Fabrice Chemla

Addition of Metal Enolate Derivatives to Unactivated Carbon−Carbon Multiple Bonds

2.2. Group 8: Iron-Mediated Additions 2369 2.3. Group 10: Palladium and Platinum 2370 2.3.1. Palladium(II)-Mediated Additions 2370 2.3.2. Platinum(II)-Mediated Additions 2380 2.4. Group 11: Copper, Silver, and Gold 2381 2.4.1. Copper(II)-Mediated Additions 2381 2.4.2. Silver(I)-Mediated Additions 2382 2.4.3. Gold(I)-Mediated Additions 2382 2.5. Group 12: Zinc(II)-Mediated Additions 2383 2.5.1. Carbozincation with Azaenolates 2383 2.5.2. Carbozincation with Ester and Amide Enolates 2388

C-H activation/functionalization catalyzed by simple, well-defined low-valent cobalt complexes.

A facile C-H activation and functionalization of aromatic imines is presented using low-valent cobalt catalysts. Using Co(PMe3)4 as catalyst we have developed an efficient and simple protocol for the C-H/hydroarylation of alkynes with an anti selectivity. Deuterium-labeling experiments, DFT calculations coupled with the use of a well-defined catalyst have for the first time shed light on the elusive black box of cobalt catalyzed C-H functionalization.

High-Yielding Synthesis of Sphingoid-Type Bases

An efficient methodology for the synthesis of sphingoid-type bases is reported. It involves the stereoselective addition of a racemic 3-alkoxy allenylzinc to enantiopure N-tert-butylsulfinyl imines and a cross-metathesis reaction as the key steps. It has been successfully applied to the syntheses of sphinganine and naturally occurring bioactive related compounds, among which the hydrolysis product of clavaminol H and two spisulosines. All of these compounds have been prepared in six steps from N-tert-butylsulfinyl imines in high overall yields (>56%).

Alkynyl - Oxiranes and Aziridines: Synthesis and Ring Opening Reactions with Carbon Nucleophiles

Syntheses of alkynyl- oxiranes and aziridines are rewieved. These compounds can serve as substrates in ring opening reactions with carbon nucleophiles to give allenyl- or homopropargylalcohols and amines.

Allenylzinc reagents: new trends and synthetic applications

The last developments in our research efforts involving allenylzinc reagents are summarized. These interesting organometallic compounds allow the stereoselective and enantioselective synthesis of acetylenic epoxides, aziridines and amino alcohols. Some synthetic applications of these highly functionalized substrates are also presented through the synthesis of homopropargylic alcohols and allenic ketones. Further applications in the total synthesis of heterocyclic natural products are also discussed.

Synthesis of (-)-swainsonine and (-)-8-epi-swainsonine by the addition of allenylmetals to chiral α,β-alkoxy sulfinylimines.

The asymmetric synthesis of (-)-swainsonine and (-)-8-epi-swainsonine is reported through the addition of either the allenylzinc or the allenyl lithio cyanocuprate reagents derived from [3-(methoxymethoxy)prop-1-ynyl]trimethylsilane to enantiopure α,β-dialkoxy N-tert-butanesulfinylimines derived from d-erythronolactone.

Expeditious Synthesis of a Common Intermediate of l-1-Deoxyallonojirimycin and l-1-Deoxymannojirimycin

The expeditious synthesis of a common intermediate of L-1-deoxyallonojirimycin (L-allo-DNJ) and L-1-deoxymannojirimycin (L-manno-DNJ) is reported. This intermediate is obtained in highly diastereo- and enantioselectivity with 38.4% overall yield in six steps involving the unprecedented ring-closing metathesis of a tert-butylsulfinyl allylamine as the key step.

C2-Alkylation and Alkenylation of Indoles Catalyzed by a Low-Valent Cobalt Complex in the Absence of Reductant

Herein an extremely versatile, well-defined, low-valent cobalt catalyst [Co(PMe3)4] capable of intermolecular and intramolecular imine-directed C2-alkylation and alkenylation of indoles is reported. The reaction proceeds in the absence of reducing agents or additives, affording a range of substituted indoles and dihydropyrroloindoles in high yields and regioselectivities. With the aid of deuterium labeling studies and DFT (Density Functional Theory) calculations, a mechanism is proposed that is based on a Ligand-to-Ligand Hydrogen Transfer pathway.

Trans-Selective Radical Silylzincation of Ynamides†

The silylzincation of terminal ynamides is achieved through a radical-chain process involving (Me3Si)3SiH and R2Zn. A potentially competing polar mechanism is excluded on the basis of diagnostic control experiments. The unique feature of this addition across the C≡C bond is its trans selectivity. One-pot electrophilic substitution of the C(sp2)-Zn bond by Cu(I)-mediated C-C bond formation and subsequent manipulation of the C(sp2)-Si bond provides a modular access to Z-α,β-disubstituted enamides.

Stereo- and enantioselective synthesis of acetylenic 2-amino-1,3-diol stereotriads.

The high-yielding and highly efficient stereoselective synthesis of enantiopure anti,anti and syn,anti acetylenic 2-amino-1,3-diol stereotriads from alpha-alkoxy-tert-butanesulfinylimines bearing a stereocenter alpha to the imino group is reported. The stereoselectivity of the reaction of these tert-butanesulfinyl (tBS)-imines with allenylzinc (+/-)-1 was found to be controlled only by the configuration of the tBS group. An excellent kinetic resolution of the racemic allenylzinc species was observed, allowing a high stereocontrol no matter what the configuration or the protecting group of the alpha-alkoxy group.