Regioselective Reduction of 3-Sulfonyl Glutarimides to 3,4-Dihydro-5-sulfonylpyridin-2-ones. Formal Synthesis of the Indolizidine 8a-epi-Dendroprimine

Abstract

Sodium borohydride regioselectively reduced various 3-sulfonyl glutarimides 1 to hydroxy piperidones 2, which were further dehydrated to 3,4-dihydro-5-sulfonylpyridin-2-ones 3 in the presence of boron trifluoride. Formal synthesis of 8a-epi-dendroprimine (4) possessing an indolizidine ring system has been accomplished via intramolecular radical cyclization of cyclic vinyl sulfone 5.

Synthetic Applications of Sulfur-Substituted Indolizidines and Quinolizidines

“…A mixture of compound 10 (54.2 mg, 0.36 mmol) and PtO 2 (12 mg) in ethyl acetate (2 mL) was stirred vigorously under a balloon of hydrogen at room temperature for 24 h. The mixture was diluted with ethyl acetate, filtered through Celite, dried (MgSO 4 ), and evaporated under vacuum to give product 11 (52.5 mg, 96%) as a colorless liquid. Its spectral data are identical with the literature values …”

“…Compound 10 was hydrogenated to give the cis-product 11 , which has identical spectral data with the literature values . Compound 11 further reacted with methyllithium, acetic acid, and NaBH 4 to give 8a- epi -dendroprimine (Scheme ), which shows a Bohlmann band at 2793 cm −1 in the IR spectrum indicating that the lone pair electrons of nitrogen as well as the H 5 and H 8a are at the axial position.…”

Synthesis of 2,4,6-Trisubstituted Chiral Piperidines and (−)-Dendroprimine by One-Pot Asymmetric Azaelectrocyclization Protocol

“…Finally, the reduction of the lactam amide group of 22 by LiAlH 4 under ether reflux conditions provided (−)-dendroprimine. The spectral data ( 1 H and 13 C NMR) were in good agreement with those published in the literature. ,8c …”

“…After being established as an efficient route to three diastereomeric 2,4,6-trisubstituted piperidines, a synthetically unique route to (−)-dendroprimine has now been envisioned (Schemes and ). ,

3 Stereoselective Synthesis of 2,4,6-Substituted Piperidine 19 via One-Pot Azaelectrocyclization toward (−)-Dendroprimine

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Stereocontrolled Synthesis of Substituted Chiral Piperidines viaOne-Pot Asymmetric 6π-Azaelectrocyclization: Asymmetric Syntheses of(−)-Dendroprimine, (+)-7-Epidendroprimine, (+)-5-Epidendroprimine, and (+)-5,7-Epidendroprimine

“…To demonstrate the established protocol for the polysubstituted piperidine synthesis, we examined the asymmetric synthesis of an indolizidine alkaloid, (−)-dendroprimine ( 34 ), which was isolated from Dendrobium primulinum Lindl ( Orchidaceae ) and characterized by Luning and his co-workers in 1965 . The relative configuration of the stereogenic centers of dendroprimine was determined by the synthesis of the four racemic diastereomers of this indolizidine alkaloid, and the absolute configuration was also determined by the same group in 1972. , The enantioselective synthesis of (−)-dendroprimine ( 34 ) and its two isomers were reported by Gelas-Mialhe in 2004, and the synthesis of (−)-5,7-epi-dendroprimene ( 54 ) was reported by other two groups …”