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. 2019 Apr 5;21(7):2346-2351.
doi: 10.1021/acs.orglett.9b00624. Epub 2019 Mar 12.

Structure and Reactivity of Highly Twisted N-Acylimidazoles

Elizabeth A Stone  1 , Brandon Q Mercado  1 , Scott J Miller  1
Affiliations

Structure and Reactivity of Highly Twisted N-Acylimidazoles

Elizabeth A Stone et al. Org Lett. .

Abstract

A modular and efficient synthesis of highly twisted N-acylimidazoles is reported. These twist amides were characterized via X-ray crystallography, NMR spectroscopy, IR spectroscopy, and DFT calculations. Modification of the substituent proximal to the amide revealed a maximum torsional angle of 88.6° in the solid state, which may be the most twisted amide reported for a nonbicyclic system to date. Reactivity and stability studies indicate that these twisted N-acylimidazoles may be valuable, namely as acyl transfer reagents.

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Figures

Figure 1.
Figure 1.
Examples of imidazole-containing compounds., ,
Figure 2.
Figure 2.
Characteristics of amides. (a) Amide bond resonance, inducing a planar structure. (b) Winkler-Dunitz distortion parameters for describing twist amides, with (c) select examples.
Figure 3.
Figure 3.
An overlay of the crystal structure (maroon) and geometry optimized structure (navy) of 7a (top) and 8a (bottom) is shown on the left (B3LYP/6–311++G(d,p)). Select crystal packing motif of 7a (top) and 8a (bottom) with intermolecular interactions highlighted in turquoise and distances in Å indicated, 50% ellipsoids. A symmetry equivalent Br-π interaction in 7a is omitted for clarity.
Scheme 1.
Scheme 1.
Synthesis of Highly Twisted N-Benzoyl Imidazoles.
Scheme 2.
Scheme 2.
Amide Reactivity of N-Acyl Imidazoles 7b and 8b. Suzuki–Miyaura cross coupling and deprotection conditions are shown in Scheme 1. Crystal structure of N-to O-benzoyl migration product (9) shown on right with hydrogens omitted for clarity, 50% ellipsoids.
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