RESUMO
A first stereodivergent strategy for the asymmetric synthesis of all stereoisomers of 1-hydroxymethylpyrrolizidine alkaloids is developed using an asymmetric self-Mannich reaction as a key step. An anti-selective self-Mannich reaction of methyl 4-oxobutanoate with the PMP-amine catalyzed by a chiral secondary amine is successfully optimized for the asymmetric synthesis of (+)-isoretronecanol and (-)-isoretronecanol. A syn-selective self-Mannich reaction catalyzed by proline is utilized for the asymmetric synthesis of the diastereomer, (+)-laburnine, and its enantiomer, (-)-trachelanthamidine.
RESUMO
A direct N-heterocyclic carbene (NHC) catalysis of maleimides with alkyl aldehydes is established for the synthesis of 3-acylsuccinimides. The first dynamic kinetic resolution of 3-acylsuccinimides is accomplished through asymmetric transfer hydrogenation. These two catalytic methodologies are utilized for the synthesis of each enantiomer of trans-paraconic acids in three steps and cis-paraconic acids in four steps with good yields and high stereoselectivities. This stereodivergent synthetic methodology is applied for the synthesis of seven bioactive paraconic acid natural products.
RESUMO
( R)-Paraconyl alcohol is found to be a key intermediate for the syntheses of many γ-butyrolactone autoregulators. The chiral auxiliary approach and enzymatic resolution are the two common strategies employed so far in the literature for the asymmetric synthesis of ( R)-paraconyl alcohol. Herein, we report the first organocatalytic approach for the short asymmetric synthesis of ( R)-paraconyl alcohol in four steps and by a single column purification. Asymmetric syntheses of IM-2, SCB2, and A-factor γ-butyrolactone autoregulators were achieved from ( R)-paraconyl alcohol in three steps.
