Enantioselective Synthesis of Lythraceae Alkaloid Lasubine II via Optically Active 2-Isoxazoline

Enantioselective synthesis of Lythraceae alkaloid lasubine II was achieved via optically active 2-isoxazoline, which was available by the asymmetric 1,3-dipolar cycloaddition of nitrile oxide to an achiral 2-propen-1-ol using diisopropyl (R,R)-tartrate as a chiral auxiliary.The plants of Lythraceae family are widely distributed in different regions of the world and more than 40 alkaloids have been isolated from them.Most of these alkaloids possess a 2,4-disubstituted quinolizidine ring system. 1 Lasubine II, isolated from the leaves of Lagerstroemia subcostata Koehne, 2 consists of trans-quinolizidine framework.Racemic lasubine II has been synthesized by several methods, for example, Mannich reaction of isopelletierine with substituted benzaldehyde, 3a nitrone cycloadditions, 3b,c two successive cyclization of acyclic γ-amino alcohol, 3d conjugate addition to N-acyldihydropyridone, 3e addition of 2-siloxy-1,3-diene to N-acyliminium ion, 3f cyclization of allylsilane on N-acyliminium ion.3g However, to the best of our knowledge, there was no report on the total synthesis of optically active form.Recently, we reported an efficient enantioselective 1,3-dipolar cycloaddition of nitrile oxides to achiral allylic alcohols using diisopropyl (R,R)-tartrate [(R,R)-DIPT] as a chiral auxiliary to give the corresponding optically active 2-isoxazolines. 4 The utility of the present asymmetric 1,3-dipolar cycloaddition in the challenging arena of synthesis of lasubine II was explored.Herein, we describe the enantioselective synthesis of lasubine II starting from the optically active 2-isoxazoline via the sequential reduction and cyclization processes.