Pd(0)-Catalyzed Tandem Deprotection/Cyclization of Tetrahydro-β-carbolines on Allenes: Application to the Synthesis of Indolo[2,3‑<i>a</i>]quinolizidines

The pallado-catalyzed tandem deprotection/cyclization reaction of enantioenriched <i>N</i>-allyl tetrahydro-β-carbolines on allenes is described. The first step generates in situ a deprotected tetrahydro-β-carboline, which then undergoes a cyclization on the allene function via an intermediate π-allyl Pd­(II) derivative. This reaction results in the synthesis of various chiral indolic tetracycles (mainly indolo­[2,3<i>a</i>]­quinolizidine derivatives) presenting a vinyl function

Asymmetric Synthesis of Polyhydroxylated <i>N</i>-Alkoxypiperidines by Ring-Closing Double Reductive Amination: Facile Preparation of Isofagomine and Analogues

A de novo synthesis of novel polyhydroxylated <i>N</i>-alkoxypiperidines based on the ring-closing double reductive amination of 1,5-dialdehydes, obtained by oxidative cleavage of cyclopentene derivatives, with O-substituted hydroxylamines is reported. Isofagomine was accessed by cleavage of the N–O bond of an <i>N</i>-alkoxypiperidine

Domino Formation of Enamines - Intramolecular Cyclizations to 1‑Aminotetralins from γ‑Arylallene Aldehydes and Amines

1,5-/1,6-Allenals conjugated to an aromatic ring undergo a cyclization, in the presence of an amine, that leads to tricyclic compounds including the 1-aminotetralin scaffold. This domino process combines the <i>in situ</i> formation of the enamine and the cyclization affording the tricyclic 1-aminotetralins in very high diastereoselectivities

Study of the Total Synthesis of (−)-Exiguolide

In this article, we disclose the various routes and strategies we had to explore before finally achieving the total synthesis of (−)-exiguolide ((−)-<b>1</b>). Two first types of approaches were set, both relying on the Trost’s domino ene–yne coupling/oxa-Michael reaction that we choose for its ability to control the geometry of the methylacrylate-bearing tetrahydropyrane ring <i>B</i>. In our first approach, we expected to assemble the two main fragments (C14–C21 and C1–C13) by creating the C13–C14 bond through a palladium(0)-catalyzed cross-coupling, but this step failed, unfortunately. In the second approach, which was more linear, we created the C16–C17 bond through condensation of a lithium acetylide on a Weinreb amide, and we assembled the C1–C5 and C6–C21 subunits through Trost’s domino ene–yne coupling/oxa-Michael reaction. These two approaches served us to design an ameliorated third strategy, which finally led to the total synthesis of (−)-exiguolide

Synthesis, Characterization, and Coupling Reactions of Six-Membered Cyclic P‑Chiral Ammonium Phosphonite–Boranes; Reactive <i>H</i>‑Phosphinate Equivalents for the Stereoselective Synthesis of Glycomimetics

Stereoselective syntheses of P-chiral ammonium phosphonite-borane complexes in the <i>gluco</i>- and <i>manno</i>-like series have been developed from P­(V) phostone derivatives. The coupling reactions of these phostone donors with alcohols have been investigated with particular emphasis on the influence of protecting groups and conditions on stereoselectivity. The phosphonite–borane complexes may be applied directly in the coupling reactions and the products oxidized in situ to give phostone-mimetics of disaccharides. On the basis of these studies, successful protocols were established for the synthesis of β-gluco and α- and β-manno-configured phostones of primary alcohols. Deprotection of the dimeric compounds leads to novel families of α- or β-(1→6)-linked glycomimetics

Synthesis, Characterization, and Coupling Reactions of Six-Membered Cyclic P‑Chiral Ammonium Phosphonite–Boranes; Reactive <i>H</i>‑Phosphinate Equivalents for the Stereoselective Synthesis of Glycomimetics

Stereoselective syntheses of P-chiral ammonium phosphonite-borane complexes in the <i>gluco</i>- and <i>manno</i>-like series have been developed from P­(V) phostone derivatives. The coupling reactions of these phostone donors with alcohols have been investigated with particular emphasis on the influence of protecting groups and conditions on stereoselectivity. The phosphonite–borane complexes may be applied directly in the coupling reactions and the products oxidized in situ to give phostone-mimetics of disaccharides. On the basis of these studies, successful protocols were established for the synthesis of β-gluco and α- and β-manno-configured phostones of primary alcohols. Deprotection of the dimeric compounds leads to novel families of α- or β-(1→6)-linked glycomimetics

Dissecting the Gold(I)-Catalyzed Carboaminations of <i>N</i>‑Allyl Tetrahydro-β-carbolines to Allenes

<i>N</i>-Allyl tetrahydro-β-carbolines undergo gold-catalyzed cyclizations that lead to tetracyclic compounds, resulting from both ring closure and the transfer of the allylic group from the nitrogen to the carbon backbone. The final skeleton obtained depends on the nature of both the R² group of the allene and the R³ group of the allylic residue. Mechanistic studies and DFT calculations allowed the determination of all the mechanistic pathways involved in these processes, stemming from a common intermediate that evolves differently according to the substituents nature

Dissecting the Gold(I)-Catalyzed Carboaminations of <i>N</i>‑Allyl Tetrahydro-β-carbolines to Allenes

<i>N</i>-Allyl tetrahydro-β-carbolines undergo gold-catalyzed cyclizations that lead to tetracyclic compounds, resulting from both ring closure and the transfer of the allylic group from the nitrogen to the carbon backbone. The final skeleton obtained depends on the nature of both the R² group of the allene and the R³ group of the allylic residue. Mechanistic studies and DFT calculations allowed the determination of all the mechanistic pathways involved in these processes, stemming from a common intermediate that evolves differently according to the substituents nature

Alternative Synthesis of P‑Chiral Phosphonite-Borane Complexes: Application to the Synthesis of Phostone–Phostone Dimers

An improved strategy for the synthesis of P-chiral gluco- and manno-phosphonite-borane complexes is described on the basis of the addition of diethyl phosphonite-borane to a glucal-derived aldehyde, followed by a cyclization coupled with an ethyl/methyl exchange. This direct P­(III) strategy facilitates the obtention of various P-chiral phosphonite-boranes, of which further coupling reactions are described leading to the selective synthesis of two phostone dimers

Synthesis and Evaluation of Di- and Trimeric Hydroxylamine-Based β‑(1→3)-Glucan Mimetics

Di- and trimeric hydroxylamine-based mimetics of β-(1→3)-glucans have been accessed by an asymmetric synthesis route featuring an iterative double ring-closing reductive amination reaction. These oligomeric hydroxylamines are demonstrated to inhibit the staining of human neutrophils and of mouse macrophages by fluorescent anti-CR3 and anti-dectin-1 antibodies, respectively, and to stimulate phagocytosis, all in a linkage-dependent manner suggestive of binding to the lectin domains of complement receptor 3 (CR3) and dectin-1. The ability of these relatively short mimetics to bind to CR3 and dectin-1, as compared to the greater degree of polymerization required in β-(1→3)-glucans, is discussed in terms of the increased hydrophobicity of the α-face on replacement of the glycosidic bond by the hydroxylamine linkage