Preparation of opium alkaloids by palladium catalyzed bis-cyclizations. Formal total synthesis of morphine

✍ Scribed by Chang Y. Hong; Larry E. Overman

• Book ID: 104214430
• Publisher: Elsevier Science
• Year: 1994
• Tongue: French
• Weight: 219 KB
• Volume: 35
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)73208-4

✦ Synopsis

Absbxacf. Palladium catalyzed cyclization of hydroisoquinoline dlene 10 to afford the pentacyclic opiate 11 is the central step in a new synthesis of opium alkaloids. We recently described a oew asymmetric synthesis of opium alkaloids in which an intmmoIecular Heck arylation was a central step (e.g., eq l)?J This palladium catalyzed conversion forges the key quaternary center of the morphinan and opium alkaloid skeleta and is notably flexible with reganl to the electronic character of the aromatic ring .2 However, this approach to opium alkaloids has the shortcoming that the dibydrobenzofurau ring must be fabricated subsequently to the Heck cyclization step (e.g., 2 + 3). A mom atuactive coustruction of tbe opiate skeleton by a palladium catalyzed bis-cyclization is suggested in eq 2. In the case of the hydroisoqulnoline 1,fdlene substrate 4 (X = CH2), this conversion bas precedent in the kuown preparation ofdibydroben&iuans iiom the palladium catalyzed reaction of 13-dienes and 2-iodopheuolsP Herein we repat the succe&ul use of a palladium catalyzed bis-cyclization to assemble the opiate alkaloid skeleton.