A New Synthesis of All Four Stereoisomers of 2-(2,3-Dihydroxypropyl)piperidine via Iterative Asymmetric Dihydroxylation To Cause Enantiomeric Enhancement. Application to Asymmetric Synthesis of Naturally Occurring Piperidine-Related Alkaloids

Abstract

Both enantiomers of 2-(2-propenyl)piperidine 1 (76−88% ee), prepared via the first asymmetric dihydroxylation (AD) of 5-hexenyl azide, underwent the second AD to provide all four of the stereoisomeric 2-(2,3-dihydroxypropyl)piperidines 2 with enantiomeric enhancement (>98% ee). An asymmetric synthesis, starting from 2, of several 2-(2-hydroxyalkyl)piperidine alkaloids [(−)-halosaline, (+)-N-methylallosedridine, (+)-8-ethylnorlobelol, (+)-sedridine, (+)-allosedridine, (−)-allosedridine, and (+)-N-methylsedridine] and the ant defense alkaloids [(+)-tetraponerine-3 (T-3), T-4, T-7, and T-8] is demonstrated.

History, chemistry and biology of alkaloids from Lobelia inflata

“…This strategy was also applied to the synthesis of numerous piperidine derivatives and some ant defence alkaloids. 33,34 The synthesis started from the commercially-available 5-hexenol 53 (Scheme 12). Tosylation of the hydroxyl group followed by substitution with sodium azide furnished 52 in 69% yield over two steps.…”

Short enantioselective synthesis of sedridines, ethylnorlobelols and coniine via reagent-based differentiation

“…1H, br s);13 C NMR (100.6 MHz, CDCl 3 ): d 9.9, 24.6, 25.9, 30.5, 31 5,. 41.6, 46.7, 54.7, 70.2; mp 63°C; [a] D = +17.5 (c 0.80, EtOH).…”

Boron trifluoride etherate-assisted ring opening of ethylene oxide by a chiral organolithium: enantioselective synthesis of (R)-N-Boc-2-(2-hydroxyethyl)pyrrolidine

“…1). Compound 1 is a versatile precursor used in the construction of natural products such as anthramycin, 16 lydicamycin, 17 halosaline, 18 and cuscohygrine, 19 as well as many bioactive molecules such as Clemastine (antihistamine), 20 and SB-269970 (5HT 7 receptor antagonist). 21 The most commonly used methods to synthesize compound (R)-1 involved multi-step sequences from expensive, chiral starting materials such as D D-prolinol or D Dproline, [21][22][23][24] which are not suitable for large-scale synthesis.…”