Michèle P. Bertrand

Et3B- and Et2Zn-Mediated Radical Additions to Glyoxylate Imines, Compared Stereoinductions

Abstract 1,3-Stereoinduction in the addition of alkyl radicals to glyoxylic imines derived from various chiral amines has been investigated. New synthetic methodologies involving Et 3 B and Et 2 Zn as mediators have been compared. Dihydro-1,4-oxazin-2-one ( 2b ) gave the highest d.e. but no chemoselectivity. Open chain analogues derived from β-alkoxyamines led to good stereoinduction when the reaction was performed with Et 2 Zn which is a bidentate complexing reagent.

Tandem radical addition–aldol condensations: evidence for the formation of zinc enolates in diethylzinc mediated radical additions to N-enoyloxazolidinones

Diethylzinc mediated addition of alkyl radicals to chiral N-enoyloxazolidinones is immediately followed by homolytic substitution at zinc leading to a zinc enolate; the trapping of the latter in a subsequent aldol condensation serves as a useful mechanistic probe; overall this reaction sequence constitutes a novel example of a one pot, three-component, radical-polar crossover reaction.

Chemoenzymatic Dynamic Kinetic Resolution of Primary Amines Catalyzed by CAL-B at 38-40 °C

The (R)-selective chemoenzymatic dynamic kinetic resolution of primary amines was performed at 38-40 °C in MTBE, in good to high yields and with high enantiomeric excesses. These reactions associating CAL-B to octanethiol as radical racemizing agent were carried out in the presence of methyl β-methoxy propanoate as acyl donor, under photochemical irradiation at 350 nm in glassware.

One-pot Crabbé homologation-radical cascade cyclisation with memory of chirality

The tandem Crabbé homologation-radical rearrangement of terminal enediynes leads, in a one-pot procedure, to the enantioselective synthesis of six- and seven-membered ring α-aminoesters bearing a quaternary stereocenter based on the phenomenon of memory of chirality.

Spin-Trapping Evidence for the Formation of Alkyl, Alkoxyl, and Alkylperoxyl Radicals in the Reactions of Dialkylzincs with Oxygen

The reactions of dialkylzincs (Me(2)Zn, Et(2)Zn, and nBu(2)Zn) with oxygen have been investigated by EPR spectroscopy using spin-trapping techniques. The use of 5-diethoxyphosphoryl-5-methyl-1-pyrrroline N-oxide (DEPMPO) as a spin-trap has allowed the involvement of alkyl, alkylperoxyl, and alkoxyl radicals in this process to be probed for the first time. The relative ratio of the corresponding spin-adducts depends strongly on the nature of the R group, which controls the C-Zn bond dissociation enthalpy, and on the experimental conditions (excess of spin-trap compared with R(2)Zn and vice versa). The results have demonstrated that Et(2)Zn and, to a lesser extent, nBu(2)Zn are much better traps for oxygen-centered species than Me(2)Zn. When the dialkylzincs were used in excess with respect to the spin-trap, the concentration of the oxygen-centered radical adducts of DEPMPO was much lower for Et(2)Zn and nBu(2)Zn than for Me(2)Zn. A detailed reaction mechanism is discussed and C-Zn, O-Zn, and O-O bond dissociation enthalpies for the proposed reaction intermediates were calculated at the UB3LYP/6-311++G(3df,3pd)//UB3LYP/6-31G(d,p) level of theory to support the rationale.

Stereocontrol in radical cyclizations on sugar templates

Abstract The radical cyclization of alkyl hex-2-enopyranosides provides a stereocontrolled route to fused furanopyranes. The intermediate radical is generated either via the reduction of the appropriate halide by tin hydride or via sulfonyl radical addition to allyl hex-2-enopyranosides. The two methodologies are compared with respect to diastereoselectivity. Stereocontrol is discussed on the basis of conformational preference in the transition state.

Synthesis and selective transformation of nitrogen-containing compounds via radical pathways

Abstract This account presents the recent contribution of our group to the development of radical methodologies, and their application to the synthesis and the reactivity of nitrogen-containing compounds. The scope of several cascade processes involving sulphur-centred radicals is discussed first, then the synthetic potential of radical additions to C=N bonds mediated by triethylborane and diethylzinc is examined. Special attention is given to 1,3-stereoinduction in the perspective of enantioselective synthesis.

Kinetic studies on the formation of sulfonyl radicals and their addition to carbon-carbon multiple bonds.

The reactions of α-hydroxyl and α-alkoxyl alkyl radicals with methanesulfonyl chloride (MeSO(2)Cl) have been studied by pulse radiolysis at room temperature. The alkyl radicals were produced by ionizing radiation of N(2)O-saturated aqueous solution containing methanol, ethanol, isopropanol, or tetrahydrofuran. The transient optical absorption spectrum consisted of a broad band in the region 280-380 nm with a maximum at 320 nm typical of the MeSO(2)(•) radical. The rate constants in the interval of 1.7 × 10(7)-2.2 × 10(8) M(-1) s(-1) were assigned to an electron-transfer process that leads to MeSO(2)Cl(•-), subsequently decaying into MeSO(2)(•) radical and Cl(-). The rate constants for the addition of CH(3)SO(2)(•) to acrolein and propiolic acid were found to be 4.9 × 10(9) M(-1) s(-1) and 5.9 × 10(7) M(-1) s(-1), respectively, in aqueous solutions and reversible. The reactivity of tosyl radical (p-CH(3)C(6)H(4)SO(2)(•)) toward a series of alkenes bearing various functional groups was also determined by competition kinetics in benzene. The rate constants for the addition of tosyl radical to alkenes vary in a much narrower range than the rate constants for the reverse reaction. The stabilization of the adduct radical substantially contributes to the increase of the rate constant for the addition of tosyl radical to alkenes and, conversely, retards the β-elimination of tosyl radical.

Switching from (R)- to (S)-selective chemoenzymatic DKR of amines involving sulfanyl radical-mediated racemization

Chemoenzymatic dynamic kinetic resolution (DKR) of amines involving sulfanyl radical-induced racemization happened to be the very first switchable DKR process allowing the synthesis of either (R)- or (S)-amides, in good yield and high enantiomeric excess, depending on the nature of the enzyme; the different steps of the development of (S)-selective DKR are discussed.

Double Transfer of Chirality in Organocopper-Mediated bis(Alkylating) Cycloisomerization of Enediynes†

An original synthesis of chiral benzofulvenes triggered by organocopper reagents is reported. These enantiopure products are available through a highly chemo-, regio-, diastereo-, and enantioselective bis(alkylating) cycloisomerization process. A double chirality transfer (central-to-axial-to-central) is observed.