Total Synthesis of Lamellarins G, J, L, and Z Using One-Pot Halogen Dance/Negishi Coupling

Abstract

A bottom-up synthesis of lamellarins G, J, L, and Z was achieved via one-pot halogen dance/Negishi coupling of a lithiated dibromopyrrole derivative. The easily accessible dibromopyrrole bearing an ester moiety underwent halogen dance smoothly at −78 °C within 10 min. The resultant α-pyrrolyllithium was transmetalated to the corresponding organozinc species, which was then coupled with an aryl iodide in the presence of catalytic palladium to provide the fully substituted pyrrole. Subsequent halogen–lithium exchange was performed to incorporate a boronate group exclusively at the β position proximal to the ester moiety. This synthetic intermediate allowed stepwise diarylation for the total synthesis of lamellarins G, J, L, and Z.

Exploring the boundaries of ferrocenesulfonyl fluoride chemistry

“…Although this is the first time that a one-pot 'halogen dance' reaction-Negishi cross-coupling has been reported in the ferrocene series, related examples from 2,5-or 2,3-dibromothiophenes have been recently documented by Okano. 88,89 We next attempted to apply the same isomerization conditions to the substrate 5f and isolated the isomers 6e and 6f in 38 and 13% yield, respectively, after methanolysis (16% of deiodinated product 3b was also obtained). The combination of the long-range acidifying properties of the sulfonyl fluoride group, combined with the moderate adjacent protecting group ability of the phenylthio substituent, could explain why both the 3 and 4 positions of the substrate 5f can be deprotolithiated.…”

Recent advances in the synthesis of chromenone fused pyrrolo[2,1-a]isoquinoline derivatives

“…In parallel to this, Okano and colleagues 79 also reported the syntheses of a series of lamellarins (lamellarin G, J, L, and Z) starting from a dibromopyrrole carboxylate derivative by the construction of both coumarin as well as pyrrolo[2,1- a ]isoquinolines rings (Scheme 21). The protocol of the reactions proceeded through one-pot halogen dance/Negishi coupling of a lithiated dibromopyrrole derivative, transmetalation, ligand-controlled regioselective stepwise diarylation via Suzuki–Miyaura coupling, selective hydrogenolysis, and acid catalyzed lactone formation.…”

Recent Advances in Biologically Active Coumarins from Marine Sources: Synthesis and Evaluation

“…Okano et al also described the total synthesis of some lamellarins using a one-pot lithiation/Negishi coupling methodology [ 111 , 112 ]. In addition, novel technologies such as photocatalysis and electrosynthesis also proved to be effective in the construction of the core [ 113 ].…”