Teleocidin B4 core

The teleocidin B4 core 15 is synthesized from the Shiff base of 2-/< //-butyl-5-methoxyaniline, as shown in Scheme 16.161 The key sequence of this synthesis consists of two G-H bond functionalizations, alkenylation and oxidative carbonylation of two methyl groups, via palladacycle formations. 

N- [4-[ 1 -Ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glu-tamic acid as an antifolate was synthesized by Gangjee and colleagues [107], and palladium-catalyzed alkoxycarbonylation of aryl triflate was applied. A palladium-mediated carbonylative C-H activation was developed by Sames and team and applied in the total synthesis of teleocidin B4 core (Scheme 10.24) [108]. 

Heteroatom-directed C(sp )-H bond fimctionalizalion with stoichiometric transition metals was first disclosed in 1984 [1]. In 2002, Sames and coworkers developed an efficient route to constmct the teleocidin B4 core via the activation of C(sp )-H bond to prepare two diastereomeric paUadacycle key intermediates [2]. As a follow-up work, Ru3(CO)i2-catalyzed arylation of various C(sp )-H bonds with arylboronate esters using pyridine, pyrimidine, and amidine as directing groups was reported (Scheme 1.1) [3]. The use of ketones as solvent was necessary for a successfid arylation, mainly due to the trapping effect of the ruthenium hydride species. Despite of its efficiency, this transformation needs elevated temperatures (150 °C). Further, pyridine-directed a-C(sp )-H arylation of piperidines with arylboronate esters was developed with alcohols as solvent [4]. 

As a recent elegant application of coordination-directed C—activation and subsequent C—C bond formation, Sames synthesized the core of teleocidin B4 [182]. 

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