ChemInform Abstract: Concise Synthesis of Pyrrolidine and Indolizidine Alkaloids by a Highly Convergent Three-Component Reaction (original) (raw)
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Short, enantiogenic syntheses of (-)-indolizidine 167B and (+)-monomorine
Journal of the American Chemical Society, 1991
X 50 mL). The CH2CIz extracts were combined, washed with 25 mL of HzO, and dried over NazS04. Removal of solvent in a rotary evaporator gave a solid that was recrystallized (twice) from heptane/toluene giving 56.3 mg (68%) of 7e as light yellow needles: mp 179-180 "C; IR (Nujol) 1675, I-[(p-Cynnoknzyl)oxy~Zmetbyl-9,1O-anthrpquirone (7d). A mixture of 2 (49.5 mg, 0.208 mmol), K2COo (2.2, 15.9 mmol), andp-cyanobenzyl bromide (2.17 g, 11.1 mmol) in 50 mL of 2-butanone was heated to reflux for 75 min. After cooling, the reaction mixture was diluted with 60 mL of H 2 0 and extracted with CH2CI2 (2 X 50 mL). The CH2CI2 extracts were combined, washed with H 2 0 (30 mL), and dried over Nafi0,. Removal of solvent in a rotary evaporator gave yellow crystals. Excess pcyanobenzyl bromide was removed by sublimation (0.1 mmHg, -70 "C). The residue was decolorized (norit) and recrystallized from toluene. Recrystallization gave 26.6 mg of 7d (42%): mp 222-223 "C; IR (Diffuse reflectance in KBr) 2227, Abstract: The enantiogenic syntheses of (-)-indolizidine 167B (1) and (+)-monomorine (2) are described. D-Norvaline and L-alanine are converted into their 1-pyrrole derivatives by reaction with 2,s-dimethoxytetrahydrofuran. Thereafter, Amdt-Eistert homologation of the N-alkanoic acid substituent, followed by rhodium(I1) acetate catalyzed decomposition of its a-diazo ketone derivative, provides the relevant bicyclic precursors, the vested chirality of which directs catalytic hydrogenation affording 1 and 2. Provision for the 5-butyl side chain in 2 is made by prior Lewis acid catalyzed rearrangement of the mixed anhydride obtained from butyryl chloride and the pyrrole analogue of L-alanine. ~ ~~~~ (1) Lamberton, J. (1). A solution of 16 (60 mg, 0.34 mmol) in aqueous HCI (6 N, 20 mL) containing HOAc (2 mL) was hydrogenated over Pt02 (77 mg, 0.34 mmol) at an initial pressure of 15 bar for 16 h." The solution was filtered through Celite, neutralized by adding Na2C03, and extracted with CH2C12 (3 X 30 mL). The combined organic layers were washed with brine (2 X IO mL), dried (MgSO,), and evaporated by distillation. The product was purified by chromatography (A1203, pH 9.5, pentane-(loo), 80 (37); [a]"~ = 103.3' (C 0.97, MeOH). H y d r q e~t i~~ (SR,9R)-5-PrapyloctPhyddnd0Ildnddizine [(-)-Indollzine
Synthesis of indolizidine alkaloids via the intramolecular imino Diels-Alder reaction
Journal of the American Chemical Society, 1981
An intramolecular imino Diels-Alder strategy has been developed for total synthesis of the indolizidine alkaloids 6-coniceine (l), tylophorine (2), elaeokanine A (3), and elaeokanine B (4). In all cases, an acyl imine dienophile was generated thermally in situ from a methylol acetate precursor. Diene-methyl01 acetate 8 has been cyclized via 10 to lactam 11, which was converted to 6-coniceine. Similarly, intermediate methylol acetate 18 was transformed via 19 and 20 to pentacyclic lactam 21, and then to tylophorine. In the syntheses of elaeokanine A and B, a masked diene precursor, in the form of a dihydrothiophene dioxide system, was prepared. Thus, compound 35 was cyclized via intermediate 23b to afford bicyclic lactams 37 and 39 in a 5:4 ratio. These products were subsequently converted to 3 and 4.
Organic & Biomolecular Chemistry, 2005
Investigations aimed at the enantioselective total synthesis of indolizidine 223A, a recently described 5,6,8-trisubstituted indolizidine alkaloid from a dendrobatid frog, are described. tert-Butyl (2R,3R)-3amino-2-ethylhexanoate and its (2S,3R)-diastereomer, prepared in several steps from lithium N-benzyl-N-[(1R)-1-phenylethyl]amide and tert-butyl (2E)-hex-2-enoate by the Davies protocol, served as chiral building blocks from which two complementary suites of diastereomeric intermediates were made en route to pivotal tert-butyl 3-[2-(alkoxycarbonylmethylene)pyrrolidin-1-yl]-2-ethylhexanoate intermediates 20 and 21. Cyclisation of these enaminones, achieved by acid hydrolysis of the tert-butyl esters and activation of the liberated carboxylic acids as mixed anhydrides, afforded 6-ethyl-7-oxo-5-propyl-1,2,3,5,6,7-hexahydroindolizine-8-carboxylate esters 28 and 29. Several further transformations of these potential scaffolds for the synthesis of the target alkaloidal systems are also reported.
An expedient synthesis of diversified pyrrolizines and indolizines
Tetrahedron Letters, 2004
A general and rapid synthesis of new families of pyrrolizines and indolizines in good overall yields via an intramolecular [3+2] cycloaddition reaction is described. Diversity of substitutions can be achieved by the appropriate choice of readily available starting materials. The experimental procedures are straightforward and are performed under neutral conditions. New syntheses are also described for the preparation of N-propargylic 2-amino-benzaldehydes and S-propargylic 2-thiobenzaldehydes.