A Facile Route to Indolo[2,1-a]isoquinolines and Dibenzopyrrocoline Alkaloids

Abstract

Treatment of 1-(2'-bromobenzyl)-3,4-dihydroisoquinolines 2 in the presence of K(2)CO(3) in boiling DMF efficiently provided a variety of alkoxy-substituted indolo[2,1-a]isoquinolines 3. Application of this cyclization to 7-benzyloxyisoquinoline derivatives, followed by further elaboration of the resultant 2-benzyloxy-5,6-dihydroindolo[2,1-a]isoquinolines 16a,b, led to the formal synthesis of dibenzopyrrocoline alkaloids, (+/-)-cryptaustoline (1a) and (+/-)-cryptowoline (1b).

Phosphane‐Free Pd0‐Catalyzed Cycloamination and Carbonylation with Pd(OAc)2 and Cu(OAc)2 in the Presence of K2CO3: Preparation of Benzocyclic Amines and Benzolactams

“…Indolo[2,1‐ a ]isoquinolines with a substituent at their 8‐position, such as 8b , cannot be produced by the benzyne method 18,19. Cyclization with K 2 CO 3 /DMF19l–19n or aryl radical cyclization19j are able to give both types of indolizines from the 3,4‐dihydroisoquinoline derivatives but not from the tetrahydro derivatives. The benzyl ethers 7d and 7e have been transformed into the dibenzopyrrocoline alkaloids cryptowoline and cryptaustoline 18a.…”

Synthesis of indolo[2,1‐a]isoquinolines by CF3COOH‐induced cyclization

“…These are essentially identical with the reported spectral data. [ 39,63 ] A less mobile fraction with R f 0.2‐0.4 gave 8 as a colorless oil (13 mg, 33%); IR (neat): 1664 (CO) cm −1 ; 1 H NMR (270 MHz, CDCl 3 ): δ 3.09 (t, 2H, CH 2 , J = 6.7 Hz), 3.69 (s, 3H, OCH 3 ), 3.83 (s, 3H, OCH 3 ), 4.42 (t, 2H, CH 2 , J = 6.7 Hz), 6.39 (d, 1H, 2′‐H, J = 2.0 Hz), 6.51 (dd, 1H, 6′‐H, J = 8.0, 2.0 Hz), 6.75 (d, 1H, 5′‐H, J = 8.0 Hz), 7.36‐7.42 (m, 3H, 5‐, 6‐, and 7‐H), 7.55 (q, 1H, 2‐H, J = 1.7 Hz), 8.37‐8.42 (m, 1H, 4‐H) ppm; 13 C NMR (100.5 MHz, CDCl 3 ): δ 35.6 (CH 2 ), 49.4 (CH 2 ), 55.7 (OCH 3 ), 55.9 (OCH 3 ), 109.1 (C), 110.2 (CH), 111.5 (CH), 111.7 (CH), 116.9 (q, CF 3 , J = 291.0 Hz), 120.7 (CH), 122.7 (CH), 123.9 (CH), 124.5 (CH), 127.0 (C), 129.4 (C), 136.3 (C), 137.8 (q, CH, J = 5.0 Hz), 148.3 (C), 149.2 (C), 174.7 (q, CO, J = 35.5 Hz) ppm; EI‐MS: m/z 377 (M + , 34.7), 308 (47.2), 226 (8.1), 151 (100), 129 (12.0); HR‐MS calcd for C 20 H 18 NF 3 O 3 377.12385, found 377.12371.…”

“…[ 12,51‐59 ] . We have also reported some synthetic methods based on radical cyclization, [ 60 ] K 2 CO 3 /DMF‐induced cycloamination, [ 61–63 ] or phosphine‐free Pd(0)‐catalyzed cycloamination, [ 64 ] which have been developed for cyclization in route A shown in Figure 1. The present study deals with a new method for route B, which completes with an isoquinoline nucleus fusion.…”

Simple and one-pot synthesis of new heterocyclic compounds in three-component reactions between isoquinoline or phenanthridine and acetylenic esters in the presence of N-heterocycles or 1,3-dicarbonyl compounds

“…24 Isoquinoline is also present in various natural products such as cryptaustoline and cryptowoline. 25 They are known to exhibit various biological activities [26][27][28][29][30][31][32][33][34] such as antileukaemic, 35 tubulin polymerization inhibitory 36 and anti-tumour activities. 37 As previously reported, 38 reaction between phenanthridine and two mol equivalents of dimethyl acetylenedicarboxylate, leads to the…”