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.

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.

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.

Unprecedented in situ oxidative ring cleavage of isoxazolidines: diastereoselective transformation of nitronic acids and derivatives into 3-hydroxymethyl 4-nitro tetrahydrofurans and pyrrolidines.

[reaction: see text] Nitronic acids undergo an intramolecular 1,3-dipolar cycloaddition to unactivated double bonds, and the resulting isoxazolidines spontaneously evolve by an unprecedented in situ oxidative ring cleavage. The extension of this transformation to silyl nitronates results in a general diastereoselective construction of hydroxymethyl nitro functionalized tetrahydro-furans and -pyrrolidine having up to four consecutive stereogenic centers.