Olga Staszewska-Krajewska

Synthesis of polyhydroxylated quinolizidine and indolizidine scaffolds from sugar-derived lactams via a one-pot reduction/Mannich/Michael sequence.

A direct approach to the synthesis of indolizidine and quinolizidine scaffolds of iminosugars is described. The presented strategy is based on a one-pot sugar lactam reduction with Schwartzs reagent followed by a diastereoselective Mannich/Michael tandem reaction of the resulting sugar imine with Danishefskys diene. The stereochemical course of the investigated reaction has been explained in detail. The obtained bicyclic products are attractive building blocks for the synthesis of various naturally occurring polyhydroxylated alkaloids and their derivatives.

A practical preparation of the key intermediate for penems and carbapenems synthesis

A novel, practical and stereoselective synthesis of (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone, a key intermediate in the preparation of β-lactam antibiotics is reported. The crucial step of the synthesis is based on the Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade between silyl protected (R)-3-butyn-2-ol and the nitrone derived from benzyl hydroxylamine and benzyl glyoxylate. The obtained adduct is subjected to debenzylation with sodium, or lithium in liquid ammonia followed by oxidation with lead tetraacetate to afford the final product.

Bispyrrolylbenzene anion receptor: from supramolecular switch to molecular logic gate.

We have designed anion receptor 4 based on a conformationally labile bispyrrolylbenzene framework, the conformation of which can be changed by appropriate anionic stimuli. In the absence of fluoride anion, the pyrrole moieties rotate freely at room temperature. However, when the concentration of fluoride anion exceeds 2 equivalents, the rotation of the pyrrole units slows down and the conformation of the receptor changes to anti-anti. DFT calculations have shown that this change is due to binding of a third fluoride anion through C-H interaction. Anion receptor 4 can also serve as a molecular logic gate. Anionic inputs such as fluoride and dihydrogenphosphate allow the realization of INHIBIT and NAND logic gate functions with absorption and fluorescence as readouts, respectively.

Ferrier-Petasis rearrangement of 4-(vinyloxy)azetidin-2-ones: an entry to carbapenams and carbacephams.

Trimethylsilyl triflate promotes Ferrier-Petasis rearrangement of 4-(vinyloxy)-, 4-(propenyloxy)-, and 4-(isopropenyloxy)azetidin-2-ones to corresponding 4-(carbonylmethyl)azetidin-2-ones. The latter compounds may serve as attractive intermediates in the synthesis of carbapenem antibiotics. To illustrate the potential of this reaction, selected rearrangement products have been transformed into carbapenams.

Synthesis of Thienamycin methyl ester from 2-deoxy- d -ribose via Kinugasa reaction

A novel synthesis of thienamycin is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from d-lactic acid and suitable, partially protected, five-membered cyclic nitrone obtained from 2-deoxy-d-ribose. The reaction was performed in the presence of tetramethylguanidine as a base to provide 5,6-trans substituted carbapenam as the main product. Thus obtained carbapenam 11 with (5R,6S) configuration at the azetidinone ring was subsequently subjected to oxidation/deprotection/oxidation reaction sequence to afford the β-keto ester 20, which was directly transformed into N,O-protected methyl ester of thienamycin.

A nitrogen NMR and X-ray investigation of some mesoionic 1,3-diazoles, 1,3-oxazoles and 1,3-thiazoles

Abstract 14 N, 15 N and 17 O NMR and data are reported for some mesoionic 1,3-diazoles, 1,3-oxazoles and 1,3-thiadiazoles. Additionally, 15 N CP/MAS NMR data are also given for five mesoionic 1,3-diazoles. The relation between compound structures and NMR parameters has been discussed. 15 N chemical shift values for diazoles, taken from CP/MAS NMR measurements, are very similar to the values observed for compounds in the solution. These imply the structure similarity of compounds in both phases, and allow excluding the chain–ring equilibrium in the solution. The cyclic, ‘mesoionic’ structure of 1,3-diazole have been confirmed by X-ray diffraction study.

Pd-Catalyzed Carbonylative Carboperfluoroalkylation of Alkynes. Through-Space 13C–19F Coupling as a Probe for Configuration Assignment of Fluoroalkyl-Substituted Olefins

A four-component Pd-catalyzed protocol for direct synthesis of perfluoroalkyl-substituted enones is reported. Under mild conditions and low catalyst loading, alkynes, iodoperfluoroalkanes, (hetero)arylboronic acids, and carbon monoxide are assembled into highly elaborate products with good yields and excellent regio- and stereoselectivities. The configuration of the products was confirmed by the observation of through-space 13C-19F couplings, accessible through the analysis of routine 13C NMR spectra.

1,3-Dipolar cycloaddition of a cyclic nitrone derived from 2-deoxy-D-ribose to α,β-unsaturated lactones: An entry to carbapenem antibiotics.

1,3-Dipolar cycloadditions of 2-deoxy-D-ribose-derived L-threo five-membered cyclic nitrone to α,β-unsaturated γ- and δ-lactones were investigated. Cycloadducts obtained from δ-lactones, after NO bond cleavage, opening of the lactone ring, and protection of hydroxyl groups were subjected to β-lactam ring formation by using Mukaiyamas salt. Cycloadducts from γ-lactones subjected to the same reaction sequence undergo β-elimination of a water molecule to provide pyrrolidine-substituted unsaturated γ-lactones.

Reverse regioselectivity in Pd(0)/InI-mediated allylation of aldehydes with ε-amido-allylindiums generated from β-lactams. A new entry to non-racemic highly substituted γ-butyrolactones

e-Amido-allylindiums generated from N-Ts-β-lactams in the presence of 2 eq. of InI, catalytic amounts of Pd(PPh3)4 and 5 eq. of CF3CO2H react regio- and stereoselectively with a number of aromatic and aliphatic aldehydes to afford γ-butyrolactones as the exclusive products in high yield.

Hydrogen Bonds Involving Cavity NH Protons Drives Supramolecular Oligomerization of Amido‐Corroles

trans-A2 B-Corroles with amide substituents at different positions versus the macrocyclic core have been synthesized. Their self-organizing properties have been comprehensively evaluated both in solid-state and in solution. The rigid arrangement of the amide functionality with the corrole ring led to the formation of strong intramolecular interactions and precluded intermolecular interactions. Replacement of sterically hindered C6 F5 substituents at positions 5 and 15 with smaller electron-withdrawing CO2 Me groups resulted in significant changes in the self-assembly pattern. With these substituents, tetramers formed in a crystalline state, in which one of the H-pyrrole subunits is out of the corrole plane. This allows the N-H group to form a hydrogen bond with a neighboring carbonyl group of the n-butyl amide fragment. DOSY NMR studies showed that amido-corroles bearing the OCH2 CONHnBu motif formed dimers in millimolar solutions in nonpolar solvents and the dimers existed in equilibrium with monomers. However, the corroles possessing meso-ester groups did not form dimers in polar tetrahydrofuran. Comprehensive optical studies allowed the absorption and emission features of the monomer corroles to be characterized in dilute solutions.