Palladium catalysis in the total synthesis of a natural alkaloid
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص1098-1099
2025-08-11
456
Palladium catalysis in the total synthesis of a natural alkaloid
We take our leave of palladium by presenting a synthesis of an alkaloid, N-acetyl clavicipitic acid methyl ester, by Hegedus. The power of organometallic chemistry is illustrated in five of the steps in this seven-step process (the metals are highlighted in orange). Each of the organo metallic steps catalysed by Pd (0) or Pd (II) has been described in this chapter. The overall yield is 18%, a remarkably good result for a molecule of such complexity. The fi rst step is to make an indole by Pd(II)-catalysed cyclization in the presence of benzo quinone as reoxidant. The nucleophilic nature of the 3-position of the indole was exploited to introduce the required iodide functionality. Rather than direct iodination, a high-yielding two-step procedure involving mercuration followed by iodination was employed.
Aryl iodides are more reactive towards oxidative addition than aryl bromides, and a selective Heck coupling (without phosphine ligands) with an unsaturated side chain left the bromide in place. A second Heck reaction of this bromide with an allylic alcohol was used to introduce a second side chain. Cyclization of the amide on to the allylic alcohol was achieved with palladium catalysis, not as might have been expected with palladium (0) but instead with palladium (II), to produce the seven-membered ring. Finally, the conjugated double bond was reduced and the sulfonamide removed under photolytic conditions.
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