Palladium-catalyzed acyldemetallation of organomercurials in aqueous media

Palladium- and iodide ion-catalyzed acyldemercuration of R₂Hg(RHgI) by aroyl chlorides (ArCOCI) can be carried out in aqueous media. Nonsymmetrical ketones (ArCOR) are obtained in high yields along wiht oxidative demercuration products (R₂) in trace quantities. The possible reaction mechanism and the role of the iodide ion are discussed.     

Selective cleavage of methoxy protecting groups in carbohydrates

The selective cleavage of methoxy protecting groups next to hydroxy groups is achieved using a radical hydrogen abstraction reaction as the key step. Under the reaction conditions, the hydroxy group generates an alkoxyl radical that reacts with the sterically accessible adjacent methoxy group, which is transformed into an acetal. In the second step, the acetals are hydrolyzed to give alcohols or diols. A one-pot hydrogen abstraction-hydrolysis procedure was also developed. Good yields were usually achieved, and the mild conditions of this methodology were compatible with different functional groups and sensitive substrates such as carbohydrates.     

Wavelength-selective cleavage of o-nitrobenzyl and polyheteroaromatic benzyl protecting groups

Evaluation of the wavelength-selective cleavage of five photolabile protecting groups from two different families has been performed. Alanine, as a model bifunctional target molecule was masked at the amino terminal with o-nitrobenzyl group and at the carboxylic terminal with benzyl-type nitrogen and oxygen polyheteroaromatics, namely acridine, (thioxo)benzocoumarin and a coumarin built on the julolidine nucleus. The photosensitivity of the corresponding alanine conjugates was studied at selected wavelengths with HPLC/UV and ¹H NMR monitoring. The release of the fully deprotected molecule could be achieved by sequential irradiation in variable irradiation times, which were dependent on the heteroaromatic group used.     

Palladium-catalyzed carbonylation of haloindoles: no need for protecting groups

[reaction: see text] For the first time, palladium-catalyzed carbonylations of unprotected bromoindoles have been performed successfully with different N- and O-nucleophiles. Various indole carboxylic acid derivatives are accessible in excellent yield. For example, aminocarbonylation of 4-, 5-, 6-, or 7-bromoindole with arylethylpiperazines provides a direct one-step synthesis for CNS active amphetamine derivatives.     

Palladium-catalyzed phenylation and vinylation of aryl halides in aqueous media

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, p. 2672, November, 1990.     

Selective acidolytic cleavage of aralkyl carbonyl amino protecting groups

The acidolytic cleavage of a series of new N-aralkyloxycarbonyl protecting groups has been found to proceed as a first-order reaction, the rate of cleavage being dependent on the stability of the corresponding aralkyl carbonium ions. Some of the groups are cleaved at much the same rate as the N-trityl residue and up to 60000 times faster than the t-butyloxycarbonyl (Boc) group. The rate is also strongly influenced by the acidity of the reaction media. The relative rates at which aralkyloxycarbonyl and Boc groups are split off can be largely controlled by appropriate selection of the reaction conditions. The implications of these findings for peptide syntheses are discussed and the use of the 2-(p-diphenyl)-isopropyloxycarbonyl residue as an especially suitable N-protecting group is proposed.     

Endocyclic cleavage in glycosides with 2,3-trans cyclic protecting groups

An endocyclic pathway is proposed as a reaction mechanism for the anomerization from the β (1,2-trans) to the α (1,2-cis) configuration observed in glycosides carrying 2,3-trans cyclic protecting groups. This reaction occurs in the presence of a weak Lewis or Br?nsted acid, while endocyclic cleavage (endocleavage) in typical glycosides was observed only when mediated by protic media or strong Lewis acids. To rationalize the behavior of this class of compounds, the reaction mechanism and the promoting factors of the endocleavage are investigated using quantum-mechanical (QM) calculations and experimental studies. We examine anomerization reactions of thioglycosides carrying 2,3-trans cyclic protecting groups, employing boron trifluoride etherate (BF(3)·OEt(2)) as a Lewis acid. The estimated theoretical reactivity, based on a simple model to predict transition state (TS) energies from the strain caused by the fused rings, is very close to the TS energies calculated by the TS search along the C1-C2 bond rotation after the endo C-O bond breaking. Excellent agreement is found between the predicted TS energies and the experimental reactivity ranking. The series of calculations and experiments strongly supports the predominance of the endocyclic rather than the exocyclic mechanism. Furthermore, these investigations suggest that the inner strain is the primary factor enhancing the endocleavage reaction. The effect of the cyclic protecting group in restricting the pyranoside ring to a (4)C(1) conformation, extensively discussed in conjunction with the stereoelectronic effect theory, is shown to be a secondary factor.     

An efficient protocol for copper-free palladium-catalyzed Sonogashira cross-coupling in aqueous media at low temperatures

A thorough study on copper-free Sonogashira cross-couplings in water was carried out using the palladacycle, [{Pd(μ-Cl){κ²-P,C-P(ⁱPr)₂(OC₆H₃-2-Ph)}}₂] as pre-catalyst with different bases and palladium concentrations. The highly active pre-catalyst imparts good to near quantitative yields using a concentration of 0.25 mol % at 40 °C. This broadly applicable protocol exhibits high tolerance of functional groups and substitution patterns.     

Palladium-catalyzed mono-N-allylation of unprotected anthranilic acids with allylic alcohols in aqueous media

Palladium-catalyzed N-allylation of anthranilic acids 1a-j with allyl alcohol 2a in the presence of Pd(OAc)(2), sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) in THF-H(2)O at room temperature gave only mono-N-allylated anthranilic acids 3a-j in good yields (70-98%). The reactions of 4-bromoanthranilic acid 1i with 2-methyl-3-buten-2-ol 2b showed complete chemoselectivity in N-allylation (neutral conditions) and C-vinylation (basic conditions). In our catalytic system, the keys to success are use of an unprotected anthranilic acid as a starting material and the presence of water in the reaction medium. The carboxyl group of anthranilic acid and water may play important roles for the smooth generation of the π-allyl palladium species by activation of the hydroxyl group of the allylic alcohol.     

Palladium-catalyzed coupling reaction of propargylic oxiranes with arylboronic acids in aqueous media

A novel type of coupling reaction has been developed by the palladium-catalyzed reaction of propargylic oxiranes with arylboronic acids, in which anti-substituted 4-aryl-2,3-allenols were produced in a highly diastereoselective manner. A chiral-substituted allene has been synthesized from the reaction of a chiral propargylic oxirane without loss of the chirality.     

Palladium-catalyzed carbonylative coupling of benzyl chlorides with aryl boronic acids in aqueous media

A novel chemoselective protocol for the carbonylative Suzuki coupling of benzyl chlorides with aryl boronic acids at low pressure of carbon monoxide has been developed. Applying a commercially available palladium acetate/PCy₃ catalyst system in the presence of potassium phosphate as the base and water as the solvent the coupling reactions proceeded smoothly. To demonstrate the general applicability 12 different α-arylated acetophenones have been synthesized in moderate to good yields (41-78%) under mild conditions.     

A new reagent for the cleavage of NPS-amino protecting groups in peptide synthesis.

The value of several reagents capable of removing quantitatively the α-amino protecting group of NPS-aminoacyl- or peptidyl-derivatives is assessed, by comparison with the reagents currently used, i.e. hydrogen chloride, RS^–-nucleophiles or alkyl thioamides, especially with regard to reaction specificity and end-product solubility. New reagents proposed, 3-nitro-4-mercapto-benzoic acid, and its methyl ester, appear to optimize the numerous, and often competing, requirements. These were probed, under conditions suitable for both conventional and solid-phase methods, on a series of model compounds, including diversely protected amino acids and short peptides, as well as for the actual synthesis of a triacontapeptide by the stepwise, solid-phase approach.     

An efficient method for synthesis of phenacyl derivatives under homogeneous phase transfer catalyst condition in aqueous media

In this letter,a mild and efficient procedure for synthesis of phenacyl derivatives under homogenous catalysis in the presence of tetrabutylammonium bromide in aqueous media is described.The nucleophilic substitution reactions were performed under ecofriendly conditions and gave the corresponding products in high yields and short reaction times.     

Catechol boron halides: mild and selective reagents for cleavage of common protecting groups

Catechol boron halides (1,X=Cl, Br) cleave certain ether, ester and carbamate protecting groups under mild conditions. The scope and selectivity of these readily available reagents has been examined.     

Simple deprotection of acetal type protecting groups under neutral conditions

When acetals such as MOM ethers, MEM ethers, and THP ethers were heated in ethylene glycol or propylene glycol, solvolysis proceeded smoothly to produce alcohols in excellent yield. This reaction is a very promising method for chemoselective deprotection of acetal type protecting groups.     

Picolinyl group as an efficient alcohol protecting group: cleavage with Zn(OAc)2·2H2O under a neutral condition

As an efficient alcohol protecting group, picolinates (Pic), prepared from the corresponding alcohols using commercial picolinoyl chloride, are readily cleaved by Zn(OAc)₂ or Cu(OAc)₂, even in the presence of other common alcohol protecting groups. Moreover, the picolinyl group at C-2 position in carbohydrates can be selectively cleaved to give methyl 4,6-O-benzylidene-3-O-picolinyl-α-d-glucopyranoside and 3-O-picolinyl methyl-4,6-O-benzylidene-α-d-galactopyranoside in good yields.     

Amino-acid synthesis in aqueous media under ultrasonic irradiation

The now-famous “Miller-Urey experiment” used a reduced mixture of gases to form basic organic molecules, such as amino acids. Since then, several methods have tried to reproduce the synthesis of amino acids under unusual conditions. All authors agree that the formation mechanisms of amino acids under such conditions might be of radical origin. If so, sonochemistry, known to enhance or to promote radical pathways, should be a powerful tool to access the synthesis of these compounds. We explored the feasibility of amino acid synthesis under ultrasonic irradiation in aqueous medium under a reductive atmosphere. The effects of several experimental parameters such as incident ultrasound frequency, temperature, nature and concentration of initial reactants, reaction time, and acoustic energy were explored.