Novel ruthenium-catalyzed cleavage of allyl protecting group in lactams

A convenient and general method of synthesis of NH-lactams via Grubbs’ carbene promoted isomerization of the respective N-allyl lactams followed by RuCl₃-catalyzed enamide cleavage has been developed.     

Efficient tandem process for the catalytic deprotection of N-allyl amides and lactams in aqueous media: a novel application of the bis(allyl)-ruthenium(IV) catalysts [Ru(eta3:eta2:eta3-C12H18)Cl2] and [{Ru(eta3:eta3-C10H16)(micro-Cl)Cl}2

An operationally simple and highly efficient methodology for the removal of the allyl protecting group in amides and lactams has been developed by using the commercially available bis(allyl)-ruthenium(IV) catalysts [Ru(eta(3):eta(2):eta(3)-C(12)H(18))Cl(2)] (C(12)H(18)=dodeca-2,6,10-triene-1,12-diyl) and [{Ru(eta(3):eta(3)-C(10)H(16))(micro-Cl)Cl}(2)] (C(10)H(16)=2,7-dimethylocta-2,6-diene-1,8-diyl). The tandem process, which takes place in aqueous media and proceeds in a one-pot manner, involves the initial isomerization of the C=C bond of the allyl unit and subsequent oxidative cleavage of the resulting enamide.     

Ruthenium-catalyzed chemoselective N-allyl cleavage: novel Grubbs carbene mediated deprotection of allylic amines

A novel application of the Grubbs carbene complex has been discovered. The first examples of the catalytic deprotection of allylic amines with reagents other than palladium catalysts have been achieved through Grubbs carbene mediated reaction. Significantly, the catalytic system directs the reaction toward the selective deprotection of allylic amines (secondary as well as tertiary) in the presence of allylic ethers. A variety of substrates, including enantiomerically pure multifunctional piperidines, are also usable. The new method is more convenient, chemoselective, and operationally simple than the palladium-catalyzed method. The current mechanistic hypothesis invokes a nitrogen-assisted ruthenium-catalyzed isomerization, followed by hydrolysis of the enamine intermediate. We believe that the reactive species involved in the reaction may be an Rubond;H species rather than the Grubbs carbene itself. Thus, the isomerization may occur according to the hydride mechanism. The synthetic utility of this ruthenium-catalyzed allyl cleavage is illustrated by the preparation of indolizidine-type alkaloids.     

Synthesis,structures and properties ofN-(trihalogermylmethyl)-substituted amides,lactams and imides,the derivatives of the five-coordinate germanium

The formation of trichlorogermyl-substituted amides, lactams, and imides occurs when 2Et₂O·HGeCl₃ is condensed with compounds possessing the -NCH₂Cl fragment and equally well when HGeCl₃ interacts with compounds containing -NCH₂OH and-NCH₂OSiMe₃ groups. In some cases, the use of the latter is more advantageous from the preparative point of view. In compounds thus obtained, the germanium is five-coordinate due to the coordination . Deceased August 13, 1993. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1793–1799, October, 1993.     

N‐chloro amides,lactams, carbamates,and imides. New classes of initiators for the metal‐catalyzed living radical polymerization of methacrylates

Metal‐catalyzed living radical polymerization of methyl methacrylate initiated with N‐chloro amides (N‐chloro N‐ethyl propionamide, N‐chloro benzanilide, N‐chloro methylbenzamide, and N‐chloro acetanilide), lactams (N‐chloro caprolactam and N‐chloro 2‐pyrrolidinone), carbamates or urethanes (N‐chloro ethylcarbamate or N‐chlorourethane), imides (N‐chloro phtalimide, N‐chloro succinimide, trichloroisocyanuric acid, and N‐chloro saccharin) and catalyzed with the self‐regulated catalytic system Cu₂S/2,2′‐bipyridine is reported. The initiation efficiency of these initiators is determined by their structure. Regardless of the initiator efficiency, in all cases, poly (methyl methacrylate) with narrow molecular weight distribution and functionalized chain‐ends was obtained. These new classes of initiators open new strategies for the functionalization of polymer chain‐ends and for the synthesis of complex architectures by graft copolymerization initiated from N‐chloro proteins, aliphatic, aromatic and semiaromatic polyamides, and polyurethanes. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5283–5299, 2005     

A facile cleavage of allyl ethers on solid phase

A simple and efficient protocol for the cleavage of allyl ethers on solid phase using a palladium(0)-catalyzed allyl transfer reaction is reported.     

Azido-Schmidt reaction for the formation of amides, imides and lactams from ketones in the presence of FeCl3

Ketones undergo smooth rearrangement with TMSN₃ in the presence of FeCl₃ under extremely mild conditions to provide the corresponding amides, imides and lactams in good yields with high selectivity. This method is very useful for the preparation of a wide range of amides, imides and lactams from ketones. The use of FeCl₃ makes this method simple, convenient and cost-effective.     

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.     

Synthesis and the keto-enol equilibrium of 2-acyl lactams

Condensation of N-substituted lactams with carboxylic acid esters was studied. A wide range of substituted 2-acyl lactams with different ring sizes were synthesized. The structure of 2-acyl lactams (primarily, the ring size) was found to influence the keto-enol tautomerism.     

A practical oxidative method for the cleavage of hydrazide N[bond]N bonds

The selective N-oxidation of the most nucleophilic amino nitrogen atom in hydrazides is central to the development of an unprecedented methodology for the cleavage of their N[bond]N bonds under oxidative conditions. Treatment of a series of hydrazides 1-9 with peracids such as magnesium monoperoxyphtalate hexahydrate (MMPP.6 H(2)O) or meta-chloroperbenzoic acid (m-CPBA) afforded the corresponding amides 10-16 in good-to-excellent yields (80-92 %). The extension of the methodology to carbamate-like substrates such as 17 and 18 was also investigated, but in this case the process is synthetically useless in view of the low yields observed of carbamates 19 and 20 (approximately 15 %). Experiments carried out with equivalent amounts of oxidant produced nitrones, such as 26, proceeding from the dialkylamino moiety, and (1)H NMR experiments indicated that this product is formed by fast conversion of the parent hydrazide, without detection of the expected hydrazide N-oxides. In addition, the over oxidation of 26 into nitronate 25 proceeds through an unknown intermediate. This oxidative N[bond]N bond cleavage by peracids is an alternative method for the deamination of hydrazides, and constitutes the only solution compatible with substrates carrying functionalities sensitive to reducing conditions.     

Weapons in disguise--activating mechanisms and protecting group chemistry in nature

Bioactive natural products often possess uniquely functionalized structures with unusual modes of action; however, the natural product itself is not always the active species. We discuss molecules that draw on protecting group chemistry or else require activation to unmask reactive centers, illustrating that nature is not only a source of complex structures but also a guide for elegant chemical transformations which provides ingenious chemical solutions for drug delivery.     

The development of N-aryl trifluoroacetimidate-based benzyl and allyl protecting group reagents

An exploration of the role of para-substituents on the balance between stability and reactivity of N-phenyl trifluoroacetimidates prompted the discovery of new reagents for the addition of allyl and benzyl protecting groups, namely O-allyl and O-benzyl N-(p-nitrophenyl)trifluoroimidates. These compounds are stable and crystalline at ambient temperature, making them ideal alternatives to existing benzylating and allylating reagents used under acidic conditions.     

Selective cleavage of the N-propargyl group from sulfonamides and amides under ruthenium catalysis

The selective cleavage of the N-propargyl group from sulfonamides and amides under ruthenium catalysis is described. The reaction tolerates a broad range of functional groups, and the desired products were obtained in 10–95% yield.     

Synthetic Reactions Using Low‐valent Titanium Reagents Derived from Ti(OR)4 or CpTiX3 (X = O‐i‐Pr or Cl) in the Presence of Me3SiCl and Mg

In the presence of Me₃SiCl, Ti(OR)₄ or CpTiX₃ (X = O‐i‐Pr or Cl) is reduced by Mg powder in THF to gradually generate a specific low‐valent titanium (LVT) species that mediates several synthetic reactions. The LVT‐catalyzed C–O bond‐cleaving reactions of allyl and propargyl ethers and esters generate parent alcohols and carboxylic acids, respectively. O‐allyl and propargyl carbamates are also readily deprotected by the LVT to afford parent amines. In addition, the respective reductive N–S or O–S bond cleavage of sulfonamides or sulfonyl esters mediated by the LVT was developed as a novel facile deprotection method. The reagent catalyzes intra‐ and intermolecular alkyne or alkyne/nitrile cycloaddition to produce substituted benzenes and pyridines, while epoxides and oxetanes are reduced to alcohols via an LVT‐mediated homolytic ring opening. The McMurry coupling of aryl aldehydes and ketones proceeds with the LVT under homogeneous and mild reaction conditions and is effective for the polymerization of aromatic dialdehydes, generating conjugated polymers. Finally, imino‐pinacol coupling of imines is mediated by the LVT to provide 1,2‐diamines.