Divergent approach to the synthesis of (-)-balanol heterocycle and cis-3-hydroxypipecolic acid based on chiral 2-aminoalkanol equivalent. (29th January 2021)

• Record Type: Journal Article
• Authors: Chavan, Subhash P.; Kalbhor, Dinesh B.; Gonnade, Rajesh G.
• Is Part Of: Tetrahedron. Volume 80(2021)
• Publication Date: 2021-01-29
• Subjects: Hexahydroazepine -- Amino-alcohol -- Protein kinase -- Desymmetrization -- Piperidine alkaloids; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2020.131773
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Enantioselective synthesis of the hexahydroazepine core of (−)-balanol and formal synthesis of cis -3-hydroxypipecolic acid from a common intermediate have been accomplished by a divergent path. The common intermediate was accessed from a favorably protected enantiomerically pure 2-amino-1, 3, 4-butanetriol (ABT) equivalent via oxidation and Wittig olefination. The synthesis of (−)-balanol heterocycle featured tandem reduction/acetal-deprotection/γ-lactonization reaction and a one-pot azide reduction followed by seven membered aza-heterocycle formation while the route to cis -3-hydroxypipecolic acid highlighted the base induced piperidine ring formation and regioselective benzylidine-acetal cleavage. Graphical abstract: Image 1 Highlights: Synthesis of piperidine/hexahydroazepine core is accomplished. Benzylidene acetal is used as prominent chiral C4 building block. Involves the tandem reduction/acetal deprotection/ γ -lactonization reaction.