Catalytic asymmetric Staudinger reactions to form beta-lactams: an unanticipated dependence of diastereoselectivity on the choice of the nitrogen substituent

There are relatively few methods for the catalytic asymmetric synthesis of beta-lactams, and those that have been reported are generally cis selective. This communication describes the first catalytic enantioselective Staudinger reactions that preferentially furnish trans beta-lactams (trans = relationship of Ph to R1). The key to this method is the use of an N-triflyl protecting group for the imine. Along with serving as interesting targets in their own right, N-triflyl beta-lactams readily react with nucleophiles to generate useful families of compounds, such as gamma-amino alcohols and beta-amino acids.     

Cu(I)/bis(azaferrocene)-catalyzed enantioselective synthesis of beta-lactams via couplings of alkynes with nitrones

As a consequence of the wide-ranging significance of beta-lactams (e.g., use as drugs and as chiral building blocks), a great deal of effort has been dedicated to the development of methods for their stereoselective synthesis. Although considerable progress has been achieved, nearly all of the approaches that have been described are based on the use of chiral precursors; direct catalytic enantioselective routes to beta-lactams are rare as well as limited in scope. In this communication, we establish that, using a new C2-symmetric planar-chiral bis(azaferrocene) ligand, we can generate beta-lactams with very good enantiomeric excess and cis diastereoselection via catalytic enantioselective Kinugasa reactions (couplings of alkynes with nitrones). Appealing attributes of this process include the ready availability of the starting materials, the functional-group tolerance of the reaction, and the convergency of the approach.     

Column asymmetric catalysis for beta-lactam synthesis

[structure] A catalytic asymmetric reaction process was designed involving the use of solid-phase reagents and catalysts that constitute the packing of a series of "reaction columns". This process was applied to the catalytic asymmetric synthesis of beta-lactams, yielding pure product after crystallization with exceptional enantio- and diastereoselectivity.     

Asymmetric catalysis on sequentially-linked columns.

We report a catalytic asymmetric reaction process that involves the use of solid-phase reagents and catalysts that constitute the packing of a series of "reaction columns". This process was applied to the catalytic asymmetric synthesis of beta-lactams, to yield pure products with excellent enantio- and diastereoselectivity. We have identified several advantages to conducting chemical reactions on sequential columns, including ease of catalyst and reagent recovery and simplified purification steps that preclude the need for chromatography.     

Bifunctional asymmetric catalysis: a tandem nucleophile/Lewis acid promoted synthesis of beta-lactams

[reaction: see text]. We describe a superior procedure for the catalytic, asymmetric synthesis of beta-lactams using a bifunctional catalyst system consisting of a chiral nucleophile and an achiral Lewis acid.     

Rhodium-catalyzed rearrangement of alpha-diazo thiol esters to thio-substituted ketenes. Application in the synthesis of cyclobutanones, cyclobutenones, and beta-lactams

Exposure of alpha-diazo thiol esters (1) to the action of catalytic rhodium(II) acetate leads to a remarkably facile "thia-Wolff rearrangement", producing thio-substituted ketenes which combine with a variety of ketenophiles to provide access to alpha-thiocyclobutanones, cyclobutenones, and beta-lactams. Reductive desulfurization of these cycloadducts takes place under mild conditions and in excellent yield, and this sequence thus represents a useful new alternative to the existing dichloroketene-based methodology for the synthesis of four-membered carbocycles and heterocycles.     

Generation of ketenes from acid chlorides using NaH/crown ether shuttle-deprotonation for use in asymmetric catalysis

[reaction: see text] We describe methodology for the in situ generation of reactive monosubstituted ketenes from acid chlorides through a shuttle deprotonation process using NaH as an inexpensive stoichiometric base and a crown ether cocatalyst. We have successfully applied this new procedure to the catalytic, asymmetric synthesis of beta-lactams and alpha-haloesters.     

Synthesis of novel N-sulfonyl monocyclic beta-lactams as potential antibacterial agents

New cis monocyclic beta-lactams were synthesized by [2+2] Staudinger cycloaddition reactions of the imine (3,4-dimethoxybenzylidene)-(4-methoxyphenyl)-amine and ketenes derived from different acyl chlorides and Et3N. These monocyclic beta-lactams were then cleaved by ceric ammonium nitrate (CAN) to give NH-monocyclic beta-lactams, which in turn were converted to N-sulfonyl monocyclic beta-lactams by treatment with four different sulfonyl chlorides in the presence of Et3N and 4,4-dimethyl-aminopyridine (DMAP).     

A catalyst that plays multiple roles: asymmetric synthesis of beta-substituted aspartic acid derivatives through a four-stage, one-pot procedure

We report a new method for the catalytic, asymmetric synthesis of beta-substituted aspartic acid derivatives in which the nucleophilic catalyst serves up to four discrete roles in a one-pot procedure: catalytic dehydrohalogenation of acid chlorides to form ketenes; catalytic dehydrohalogenation of alpha-chloroamines to form the corresponding imines; catalyzed [2 + 2]-cycloaddition to produce intermediate acyl beta-lactams; and finally, nucleophilic ring opening to afford optically enriched beta-substituted aspartic acids in high enantioselectivity and diastereoselectivity.     

Ruthenium porphyrin catalyzed intramolecular carbenoid C[bond]H insertion. Stereoselective synthesis of cis-disubstituted oxygen and nitrogen heterocycles

[reaction: see text] A ruthenium porphyrin-catalyzed stereoselective intramolecular carbenoid C[bond]H insertion is described. Using [Ru(II)(TTP)(CO)] as catalyst, aryl tosylhydrazones are converted to 2,3-dihydrobenzofurans, 2,3-dihydroindoles, and beta-lactams in good yields and remarkable cis selectivity (up to 99%). Enantioselective synthesis of 2,3-dihydrobenzofurans is also achieved with [Ru(II)(D(4)-Por*)(CO)] as catalyst, and up to 96% ee is attained.     

Three- and four-membered rings from cycloadditions of 1,3-thiazolium-4-olates and aldehydes

2-Aminothioisomünchnones, a well-known family of masked dipoles, react with aromatic aldehydes in a domino cascade reaction that produces episulfides (thiiranes) or beta-lactams (2-azetidinones). This sequence is initiated by a [3+2] dipolar cycloaddition followed by ring opening of cycloadducts and intramolecular rearrangement to afford these unusual ring contractions. The nature of the reaction products depends on the structural characteristics of the starting dipole and the experimental conditions. Episulfides are obtained selectively as cis isomers with respect to both aryl groups, whereas beta-lactams are produced as cis/trans mixtures. These structural features were determined unequivocally by X-ray crystallographic analysis. The beta-lactams still possessed a flexible acyclic chain containing sulfur, a salient lead modification of the bioactive cyclic penems and cephems. The preferential production of exo transition structures was rationalized with the aid of computational calculations at the B3LYP/6-31G* level.     

Molecular modeling and chemical reactivity of sanfetrinem and derivatives

The indiscriminate use of beta-lactams has considerably diminished their efficiency as a result of bacteria developing effective defense mechanisms against them. Recent pharmaceutical research has led to the synthesis of tricyclic beta-lactam antibiotics known as "tricyclic carbapenems" or "trinems". In this work, we studied the chemical reactivity, an essential property for antibiotic action, of trinems and found it to be similar to that of cephalosporins. Also, we elucidated the interaction pattern for sanfetrinem and 4beta-methoxy trinem and compared it to that for classical beta-lactams. The behavior of both trinems was found to be similar to that of penicillin G toward Staphylococcus aureus PC1, and that of cephalothin and imipenem toward Enterobacter cloacae P99.     

The direct organocatalytic asymmetric mannich reaction: unmodified aldehydes as nucleophiles

The unprecedented application of unmodified aldehydes as nucleophilic donors in direct catalytic asymmetric Mannich-type reactions is disclosed in a full account. Our efforts in broadening the applicability of chiral pyrrolidine-based catalysts in direct asymmetric Mannich-type reactions led to the highly diastereo- and enantioselective and concise synthesis of functionalized alpha- and beta-amino acids, beta-lactams, and amino alcohols.     

Enantioselective hydrogenation of tetrasubstituted olefins of cyclic beta-(acylamino)acrylates

Hydrogenation of a series of cyclic beta-(acylamino)acrylates with tetrasubstituted olefins has been accomplished successfully with the use of Ru catalysts with chiral biaryl ligands such as C3-TunaPhos, and up to over 99% ee's have been achieved. This methodology provides an efficient catalytic method for the synthesis of both cis and trans chiral cyclic beta-amino acid derivatives.     

Solid-phase synthesis of beta-lactams via the ester enolate-imine condensation route

The ester enolate-imine condensation route to beta-lactams via an immobilized ester enolate has been achieved for the first time. The key reaction in the synthesis is the cyclization of the resin bound ester dianion and an imine. Traceless cleavage from the T1-triazene linker system yields the desired beta-lactams.     

The bis-barium complex of a butterfly crown ether as a phototunable supramolecular catalyst

Reversible phototuning of the catalytic efficiency of the bis-barium complex of azobis(benzo-18-crown-6) in the basic ethanolysis of anilide derivatives has been achieved by light-induced cis right arrow over left arrow trans interconversion of the azobenzene spacer unit of the catalyst. The geometry of the productive catalyst-substrate complex is more favorable when the concave cis form of the catalyst is involved. Continuous photoregulation of the catalytic activity at any intermediate value between the "HIGH" and "LOW" levels was achieved by proper adjustment of the excitation wavelength or the irradiation time. The complete and relatively fast interconvertibility of photostationary states allowed the activity of the catalyst to be repeatedly photoswitched "HIGH" and "LOW" in the course of the same run.     

One-pot preparation of piperazines by regioselective ring-opening of non-activated arylaziridines

Herein we report a new straightforward synthesis of cis and trans 2,5-disubstituted N,N-dialkylpiperazines, even in enantioenriched form, by reacting non-activated N-alkyl arylaziridines in the presence of a catalytic amount of a Lewis acid. A stereochemical and NMR investigation revealed useful mechanistic insights for this process.     

烯烃及其衍生物催化异构反应的研究进展

烯烃及其衍生物异构化是一种利用碳碳双键沿骨架碳链发生位置迁移或顺反构型变换构建新烯烃的合成方法,对于有机合成、日用化学品合成、原料油应用和天然产物合成等均有着举足轻重的作用。本文综合论述了自1960年代以来烯烃及其衍生物异构化的五种催化体系的研究进展,重点结合笔者的研究工作,介绍光催化在有机化合物中碳碳双键异构反应中的应用及其发展趋势。     

Synthesis of analogs of juvenile hormone on the basis of the telomerization reaction of piperylene with sulfones

Conclusions The catalytic telomerization of the cis and trans isomers of piperylene with sulfones containing an available hydrogen atom was investigated. The synthesis of compounds having juvenile hormone activity was shown to be possible on the basis of the telomers of piperylene.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 874–879, April, 1986.     

Triphenylphosphine dibromide and dimethylsulfide dibromide as versatile reagents for beta-lactam synthesis

Triphenylphosphine dibromide and dimethylsulfide dibromide are efficient reagents for the direct synthesis of beta-lactams from carboxylic acids and imines avoiding the use of acid halides as starting materials. Synthesis of 4-imino-beta-lactams are also briefly described. A potential synthesis of N-unsubstituted beta-lactams is made.