471-10-3Relevant articles and documents
Formamide-Catalyzed Nucleophilic Substitutions: Mechanistic Insight and Rationalization of Catalytic Activity
Hilt, Gerhard,Huy, Peter H.,Kohlmeyer, Corinna,Sch?fer, André
, p. 11567 - 11577 (2020/11/17)
Herein, detailed mechanistic investigations into formamide-catalyzed nucleophilic substitution (SN) of alcohols are reported. Alkoxyiminium chlorides and hexafluorophosphates were synthesized and characterized as a key intermediate of the catalytic cycle. The determination of reaction orders and control experiments indicated that the nucleophilic attack of the formamide catalyst onto the reagent BzCl is the rate-determining step. Linear free energy relationship revealed a correlation between the quantified Lewis basicity strength of formamides by means of 11B NMR spectroscopy and their catalytic activity in SN-transformations. The observed difference in catalytic ability was attributed to the natural bond order charge, dipole moment, and Sterimol parameter B5. Importantly, this rationalization enables the prediction of the capacity of formamides to promote SN-type transformations in general.
Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency
Stach, Tanja,Dr?ger, Julia,Huy, Peter H.
supporting information, p. 2980 - 2983 (2018/05/28)
A practical method for the nucleophilic substitution (SN) 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 SN-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.
Formamides as Lewis Base Catalysts in SNReactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers
Huy, Peter H.,Motsch, Sebastian,Kappler, Sarah M.
supporting information, p. 10145 - 10149 (2016/08/16)
A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.
