyl]sulfide bis(hexafluorophosphate) (DPSP) was used as the catalyst. On the other hand, calixarene 1 containing propargyl ether groups had the highest photochemical reactivity when 4-morpholino-2,5-dibuthoxybenzenediazonium hexafluorophosphate (MDBZ) was used as the catalyst. It was also found that the prepared carixarene derivatives containing cationically polymerizable groups such as propargyl, allyl, vinyl, and also 1-propenyl ethers have good thermal stability. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1805–1814, 1999     

Bis(nitro- and polynitromethyl-ONN-azoxy)azoxyfurazans and some of their derivatives

Reaction of diamino derivative of azoxyfurazan with 2,2-dimethyl-5-nitro-5-nitroso-1,3-dioxane in the presence of dibromoisocyanuric acid afforded bis(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl-ONN-azoxy)azoxyfurazan. The reaction of the latter with AcCl/MeOH and further transformations of the product gave the first representative of substituted (mono- and polynitroalkyl-ONN-azoxy)azoxyfurazans, e.g. bis(nitromethyl-ONN-azoxy)azoxyfurazan, bis(dinitromethyl-ONN-azoxy)azoxyfurazan, bis(trinitromethyl-ONN-azoxy)azoxyfurazan, and some of their derivatives.     

Spirodienone derivatives of a spherand-type calixarene

Oxidation of the spherand-type calixarene 4 with 1 or 2 equiv of phenyltrimethylammonium tribromide/base afforded mono- and bis(spirodienone) derivatives (8b and 9, respectively). The spirodienone groups are derived from the oxidation of two phenols connected by a common methylene group. NOESY data indicated that 9 possesses a "head to tail" arrangement of the spirodienone groups. Oxidation of 4 with 3 equiv of the oxidizing reagent afforded two tris(spirodienone) calixarene derivatives 11 and 10 with C(1) and C(3) symmetries, respectively. The same tris(spirodienone) products were obtained by oxidation of 9 with I(2)/aq KOH. Tris(spirodienone) 11 displayed NOE cross-peaks in the NOESY NMR spectrum consistent with a nonalternant disposition of carbonyl and ether groups. Upon heating 10 and 11 isomerize in the solid state and in solution. The major component in the equilibration mixtures is 11, indicating that this is the thermodynamically more stable tris(spirodienone) isomer.     

New Chiral Calixarene Derivatives： Syntheses and Their Chiral Recognition Toward Amino Acids by UV-Vis Spectroscopy

Three novel types of chiral calixarene derivatives 5, 8, and 10 were designed and synthesized by introducing chiral units to parent calixarenes. Their chiralities were confirmed by rotational analysis. Chiral recognition properties of these host compounds towards L- and D-threonine were studied by UV-Vis spectroscopy. The results indicated that calixarene derivatives 5 and 8 exhibited good chiral recognition capabilities toward L- or D-threonine. Although calixarene derivative 10 had no evident chiral recognition ability, the supramolecules of calixarene derivative 10 with L- or D-threonine showed a hypochromic effect or hyperchromic effect respectively. Therefore, calixarene derivative 10 might serve as a good chiral UV-indicator.     

Synthesis and Antimicrobial Activity of Some Novel Substituted Bis‐Pyridone,Pyrazole, and Thiazole Derivatives

A variety of novel bis‐heterocyclic derivatives were synthesized via the reaction of bis‐cyanoacetanilide derivative 3 with various aromatic aldehydes (1:2 molar ratio), to give the corresponding bis‐arylidene derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m . On the other hand, reacting compound 3 with substituted 2‐hydroxybenzaldehydes 6a , 6b , 6c afforded 2‐iminochromene‐3‐carboxamides 7a , 7b , 7c . The reaction of compound 5 with malononitrile afforded the novel bis‐pyridones 9a , 9b , 9c , 9f , 9g , 9h . The reaction of 5 with hydrazine derivatives afforded pyrazoles 11a , 11b , 11c , 11d , 11e , 11f , respectively. Compound 3 reacts with phenyl isothiocyanate in the presence of potassium hydroxide at room temperature followed by addition of some different halo‐carbonyl compounds to afford bis‐poly‐functionalized thiazole derivatives 13a , 13b , 13c . The bis‐enamine derivative 15 reacts also with hydrazine hydrate, guanidine, and hydroxylamine to give bis‐pyrazole 17 , pyrimidine 19 , and isoxazole 21 derivatives, respectively. Some of the newly synthesized compounds show moderate to high antimicrobial activity.     

Synthesis and structural characterization of trivalent amino acid derived chiral phosphorus compounds

Reaction of the N-toluenesulfonyl derivatives of (S)-alanine, phenylalanine, and valine (4-6) with PhPCl(2) gave in high yield the 4-methyl, benzyl, and isopropyl derivatives (7-9) of 2-phenyl-1-p-toluenesulfonyl-1,3,2-oxazaphospholidin-5-one. The ratios of the (2S,4S)/(2R,4S) diastereomers (cis/trans isomers) were 1:1, 2:1, and 10:1 for the methyl, benzyl, and isopropyl derivatives 7a,b, 8a,b, and 9a,b, respectively. For 7a,b, both isomers could be crystallized, but for the others only the major isomers were isolable. The X-ray crystal structure of 9a shows that the isopropyl and phenyl groups are mutually cis and that the tolyl moiety is oriented s-trans to both the isopropyl and phenyl groups. Reaction of 6 with Cl(2)PCH(2)CH(2)PCl(2) (10) gave a 56:38:7 mixture of the cis/cis, cis/trans, and trans/trans diphosphorus heterocycles 11a-c. The major isomer could be crystallized and isolated free of the other diastereomers. Reaction of 6 with EtPCl(2) gave a 6:1 mixture of cis/trans isomers of the ethyl-substituted heterocycles 12a,b as an inseparable oil but allowed confirmation of the structure of 11a. Slow epimerization at phosphorus may occur by inversion but more likely by ring opening/closure, since 7b, 9a, and 11a give rise upon standing in solution to mixtures containing starting material and 7a, 9b, and 11b, respectively, along with the free amino acid derivatives 4 and 6. The NMR spectra, and in particular the coupling constants between the alpha-hydrogen atom of the amino acid moiety and phosphorus, were used to establish the identities of the cis and trans isomers. Reaction of 9a with (THF)W(CO)(5) gave the phosphorus-ligated adduct (9a)W(CO)(5) (13), and the IR spectrum of this complex shows that 9a is a strongly electron-withdrawing ligand. The geometry of the sulfonamide moiety is discussed in detail, as are the (1)H NMR coupling constants. The data are consistent with the presence of little steric interaction between the cis isopropyl and phosphorus substituent in 9a, 11a, and 12a and orientation of the tolyl moiety s-cis to the isopropyl group in 9b, 12b, and 13.     

双(烷基环戊二烯基)金属二卤和二芳氧基衍生物的研究

本文报导烷基环戊二烯基钠与金属氯化物反应合成钛、锆和铪的双(烷基环戊二烯基)金属二氯化物以及通过卤素交换制备双(烷基环戊二烯基)钛的二氟化物的方法。同时报导了以上的二氯化物与酚反应制备的一系列芳氧基金属衍生物。本文还讨论了金属、卤素、烷基对于质子化学位移的影响并探讨了主要红外吸收峰的归属。     

Syntheses and Characterization of Ten-Membered Cyclic and Large Bite Acyclic Bis(phosphines)

Reaction of bis(dichlorophosphino)aniline with CH 2 bridged bis(phenols) or substituted diamine gives the 10-membered heterocyclic phosphorochloridities in quantitative yield. The bis(phenols) also react with chlorodiphenylphosphine to afford the bulky acyclic bis(phosphinites).     

Study of chemoselective asymmetric hydrogenation of (1-bromo-1-alkenyl)boronic esters with iridium–PˆN complexes

In this paper we report the first chemoselective asymmetric hydrogenation of (1-bromo-1-alkenyl)boronic esters, which constitutes a new route to (α-bromoalkyl)boronic esters. The study demonstrates that excellent chemoselectivities along with full conversions can be obtained for hydrogenation of alkyl substituted derivatives with iridium–PˆN complexes. Moreover, acyclic alkyl derivatives afford (α-bromoalkyl)boronic esters in good enantioselectivities ranging from 64 to 73% ee. A cyclic alkyl derivative was obtained only in a nearly racemic form. The (1-bromo-1-alkenyl)boronic esters appear to be less reactive towards homogenous hydrogenation conditions than their chloro analogues as demonstrated by the higher catalyst loadings required to achieve full conversions for alkyl derivatives and lower conversions observed for the aryl substituted derivatives.