α‐Halogenoacetanilides as Hydrogen‐Bonding Organocatalysts that Activate Carbonyl Bonds: Fluorine versus Chlorine and Bromine

Abstract

α-Halogenoacetanilides (X=F, Cl, Br) were examined as H-bonding organocatalysts designed for the double activation of CO bonds through NH and CH donor groups. Depending on the halide substituents, the double H-bond involved a nonconventional CH⋅⋅⋅O interaction with either a HCXn (n=1-2, X=Cl, Br) or a HCAr bond (X=F), as shown in the solid-state crystal structures and by molecular modeling. In addition, the catalytic properties of α-halogenoacetanilides were evaluated in the ring-opening polymerization of lactide, in the presence of a tertiary amine as cocatalyst. The α-dichloro- and α-dibromoacetanilides containing electron-deficient aromatic groups afforded the most attractive double H-bonding properties towards CO bonds, with a NH⋅⋅⋅O⋅⋅⋅HCX2 interaction.

Torsional and Electronic Factors Control the C−H⋅⋅⋅O Interaction

“…In the context of designinga nd developing new folded systems and hydrogen-bonding organocatalysts that exploit the CÀH···O hydrogen bond as as tructural element, it is clearthat ac ombination of favourablee lectronica nd torsional effects is ap rerequisite for such interactions to be conformationally influential. [39]…”

Capturing the Monomeric (L)CuH in NHC‐Capped Cyclodextrin: Cavity‐Controlled Chemoselective Hydrosilylation of α,β‐Unsaturated Ketones

“…We then performed a non‐covalent‐interaction analysis (NCI) on the TSs, looking for additional weak interactions in these catalytic pockets, and could indeed detect attractive interactions between the C−H groups of the CD and the carbonyl oxygen of the substrate. The activation of a C=O bond by a C−H bond has been rarely invoked, usually with a polarized C−H bond next to a quaternary ammonium group or in conjunction with another H‐bond . For α‐ICyD, this interaction is much stronger in TS‐α‐1,2 than in TS‐α‐1,4.…”

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

“…The involvement of the ortho C–H bond in the binding event with Lewis-basic sites was proposed by Etter in the late 1980s and later demonstrated by Schreiner in a detailed study of hydrogen-bonding thiourea organocatalysts containing a 3,5-bis(trifluoromethyl)phenyl group as the privileged motif [56–58]. A recent example of utilizing such interactions in catalysis was demonstrated by Bibal and co-workers [58].…”

“…A recent example of utilizing such interactions in catalysis was demonstrated by Bibal and co-workers [58]. In this study, Bibal and co-workers explored the use of α-halogenated acetanilides L14 and L15 as hydrogen-bonding organocatalysts that activate the carbonyl functionality of lactide and thus enhance their reactivity toward ROP (Scheme 11).…”

“…Mixed N–H/C–H two hydrogen bond donors L14 and L15 as organocatalysts for ROP of lactide by Bibal and co-workers [58]. …”