Acid-catalysed epimerization of indolo[2,3-a]quinolizidine derivatives: Role of the nitrogen lone pairs in the mechanism

Diastereoselective Syntheses of Indoloquinolizidines by a Pictet−Spengler/Lactamization Cascade

“…It is well documented that the stereogenic center formed in the Pictet−Spengler reaction is subject to epimerization . No epimerization was observed when pure 9a or the C12 epimer of 9a was treated with TFA at 50 °C in DCM . It is plausible that the diastereoselectivity of the overall cascade reaction is determined by the differential rates of lactamization of intermediate 8a and 8a′ (Figure ).…”

Diverse Asymmetric Quinolizidine Synthesis: A Stereodivergent One‐Pot Approach

“…Or, by initial protonation of the amide and breaking of the carbonnitrogen bond forming an intermediate ten-membered ring that will undergo intramolecular cyclization to the thermodynamic more stable product. [29] In contrast to the indole and 3,5-dimethoxyphenyl amides 2a and 14a, the one-pot reaction of thiophene and 3,4-dimethoxy amides 12a and 3a using refluxing TFA for the N-acyliminium ion cyclization favored the kinetic product 10ba-thienoA C H T U N G T R E N N U N G [3,2-a]quinolizidine 18aa and 11ba-9,10-dimethoxybenzo[a]quinolizidine 10aa in 61:39 dr and 62:38 dr, respectively, and not the thermodynamic product (Table 5, entry 2 and Table 8, entry 1). Furthermore, for the kinetic product Comparing these results with the one-pot reaction starting from 3,4-dimethoxyphenyl amide 3a and cinnamaldehyde 1a with 40 mol% tin(IV) chloride, full conversion was obtained to the thermodynamic product 11bb-10 in 74:26 dr after only 1 h ( Table 8, entry 2).…”

Fischer indolization of octahydroindol-6-one derivatives revisited: diastereoisomerization and racemization processes

“…16,17 This stereolability has also been described in compounds bearing units of 3-(a-aminomethyl)indole. 18 A plausible mechanism for the diastereosiomerization, leading to pyrrolocarbazole (À)-8 from (À)-1, is depicted in Scheme 4.…”