A simple approach to highly functionalized benzo[b]furans from phenols and aryl iodides via aryl propargyl ethers

A variety of mono- and disubstituted phenols are alkylated with propargyl bromide to give phenyl 2-propynyl ethers, which were further coupled with aryl iodides under Sonogashira reaction conditions to give 3-phenoxy-1-aryl-1-propyne derivatives. The latter compounds underwent an initial Claisen rearrangement followed by ring closure to give functionalized benzo[b]furans in moderate to good yields.     

A mild, efficient and selective deprotection of t-butyldimethylsilyl-protected phenols using cesium carbonate

A mild and efficient method for the deprotection of aryl t-butyldimethysilyl (TBS) ethers is described. The protecting group TBS could be cleaved from aryl silyl ethers using cesium carbonate in DMF-H₂O at room temperature to give the corresponding phenols in excellent yields. The reaction conditions allowed selective deprotection of aryl TBS-protected phenols in the presence of TBS, phenyloxycarbonyl or tetrahydropyranyl-protected alcohols.     

An efficient catalyst system for diaryl ether synthesis from aryl chlorides

The combination of 2-phosphino-substituted N-arylpyrroles or related indoles (cataCXium^®P) and Pd(OAc)₂ allows for efficient cross-coupling reactions of aryl chlorides and phenols to give diaryl ethers. A variety of aryl and heteroaryl chlorides can be coupled with substituted phenols showing unprecedented catalyst turnover numbers.     

On the mechanism of intramolecular photocycloaddition of substituted o-allylphenols to cyclic ethers

Osmometric and NMR techniques were used in order to study the ionic mechanism for the intramolecular photocycloaddition reaction of o-allyl phenols (1) to give cyclic ethers (2) + (3). The role of the intramolecular H-bond between the OH group and the π-electrons of the allylic group was ascertained. based on the results of the photocyclization, osmometric and NMR measurements the substituents can be divided into 3 groups according to their effect on the above intramolecular interaction.     

One-pot syntheses of 2,6-diiododiaryl ethers from <Emphasis Type="Italic">para</Emphasis>-EWG-substituted phenols by diacetoxyiodobenzene

2,6-Diiododiaryl ethers are not only useful blocks to construct substituted diaryl ethers but are also characteristic drug precursors. In this research, a one-pot tandem oxidation of phenols substituted with electron-withdrawing group at the para position by excess diacetoxyiodobenzene is proven as a novel and efficient method for preparing 2,6-diiododiaryl ethers. Using this method, three new 2,6-diiododiaryl ethers, namely, methyl 3,5-diiodo-2-methoxy-4-phenoxybenzoate (2), methyl 3,5-diiodo-4-phenoxybenzoate (6), and 1-(2,6-diiodo-4-nitrophenoxy)benzene (7) were readily obtained from the corresponding phenols, and the yields were good.     

Enantioselective synthesis of β-amino acids. Part 10: Preparation of novel α,α- and β,β-disubstituted β-amino acids from (S)-asparagine

Perhydropyrimidinone (S)-1 is alkylated with very high diastereoselectivity to give trans products (2S,5R)-3, (2S,5R)–4 and (2S,5R)-5. Dialkylation of (S)-1 also proceeds with complete stereoselectivity to afford adducts (2S,5R)-6, (2S,5S)-6, (2S,5R)-7 and (2S,5S)-7. Hydrolysis (6N HCl, 100°C) of monoalkylated derivative (2S,5R)-3 gives enantiopure α-substituted β-amino acid (R)-8. Hydrolysis of dialkylated adducts 6 and 7 affords enantiopure α,α-disubstituted β-amino acids (R)- or (S)-9 and (R)- or (S)-10. Related iminoester (2S,6S)-2 is alkylated with complete diastereoselectivity to give products (2S,6S)-11–13 whose hydrolysis under relatively mild conditions (2N CF₃CO₂H, CH₃OH, 100°C) affords enantiopure N-benzoylated β,β-disubstituted β-amino acid esters (S)-14–16, with intact double bonds in the olefinic substituents.     

Highly efficient trialkylsilylcyanation of aldehydes, ketones and imines catalyzed by a nucleophilic N-heterocyclic carbene

The synthetic utility of N-heterocyclic carbenes was demonstrated by the trialkylsilylcyanation of aldehydes, ketones and imines. In the presence of a catalytic amount of 3a, the reactions with Me₃SiCN proceeded smoothly to give the corresponding cyanohydrin trimethylsilyl ethers or amino nitrile derivatives in good to excellent yields.     

γ-Alkylation of unsaturated ketones and esters: zinc bromide-catalysed alkylation of O-silylated dienolates

The O-silylated dienolates of unsaturated ketones and esters can be alkylated using zinc bromide catalysis to give predominantly the γ-alkylated carbonyl compounds. The substitution pattern of the substrate (1), favours, in certain cases, very high or complete γ-selectivity.     

Synthesis of new lariat ethers containing polycyclic phenols and heterocyclic aromatic compound on graphite surface via mannich reaction

Synthesis of novel lariat ethers containing polycyclic phenols and heterocyclic aromatic compound using graphite via Mannich reaction are herein described. For this purpose N-(methoxymethyl) azacrown ether 4 was synthesized in nearly quantitative yield. The reaction of N-(methoxymethyl) azacrown ether 4 with polycyclic phenols and heterocyclic aromatic compound was performed in 10-20 min in the presence of graphite. The graphite powder can be reused up to five times after simple washing with acetone.     

An efficient BINAM-copper(II) catalyzed Ullmann-type synthesis of diaryl ethers

A wide range of diaryl ethers are synthesized from the corresponding aryl iodides and phenols through Ullmann type coupling reactions in the presence of a catalytic amount of easily available BINAM-Cu(OTf)₂ complex under mild reaction conditions. Less reactive aryl bromides have also been shown to react with phenols under identical reaction conditions to give good yields of the diaryl ethers without increasing the reaction temperature and time.     

Enamine chemistry—XIX: Preparation and alkylation of cyclic and non-cyclic enamino-thiones

Enamino-thiones of the general type ArC(S)CH:CHNR₂,3(Ar=phenyl p-methoxyphenyl and p-bromophenyl NR₂= pyrrolidinyl piperidinol were prepared by reacting the corresponding enaminones 2 with 2,4-bis-(4-methoxyphenyl) 1,3,2,4-dithiadiphosphetane 2,4-disultide 1. The compounds 3 were reacted with methyl iodide and ethyl iodide to give exclusively S-alkylated iminium iodides 4 and 5, in quantitative overall yields N phenyl-2,3,5,6,7,8-hexahydro-4-qumolinethione, 8, and 2-methyl-N phenyl-2, 3,5,6,7,8-hexahydro-4-quinolmethione 9, were alkylated with methyl iodide ethyl iodide and benzyl bromide giving S-alkylated hexahvdro quinolinium halides. 10 and 11, respectively in high yields. The stereochemistry of the compounds of types 4 and 5 is discussed in detail.     

Übergangsmetall-Carbin-Komplexe: CIII. Aktivierung von Ethylisocyanid an elektronenreichen Metallzentren; Synthese von einkernigen Wolfram-Aminocarbin-Komplexen des Typs Tp′(CO)2 WCN(R)Et (R  Me,Et)

A large-scale, high-yield synthesis of the aminocarbyne complexes Tp′(CO)₂WCN(R)Et (5: R  Me; 6: R  Et) [Tp′ = hydridotris(3,5-dimethylpyrazol-1-yl)borate] is reported, starting from Tp′W(CO)₃I (2). The first step of the synthetic procedure involves thermal decarbonylation of 2 with EtNC to give cis-Tp′W(CO)₂(CNEt)I (3). Complex 3 is then reduced with Na/Hg to give the metallate Na[Tp′W(CO)₂(CNEt)] (4). Finally, complex 4 is alkylated with RI (R  Me, Et) exclusively at the isocyanide nitrogen to give the aminocarbyne complexes 5 and 6. In contrast, the metallates Na[(η⁵-C₅R′₅)W(CO)₂(CNEt)] (R′  H, Me) undergo alkylation with RI at the metal centre to afford the W^II alkyl complexes cis/trans-(η-C₅R′₅)W(CO)₂(CNEt)R. This difference in reactivity is ascribed to the steric demands of the Tp′ ligand, which shields the metal centre from the incoming electrophile.     

Convenient syntheses of fluorous phenols of the formula HOC6H5−n((CH2)3(CF2)7CF3)n (n=1, 2) and the corresponding triarylphosphites

The aldehydic benzyl ethers PhCH₂OC₆H₄CHO (2; a/b = para/meta series) are readily available from the corresponding phenols and react with Wittig reagents derived from [Ph₃PCH₂CH₂R_f8]⁺I⁻ (R_f8=(CF₂)₇CF₃) to give PhCH₂OC₆H₄CHCHCH₂R_f8 (86-93%, Z major). Reactions with H₂ over Pd/C give the fluorous phenols HOC₆H₄(CH₂)₃R_f8(4a,b; 87-91%). Condensations with PCl₃ and NEt₃ (3.0:1.0:3.3 mol ratio) give the fluorous phosphites P[OC₆H₄(CH₂)₃R_f8]₃(5a,b; 92-94%), but traces of 4a,b are difficult to remove. The phthalate-based benzyl ethers PhCH₂OC₆H₃(COOR)₂ (7; ,5/3,4 OC₆H₃-3,n-(R)₂ series) are easily accessed and reduced with LiAlH₄ to the diols PhCH₂OC₆H₃(CH₂OH)₂(8c,d; 89-90%). Diol 8c and the Dess-Martin periodinane react to give the dialdehyde PhCH₂OC₆H₃(CHO)₂ (9c; 95%). This is elaborated by a sequence analogous to 2→4→5 to the fluorous phenol HOC₆H₃((CH₂)₃R_f8)₂ (11c; 97%/96%, two steps) and phosphite P[OC₆H₃((CH₂)₃R_f8)₂]₃ (12c, 92%), from which traces of 11c are difficult to remove. Diol 8d can be similarly elaborated to 11d, but the dialdehyde 9d is labile and the combined yield of the Dess-Martin/Wittig steps is 32%. The CF₃C₆F₁₁/toluene partition coefficients of 11c,d, and 12c (two pony tails; 70:30, 72:28, 92:8) are much higher than those of 4a and b (one pony tail; 12:88, 14:86).     

Carbenkomplexe aus koordinierten 2-siloxyphenylisocyaniden

2-Trimethylsiloxyphenylisocyanide (2) reacts with W(CO)₅(THF) to give the complex [W(CO)₅(2-Me₃SiO-C₆H₄-NC)]. Upon hydrolysis of the SiO bond with KF/MeOH the heterocarbene complex (benzoxazolin-2-ylidene)tungsten(pentacarbonyl) (5) is formed via intramolecular nucleophilic attack of the phenolic oxygen atom at the isocyanide carbon atom. (Benzoxazole)tungsten(pentacarbonyl) (6) is formed as a side product in this reaction. The heterocarbene complex 5 can be deprotonated and alkylated at the ring nitrogen giving (N-methylbenzoxazolin-2-ylidene)tungsten(pentacarbonyl) (7). Complexes 5, 6 and 7 were characterized by X-ray diffraction studies.     

Di(1H,1H,2H,2H-perfluorooctyl)-dibenzo-18-crown-6: A “light fluorous” recyclable phase transfer catalyst

A series of dibenzo-18-crown-6 lariat ethers containing two C₇H₁₅ (11), (CH₂)₂C₆F₁₃ (14), (CH₂)₂C₈F₁₇ (15), NHC₇H₁₅ (18) and NHCH₂C₆F₁₃ (19) sidearms were prepared and the single crystal X-ray structure of cis-4,4′-di(1H,1H,2H,2H-perfluorodecyl)-dibenzo-18-crown-6 (15a) is reported. The “light fluorous” dibenzo-18-crown-6 ether (14) has emerged as a stable and robust PTC catalyst, which can be recycled efficiently by fluorous solid-phase extraction, and gives better PTC catalytic activity compared to the parent, non-fluorinated PTC catalyst, dibenzo-18-crown-6, and the alkylated derivative (11) in aliphatic and aromatic nucleophilic substitutions.     

Synthesis of new chiral 18-crown-6 ethers from d-xylose

Short and efficient syntheses of chiral 18-crown-6 ethers 1–4 containing two ethylenoxyethyl-bridged d-xylo and d-ribofuranoside moieties starting from d-xylose are reported. Crown ethers 1, 2 and 4 are C₂-symmetric while 3 is unsymmetrical.     

Asymmetric [2,3] Wittig rearrangement of crotyl furfuryl ethers

Asymmetric Wittig rearrangement of crotyl furfuryl ethers was investigated in diastereo- and enantioselective manners. Both (2S,3Z)- and (2S,3E)-3-penten-2-yl furfuryl ethers 3 and 9 rearranged with complete chirality transfer to give the syn- and anti-isomers 4 and 10, respectively. Enantioselective Wittig rearrangement of both (Z)-and (E)-crotyl furfuryl ethers 15 and 17 using butyllithium and (−)-sparteine was examined to afford (1S,2R)-1-(2-furyl)-2-methyl-3-buten-ol 16 in up to 43% ee.     

Mass spectrometry of onium salts—I. Studies on anilinium oxides

The mass spectra of the three isomeric trimethylanilinium oxides and their methyl-d₃ analogues show that the m- and p- isomers undergo intermolecular trans-O-alkylation before evaporation. In the o-isomer, only 10% transalkylated product is observed and there is strong evidence that most of this isomer evaporates without undergoing structural changes. By indirect introduction, however, the o-isomer showed only transalkylated product. The most important fragmentation patterns on electron-impact are α-cleavage on the N-methyl carbon or expulsion of the O-substituent with formation of a quinoid structure. The latter dominates for the o- and p-methyl ethers while the former is the most important pathway for the m-isomer and for the corresponding phenols. Lower fragments are of modest intensity.     

Reactions of fluoroalkanesulfonyl azides with vinyl ether and tetrakis(dimethylamino)ethylene

The reactions of fluoroalkanesulfonyl azides 1 with some electron-rich olefins have been studied. Alkyl vinyl ethers reacted with 1 readily at 0 °C or room temperature (RT) and did not give the corresponding N-fluoroalkanesulfonyl azilidines but 1-fluoroalkanesulfonyl-1,2,3-triazolines 3, which decomposed slowly at room temperature to form 1,4-fluoroalkanesulfonyl-2,5-alkoxyl-piperazines 4 with elimination of nitrogen gas. In contrast, more electron-rich alkene, tetrakis(dimethylamino)ethylene (TDAE) reacted with 1 affording N-fluoroalkanesulfonyl bis(dimethylamino)amidines 6 accompanying the release of N₂. Reaction mechanisms are discussed.     

A room temperature alternative of the Claisen rearrangement route to ortho allylated phenols: unique reactivity pattern of allylindium reagents

Quinol ethers and quinone monoketals are shown to undergo formal anti-Michael addition reactions with allylindium reagents at room temperature to give only ortho allylated phenols in good yields.