Asymmetric syntheses of (−)-hastanecine, (−)-turneforcidine and (−)-platynecine

Abstract

a b s t r a c tConcise total asymmetric syntheses of three diastereoisomeric 1-hydroxymethyl-7-hydroxy substituted pyrrolizidines, (À)-hastanecine, (À)-turneforcidine and (À)-platynecine, are reported. The doubly diastereoselective conjugate additions of lithium (R)-or (S)-N-benzyl-N-(a-methylbenzyl)amide to tertbutyl (R,E)-4-(triethylsilyloxy)hepta-2,6-dienoate [which was prepared (in 96:4 e.r.) via Lewis acid mediated catalytic asymmetric allylation of tert-butyl (E)-4-oxobut-2-enoate] proceeded in both cases under the dominant control of the lithium amide reagent. Subsequent diastereoselective enolate allylations installed the required stereogenic centres, and the pyrrolizidine ring system was rapidly accessed by a two-step protocol (viz. ozonolysis and one-pot hydrogenolysis/double reductive cyclisation), to complete the asymmetric syntheses of (À)-hastanecine, (À)-turneforcidine and (À)-platynecine in 17, 8 and 24% overall yield, respectively, in eleven steps from commercially available 2,2-dimethoxyacetaldehyde in each case.

New Advances in the Synthetic Application of Enantiomeric 1-Phenylethylamine (α-PEA): Privileged Chiral Inducer and Auxiliary

“…Later, the same strategy was applied for the synthesis of (−)-isoretronecanol and (−)-trachelantamidine [52] (Scheme 31). Following the elaborated synthetic methodology, this research group obtained the next compounds of this class [53,54] (Scheme 30). Natural pyrrolizidine alkaloids consist of two fused five-membered rings with a nitrogen atom at the bridgehead (Scheme 31).…”

“…Later, the same strategy was applied for the synthesis of (−)-isoretronecanol and (−)-trachelantamidine [ 52 ] ( Scheme 31 ). Following the elaborated synthetic methodology, this research group obtained the next compounds of this class [ 53 , 54 ] ( Scheme 30 ).…”

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

“…The stereoselectivity estimated from the theoretical calculations matches the experimental dr very closely. It has been reported that the chiral α-phenylethyl auxiliary is readily removed by hydrogenolysis after acting as a valuable inductor for asymmetric synthesis [36][37][38][39][40][41][42][43]71 Hence, it is expected that such auxiliary can be removed in a like manner for most of the products obtained in the current study without affecting their functionalities. Experimental studies are being carried out to test this idea, and the results will be reported in due course.…”

“…34,35 Among the chiral auxiliaries used in asymmetric synthesis, those based on the 1-phenylethylamino group-containing scaffolds proved to be very efficient in many diastereoselective processes. [36][37][38][39][40][41][42][43] On the basis of the previously developed regioselective synthesis of N-substituted 4-oxazolin-2-ones 1 and 4-methylene-2-oxazolidinones 2, resulting from the condensation of α-ketol 3a and isocyanates 4 (Scheme 1), 44,45 in a preliminary report, we presented the one-pot synthesis of the optically pure version of heterocycles 1-2 by introducing the N-(S)-methylbenzyl moiety as the chiral auxiliary. 46 Although this methodology was also efficient for the preparation of the corresponding 3-substituted 4-oxazolin-2-thiones 6 and 4methylene-1,3-oxazolidin-2-thiones 7, 47 these heterocycles were not able to undergo further reactions when utilizing the thioenamide functionality as a nucleophile.…”

“…It is possible to carry out this synthetic approach via aldol, Mannich, Michael condensations, addition to metal π‐double and π‐triple activated C–C bonds, and Heck arylation, as well as in cascade vicinal difunctionalization or pericyclic reactions, leading to the formation of complex molecules with the generation of a number of stereogenic centers, including the total synthesis of natural products . Among the chiral auxiliaries used in asymmetric synthesis, those based on the 1‐phenylethylamino group‐containing scaffolds proved to be very efficient in many diastereoselective processes …”