Regio- and Stereoselective Lithiation and Electrophilic Substitution Reactions of <i>N</i>-Alkyl-2,3-diphenylaziridines: Solvent Effect^†

The lithiation reaction of cis- and trans-N-alkyl-2,3-diphenylaziridines has been investigated. While cis-diphenylaziridines do not undergo any lithiation upon treatment with organolithiums, the lithiation reaction of the trans counterparts is completely α-regioselective and the stereochemical course of the lithiation-trapping sequence is solvent dependent:  inversion of configuration in coordinating solvents (THF or toluene/crown ether) and retention in hexane, ether, or toluene. The preparation of stereodefined functionalized N-alkyl-2,3-diphenylaziridines is described

α- vs Ortho-Lithiation of <i>N</i>-Alkylarylaziridines: Probing the Role of the Nitrogen Inversion Process

The lithiation reaction of monophenyl- and diphenylaziridines has been investigated in detail in an effort to understand why the former undergo exclusively or mainly ortho-lithiation while the latter are lithiated exclusively at the α-position. Evidence is reported that ruled out the possibility that the α-lithiation, observed for the diphenylaziridines, is the result of an ortho- to α-translocation phenomenon, thus substantiating a direct α-deprotonation process. The role of the aziridine nitrogen lone-pair has been considered: dynamics at the aziridine nitrogen as well as complex-induced proximity effects seem to be responsible for the observed regioselectivity in both monophenyl and diphenylaziridines. It turns out that, by tuning the reaction conditions for the lithiation of trans-1-alkyl-2-methyl-3-phenylaziridines, it is possible to generate with high regioselectivity α- and/or ortho-lithiated aziridines, which can be stereoselectively functionalized by electrophilic trapping. A regioselective ortho-functionalization of diphenylaziridines is made possible by halogen− or tin−lithium exchange and by deprotonation of bis-deuterated aziridines

Directed Ortho Lithiation of <i>N</i>-Alkylphenylaziridines

The ortho lithiation−trapping sequence of phenylaziridines is described. This methodology, which counts on the ability of the aziridino group to act as a directed metalation group (DMG), provides an easy access to functionalized arylaziridines as well as to phthalans and phthalides. The importance of the aziridine N-substituent in this DoM reaction is stressed as well

BH₃-Promoted Stereoselective β-Lithiation of <i>N</i>-Alkyl-2-phenylaziridines

BH3 complexes of N-alkyl-2-phenylaziridines have been synthesized and their structure and stereochemistry proved with DFT calculations and NMR experiments. It has been demonstrated that the Lewis acid complexation is able to promote a regioselective β-lithiation in 2-phenylaziridino−borane complexes. The lithiated intermediates were configurationally stable, allowing an enantioselective preparation of cis-2,3-disubstituted aziridines

Regio- and Stereoselective Lithiation of 2,3-Diphenylaziridines: A Multinuclear NMR Investigation

The α-lithiation-trapping sequence of trans-N-alkyl-2,3-diphenylaziridines (s-BuLi or s-BuLi/TMEDA), taking place with a stereochemistry which dramatically depends on the solvent coordinating ability (inversion of configuration in THF and retention in toluene), has been carefully investigated. 1H,13C, and 7Li multinuclear NMR investigations at low temperature suggest that two differently configured lithiated aziridines (monomeric cis-1-Li in THF and dimeric trans-1-Li in toluene) are involved

Synthesis of Optically Active Arylaziridines by Regio- and Stereospecific Lithiation of <i>N</i>-Bus-Phenylaziridine

α,α-Disubstituted aziridines can be produced in good yields by selective lithiation of N-tert-butylsulfonyl-2-phenylaziridine (n-BuLi/TMEDA, Et2O) at the benzylic position and subsequent trapping with a range of electrophiles. Repetition of the lithiation/electrophilic trapping sequence provides a stereocontrolled route to trisubstituted aziridines. Using (R)-N-tert-butylsulfonyl-2-phenylaziridine, the α,α-disubstituted aziridines can be produced as single enantiomers (er >98:2), indicating that the intermediate organolithium is configurationally stable. Efficient aziridine ring-opening reactions leading to 1,2-diamines and 1,4-diamines are also reported

Lithiation of <i>N</i>-Alkyl-(<i>o</i>-tolyl)aziridine: Stereoselective Synthesis of Isochromans

The lithiation reaction of o-tolylaziridine 1 has been investigated by using the aziridine ring capability to act as a directing metalation group. Trapped with electrophiles, the resulting o-aziridinyl benzyllithium 1-Li gives access to several functionalized aziridines 2a−j. The hydroxyalkylated derivatives 2d−j were converted into important scaffolds such as isochromans 3a−d. A stereoselective preparation of isochromans (R)-3b, (1R,3S)-3d, and (1R,3R)-3d has been developed starting from enantioenriched o-tolylaziridine

Lithiation of <i>N</i>-Alkyl-(<i>o</i>-tolyl)aziridine: Stereoselective Synthesis of Isochromans

The lithiation reaction of o-tolylaziridine 1 has been investigated by using the aziridine ring capability to act as a directing metalation group. Trapped with electrophiles, the resulting o-aziridinyl benzyllithium 1-Li gives access to several functionalized aziridines 2a−j. The hydroxyalkylated derivatives 2d−j were converted into important scaffolds such as isochromans 3a−d. A stereoselective preparation of isochromans (R)-3b, (1R,3S)-3d, and (1R,3R)-3d has been developed starting from enantioenriched o-tolylaziridine

Expedient Preparation of Nazlinine and a Small Library of Indole Alkaloids Using Flow Electrochemistry as an Enabling Technology

An expedient synthesis of the indole alkaloid nazlinine is reported. Judicious choice of flow electrochemistry as an enabling technology has permitted the rapid generation of a small library of unnatural relatives of this biologically active molecule. Furthermore, by conducting the key electrochemical Shono oxidation in a flow cell, the loading of electrolyte can be significantly reduced to 20 mol % while maintaining a stable, broadly applicable process

DataSheet_1_Exploring the xylem-sap to unravel biological features of Xylella fastidiosa subspecies pauca ST53 in immune, resistant and susceptible crop species through metabolomics and in vitro studies.docx

Xylella fastidiosa subsp. pauca ST53 (Xfp) is a pathogenic bacterium causing one of the most severe plant diseases currently threatening the olive-growing areas of the Mediterranean, the Olive Quick Decline Syndrome (OQDS). The majority of the olive cultivars upon infections more or less rapidly develop severe desiccation phenomena, while few are resistant (e.g. Leccino and FS17), being less impacted by the infections. The present study contributes to elucidating the basis of the resistance phenomenon by investigating the influence of the composition of the xylem sap of plant species on the rate of bacterial multiplication. Xylem saps from Xfp host and non-host species were used for growing the bacterium in vitro, monitoring bacterial growth, biofilm formation, and the expression of specific genes. Moreover, species-specific metabolites, such as mannitol, quinic acid, tartaric acid, and choline were identified by non-targeted NMR-based metabolomic analysis in olive, grapevine, and citrus. In general, the xylem saps of immune species, including grapevine and citrus, were richer in amino acids, organic acids, and glucose. The results showed greater bacterial growth in the olive cultivar notoriously susceptible to Xfp (Cellina di Nardò), compared to that recorded in the resistant cultivar Leccino. Conversely, higher biofilm formation occurred in Leccino compared to Cellina di Nardò. Using the xylem saps of two Xfp-immune species (citrus and grapevine), a divergent bacterial behavior was recorded: low planktonic growth and biofilm production were detected in citrus compared to the grapevine. A parallel evaluation of the expression of 15 genes showed that Xfp directs its molecular functions mainly to virulence. Overall, the results gained through this multidisciplinary study contribute to extending the knowledge on the host-pathogen interaction, while confirming that the host response and resistance mechanism have a multifactorial basis, most likely with a cumulative effect on the phenotype.</p