Approaches to Styrenyl Building Blocks for the Synthesis of Polyene Xanthomonadin and its Analogues

Abstract

A number of aryl building blocks for the synthesis of two xanthomonadin natural product pigments, as well as a related analogue, were accessed using a divergent hydroboration/bromoboration approach from a key alkynyl intermediate. A new approach towards substitution patterns around the ring was adopted following the isolation of an unexpected regioisomer from the bromination reaction. Potential coupling reactions onto these building blocks were explored, with a successful Sonogashira coupling performed on the key alkynyl intermediate, and with the key debrominated styrenyl boronate ester intermediate functionalised both by preliminary Suzuki–Miyaura coupling and by iododeboronation/Heck–Mizoroki coupling. Coupling reactions with brominated styrenyl intermediates proved much more challenging due to the instability of the intermediates to cross‐coupling, but some studies have shown promise.

Haloboration: scope, mechanism and utility

“… 94,95 Thus, haloboration/cross-coupling sequences can be applied in the synthesis of olefinic natural products ( Scheme 25 ). 96 The inherent instability of polyene boronic acids can be circumvented by either using them directly without further purification or using the MIDA boronate derivatives. Indeed, only 12 different MIDA boronates derived inter alia from the haloboration product of acetylene are necessary to build most polyene natural products via consecutive Suzuki–Miyaura reactions.…”