Palau’chlor: A Practical and Reactive Chlorinating Reagent

Abstract

Unlike its other halogen atom siblings, the utility of chlorinated arenes and (hetero)arenes are twofold: they are useful in tuning electronic structure as well as acting as points for diversification via cross-coupling. Herein we report the invention of a new guanidine-based chlorinating reagent, CBMG or “Palau’chlor”, inspired by a key chlorospirocyclization en route to pyrrole imidazole alkaloids. This direct, mild, operationally simple, and safe chlorinating method is compatible with a range of nitrogen-containing heterocycles as well as select classes of arenes, conjugated π-systems, sulfonamides, and silyl enol ethers. Comparisons with other known chlorinating reagents revealed CBMG to be the premier reagent.

Predictive Model for Site-Selective Aryl and Heteroaryl C–H Functionalization via Organic Photoredox Catalysis

“…46,47 However, pyrazoles deviate from this trend, with N -methylpyrazoles reacting at the 5-position, likely because the transient cation radical intermediate behaves as a distonic iminium radical instead of a delocalized arene cation radical. For this reason, 8d is not functionalized because the iminium position bears the 5-methyl substituent.…”

Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse

“…Historically, as has been the underlying motivation of this review article, natural product chemistry has led to the discovery and characterization of novel halogenation biocatalysts, which, in turn, have inspired the development of novel halogenating chemical catalysts as well. 429 This process has not been exhausted. A recent report describing the structure elucidation and biosynthetic gene cluster discovery of cyanobacterial bartolosides has uncovered a potentially novel diiron-dependent halogenase, 430,431 with homologs present in other cyanobacteria, including in a cyanobacterial gene cluster encoding the production of structurally analogous halogenated cyclophane natural products.…”

Derivatization of agelastatin A leading to bioactive analogs and a trifunctional probe

“…6a Iodination with N -iodosuccinimide (NIS) promoted by (InOTf) 3 13 gave 14-iodo 2 in 74% yield (Scheme 1) which enabled subsequent functionalization of C14 through chemoselective Pd-mediated reactions. Initial chlorination conditions employing standard conditions (NCS) gave complex mixtures, however chlorination of AglA with Palau’chlor ® 14 gave a mixture of the desired 14-chloro AglA 3 (24%) and AgelB 4 (30%) along with traces of C13,C14-dichlorinated derivative detected by LCMS. Modified reaction conditions allowed access to AgelB ( 4 ) in 5 minutes using KBr and selectfluor ® , as brominating agent.…”