N-Acetyl- -clavicipitic acid methyl ester

We end this section with a synthesis of N-acetyl clavicipitic acid methyl ester, an ergot alkaloid, by Hegedus. The power of orga no-transition-metal chemistry is illustrated in five steps of this seven-step process. Each of the organometallic steps catalysed by Pd(0) or Pd(II) has been described in this chapter. The overall yield is 18%, a good result for a molecule of such complexity. 

Scheme 28. An illustration of the efficacy of palladium chemistry in the total synthesis of N-acetyl-( )-clavicipitic acid methyl ester...

As described in Section 4.1. (Scheme 29), in the frequently reviewed synthesis of N-acetyl ( )-clavicipitic acid methyl ester (167) by Hegedus [80, 81], intramolecular aminopalladation of 164 was accomplished by a Pd(n)-catalyzed process lo give the tricyclic azepinoindole 16S. 

Hegedus synthesis of ( )-clavicipitic acid N-acetyl methyl ester culminated in the Pd-induced cyclization of 238 to 239, the latter of which was reduced to the target mixture [251], Substrate 238 was prepared via a Heck reaction with the corresponding 4-bromo compound 223 and 2-methyl-3-buten-2-ol (83%). The cyclization also occurs with tosic acid (97%). 

---