Oxindoles, ring synthesis

Okita, T. and Isobe, M. 1994. Synthesis of the pentacyclic intermediate for dynemicin a and unusual formation of spiro-oxindole ring. Tetrahedron 50 11143-11152. 

In the presence of tetramethyltin, 1-bromonauclefine reacts with CO in a Pd-catalyzed carbonylation to give the alkaloid naucletine [202], Dong and Busacca effected a new synthesis of tryptamines and tryptophols via a Rh-catalyzed hydroformylation of functionalized anilines that are prepared by a standard Heck reaction, as shown for the preparation of tryptamine sulfonamide 325 [423]. This reaction is applicable to ring-substituted tryptamines (Cl, Br, F. OMe, CF3). Likewise, the Rh-catalyzed carbonylation of o-alkynylanilines, which were prepared by a Pd-catalyzed Sonogashira coupling, leads to oxindoles (60-86% yields) [424],... 

In most indigo syntheses the indole structure is built up by ring closure of appropriate benzene derivatives by C-N or C-C bond formation. Examples of C-N bond formation include von Baeyer s 1878 synthesis from phenylacetic acid (3) via oxindole (4). 

A good deal of effort has been devoted to the preparation of derivatives of the cyclohepta[cd]indole and bicyclo[4.3.1]decane ring systems, that can be considered related to the ABC and CD ring systems of welwistatin, respectively, but much of this work cannot be translated easily to methods relevant to welwistatin synthesis. For instance, many successful approaches to the cyclohepta[cd] indole system are based on intramolecular radical cycliza-tions [12] or Heck reactions [13]. In many published examples, a substituent at the indole C-2 avoids the competing reaction at this position, but this device renders the reaction products inadequate to achieve the oxindole struc-... 

Intramolecular cyclizations have been used to prepare a variety of ring sizes. Carbon-carbon bond formation resulting in oxindole formation has been done in this manner by intramolecular reaction of A-acyl-o-chloroanilines (equation 85)571,572. A similar process has been used to prepare isoquinolinones571,573,574. Cephalotaxinone, an intermediate in the synthesis of the anti-leukaemia agent cephalotoxin, has been prepared by reaction of a complex enone iodide with base (equation 86)575. This reaction may occur via a radical mechanism and it has been used to prepare larger rings in reasonable yields540. 

---