Pummerer Synthesis of Chromanes Reveals a Competition between Cyclization and Reductive Chlorination

Abstract

The competition between an unprecedented reductive chlorination and the Pummerer reaction was studied and applied to the synthesis of benzofused oxygen heterocycles including 3-aminochromanes and in the intramolecular chlorination of activated aromatic rings. The use of (COCl) 2 as a Pummerer activator showed substantial activity, producing α-chlorinated sulfides that can undergo Pummerer−Friedel−Crafts cyclization. If the aromatic ring has electron-donating groups in position three, then the reaction follows a different pathway, yielding the reductive chlorination products, where the chlorine atom comes from a sulfonium salt.

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

“…Oxalyl chloride has been used as an activator in Pummerer reactions . In these types of reactions, α‐chlorinated sulfides were observed, demonstrating that they can react with Lewis acids or bases, leading to the formation of thionium ions or nucleophilic substitutions.…”

“…Therefore, the base is essential for carrying out the deprotonation to IV , and the intramolecular protonation/deoxygenation leads to the sulfide as the product and the ketone as the oxidized functional group. Previously, we have described an intramolecular reductive chlorination of some special sulfoxides, but we did not identify the utility of chlorosulfonium salts in intermolecular reductions. Herein, we hypothesize that the use of strong nucleophilic aromatics could eliminate the requirement for a base (Scheme b).…”

Six-membered ring systems: with O and/or S atoms

“…A single example of thiochroman was also prepared in 71% yield, after 10 days of reaction (19CC4479). Reductive chlorination of substituted (3-phenylsulfinyl)propoxybenzenes using (COCl) 2 in dichloromethane at 0 C affords o-chlorophenol sulfides which underwent PummerereFriedeleCrafts cyclization in the presence of BF 3 •Et 2 O to give 4-thiophenylchromans (19OL6903). Various 4-methyl-4-thiophenylmethylchromans are synthesized via palladium-catalyzed carbothiolation of 1-iodo-2-(3-methylbut-3-en-1-yloxy)benzenes with triisopropylsilyl thioethers in the presence of cesium carbonate in toluene at 100 C (19OL8280).…”