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Die Metall‐katalysierte Hydrierung ist eine effektive Methode, um leicht verfügbare Aromaten in gesättigte Motive zu überführen. Allerdings sind derzeitige Hydrierungsstrategien auf die Bildung von C‐H‐ und N‐H‐Bindungen beschränkt. Dabei führt die schrittweise Addition von Wasserstoff zu reaktiven, ungesättigten Zwischenprodukten, die schnell weiter reduziert werden. Im Gegensatz dazu bietet die Unterbrechung der vollständigen Hydrierung durch zusätzliche Funktionalisierung ungesättigter Zwischenprodukte großes Potenzial zur Erhöhung der chemischen Komplexität in einem einzigen Reaktionsschritt. Das Überwinden der vollständigen Reduktion in der Aromatenhydrierung wurde bisher nur selten demonstriert. In dieser Arbeit berichten wir über die Synthese begehrter, enantioangereicherter δ‐Lactame aus Oxazolidinon‐substituierten Pyridinen und Wasser durch einen unterbrochenen Hydrierungsmechanismus. [ABSTRACT FROM AUTHOR]

A series of new C28-amino-lupanes bearing A-azepano- and A-seco-3-amino-fragments was synthesized from 3,28-dioximino-betulin and evaluated for cytotoxicity toward the NCI-60 cancer cell line panel and antimicrobial activity against key ESKAPE pathogens. A-azepano-28-amino-betulin exhibited remarkable activities with GI50 ranging from 1.16 to 2.27 μM against all panel with the highest activity toward leukemia, colon cancer, non-small cell lung cancer and breast cancer. The replacement of the hydroxyl group at C28 in the structure of azepanobetulin to the amino group did not show a strong effect on the cytotoxic activity. Both compounds were ∼5 and ∼4 times more active than doxorubicin against colon cancer HCT-15 and ovarian cancer NCI/ADR-RES cell lines, thus these A-azepano-lupane triterpenoids are the promising agents for future anticancer drug development. The ability of A-azepanobetulin to inhibit cell growth may be associated with its cytostatic effect, which, depending on the cell line, is associated with the arrest either S or G1 phase of cell cycle. 3-Amino-3,4-seco-28-amino-lup-4(23),20(29)-dien exhibited significant bacteriostatic effect against methicillin-resistant Staphylococcus aureus (MIC ≤ 0.25 μg/mL) that exceeds the effect of the clinically used antibiotic vancomycin. [ABSTRACT FROM AUTHOR]

A new, transformative methodology for the preparation of diketopyrrolopyrroles from aldehydes, primary amines, nitriles, and diethyl oxalacetate has been developed. It is now possible to prepare diketopyrrolopyrroles bearing an ordered arrangement of three different substituents from abundant and commercially available materials, allowing the independent regulation of all desired physicochemical properties. For the first time very electron‐rich (carbazol‐3‐yl, dimethylaminophenyl, pyrrolo[3,2‐b]pyrrolyl), and sterically hindered substituents (naphthalen‐1‐yl, quinolin‐4‐yl, acridin‐9‐yl, imidazo[1,5‐a]pyridin‐1‐yl, 2‐bromophenyl etc.) can be appended to the diketopyrrolopyrrole core by condensation of an appropriate nitrile with a pyrrolidin‐2‐one intermediate. Even greater synthetic possibilities are related to the fact that such demanding substituents as 4‐dimethylaminophenyl, indol‐3‐yl, and 2‐methoxyphenyl can be incorporated from aldehyde precursors, bypassing problems with the nitriles reactivity. [ABSTRACT FROM AUTHOR]

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of β‑lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].). [ABSTRACT FROM AUTHOR]

By means of the annulation of easy-to-handle yet sufficiently reactive (Sp)-2-formylferrocenecar- bonyl fluoride with the hydrochlorides of cysteamine and the methyl esters of enentiomer cysteines conducted in dichloromethane at room temperature in the presence of pyridine, the first members of 2,3-dihydroferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8bH)-ones with the elements of planar- and central chirality were prepared as single enantiomers. An atom economic procedure was also elaborated for the synthesis of these organometallic heterocycles directly exploring (Sp)-2-formylferrocenecarboxylic acid in situ activated by CDI and TFA, sequentially added to the reaction mixture. The relative and consequently, the absolute, configuration of the isolated diastereomers was determined by NMR measurements supported by DFT structural optimization. On the basis of the results of synthetic control experiments and a series of further DFT modelling studies, including energetic and MO analysis of the iminium intermediates, we propose a mechanism for the thiazolidine-forming annulations that proceed via primary N-acylation followed by proton-mediated cyclocondensation and subsequent diastereoselective sulfhydryl-attack on the resulting iminium center.

The use of arylglyoxal as starting material in Passerini and Ugi reactions affords β-ketoamides. This has allowed to study keto-enol tautomerism in these systems and assess the way in which the presence of acyloxy or aminoacyl groups bound to the C2 position affects such tautomerism, and to investigate the reactivity of both the enol and carbonyl forms. In this work we also prove the versatility of the Passerini reaction, since depending on the conditions to which the corresponding adducts are subjected different products of synthetic interest can be obtained.

Tertiary allylic alcohols equipped with a carboxyl group can be smoothly aminated under ambient conditions by a conceptually new and stereoselective protocol under palladium catalysis. The in situ formed Z‐configured γ‐amino acid cyclizes to afford an α,β‐unsaturated γ‐lactam, releasing water as the only byproduct. This practical catalytic transformation highlights the use of a carboxyl group acting as an activating and stereodirecting functional group to provide a wide series of pharma‐relevant building blocks. Various control reactions support the crucial role of the carboxyl group in the substrate to mediate these transformations. [ABSTRACT FROM AUTHOR]

The development of a general platinum‐catalyzed desaturation of N‐protected lactams, ketones, and lactones to their conjugated α,β‐unsaturated counterparts is reported. The reaction operates under mildly acidic conditions at room temperature or 50 °C. It is scalable and tolerates a wide range of functional groups. The complementary reactivity to the palladium‐catalyzed desaturation is demonstrated in the efficient conversion of iodide, bromide, and sulfur‐containing substrates. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of optically active interlocked and non‐interlocked 2‐azetidinones by intramolecular cyclization of N‐(α‐methyl)benzyl fumaramide [2]rotaxanes is described. Two different strategies of asymmetric induction were tested in which the chiral group was located either proximal or distal to the reacting center of the thread. During these experiments, an interesting equilibration process inside the macrocyclic void occurred, thus leading to the cyclization through the (α‐methyl)benzyl carbon atom and giving rise to β‐lactams, with a quaternary carbon atom, in an enantio‐ and diastereocontrolled manner. This cyclization also proceeds in kinetically stable chiral pseudo[2]rotaxanes, thus allowing further dethreading to provide enantioenriched 3,4‐disubstituted trans‐2‐azetidinones. The stereochemical outcomes of the cyclizations inside and outside the macrocycle demonstrated noticeable differences. [ABSTRACT FROM AUTHOR]

Abstract: A direct and catalytic method is reported here for β‐arylation of N‐protected lactams with simple aryl iodides. The transformation is enabled by merging soft enolization of lactams, palladium‐catalyzed desaturation, Ar−X bond activation, and aryl conjugate addition. The reaction is operated under mild reaction conditions, is scalable, and is chemoselective. Application of this method to concise syntheses of pharmaceutically relevant compounds is demonstrated. [ABSTRACT FROM AUTHOR]

A strategy to control the switch between a non-cycloaddition reaction and a cycloaddition reaction of enals, using N-heterocyclic carbene (NHC) catalyisis, has been developed. The new scalable protocol leads to γ-amino-acid esters bearing a tetrasubstituted stereocenter in good yields and high stereoselectivities by homo-Mannich reactions of enals and isatin-derived ketimines. By simply changing the N-ketimine substituent to an ortho-hydroxy phenyl group, the corresponding spirocyclic oxindolo-γ-lactams are obtained. [ABSTRACT FROM AUTHOR]

The first general asymmetric synthesis of γ,γ-disubstituted γ-amino acids by copper-catalyzed ring opening of nonstrained lactones with amines is reported. This approach features ample scope, operational simplicity, and wide functional-group diversity. The catalytic process allows access to a series of highly functionalized enantioenriched γ-amino acids featuring quaternary stereocenters with excellent enantiomeric ratios of up to 98:2 and excellent yields of up to 98 %. [ABSTRACT FROM AUTHOR]

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). [ABSTRACT FROM AUTHOR]

Palladium(II)-catalyzed C−H carbonylation reactions of methylene C−H bonds in secondary aliphatic amines lead to the formation of trans-disubstituted β-lactams in excellent yields and selectivities. The generality of the C−H carbonylation process is aided by the action of xantphos-based ligands and is important in securing good yields for the β-lactam products. [ABSTRACT FROM AUTHOR]

A new approach for the divergent total syntheses of (±)-vincaminorine, (±)-N-methylquebrachamine, (±)-quebrachamine, (±)-minovine and (±)-vincadifformine, each in less than 10 linear steps starting from a single δ-lactam building block, is reported. Key to our route design is the late-stage generation of reactive enamine functionality from stable indole-linked δ-lactams via a highly chemoselective iridium(I)-catalyzed reduction. The efficiently formed secodine intermediates subsequently undergo either a formal Diels-Alder cycloaddition or a competitive Michael addition/reduction to access aspidosperma-type alkaloids in excellent diastereoselectivities. Product selectivity could be controlled by changing the indole N-protecting group in the reductive cyclization precursors. An asymmetric variant of this synthetic strategy for the synthesis of (+)-20-epi-ibophyllidine is also described. [ABSTRACT FROM AUTHOR]

The fungal secondary metabolite aspergillomarasmine A (AMA) has recently been identified as an inhibitor of metallo-β-lactamases NDM-1 and VIM-2. Described herein is an efficient and practical route to AMA and its related compounds by a sulfamidate approach. In addition, a series of derivatives has been prepared and tested for biological activity in an effort to explore preliminary structure activity relationships. While it was determined that natural LLL isomer of AMA remains the most effective inactivator of NDM-1 enzyme activity both in vitro and in cells, the structure is highly tolerant of the changes in the stereochemistry at positions 3, 6, and 9. [ABSTRACT FROM AUTHOR]

Reported is the development of a novel catalytic cascade reaction facilitating the modular synthesis of cyclic tertiary amines from simple lactam substrates and secondary alcohols. Using a single molecular ruthenium-triphos catalyst in the presence of molecular hydrogen enabled the versatile formation of various amines in high yield with excellent selectivity. Extending the reaction system to using an alcohol as the hydrogen transfer reagent allowed the reduction of lactams without the need for molecular hydrogen. [ABSTRACT FROM AUTHOR]

A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α-bromo-β-ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α,β-epoxy-γ-lactam. Furthermore, the absolute configuration of naturally occurring (+)-rubrobramide was determined by vibrational circular dichroism. (±)-Flavipucine and (±)-isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α-bromo-β-ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)-flavipucine, which was converted into (±)-isoflavipucine by thermal isomerization. [ABSTRACT FROM AUTHOR]

Described herein is that the catalytic construction of N-substituted five- and six-membered lactams from keto acids with primary amines by reductive amination, using an indium/silane combination. This relatively benign and safe catalyst/reductant system tolerates the use of a variety of functional groups, especially ones that are reduction-sensitive. A direct switch from synthesizing lactams to synthesizing cyclic amines is achieved by changing the catalyst from In(OAc)3 to InI3. This conversion occurs by further reduction of the lactam using the indium/silane pair. [ABSTRACT FROM AUTHOR]

The development of a tailored tridentate ligand enabled the synthesis of a molecular ruthenium-triphos catalyst, eliminating dimerization as the major deactivation pathway. The novel catalyst design showed strongly increased performance and facilitated the hydrogenation of highly challenging lactam substrates with unprecedented activity and selectivity. [ABSTRACT FROM AUTHOR]

A highly facile, efficient, and enantioselective bromolactamization of olefinic amides was effected by a carbamate catalyst and ethanol additive. The amide substrates underwent N-cyclization predominantly to give a diverse range of enantioenriched bromolactam products containing up to two stereogenic centers. [ABSTRACT FROM AUTHOR]

Cyclopropanes fused to pyrrolidines are important structural features found in a number of marketed drugs and development candidates. Typically, their synthesis involves the cyclopropanation of a dihydropyrrole precursor. Reported herein is a complementary approach which employs a palladium(0)-catalyzed CH functionalization of an achiral cyclopropane to close the pyrrolidine ring in an enantioselective manner. In contrast to aryl-aryl couplings, palladium(0)-catalyzed CH functionalizations involving the formation of C(sp3)C(sp3) bonds of saturated heterocycles are very scarce. The presented strategy yields cyclopropane-fused γ-lactams from chloroacetamide substrates. A bulky Taddol phosphonite ligand in combination with adamantane-1-carboxylic acid as a cocatalyst provides the γ-lactams in excellent yields and enantioselectivities. [ABSTRACT FROM AUTHOR]

Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regeneration of a reactive acyliminium ion that is then reacted with a range of nucleophilic species. [ABSTRACT FROM AUTHOR]

A mild and efficient intermolecular ring-expansion approach was developed for the synthesis of medium-ring lactams by using siloxy alkynes. Key to success is the suitable combination of a superior catalyst and an exceptional nitrogen-protecting group. Control experiments indicated that the reaction is remarkably selective toward the desired lactam formation, even with many possible non-productive pathways. [ABSTRACT FROM AUTHOR]

Das tödliche „bla ‐ bla“ der Killerbakterien: Der Naturstoff Aspergillomarasmin A (AMA) wirkte in Enterobacteriaceen vom β ‐ Lactamase ‐ Resistenztyp blaNDM ‐ 1 (NDM ‐ 1: Neu Delhi Metallo ‐ β ‐ Lactamase 1). Die Wirksamkeit des Goldstandards Meropenem konnte in Nagern durch Inhibition von NDM ‐ 1 im Zink ‐ haltigen aktiven Zentrum wiederhergestellt werden. [ABSTRACT FROM AUTHOR]

Current methods for the detection of Mycobacterium tuberculosis (Mtb) are either time consuming or require expensive instruments and are thus are not suitable for point-of-care diagnosis. The design, synthesis, and evaluation of fluorogenic probes with high specificity for BlaC, a biomarker expressed by Mtb, are described. The fluorogenic probe CDG-3 is based on cephalosporin with substitutions at the 2 and 7 positions and it demonstrates over 120 000-fold selectivity for BlaC over TEM-1 Bla, the most common β-lactamase. CDG-3 can detect 10 colony-forming units of the attenuated Mycobacterium bovis strain BCG in human sputum in the presence of high levels of contaminating β-lactamases expressed by other clinically prevalent bacterial strains. In a trial with 50 clinical samples, CDG-3 detected tuberculosis with 90 % sensitivity and 73 % specificity relative to Mtb culture within one hour, thus demonstrating its potential as a low-cost point-of-care test for use in resource-limited areas. [ABSTRACT FROM AUTHOR]

β-Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring-opening reactions. Transition-metal-catalyzed CH functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd0-catalyzed CH functionalization for aryl-aryl couplings, related reactions involving the formation of saturated C(sp3)C(sp3) bonds are elusive. Reported here is an asymmetric CH functionalization approach to β-lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp3)C(sp3) and strain-building reductive eliminations to for the four-membered ring. In general, the β-lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst. [ABSTRACT FROM AUTHOR]

The development process for syringolin A analogues having improved proteasome inhibitory and antitumor activity is described. The strategy was to first establish a convergent synthesis of syringolin A using a rare intramolecular Ugi three-component reaction in the last stage of the synthesis, so as to gain access toa set of structure-based analogues. The inhibitory activity of chymotrypsin-like activity of 20S proteasome was largely improved by targeting the S3 subsite of the β5 subunit. Cytotoxic activity was also improved by installing the membrane-permeable substituent. These biological properties are comparable to those of bortezomib, a clinically used first-line proteasome inhibitor. [ABSTRACT FROM AUTHOR]

The first copper-catalyzed intramolecular C(sp3)H and C(sp2)H oxidative amidation has been developed. Using a Cu(OAc)2 catalyst and an Ag2CO3 oxidant in dichloroethane solvent, C(sp3)H amidation proceeded at a terminal methyl group, as well as at the internal benzylic position of an alkyl chain. This reaction has a broad substrate scope, and various β-lactams were obtained in excellent yield, even on gram scale. Use of CuCl2 and Ag2CO3 under an O2 atmosphere in dimethyl sulfoxide, however, leads to 2-indolinone selectively by C(sp2)H amidation. Kinetic isotope effect (KIE) studies indicated that CH bond activation is the rate-determining step. The 5-methoxyquinolyl directing group could be removed by oxidation. [ABSTRACT FROM AUTHOR]

β-Lactam scaffolds are considered to be ideal building blocks for the synthesis of nitrogen-containing compounds. A new palladium-catalyzed oxidative carbonylation of N-allylamines for the synthesis of α-methylene-β-lactams is reported. DFT calculations suggest that the formation of β-lactams via a four-membered-ring transition state is favorable. [ABSTRACT FROM AUTHOR]

Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/IrI catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the CC bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives. [ABSTRACT FROM AUTHOR]

Ein wirkungsvoller Weckruf: Stabile α,β ‐ ungesättigte Ester wurden durch die Anlagerung eines chiralen N ‐ heterocyclischen Carbens (NHC) als Organokatalysator aktiviert. Die gebildeten Michael ‐ Akzeptoren reagierten mit Enamid ‐ Nukleophilen zu optisch reinen Produkten (siehe Schema; Ts=p ‐ Toluolsulfonyl), die in biologisch aktive δ ‐ Lactame und Piperidine überführt werden konnten. [ABSTRACT FROM AUTHOR]

Mobiler Acylrest: Die Titelreaktion liefert diastereomerenreine 3,4 ‐ disubstituierte Pyrrolidin ‐ 2 ‐ one, die sehr wichtige Strukturmotive in Naturstoffen sind, in guten bis ausgezeichneten Ausbeuten. Mechanistische Untersuchungen weisen darauf hin, dass die Transformation über eine Tandem ‐ 1,3 ‐ Acyloxywanderung und eine nachfolgende 1,5 ‐ Acyloxywanderung verläuft. [ABSTRACT FROM AUTHOR]

By means of the annulation of easy-to-handle yet sufficiently reactive (Sp)-2-formylferrocenecar- bonyl fluoride with the hydrochlorides of cysteamine and the methyl esters of enentiomer cysteines conducted in dichloromethane at room temperature in the presence of pyridine, the first members of 2,3-dihydroferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8bH)-ones with the elements of planar- and central chirality were prepared as single enantiomers. An atom economic procedure was also elaborated for the synthesis of these organometallic heterocycles directly exploring (Sp)-2-formylferrocenecarboxylic acid in situ activated by CDI and TFA, sequentially added to the reaction mixture. The relative and consequently, the absolute, configuration of the isolated diastereomers was determined by NMR measurements supported by DFT structural optimization. On the basis of the results of synthetic control experiments and a series of further DFT modelling studies, including energetic and MO analysis of the iminium intermediates, we propose a mechanism for the thiazolidine-forming annulations that proceed via primary N-acylation followed by proton-mediated cyclocondensation and subsequent diastereoselective sulfhydryl-attack on the resulting iminium center. [ABSTRACT FROM AUTHOR]

The use of arylglyoxal as starting material in Passerini and Ugi reactions affords β-ketoamides. This has allowed to study keto-enol tautomerism in these systems and assess the way in which the presence of acyloxy or aminoacyl groups bound to the C2 position affects such tautomerism, and to investigate the reactivity of both the enol and carbonyl forms. In this work we also prove the versatility of the Passerini reaction, since depending on the conditions to which the corresponding adducts are subjected different products of synthetic interest can be obtained. [ABSTRACT FROM AUTHOR]