Synthesis of 1,2-Dihydroxyindolizidines from 1-(2-Pyridyl)-2-propen-1-ol

Abstract

1-(2-Pyridyl)-2-propen-1-ol, obtained by vinylation of commercially available picolinaldehyde, resulted a good starting material for the synthesis of the indolizidine skeleton. In particular, a simple process involving bromination, reduction, and nucleophilic substitution (via elimination and addition) allowed an easy conversion of the starting material into (±)-lentiginosine in ~27% overall yield.

Organocatalyzed Aldol Reaction between Pyridine‐2‐carbaldehydes and α‐Ketoacids: A Straightforward Route towards Indolizidines and Isotetronic Acids

“…The enantioselectivity of compound 4 a could not be obtained through chiral HPLC and, thus, was evaluated by measuring the optical rotation of the sample in various solvents. The optical rotation of enantiomerically pure pyridinium 4 a was estimated based on the observation that a sample of compound 4 a in THF (Table 1, entry 9) led to indolizidine 6 a , after reduction under PtO 2 catalysis9 and benzylation of acid 5 a , with an ee value of >99 % (Scheme ). In all cases, after evaporation of the solvent at room temperature and column chromatography on silica gel (CH 2 Cl 2 /MeOH), compound 4 a was obtained as a single isomer and its structure was unambiguously determined through X‐ray diffraction studies (see below; Scheme ).…”

“…Then, the pyridinium ring was fully hydrogenated as above, under PtO 2 catalysis,9 thereby affording the corresponding indolizidines 5 a – 5 d (Scheme ). Esterification of the products with TMSCHN 2 furnished their corresponding methyl esters in good yields, but their enantiomeric excesses could not be measured by chiral HPLC.…”

Synthesis of New Indolizidine Derivatives from 1-(2-Quinolyl)-2-propen-1-ol

“…Found: C,42.22;H,2.95;N,4.01. (1aRS,9aSR,2,8,9,9a,oxireno[a]indolizine ( 6) and (1aRS,9aRS,9bSR)-1a,2,8,9,9a,9b-Hexahydrobenzo[e]oxireno[a]indolizine (7). Compound 2 (0.345 g, 1.0 mmol) was added to a suspension of PtO 2 •H 2 O (0.023 g, 0.1 mmol) in MeOH (16 mL), and the mixture was stirred at room temperature under an atmospheric pressure of hydrogen for 12 h. The solution was filtered through a celite pad, washed with MeOH and CH 2 Cl 2 , and evaporated to dryness affording a mixture of 4 and 5 as the major compounds, which was dissolved in THF (12 mL) and water (4 mL), added with solid KOH (0.168 g, 3.0 mmol), and heated at 40 °C for 24 h. The reaction crude was extracted with ethyl acetate (4 × 10 mL), and the resulting organic phase was dried over anhydrous Na 2 SO 4 and evaporated under reduced pressure.…”

“…In this context, we recently reported a facile four-step synthesis of rac -lentiginosine from 1-(2-pyridyl)-2-propen-1-ol. 9 With the aim to synthesize different analogues to test their biological properties, we then decided to apply the same methodology to 1-(2-quinolyl)-2-propen-1-ol ( 1 ) 10 to access benzo[ e ]indolizidines with a tetrahydroquinoline skeleton (Figure 1), assessed as promising targets on the basis of computational studies. 11…”

Synthesis of piperidine and quinolizidine alkaloids

“…2:1) but were consistently found to be poorer (1:1) on larger scale reactions as could be seen by integration of the diagnostic peaks in the 1 H NMR spectra ( Figure 3.4-17 and Figure 3. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The reaction yield was also significantly higher on small scale (~65%) but yields on large scale reactions ranged between 30 to 40%.…”