59204-21-6Relevant articles and documents
A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions
Huy, Peter H.,Filbrich, Isabel
, p. 7410 - 7416 (2018)
A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.
A π–Cu(II)?π Complex as an Extremely Active Catalyst for Enantioselective α-Halogenation of N-Acyl-3,5-dimethylpyrazoles
Nishimura, Kazuki,Wang, Yanzhao,Ogura, Yoshihiro,Kumagai, Jun,Ishihara, Kazuaki
, p. 1012 - 1017 (2022/01/19)
Novel chiral π–copper(II)?π complex catalyzed enantioselective α-chlorination and -bromination of N-acyl-3,5-dimethylpyrazoles are described. The π–copper(II)?π complexation of Cu(OTf)2 with 3-(2-naphthyl)-l-alanine-derived amides greatly increases the Lewis acidity and triggers the in situ generation of enolate species without an external base, which has a suppressing effect for α-chlorination and -bromination due to undesired halogen bonding. This strategy provides facile access to α-halogenated compounds in high yield with excellent enantioselectivity. X-ray crystallographic and ESR analyses of the catalyst complexes suggest that the release of two counteranions (2TfO–) from the copper(II) center might be crucial for the efficient activation of N-acyl-3,5-dimethylpyrazoles.
Enantioselective α-Chlorination Reactions of in Situ Generated C1 Ammonium Enolates under Base-Free Conditions
Stockhammer, Lotte,Weinzierl, David,B?gl, Thomas,Waser, Mario
, p. 6143 - 6147 (2021/08/18)
The asymmetric α-chlorination of activated aryl acetic acid esters can be carried out with high levels of enantioselectivities utilizing commercially available isothiourea catalysts under base-free conditions. The reaction, which proceeds via the in situ formation of chiral C1 ammonium enolates, is best carried out under cryogenic conditions combined with a direct trapping of the activated α-chlorinated ester derivative to prevent epimerization, thus allowing for enantioselectivities of up to e.r. 99:1.
Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes
Zoller, Ben,Stach, Tanja,Huy, Peter H.
, p. 5637 - 5643 (2020/09/21)
Nucleophilic substitutions (SN) are typically promoted by acid chlorides as sacrificial reagents to improve the thermodynamic driving force and lower kinetic barriers. However, the cheapest acid chloride phosgene (COCl2) is a highly toxic gas. Against this background, phenyl chloroformate (PCF) was discovered as inherently safer phosgene substitute for the SN-type formation of C?Cl and C?Br bonds using alcohols. Thereby, application of the Lewis bases 1-formylpyrroldine (FPyr) and diethylcyclopropenone (DEC) as catalysts turned out to be pivotal to shift the chemoselectivity in favor of halo alkane generation. Primary, secondary and tertiary, benzylic, allylic and aliphatic alcohols are appropriate starting materials. A variety of functional groups are tolerated, which includes even acid labile moieties such as tert-butyl esters and acetals. Since the by-product phenol can be isolated, a recycling to PCF with inexpensive phosgene would be feasible on a technical scale. Eventually, a thorough competitive study demonstrated that PCF is indeed superior to phosgene and other substitutes.
METHOD OF CONVERTING ALCOHOL TO HALIDE
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Page/Page column 50; 127; 129; 130, (2017/01/02)
The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.
CaF2 catalyzed SN2 type chlorodehydroxylation of chiral secondary alcohols with thionyl chloride: A practical and convenient approach for the preparation of optically active chloroalkanes
Zhang, Junjie,Wang, Huanxia,Ma, Yun,Wang, Youming,Zhou, Zhenghong,Tang, Chuchi
, p. 2261 - 2263 (2013/05/09)
A CaF2 catalyzed chlorodehydroxylation of chiral secondary alcohols with thionyl chloride has been developed. The chlorination reaction is effective for a wide range of alcohols, generating the corresponding chloroalkanes in good yield with high optical purity with inversion of the original configuration of the alcohol.
1,2-Dimethoxy-4,5-dimethylene: A new protecting group for acyclic amino acid derivatives prepared by Stevens rearrangement
Tayama, Eiji,Takedachi, Keisuke,Iwamoto, Hajime,Hasegawa, Eietsu
supporting information; experimental part, p. 1373 - 1375 (2012/03/27)
A new protecting group, 1,2-dimethoxy-4,5-dimethylene, for acyclic amino acid derivatives could be introduced by N,N-dialkylation with 1,2-bis(bromomethyl)-4,5-dimethoxybenzene (1) and removed via amine de-alkylation with acyl chlorides. The method can be used with base-induced [2,3] and [1,2] Stevens rearrangement products.
Catalytic asymmetric α-chlorination of 3-acyloxazolidin-2-one with a trinary catalytic system
Hamashima, Yoshitaka,Nagi, Tatsuya,Shimizu, Ryo,Tsuchimoto, Teruhisa,Sodeoka, Mikiko
scheme or table, p. 3675 - 3678 (2011/09/15)
Direct asymmetric α-chlorination of aryl acetic acid derivatives was achieved with a novel trinary activation system consisting of a catalytic amount of NiCl2/(R)-BINAP, Et3SiOTf, and a tertiary amine base. The reaction smoothly affo
Enzymatic hydrolysis and selective racemisation reactions of α-chloro esters
Haughton, Louise,Williams, Jonathan M. J.
, p. 943 - 946 (2007/10/03)
The kinetic resolution of α-chloro esters was effected with good selectivity using CLEC (Cross-Linked Enzyme Crystals) enzymes. The selective racemisation of α-chloro esters in the presence of α-chloro acids enabled a successful dynamic kinetic resolution reaction to be performed.
Enantioselective Protonation of Ketene Bis(trimethylsilyl) Acetals Derived from α-Aryl-α-haloacetic Acids Using LBA
Ishihara, Kazuaki,Nakamura, Shingo,Yamamoto, Hisashi
, p. 513 - 517 (2007/10/03)
Optically active α-halocarboxylic acids and derivatives are important and versatile building blocks in organic synthesis. Lewis acid assisted chiral Bronsted acid (LBA) was recently prepared in situ from tin(IV) tetrachloride and optically pure binaphthol
