Total Synthesis of (+)‐Elacomine and (−)‐Isoelacomine, Two Hitherto Unnamed Oxindole Alkaloids from Elaeagnus commutata

Abstract

Racemic elacomine ((%)-2), a hemiterpene spiro oxindole alkaloid from Elueagnus commutata, was synthesized in five steps from 6-methoxytryptamine (19) in 16% overall yield (Scheme 3 ) . The final oxidative rearrangement of the corresponding 8-carboline precursor (%)-21 furnished isoelacomine ((%)-22) as a by-product (6% overall yield). A more elaborate route that started from L-tryptophan furnished (+)-2 and (-)-22 with optical purities of 76% (Scheme 4 ) and established the absolute configuration of these compounds. A reinvestigation of the alkaloidal content of the roots of E. cornmututu showed that both elacomine and isoelacomine occur naturally in racemic form. ( [ a ] , = +174.8) hemiterpene oxindole alkaloid3) from the roots of the shrub Elaeagnus commutata (Elaegnaceae) [ 11. Chemical degradation studies and spectroscopic evidence led to structure proposal 1 which, however, left open the exact position of the phenolic OH group and the relative configuration at the two asymmetric centres C(3) and C(4')4). These questions were addressed subsequently by James and Williams by means of an X-ray diffraction study that allowed them to established formula 2 for this compound which they had obtained from Locock and Slywka [2]. Curiously enough, the sample investigated by X-ray crystallography must have been racemic, since the crystal was composed of alternating layers of both optical antipodes of 2, a fact that is consistent with the reported space group P2,lc. Surprisingly, the evident conflict concerning the enantiomeric purity of 2 was not commented by James and Williams, and in the context of our interest in the chemo-and diastereoselective transformation of indole alkaloids into their oxindole (1,3-dihydro-2H-indol-2-one) or pseudoindoxyl (1,2-dihydro-3H-indo1-3-one) derivatives [4-81, we decided to synthesize (+)-elacomine ((+)-2) in a way that would allow to delineate its hitherto unknown absolute configuration. Introduction. ~ In 1968, Slywka reported the isolation of a novel, optically active

Domino Pd‐Catalyzed Heck Cyclization and Bismuth‐Catalyzed Hydroamination: Formal Synthesis of Elacomine and Isoelacomine

“…The major byproducts were the deiodinated aniline and the saturated lactone 9 (R 1 = Me, R 2 = Boc), which arose from the O-enolate of palladium (Table 1, entry 1). The use of other phosphine ligands, such as bidentate ligands (1,2-bis(diphenylphosphino)ethane (DPPE)), bulky ligands (PA C H T U N G T R E N N U N G (o-tolyl) 3 ), and less electron-donating ligands (PA C H T U N G T R E N N U N G (2-furyl) 3 ), resulted in low yields of the desired product (Table 1, entries 2-4). In the absence of phosphine ligands the reaction gave a complex mixture (Table 1, entry 5).…”

“…The belimination process might be suppressed under acidic conditions so several acids, which included TfOH, HfA C H T U N G T R E N N U N G (OTf) 4 , and BiA C H T U N G T R E N N U N G (OTf) 3 [19] (Tf = triflate), were investigated in the presence of the DPPF ligand (Table 3, entries 6-8). We found that the addition of BiA C H T U N G T R E N N U N G (OTf) 3 was effective for this domino Pd-catalyzed spirooxindole formation (Table 3, entry 8). The Pd 0 -catalyzed reaction of 17 in the presence of BiA C H T U N G T R E N N U N G (OTf) 3 (10 mol %) provided spirooxindole 18 in 52 % yield with no contamination by diene 19.…”

“…We found that the addition of BiA C H T U N G T R E N N U N G (OTf) 3 was effective for this domino Pd-catalyzed spirooxindole formation (Table 3, entry 8). The Pd 0 -catalyzed reaction of 17 in the presence of BiA C H T U N G T R E N N U N G (OTf) 3 (10 mol %) provided spirooxindole 18 in 52 % yield with no contamination by diene 19. The diastereoselectivity achieved at the C-2' position remained low (diastereomeric ratio (d.r.)…”

“…To clarify the effect of the additives on the Pd 0 -catalyzed domino cyclization, intramolecular hydroamination of diene 19 with Lewis acid catalysts was next investigated. We first selected the conditions of a BiA C H T U N G T R E N N U N G (OTf) 3 or HfA C H T U N G T R E N N U N G (OTf) 4 catalyst in xylene at 130 8C, which were the same conditions employed [b] [a] Yield obtained after deprotection of the Boc group with TFA in CH 2 Cl 2 . [b] Yield based on recovered starting material.…”

“…Under these conditions, the hydroamination proceeded smoothly to give the desired spirooxindole 18 in moderate yields, as a 3:1 or 2:1 diastereomeric mixture [20] ( Table 4, entries 1 and 2). Under Shibasakis conditions [21] (PF 6 À salt and borderline metals, according to the hard and soft acids and bases principle, [22] such as BiA C H T U N G T R E N N U N G (OTf) 3 , HfA C H T U N G T R E N N U N G (OTf) 4 , and ScA C H T U N G T R E N N U N G (OTf) 3 ), the chemical yields of 18 significantly increased; compound 18 was afforded in 57-83 % yield with the same levels of diastereoselectivity (Table 4, entries 3-6). The combined use of Bi- 6 ] in dioxane gave the best results in terms of the yield of cyclized product (Table 4, entry 4).…”