Copper-cascade catalysis: synthesis of 3-functionalized indoles

A three-component reaction of indoles, sulfonyl azides and terminal alkynes afforded 3-functionalized indoles in a single step via copper-cascade catalysis.     

Gold catalysis: benzanellation versus alkylidenecyclopentenone synthesis

A series of different furan-yn-ols were prepared by a three-step sequence. Their reaction with Gagosz's catalyst Ph₃PAuNTf₂ depends strongly on the substitution pattern of the substrate and the quality of the leaving group. Benzofurans, alkylidenecyclopentenones or Meyer-Schuster type products can be obtained. Improving the leaving group quality leads to the preferred formation of benzofurans.     

Gold catalysis: no steric limitations in the phenol synthesis

Different dihydroisoindol-4-ols and 8-hydroxytetrahydroisoquinolines were prepared by the gold-catalyzed phenol synthesis. The reaction was investigated with several sterically demanding groups in the 5-position of the furan starting material. The influence of the reaction time and the catalyst on the yield was investigated.     

Rapid activation of the melibiose permease MelB immobilized on a solid-supported membrane

Rapid solution exchange on a solid-supported membrane (SSM) is investigated using fluidic structures and a solid-supported membrane of 1 mm diameter in wall jet geometry. The flow is analyzed with a new technique based on specific ion interactions with the surface combined with an electrical measurement. The critical parameters affecting the time course of the solution exchange and the transfer function describing the time resolution of the SSM system are determined. The experimental data indicate that solution transport represents an intermediate situation between the plug flow and the Hagen-Poiseuille laminar flow regime. However, to a good approximation the rise of the surface concentration can be described by Hagen-Poiseuille flow with ideal mixing at the surface of the SSM. Using an improved cuvette design, solution exchange as fast as 2 ms was achieved at the surface of a solid-supported membrane. As an application of the technique, the rate constant of a fast electrogenic reaction in the melibiose permease MelB, a bacterial ( Escherichia coli) sugar transporter, is determined. For comparison, the kinetics of a conformational transition of the same transporter was measured using stopped-flow tryptophan fluorescence spectroscopy. The relaxation time constant obtained for the charge displacement agrees with that determined in the stopped-flow experiments. This demonstrates that upon sugar binding MelB undergoes an electrogenic conformational transition with a rate constant of k approximately 250 s (-1).     

Gold catalysis: deuterated substrates as the key for an experimental insight into the mechanism and selectivity of the phenol synthesis

The second phase of the gold-catalyzed phenol synthesis, the ring opening of the intermediate arene oxide, follows general acid catalysis. The product selectivity is determined by the substrate only and can be explained by the stability of the intermediate arenium ions. Thus, even remote substitutents can be used to control the chemoselectivity of the overall reaction by electronic influences and their influence is stronger than the steric influence of neighboring substituents. This is supported by quantum chemical calculations of the intermediates. The lack of exchange of deuterium labels excludes even equilibria with acetylide or vinylidene intermediates and the observed deuterium distribution in the final products is in accord with the NIH-shift reaction. In addition, these findings now explain previously obtained results.     

Gold catalysis: phenol synthesis in the presence of functional groups

The effect of different substituents, such as bromo, chloromethyl, hydroxymethyl, formyl, acetyl, carboxy, and acylated hydroxymethyl and ammonium groups, on the furan ring of substrates in gold-catalyzed phenol synthesis has been investigated. The furan ring was also replaced by different heterocycles, such as pyrroles, thiophenes, oxazoles, and a 2,4-dimethoxyphenyl group; gold catalysis then delivered no phenols, but occasionally other products were obtained. [Ru(3)(CO)(12)] also catalyzed the conversion of 1 at a low rate, [Os(3)(CO)(12)] failed as a catalyst, and with [Co(2)(CO)(8)] the alkyne complex 19 can be obtained, it does not lead to any phenol but reacts with norbornene to give the product of a Pauson-Khand reaction. Efforts to prepare vinylidene complexes of 1 provided the only evidence for these species; in the presence of a phosphane ligand with ruthenium an interesting deoxygenation to 22 was observed. The phenol 2 c was converted to the allyl ether, a building block for para-Claisen rearrangements, and to the aryl triflate, a building block for cross-coupling reactions.     

Gold catalysis in organic synthesis: efficient cycloisomerization of alpha-aminoallenes to 3-pyrrolines

[reaction: see text] The gold(III) chloride-catalyzed cycloisomerization of various alpha-aminoallenes gave the corresponding 3-pyrrolines in good to high chemical yields. An interesting dependence of the chirality transfer and reactivity on the N-protecting group was observed. The 3-pyrrolines are highly useful intermediates for the synthesis of functionalized pyrrolines, pyrrolidines, and other natural products.     

Tandem hydroformylation/Fischer indole synthesis: a novel and convenient approach to indoles from olefins

[reaction: see text] A novel one-pot synthesis of indole systems via tandem hydroformylation/Fischer indole synthesis starting from olefins and arylhydrazines is described. This tandem procedure leads directly to 3-substituted indoles if unsubstituted phenylhydrazine is used and to 3,5- respectively 3,7-disubstituted indoles if para- or ortho-substituted arylhydrazines are used.     

Conversion of cellulose to glucose and levulinic acid via solid-supported acid catalysis

Cellulose is hydrolyzed to glucose, which is further converted to levulinic acid in the presence of surface-supported Brønsted and Lewis acid catalysts. Nafion catalysts, in particular, have the potential to be recycled or applied to a continuous flow reactor for the synthesis of these biofuel precursors.     

Gold catalysis: efficient synthesis and structural assignment of jungianol and epi-jungianol

Starting from 2-methylfuran and crotonaldehyde, both jungianol and epi-jungianol were prepared by a six-step sequence including a gold-catalyzed arene synthesis and a photochemical S(N)2-like reduction with lithium aluminum hydride. Not a single protective group was needed in the entire synthesis. With both diastereomers in hand, the stereochemical assignment in the literature could be corrected by means of a thorough (1)H NMR spectroscopic analysis and an X-ray diffraction study on an epi-jungianol derivative.     

Improved method for the diimide reduction of multiple bonds on solid-supported substrates

A mild and improved method for reducing multiple bonds on various resins with diimide is described. The simple procedure readily generates diimide from 2-nitrobenzenesulfonohydrazide and triethylamine at room temperature. A number of representative multiple bonds in various steric and electronic environments were examined, including polar double bonds such as carbonyl and azo, for ease and selectivity of reduction. A general trend of reactivity was identified which revealed, inter alia, that terminal olefins, 1,2-disubstituted olefins, electron-poor olefins, and terminal alkynes were the most easily reduced.     

Protease catalysis mediated by a substrate mimetic: a novel enzymatic approach to the synthesis of carboxylic acid amides

We present a protease-based method for the coupling of non-coded and non-amino-acid-derived amines with carboxy components. The key feature of this approach is the combination of the substrate-mimetic strategy with the ability of the cysteine protease clostripain to accept a wide spectrum of amines. Firstly, we tested the use of the 4-guanidinophenyl ester leaving group to mediate acceptance of non-coded and non-amino-acid-derived acyl residues. This employed beta-amino acid and simple carboxylic acid moieties as acyl donors, and several amino acid and peptide units as acyl acceptors. The study was completed by the use of non-amino-acid-derived acyl acceptors comprising simple amines, amino alcohols, and diamines. The results indicate that the approach presented is a useful strategy for the synthesis of peptide isosteres, peptide analogues, and organic amides. These last open a new range of synthetic applications of proteases completely beyond peptide synthesis, achieving efficient and selective acylations of non-amino-acid-derived amines under extraordinarily mild reaction conditions.     

New domino heteroannulation of enaminones: synthesis of diverse fused naphthyridines

A series of new poly-functionalized fused naphthyridine derivatives were synthesized via a three-component reaction of aldehyde, 2-aminoprop-1-ene-1,1,3-tricarbonitrile and enaminone in EtOH using EtONa as a base. During these reaction processes, the domino construction of fused naphthyridine skeleton with concomitant formation of two new pyridine rings was readily achieved via base promoted three-component reactions in a one-pot operation. The procedures are facile, avoiding time-consuming and costly syntheses, tedious work-up and purifications of precursors.     

One-pot multistep Bohlmann-Rahtz heteroannulation reactions: synthesis of dimethyl sulfomycinamate

[reaction: see text] The synthesis of dimethyl sulfomycinamate, the acidic methanolysis product of the sulfomycin family of thiopeptide antibiotics, from methyl 2-oxo-4-(trimethylsilyl)but-3-ynoate is achieved in a 2,3,6-trisubstituted pyridine synthesis that proceeds with total regiocontrol in 13 steps by the Bohlmann-Rahtz heteroannulation of a 1-(oxazol-4-yl)enamine or in 12 steps and 9% yield by three-component cyclocondensation with N-[3-oxo-3-(oxazol-4-yl)propanoyl]serine and ammonia in ethanol.     

Gold catalysis: mild conditions for the synthesis of oxazoles from N-propargylcarboxamides and mechanistic aspects

2,5-Disubstituted oxazoles are synthesized from the corresponding propargylcarboxamides under mild reaction conditions via homogeneous catalysis by AuCl(3). While monitoring the conversion via (1)H NMR spectroscopy, an intermediate 5-methylene-4,5-dihydrooxazole can be observed and accumulated up to 95%, being the first direct and catalytic preparative access to such alkylidene oxazolines. The intermediate was fully characterized and can be trapped at -25 degrees C for several weeks. Deuteration experiments show a stereospecific mode of the two first steps of the reaction.     

A facile approach to the synthesis of 5,7-disubstituted indoles via a highly selective lithium-bromine exchange of 5,7-dibromoindoles

A general approach to the synthesis of 5,7-disubstituted indoles has been developed based upon a highly selective lithium-bromine exchange reaction at the 7-position when 1-alkyl-5,7-dibromoindoles were treated with t-BuLi in ether. The resulting 5-bromo-7-lithiated indoles could react with various electrophiles to afford 5-bromo-7-substituted indoles (6) upon work-up. Without isolation of 6, the intermediates thus obtained could be exposed to a second lithium-bromine exchange reaction in a one-pot procedure and further reacted with various electrophiles to afford 5,7-disubstituted indoles (1).     

Two-step route to indoles and analogues from haloarenes: a variation on the Fischer indole synthesis

In a new variation on the Fischer indole synthesis, readily available haloarenes are converted into a wide range of indoles in just two steps by halogen-magnesium exchange and quenching with di-tert-butyl azodicarboxylate, followed by reaction with aldehydes or ketones under acidic conditions. The protocol, which is readily extended to the preparation of indole isosteres, 4- and 6-azaindoles and thienopyrroles, obviates the need to prepare potentially toxic aryl hydrazines, simultaneously avoiding undesirable anilines such as naphthylamines.     

Oxidative rearrangement of indoles: a new approach to the EFHG-tetracyclic core of diazonamide A

A new approach to the ring EFHG-tetracyclic core fragment of the marine secondary metabolite diazonamide A is described. The route is based on the oxidative rearrangement of 3-arylindole-2-carboxylates. Thus, a range of 3-arylindole-2-carboxylates (3, 8) underwent rearrangement to the corresponding 3,3-disubstituted oxindoles (4, 9) with migration of the ester group upon treatment with tert-butyl hypochlorite followed by acid. The oxindoles 9 with a 3-[2-(4-methoxybenzyloxy)]phenyl substituent underwent cyclization to the tetracyclic aminals 11 following N-protection, reduction, and treatment with methanesulfonic anhydride. The methodology was applied to the tyrosine-indole derivative 17 to give the EFHG-tetracyclic core of diazonamide A.