N-Heterocyclic carbene (NHC) catalyzed chemoselective acylation of alcohols in the presence of amines with various acylating reagents

Abstract

This edge article reports the synthesis and full characterization including X-ray analysis of three different acylazolium ions. The reactivity of these acylazolium ions as acylating reagents of amines and alcohols is discussed. Whereas benzylamine slowly reacts with the acylazolium ions, benzyl alcohol acylation does not occur. However, upon activation of the alcohol with an N-heterocyclic carbene (NHC) as catalyst, efficient esterification is achieved. Importantly, benzylester formation is obtained in the presence of benzylamine upon selective alcohol activation by the NHC. High level DFT calculations reveal that alcohol activation occurs by strong H-bond formation between the NHC and the alcohol thereby increasing the nucleophilicity of the alcohol. For oxidatively generated acylazolium ions under NHC catalysis, the carbene has a dual role (cooperative catalysis): (a) the NHC is used for generation of the acylazolium ion and (b) the NHC is used for activation of the alcohol in the subsequent acylation step. NHC-catalyzed selective acylation of benzyl alcohol in the presence of benzylamine can also be achieved with trifluoroethyl and hexafluoroisopropylesters as acylation reagents. Moreover, an enol acetate also shows high O-selectivity as a chemoselective acetylation reagent. Kinetic and mechanistic studies are provided and some examples of the chemoselective acylation of amino alcohols are presented.reaction kinetics, theoretical methods and NMR spectra. CCDC 919089 and 919090. For ESI and crystallographic data in CIF or other electronic format see

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

“…Yadav and co-workers reported the ring opening of epoxide by the Breslow intermediate 11 to provide the corresponding Aldol products [36]. Studer et al reported the preparation of acids by an oxidation of Breslow intermediates with molecular oxygen [37–39]. The highly activated Breslow intermediate 11 formed by the addition of the NHC to the aldehydes, reacts with dioxygen to form the peroxy-species, which afforded the corresponding hydroxypropyl benzoate.…”

From Additivity to Cooperativity in Chemistry: Can Cooperativity Be Measured?

“…To qualitatively check for cooperativity we prepared acylazolium ion 12 as a subsystem and analyzed its reactivity as alcohol or amine acylation reagent . If acylation is attempted in the absence of any free NHC in THF at room temperature with benzylamine and benzyl alcohol (1.5 equiv.…”

μ‐Oxo‐Dinuclear‐Iron(III)‐Catalyzed O‐Selective Acylation of Aliphatic and Aromatic Amino Alcohols and Transesterification of Tertiary Alcohols

“…Recently, chemoselective O‐acylation of a hydroxy group in the presence of an amino group that included our zinc cluster catalysts was reported . In contrast, there are only few reported O‐selective acylations using activated esters, likely because their high reactivity causes a background reaction of the more reactive amino group without the assistance of a catalyst . In addition, catalytic transesterification of sterically congested tertiary alcohols, especially synthetically useful tert ‐butanol, has never been achieved.…”