Novel photoisomerization of 1-acylindoles to 3-acylindolenines. General entry to the total synthesis of Strychnos and Aspidosperma alkaloids

Abstract

The photochemistry of the enamide system and its useful application have been well investigated;' simple enamides generally undergo a [1,3]-acyl radical shift to afford vinylogous amides Meanwhile, photoisomerizations of 1 -acylindoles of an enamide system have been described to merely provide 3-, 4-, and 6-acylindoles by the usual photo-Fries type of rearrar~gement.~ In this communication, we report the novel photorearrangement synchronized with a conversion of 1-acylindoles la-d to 3-acylindolenines 2a-d, as depicted in Scheme I, which, with R' = CH2CH2NHR2, n = 2,3, was followed by a simultaneous intramolecular ring enlargement to provide the nine-or eight-membered lactams 3a-c in a one-pot reaction, establishing a versatile entry to the total synthesis of a diverse array of Aspidosperma and Strychnos alkaloids. The general synthetic scheme is demonstrated by formula 4 in Scheme 11, with the dotted lines a or b and c.It was discovered by us that the photoisomerization of 5 wtih a 300-W high pressure mercury lamp afforded 6435 [RN-(COR')-CH=CR2R3 -RN=CH-C(COR)R2R3], which is the so far unknown reactive species, together with 7, 8, and 9, the products of the usual isomerization, in addition to the starting material 5 and The remarkable reactivities of the novel [RN(COR')-CH=CHR' -RNH-CH=C(COR')R2].2 (1) Lenz, G. R. Synthesis 1978, 489. (2) Bertele, E.; Boos, H.; Dunitz, J. D.; Elsinger, F.; Eschenmoser, A,; Felner, I.; Gribi, H. P.; Gschwend, H.; Meyer, E. F.; Pesaro, M.; Scheffold, R.

Chemistry of Bridged Lactams and Related Heterocycles

“…162 The requisite lactam was prepared via an intramolecular N -alkylation of 620 using NaH in the presence of KI/18-crown-6, followed by alkylation at the bridgehead position in very good overall yield (see also Table 18). Reduction of 621 followed divergent pathways depending on the conditions used for this step: with LiAlH 4 in refluxing dioxane, quebrachamine was formed, whereas in THF, 1,2-dehydroaspidospermidine was obtained via the bridged hemiaminal 623 .…”

Dirhodium(II) Carboxylate Catalyzed Formation of 1,2,3‐Trisubstituted Indoles from Styryl Azides

“…While a 1,2 carbonyl shift from 17 could occur to form the 2H-indole 18, this product was reported by Ban and co-workers to be unstable and prone to fragmentation upon exposure to Lewis or Brønsted acids. [21] Consequently, it appears likely that the Lewis-acidic rhodium(II) carboxylate triggers fragmentation of 17 or 18 to produce the acylium ion 19. This acylium ion could be attacked by the indole at the C3-position to reform the kinetic, [22] but unstable 18, [23] or at the anionic nitrogen atom to afford the thermodynamic indole product 12 and regenerate the rhodium(II) carboxylate catalyst.…”

Total Synthesis of Aspidosperma and Strychnos Alkaloids through Indole Dearomatization

“…Ban et al. have also developed a reduction strategy to the Aspidosperma alkaloid core (Scheme ) . Tetracyclic lactam 84 was first selectively reduced to hemiaminal 85 .…”

“…[23] Ban et al have also developed ar eduction strategy to the Aspidosperma alkaloid core (Scheme 9). [25] Te tracyclic lactam 84 was first selectively reduced to hemiaminal 85.N ext, treatment with hydrochloric acid removed the THP group and triggered the dearomatization step in at ransannular Pictet-Spengler re-action towards 1,2-dehydroaspidospermidine (86)i n4 8% yield over two steps.…”