Studies in biomimetic alkaloid syntheses. 6. Alternative pathways to secodines and their acyclic enamino acrylate analogs. Total syntheses of desethylibophyllidine, D-norvincadifformine, desethylvincadifformine, 20-methyldesethylvincadifformine, and 3-oxovincadifformine

Abstract

Reactions of methyl l,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (5a) with aldehydes gave 3,10b-alkano bridged azepines 9-14,28, and 33. On interor intramolecular quaternization and treatment with base the salts 17-20, 29, and 34 derived from aldehydes with an -proton rearranged to the A, B, C, E (and D) ring system of vincadifformine-type alkaloids through initial generation of enamino acrylate analogues 25 of secodines. A corresponding condensation and intramolecular acylation reaction gave 3-oxovincadifformine (35) in 85% yield.In earlier syntheses of vincadifformine (1), the -vincadifformines (2), and the pandolines (3) through secodine (4) intermediates,1-5 we had utilized reactions of the indoloazepine esters 5a,b with halo aldehydes 6a,b or the

Four‐Component Assembly of Natural‐Product‐Like Ring‐Fused Isoquinuclidines

“…In this way, access to ibogaine‐type compounds, with their characteristic structure of an indole and an isoquinoline connected through a seven‐membered ring (Figure 2), could be achieved in a single step (Scheme B). The masked dienophile 23 undergoes ring‐opening in the presence of aldehydes12 and has been used to synthesize the ibogaine‐type natural product catharanthine (Scheme A) in five steps 13. We hypothesized that compound 23 would participate in the multicomponent reaction under the developed conditions and afford catharanthine analogues in a single step.…”

Synthesis of propellane-containing natural products

“…In the Kuehne group synthesis of kopsanone (Scheme 50), 204 the key pentacyclic intermediate 276 came from an adaptation of a biomimetic secodine cyclization that they had investigated extensively. 211 Benzylation of the indole nitrogen and oxidative elimination of the selenyl group afforded N-oxide 267, which was ready for the Diels…”

Tandem Methodology for Heterocyclic Synthesis

“…The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. Removal of the tBoc group in 56 followed by reaction with 6-iodobenzo [1,3] ride afforded enamide 57. Treatment of this compound with Pd(OAc) 2 provided the galanthan tetracycle 58 in good yield.…”

“…Accordingly, novel strategies for the stereoselective synthesis of azapolycyclic ring systems continue to receive considerable attention in the field of synthetic organic chemistry [3][4][5][6][7][8][9]. Tandem methodology for heterocyclic synthesis represents a powerful approach for the rapid buildup of molecular complexity from potentially simple starting materials [10][11][12].…”