Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency

Abstract

A practical method for the nucleophilic substitution (S ) of alcohols furnishing alkyl chlorides, bromides, and iodides under stereochemical inversion in high catalytic efficacy is introduced. The fusion of diethylcyclopropenone as a simple Lewis base organocatalyst and benzoyl chloride as a reagent allows notable turnover numbers up to 100. Moreover, the use of plain acetyl chloride as a stoichiometric promotor in an invertive S-type transformation is demonstrated for the first time. The operationally straightforward protocol exhibits high levels of stereoselectivity and scalability and tolerates a variety of functional groups.

Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

“…While halide 4 a formed in the presence of diphenylcyclopropenone ( 2 m ) in moderate yield, application of the sterically less shielded diethyl derivative diethylcyclopropenone (DEC, 2 e ) enabled the production of 4 a in an improved yield of 88 %. In agreement with our previous findings, [5d] cyclopropenones were recognized as more competent catalysts than formamides. Despite reports on tropone ( 2 c ) promoted S N ‐transformations with (COCl) 2 , [5c,7a] in the case of the reagent PCF no product 4 a could be detected.…”

“…Lewis base catalysis provides an effective technology for the activation of alcohols to alkyl chlorides of type 4 , for example (Scheme 1 A ) [1,4–9] . Especially phosphane oxides 2 a , [4] cyclopropenones 2 b , [5a,b,d] tropone ( 2 c ) [5c] and formamides 2 d [6] have been discovered as potent catalysts for C−Cl, C−Br and C−O bond formations. Actually, these OH group exchanges are promoted by acid chlorides like oxalyl chloride ( 3 a ), BzCl ( 3 b ), AcCl ( 3 c ) and TCT ( 3 d ).…”

Synthesis and Reactivity of α‐Haloglycine Esters: Hyperconjugation in Action

“…Encouraged by our initial findings that the AcOH (cat. )/AcCl system promotes the synthesis of α‐chloroglycine 4b in a single step (Table , entry 1), several other halogenation reagents have been evaluated to optimize the synthesis of 4a–c (Scheme and Table ) . As we initially reported, water needs to be fully extruded to avoid the reaction reversibility via hydrolysis, and other oxidative side reactions .…”

Systematic Evaluation of Sulfoxides as Catalysts in Nucleophilic Substitutions of Alcohols

“…In contrast to FPyr,[10a] sulfoxide catalyst 3 2 also enabled the utilization of plain acetyl chloride (AcCl) as reagent (Scheme B ) . The higher reactivity of AcCl in comparison to BzCl requested deviations from the optimized reaction conditions such as a lower substrate 1 concentration (see Tables S10 and S11).…”

“…Recently we established a cyclopropenone catalyzed protocol for the dehydroxybromination and ‐iodination of alcohols using BzCl and sodium bromide and iodide, respectively, as halogen source . However, the application of sulfoxides of type 3 instead of cyclopropenone derivatives under elsewise identical conditions allowed the synthesis of alkyl bromides and iodides only in moderate yields (see Table S12).…”