The synthesis of quinone methides from p-quinol benzoates

A simple route to the quinone methides (1,RAr,R₁CO₂Me) is described.     

N-isopropylsulfinylimines as useful intermediates in the synthesis of chiral amines: expeditive asymmetric synthesis of the calcimimetic (+)-NPS R-568

An efficient and high-yielding approach for the asymmetric synthesis of calcimimetic (+)-NPS R-568 (1) has been developed. The key step of the synthesis is the highly diastereoselective addition of methyl Grignard to the (SS,E)-N-(3-methoxybenzylidene)-2-propanesulfinamide [5(S)], which afforded a single diastereoisomer in high yield in short reaction time.     

N-alkenyl indoles as useful intermediates for alkaloid synthesis

A mild cross-coupling reaction to access several N-alkenyl-substituted indoles has been developed. The coupling procedure involves treating a NH-indole with various alkenyl bromides using a combination of 10 mol % of copper(I) iodide and 20 mol % of ethylenediamine as the catalyst in dioxane at 110 °C in the presence of K(3)PO(4) as the base. When treated with acid, these unique enamines produce a dimeric product derived from a preferred protonation reaction at the enamine π-bond. A cationic cyclization reaction of the readily available 2-(2-(1H-indol-1-yl)allyl)cyclopentanol was utilized to construct tetracyclic indole derivatives with a quaternary stereocenter attached to the C(2)-position of the indole ring. An alternative strategy for selective functionalization at the C(2)-position of a N-alkenyl-substituted indole derivative that was also studied involves a radical cyclization of a xanthate derivative. The work described provides an attractive route to the tetracyclic core of some vinca alkaloids, including the tetrahydroisoquinocarbazole RS-2135.     

Binol quinone methides as bisalkylating and DNA cross-linking agents

The photogeneration and detection of new binol quinone methides undergoing mono- and bisalkylation of free nucleophiles was investigated by product distribution analysis and laser flash photolysis in water solution using binol quaternary ammonium derivatives 2 and 12 as photoactivated precursors. The alkylation processes of N and S nucleophiles are strongly competitive with the hydration reaction. DNA cross-linking potency of the water-soluble binol quaternary ammonium salt 2 was investigated as a pH function and compared to that of other quaternary ammonium salts capable of benzo-QM (QM = quinone methide) photogeneration by gel electrophoresis. DFT calculations in the gas phase and in water bulk on the binol and benzo quaternary ammonium salts 2 and 4 evidence structural and electrostatic features of the binol derivative which might offer a rationalization of its promising high photo-cross-linking efficiency.     

Enantioselective borane reduction of aromatic ketones using chiral BINOL derivatives as ligands in an aluminum catalyst

Chiral aluminum complex-catalyzed asymmetric borane reduction of aromatic ketones has been successfully carried out in the presence of (R)-BINOL derivatives as ligands. Secondary alcohols were obtained in high yields with good enantioselectivities (up to 90% e.e.).     

Carbon-13 NMR of quinone methides

The ¹³C NMR spectra of four ortho- and seven para-quinone methides were assigned using chemical shift and long-range carbon-proton coupling information. The carbonyl shifts are compared with those in ortho- and para-benzoquinones. The chemical shifts of the carbonyls of the p-quinone methides are observed at δ 186.2–186.4 for the three ortho-di-tert-butyl-substituted compounds and at δ 180.7–181.5 for the four ortho-oxy-substituted compounds. In the three o-quinone methides with meta, para-dioxy substituents, the carbonyl signals are at δ 184.2–185.4. The carbonyl signal of the one o-quinone methide with no oxygen substitution is shifted downfield to δ 200.9, apparently as a result of hydrogen bonding to the nearby hydroxyl.     

A facile synthesis and asymmetric catalytic activity of new 3‐substituted chiral BINOL ligands

Three new chiral ligands, (S)‐3‐(1H‐imidazol‐1‐yl)methyl‐1,1′‐binaphthol [(S)‐ 1 ], (S)‐3‐(1H‐1,2,3‐benzotriazol‐1‐yl)methyl‐1,1′‐binaphthol [(S)‐ 2 ] and (S)‐3‐(2H‐1,2,3‐benzotriazol‐2‐yl)methyl‐1,1′‐binaphthol [(S)‐ 3 ], were prepared by a simple method. They showed moderate catalytic properties for the asymmetric addition of diethylzinc to benzaldehyde in the presence of titanium tetraisopropoxide. Copyright © 2007 John Wiley & Sons, Ltd.     

An efficient synthesis of 3,3′-dipyridyl BINOL ligands

Microwave-assisted Suzuki cross-coupling between 2,2′-bis(methoxymethyl)-3,3′-bis(potassium trifluoroboronato)BINOL and a series of 2-bromo- or 2-chloropyridines provides efficient access to 3,3′-dipyridyl BINOL ligands.     

Synthesis of chiral amino epoxyaziridines: useful intermediates for the preparation of chiral trisubstituted piperidines

Chiral aminoalkyl epoxyaziridine 1 is synthesized in high yield and diastereoselectivity from L-serine. Ring opening of epoxyaziridine 1 with primary amines is carried out with total chemo- and regioselectivity, affording chiral polyfunctionalized piperidines 8. The structure of these trisubstituted piperidines is established by NMR studies.     

Aziridine ring-containing chiral ligands as highly efficient catalysts in asymmetric synthesis

Enantiomerically pure bidentate heteroorganic ligands built on an achiral skeleton containing hydroxyl and aziridine moieties as nucleophilic centers, capable of binding various organometallic reagents, have proven to be highly efficient catalysts in the enantioselective addition of diethylzinc and phenylethynylzinc to aryl and alkyl aldehydes to give the desired chiral products in high chemical yields (up to 90%) and with ees of up to 95%. The influence of the stereogenic center located in the carbon atom in the aziridine moiety on the stereochemical course of the reaction is reported.     

Isothiouronium salts as useful and odorless intermediates for the synthesis of thiaalkylimidazolium ionic liquids

A simple and odorless route for the synthesis of monocationic and dicationic thiaalkylimidazolium ionic liquids (ILs) is reported. Our approach starts with the selective monoalkylation of dihalogenated substrates by methylimidazole derivatives, followed by the synthesis of odorless isothiouronium salts via reaction with thiourea. The target ILs are obtained after sequential hydrolysis-alkylation of the isothiouronium salts followed by anion metathesis in water. After extraction, the novel thiaalkylimidazolium ILs are obtained with high purity, without the requirement of additional purification steps. In order to demonstrate their applicability, two of these task-specific ILs were employed as ligands in Ullmann and Suzuki couplings and also as charged probes to detect copper intermediates via ESI(+)-MS.     

Convenient synthesis of chiral H4-BINOL via direct hydrogenation of BINOL

<正>A simple,highly effective hydrogenation of chiral BINOL to provide H_4-BINOL in multigram scale with good yield(up to 78% yield) was developed.A series of heterogeneous catalysts was tested in the hydrogenation;;the best result was obtained with 5%Pd/ C in EtOH under the H_2 pressure of 50 bar for 2 h.This method is a more useful method for practical synthesis of optically pure H_4- BINOL than other available methods.     

Asymmetric synthesis of chiral bisoxazolines and their use as ligands in metal catalysis

Novel C₂- and C₁-symmetric chiral bisoxazolines with a cyclic backbone have been synthesized in an asymmetric manner starting from meso anhydrides. All synthetic steps are easy to perform and lead to the desired products in good overall yields. Preliminary investigations revealed the applicability of these new compounds as ligands in transfer hydrogenations and various metal-catalyzed enantioselective C–C-bond forming reactions such as cyclopropanations and Diels–Alder reactions.     

1,4-Benzodiazepine N-nitrosoamidines: useful intermediates in the synthesis of tricyclic benzodiazepines

1,4-Benzodiazepine N-nitrosoamidines have been used as scaffolds for the preparation of different tricyclic derivatives. Replacement of the N-nitrosoamidine moiety through treatment with the nucleophiles acetylhydrazine, aminoacetaldehyde dimethylacetal and 1-amino-2-propanol, followed by an acid-catalyzed cyclization step, afforded triazolo and imidazobenzodiazepines 1, 6, and 7, respectively, in good yields. When acetylhydrazine is used as a nucleophile, the overall process provides an alternative route to alprazolam (1b) and triazolam (1c), respectively.     

Photogeneration and chemistry of biphenyl quinone methides from hydroxybiphenyl methanols

The photosolvolysis of several biphenyl methanols (Ph-PhCH[Ph]OH) substituted with hydroxy or methoxy groups on the benzene ring not containing the -CH(Ph)OH moiety has been studied in aqueous solution. This work is a continuation of our studies of photosolvolysis of hydroxy-substituted arylmethanols that generate quinone methide intermediates, some of which are known to be relevant intermediates in toxicology and in biological and organic chemistry in general. In this study, we further probe the ability of the biphenyl ring system to transmit charge from the ring substituted with a potential electron-donating group (hydroxy and methoxy) to the adjacent benzene ring that contains a labile benzyl alcohol moiety. We show that in systems with a hydroxy substituent, biphenyl quinone methides (BQM) are the first formed intermediates that are detectable by nanosecond laser flash photolysis, and are responsible for the observed overall photosolvolysis reaction of these compounds. The highly conjugated BQM are found to absorb at long wavelengths (lambda(max) 580 and approximately 750 nm for the p,p' and o,p'-isomers, respectively) with relatively long lifetimes in neutral aqueous solution (500 and 30 micros, respectively). The BQM from the o,p'-isomer was found to undergo a competing intramolecular Friedel-Crafts alkylation, to give a fluorene derivative.     

Reactions of carbanions derived from α-substituted-methyl tolyl sulfones with quinone methides as Michael acceptors

Nucleophilic addition of α-halo-4-tolylsulfonyl methyl anions to quinone methides and subsequent reactions were studied. Three kinds of consecutive reaction products were isolated, depending on the substrate structures and reaction conditions. Two of them were identified as rearrangement products and one as the vicarious nucleophilic substitution (VNS) product. An unexpected 1,2-migration of the tosyl group was observed. The mechanism of the reactions is briefly discussed.     

Enantioselective synthesis of secondary alcohols in the presence of chiral ligands

The synthesis of two S-proline derivatives is described together with their use as chiral ligands for lithium in reactions of n-butyllithium with benzaldehyde to give 1-phenyl-1-pentanol with moderate optical purity. The presence of lithium salts in the reaction mixture causes a decrease in asymmetric induction.     

New aniline-containing amino alcohols from trans-(R,R)-2-(2-nitrophenyl)-3-phenyloxirane as useful intermediates for the synthesis of chiral ligands, bases, and benzoxazine nucleus

New enantiopure aniline-containing amino alcohols are directly derived from trans-(R,R)-2-(2-nitrophenyl)-3-phenyloxirane, by alternative regioselective double reductions. Subsequent selective alkylation procedures and derivatizations provide a rapid and high-yielding access to different chiral ligands, bases, and benzoxazines, without loss of optical purity.