Asymmetric Synthesis of 8-Aminoindolizidine from Chiral 2-Pyrroleimines

Abstract

1-Allyl-2-pyrroleimines obtained from (S)-valinol and (S)-phenylglycinol underwent highly diastereoselective addition of allylmagnesium chloride, used in excess amounts, to give the corresponding secondary amines with concomitant allyl to (Z)-1-propenyl isomerization of the 1-pyrrole substituent. Transformation of the 2-amino alcohol moiety to an oxazolidinone, or its cleavage and subsequent N-protection, followed by ring-closing metathesis of the two alkene groups gave the unsaturated bicyclic compound. Full hydrogenation of the alkene function and the aromatic rings afforded the indolizidine derivative as a mixture of two or three diastereomers with a ratio which was dependent on the nature of both the N-substituent and the catalyst. The two prevalent diastereomers were isolated, and their configuration was determined by X-ray crystallographic analysis.

Asymmetric syntheses of (8R,8aS)- and (8R,8aR)-8-hydroxy-5-indolizidinones: Two promising oxygenated indolizidine building blocks

“…The structure diversity and remarkable biological activities possessed by the indolizidine alkaloids make them attractive synthetic targets, which resulted in a number of ingenious total syntheses [31], and also the development of several enantiopure oxygenated indolizidine building blocks such as 13 [32], 14 [33], 15a [34], and 16a/16b [35]. On the other hand, N-protected 8-aminoindolozidines 17a/17b [36] have been synthesized in view of the synthesis of bioactive alkaloids; and both 8-indolizidinol (18) [35][36][37] and its diastereomer have been synthesized for purpose of probing the proposed biogenetic origin of secu'amaine A [38]. As a continuation of our study on the development of indolizidine building blocks [39], we now report the asymmetric synthesis of (8R,8aS)- …”

An enantioselective synthesis of α-alkylated pyrroles via cooperative isothiourea/palladium catalysis

“…In relation to this goal, bicyclic pyrrole 50 was prepared via a straightforward two step transesterification/ring closing metathesis sequence from 22 without loss in enantioselectivity (Scheme 4b). 15 Finally, we sought to evaluate this method on more complex pyrrole nucleophiles and prepared 53 via the enantioselective αallylation of functionalized pyrrole acetic acid ester 52, prepared from the NSAID tolmetin (Scheme 4c).…”

(8R,8aS)-及(8R,8aR)-8-羟基-5-吲哚里西啶酮的不对称合成:两个有用的羟基吲哚里西啶合成砌块

“…, [33] , [34] , 及 / [35] . 另一方面, 8-氨基 吲哚里西啶 / [36] 也已被合成并应用于制备某些 天然产物. 而 8-羟基吲哚里西啶( ) [35~37] 及它的非对 映异构体曾被合成以探索有关 secu'amaine A 生物起 源问题 [38] .…”