Zinc Tetrafluoroborate-Mediated Ring Expansion of -Aziridine-2-carboxylates to -2-Iminothiazolidines and -Thiazolidine-2-iminium Tetrafluoroborates and Evaluation of Antimicrobial Activity.

-2-iminothiazolidines and -thiazolidine-2-iminium tetrafluoroborates were successfully produced from --alkyl aziridine-2-carboxylates and phenyl/alkyl isothiocyanates mediated by zinc tetrafluoroborate in refluxing DCE. Reactions were performed via a complete regio- and stereoselective process to give the title iminothiazolidines and -thiazolidine-2-iminium salts in moderate to good yields (35 to 82%) with a wide substrate scope. In addition, the antibacterial activity evaluation of these compounds, as well as the minimum inhibitory concentration (MIC) determination, revealed that only four -thiazolidine-2-iminium salts showed growth inhibition against .

Straightforward synthesis of various chiral pyrimidines bearing a stereogenic center adjacent to the C-2 position, including C-terminal peptide isosteres.

The present study describes an efficient access to enantioenriched pyrimidines' derivatives from readily available Boc-AA-NH and β-enaminones. This strategy allows the synthesis of a large variety of chiral pyrimidines (18 examples) with good yields from the chiral pool. In the case of peptide isosteres, this procedure proved to be highly stereoretentive and paves the way to the construction of C-terminal modified peptidomimetics as illustrated in the synthesis of two original pyrimidines containing pseudo-dipeptides.

Dynamic Kinetic Resolution Processes Based on the Switchable Configurational Instability of Allenyl Copper Reagents.

The configurational instability of allenyl copper reagents is unveiled. An experimental study highlights the crucial role of Li and of the reaction temperature in the control of the configurational stability of allenyl copper reagents. A judicious choice of the reaction conditions allows efficient dynamic kinetic resolution processes and gives a one-pot access to homopropargylic alcohols or amines bearing up to four contiguous defined stereogenic centers.

Intertwined Analytical, Experimental and Theoretical Studies on the Formation and Structure of a Copper Dienolate.

The reaction of a silyl dienolate, a Cu(II) salt and TBAT yielding the corresponding copper dienolate is addressed. A combined NMR and cyclic voltammetry analysis first highlight the role of TBAT in the Cu(II) to Cu(I) reduction and the structure of the precatalytic species. From these first results a second set of NMR and theoretical studies enable the determination of the structure and the mechanism of formation of the copper dienolate catalytic species.

Mechanism of Enolate Transfer between Si and Cu.

Exchange of X (F, Cl, OMe) and a substituted enolate chain between SiMe and various Cu complexes was examined. Reaction mechanisms pass through a cyclic transition state in which the reaction coordinate is associated with rotation of the SiMe moiety. The dependence of the thermodynamic and kinetic features on the nature of the active and ancillary ligands was examined.

Tandem reactions involving 1-silyl-3-boryl-2-alkenes. New access to (Z)-1-fluoro-1-alkenes, allyl fluorides, and diversely α-substituted allylboronates.

The reactions of 1-silyl-3-boryl-2-alkenes with various electrophilic reagents (Selectfluor, N-halosuccinimides, benzhydryl, and propargylic alcohols in the presence of a Lewis acid, N-alkoxycarbonyliminium ion) have been investigated as new routes to α-substituted allylboronates. Further functional transformations, including allylboration, Suzuki coupling, protodeboronation, and cycloisomerization, have been carried out to illustrate the synthetic potential of these γ-borylallylsilanes.

Stereoselective and catalytic access to β-enaminones: an entry to pyrimidines.

We describe herein a highly stereoselective access to Cbz-protected β-enaminones 2 based on the NaOH catalyzed rearrangement of propargylic hydroxylamines 1. The synthetic potential of these β-enaminones is illustrated in an original synthesis of pyrimidines.

Chiral aryl-copper(III) electrophiles: new opportunities in catalytic enantioselective arylations and domino processes.

"Chiral aryl cation" equivalents: The combination of diaryliodonium salts and catalytic amounts of chiral copper complexes provides facile access to "chiral aryl cation" synthons. These reagents offer new possibilities for asymmetric arylation reactions that initiate further domino processes.

Transition-metal-catalyzed uninterrupted four-step sequence to access trisubstituted isoxazoles.

We describe herein a novel uninterrupted four-step sequence to access trisubstituted isoxazoles from readily available propargylic alcohols using sequentially iron and palladium catalytic systems. The advantages of such a strategy are illustrated by the high overall yields and the time-saving procedure that are reported.

Gold-catalyzed propargylic substitutions: Scope and synthetic developments.

This personal account summarizes our recent developments in gold-catalyzed direct substitutions on propargylic (allylic, benzylic) alcohols, with various nucleophiles (and bi-nucleophiles) based on the σ- and/or π-acidity of gold(III) complexes. Synthetic developments are also briefly described.

Diastereodivergent behavior of alkyl versus cyano allenylcuprates toward aldehydes: a key role for lithium.

The stereodivergent behavior of allenyl(cyano)- and allenyl(alkyl)cuprates toward aldehydes, providing a selective preparation of both syn- and anti-homopropargylic alcohols, is described. This study, which combines both experimental and theoretical support, shows that the copper nontransferred "dummy ligand" controls the localization of the lithium cation with respect to the allenylcuprate moiety. As a consequence, Li(+) acts as a Lewis acid activator but also controls the diastereoselectivity during the addition of allenylcuprates onto aldehydes.

A versatile iron-catalyzed protocol for the one-pot synthesis of isoxazoles or isoxazolines from the same propargylic alcohols.

The use N-sulfonyl-protected hydroxylamines as bi-nucleophiles in iron-catalyzed propargylic substitutions allows the selective one-pot synthesis of four classes of substituted isoxazoles or isoxazolines from the same propargylic alcohols (21 examples) by simply tuning the nature of the base. By using an iron(III) catalyst and a base such as triethylamine (3 equiv), isoxazoles 3 are obtained in good isolated yields (56-95%), whereas N-sulfonyl-protected isoxazolines 6 are selectively obtained (77-93% yield) by using iron and gold catalysts in the presence of a catalytic amount of pyridine (10 mol%).

Highly diastereoselective Baldwin rearrangement of isoxazolines into cis-acylaziridines.

An atom-economical and practical synthesis of cis-N-benzenesulfonamide acylaziridines through the Baldwin rearrangement of various N-benzenesulfonamide isoxazolines has been reported. A detailed experimental study revealed the beneficial effect of microwaves and pointed out the crucial role of the temperature in the reaction course. Moderate to good yields and excellent cis stereoselectivities were achieved for 13 examples.

Palladium-catalyzed cyclization of unsaturated beta-amino alcohols: a new access to enantiopure bicyclic oxazolidines.

Chiral unsaturated beta-amino alcohols possessing a dialkylamino function cyclize in the presence of Pd(II) catalysts and reoxidants to afford enantiopure bicyclic oxazolidines with total regio- and stereocontrol. The scope and limitations of this transformation have been studied.

Short enantioselective syntheses of trans-5-alkylprolines from new functionalized amino alcohols.

Amino alcohols, having an enol ether function, cyclized in acidic medium to give quantitatively diastereosomerically pure bicyclic compounds that were transformed in five steps in enantiopure trans-5-alkylproline derivatives.

Addition of hetero allenyl copper reagents to aldehydes: scope and behavior.

Cyanocuprates derived from propargylic amines or ethers react with aldehydes to give regioselectively the corresponding anti-homopropargylic alcohols with a high level of diastereoselectivity. Such selectivity could be obtained independently of the nature of the heteroatom (amine or ethers) or the acetylenic substituents. Excellent selectivities can be reached regardless of the aldehydes used, remarkably also with vinylic or acetylenic ones.

Addition of a chiral copper reagent derived from propargylic oxazolidininone to aldehydes.

[reaction: see text] The copper reagent arising from an optically pure propargylic oxazolidinone was found to react regio- and diastereoselectively with aldehydes, leading, in a one-pot procedure, to the anti homopropargylic amino alcohols derivatives in good yields.

Copper reagents: a new and efficient solution for the selective addition of metallated propargylic amines to aldehydes.

[reaction: see text] Anti alpha-amino-homopropargylic alcohols are prepared by addition of metallated propargylic amines to aldehydes. Among the four organometallic (LI, Zn, Ti, Cu) derivatives used, the most effective are the copper reagents.

Diastereoselective aldolization of alpha-aminonitriles. Diastereoselective synthesis of beta-amino alcohols and beta,gamma-diamino alcohols.

Aldolization performed by addition of lithiated N-benzyl-N-tert-butylaminoacetonitrile to aldehydes provides diastereomerically pure anti-beta-hydroxy-alpha-aminonitriles. They are transformed into syn,anti-protected beta,gamma-diamino alcohols by a two-step procedure, involving addition of a Grignard reagent and reduction. The cleavage of the N-tert-butyl group is achieved by a simple acidic treatment.