Philippe Mochirian

Stereopentads Derived from a Sequence of Mukaiyama Aldolization and Free Radical Reduction on α-Methyl-β-alkoxy Aldehydes : A General Strategy for Efficient Polypropionate Synthesis

In a stereodivergent manner, all 16 diastereomeric stereopentads 7-22 were synthesized starting with alpha-methyl-beta-alkoxy aldehydes 25 and 27. We designed an approach based on a sequence of a Mukaiyama aldolization with enoxysilane 24 followed by a hydrogen transfer reaction. Recent advancements concerning these reactions are described, and novel key intermediates are characterized in the aldol step. The synthesis of C(1)-C(11) fragment 60 of zincophorin, which contains a synthetically challenging stereopentad unit, is described attesting the usefulness of our strategy.

Stereocontrolled synthesis of C1-C17 fragment of narasin via a free radical-based approach.

An efficient synthesis of the C1-C17 western unit of narasin was achieved from (S)-Roche ester. Highlights in our synthesis include the successful exploitation of three stereoselective sequences of Lewis acid mediated reaction followed by free-radical-based hydrogen transfer.

A bidirectional approach to the synthesis of polypropionates: synthesis of C1-C13 fragment of zincophorin and related isomers.

The structure-activity study of a bioactive natural product containing polypropionate subunits requires that its stereoisomers also be evaluated. Therefore, a general approach to synthesize these motifs is necessary. We describe herein the synthesis of the C1-C13 polypropionate subunit of zincophorin and isomers thereof using a two-reaction sequence: an aldol reaction using a mixture of tetrasubstituted enoxysilanes and a hydrogen-transfer reaction, both under Lewis acid control. Selection of the appropriate Lewis acid dictates the stereochemical outcome of these reactions. From a tactical standpoint, this study shows how a polypropionate sequence can be read and constructed in two directions, either the east-west or the west-east approaches. The choice of the optimal route is influenced by the number of complexation sites that can interfere in the aldol step under bidentate Lewis acid control.

Synthesis of polypropionate motifs containing the anti–anti unit

Abstract Reported herein is the iteration of a strategy employing a Mukaiyama reaction in tandem with a hydrogen transfer reaction for the elaboration of four polypropionate motifs containing the anti – anti unit. In this process, Lewis acid acts as the key element in controlling the diastereoselectivity of each step, the outcome of which is >20:1 for all of the reactions performed.

A study of exocyclic radical reductions of polysubstituted tetrahydropyrans.

Exocyclic radical reductions were thoroughly investigated in the context of the synthesis of polysubstituted tetrahydropyrans, which are found in numerous macrolides. The radical precursors studied herein were generated by tandem cycloetherification and iodoetherification reactions or, alternatively, by semicyclic acetals substitutions. DFT calculations (BHandHLYP/TZVP) performed at the transition-state level for the hydrogen radical delivery are in good accordance with the experimental data and enabled the identification of important conformational factors that govern the selectivities obtained. This study demonstrates that both the preferred reactive conformation of the radical and steric interactions with the incoming hydride have to be considered in order to fully rationalize the levels of diastereoselection generated in acyclic free-radical processes.