Systematic Evaluation of Sulfoxides as Catalysts in Nucleophilic Substitutions of Alcohols. Issue 33 (17th August 2018)

• Record Type: Journal Article
• Authors: Motsch, Sebastian; Schütz, Christian; Huy, Peter H.
• Is Part Of: European journal of organic chemistry. Issue 33(2018)
• Page Start: 4541
• Page End: 4547
• Publication Date: 2018-08-17
• Subjects: Nucleophilic substitution -- Homogeneous catalysis -- Sulfoxides -- Organocatalysis -- Halogenation; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201800907
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : Herein, a method for the nucleophilic substitution (S N ) of benzyl alcohols yielding chloro alkanes is introduced that relies on aromatic sulfoxides as Lewis base catalysts (down to 1.5 mol‐%) and benzoyl chloride (BzCl) as reagent. A systematic screening of various sulfoxides and other sulfinyl containing Lewis bases afforded (2‐methoxyphenyl)methyl sulfoxide as optimal catalyst. In contrast to reported formamide catalysts, sulfoxides also enable the application of plain acetyl chloride (AcCl) as reagent. In addition, it was demonstrated that weakly electrophilic carboxylic acid chlorides like BzCl promote Pummerer rearrangement of sulfoxides already at room temperature. This side‐reaction also provided the explanation, why sulfoxide catalyzed S N ‐reactions of alcohols do not allow the effective production of aliphatic and electron deficient chloro alkanes. Comparison experiments provided further insight into the reaction mechanism. Abstract : Out of an in‐depth study of a range of sulfinyl compounds in the transformation of alcohols into chloro alkanes emerged (2‐methoxyphenyl)methyl sulfoxide as optimal Lewis base catalyst. While this catalyst allowed the synthesis of benzylic chlorides in turn‐over numbers up to 50, aliphatic alcohols are non‐suitable substrates due to competing Pummerer rearrangement.