Directed ortho metalation and palladium-catalyzed aryl-aryl cross-coupling reactions. Synthesis of heteroaromatics and alkaloids.

摘要

Chapter 1. A review of directed ortho metalation (DoM) and cross coupling reactions pertaining to the synthesis of aromatic and heteroaromatic compounds is presented. All the current developments in this field are described.; Chapter 2. The N-t-BOC aminophenylboronic acids derived from the DoM reaction when subjected to palladium catalyzed cross coupling reaction with a variety of 2-bromobenzaldehydes, 2-bromobenzoates, 2-bromobenzamides, and halo pyridyl esters constitute a general, efficient and a concise synthesis of phenanthridines, phenanthridinones, benzophenanthridines, and benzonaphthyridinones.; Chapter 3. The palladium catalyzed cross coupling reaction of N-t-BOC aminophenylboronic acid with N-methyl-6-bromo-3,4-methylenedioxybenzamide produced a required biaryl in high yield which led to the synthesis of an Amaryllidaceae alkaloid ismine in 45.6% overall yield. The first total synthesis of a betaine alkaloid, ungerimine, involving the key cross coupling step between a 7-bromoindoline derivative and 6-piperonal boronic acid is also described in 18% overall yield. The cross coupling methodology is also extended to prepare the lactam alkaloid, hippadine, in 24% overall yield. Approaches towards the synthesis of an antileukemic marine alkaloid, ascididemin, invoking a carbonylative cross coupling reaction of a heteroaryl triflate with pyridyl tin derivatives are also described.; Chapter 4. Ketones containing {dollar}alpha{dollar}-hydrogens upon condensation with anthranilam-ides, derived from the DoM methodology, readily give the corresponding imines. These imines when treated with equivalents of LDA undergo an anionic cyclization to afford the corresponding 4-quinolones in high yields. Attempts were made to prepare furoquinoline alkaloids via an anionic cyclization route. In an initial study, the DoM and anionic cyclization methodology were applicable to the preparation of 3-phenyl-4-hydroxy-isoquinoline.