Jean-Pierre Dulcère

Sequential organocatalyzed Michael addition/[3 + 2]-heterocyclization for the stereoselective synthesis of fused-isoxazoline precursors of enantiopure cyclopentanoids.

We propose an asymmetric synthesis of functionalized cyclopentanoids bearing up to four stereogenic centers from easily accessible nitroalkenes and unsaturated aldehydes. The overall sequence includes an enantioselective organocatalytic Michael addition and a [3 + 2]-heterocyclization between an in situ generated silylnitronate and the unactivated double bond. Finally, the fused isoxazoline can be further transformed to various cyclopentanoids.

Michael Addition Initiated Carbocyclization Sequences with Nitroolefins for the Stereoselective Synthesis of Functionalized Heterocyclic and Carbocyclic Systems

The synthesis of various heterocycles and carbocycles (tetrahydrofurans, pyrrolidines, cyclopentanes) has been achieved by using new and efficient ionic addition/cyclization sequences. Nitroolefins play an important role in the Michael addition induced ring-closing reactions (MIRC) reported in the present article, with various substituted alcohols, amines, Grignard reactants, or malonate derivatives acting as the nucleophile partner. The optimized cascade reactions were high yielding in most cases and highly stereoselective, creating up to three stereogenic centers starting from achiral substrates.

One-pot asymmetric cyclocarbohydroxylation sequence for the enantioselective synthesis of functionalised cyclopentanes

A new method has been developed for the enantioselective synthesis of highly functionalised cyclopentanes bearing up to three stereogenic centres with very high stereoselectivity. This one-pot process combines an enantioselective organocatalytic Michael addition with a highly diastereoselective [3+2]-cycloaddition-fragmentation step.

Diastereoselective Access to 3-Nitro-4-vinylidenetetrahydrofurans and 3-Nitro-4-vinylidenetetrahydropyrans and Their Conversion into 3,6-Dihydro-1,2-oxazines by Reverse Cope Elimination of Hydroxylamine Precursors

A new approach to the synthesis of unsaturated nitro-allenyl-tetrahydrofurans 3 and -tetrahydropyrans 5 has been developed, involving oxa-Michael addition/SN2′ substitution of propargyl and homopropargyl alcohol derivatives 2a and 4h on nitroalkenes 1a−g. Complete allylic 1,3-strain control during the cyclization accounts for the observed diastereoselectivity. Reduction of nitro compounds 3 and 5 with SmI2 provided new α−allenylhydroxylamines 7 and 8, which were easily isomerized into 3,6-dihydro-1,2-oxazines 9 and 10 by reverse Cope elimination.

The Cohalogenation of 1‐N‐Vinylpyrimidinediones: A New Approach to Nucleoside Analogs

A new approach to the synthesis of nucleoside analogs has been developed, which involves initial chemo- and regioselective cohalogenation of 1-N-vinylpyrimidinediones 10a,b using N-bromosuccinimide in the presence of variously substituted propargylic alcohols. Radical carbocyclization of the resulting β-bromo propargylic ethers 17-22 then leads to 3-methylenetetrahydrofurans 23-26. In such cyclizations, different reactivities have been observed for diastereomers 22a,b obtained by cohalogenation with (R)-1-benzyloxybut-3-yn-2-ol; although the expected anti 3-methylenetetrahydrofurans 27a,b were obtained, the syn diastereomers 28a,b were only the minor constituents of a mixture in which bicyclonucleosides 29a,b were the major components. The formation of 29a,b results from a 1,6-hydrogen transfer followed by cyclization, which might be favored by a CH-π interaction in radical intermediate synII.

Epoxidation with the H2O2/vilsmeier reagent system

Alkenes 1 a–d interact at −80°C in 15 min. with the Vilsmeier reagent I (Me2N=CHCl)+PO2Cl2− in presence of 30% H2O2 to yield the corresponding epoxides 3 a–d. The reaction could involve the formation of the highly reactive hydroperoxymethylenedimethylammonium salt (Me2N=CHue5f8OOH)+PO2Cl−2 II.

One-Pot Michael Addition/Intramolecular Carbocyclization of Dimethyl Propargylmalonate with Nitroalkenes: A New Stereoselective [3+2] Annulation to 1-Nitro 2-Methylenecyclopentanes

A new one-pot diastereoselective synthesis of nitro methylenecyclopentanes 3a-g has been achieved by [3+2] annulation of dimethyl propargylmalonate 2 and nitroalkenes la-g in the presence of Triton B.