Hydrogen-bonded frameworks for conformational analysis of reactive substrates

Abstract

Guanidinium organosulfonate (GS) hydrogen-bonded host frameworks were used to trap α-halopropiophenones and α-halocyclooctanones to determine their molecular structure by single crystal X-ray diffraction. The majority of encapsulated guest molecules adopted conformations expected from computational analysis and stereochemical outcomes of Grignard reactions.

Figure 1.

(A) Hydrogen-bonded sheet formed by guanidinium and organosulfonate ions. The sheet consists of one-dimensional GS “ribbons” joined by hydrogen bonds along their edges, serving as “hinges” that permit puckering, denoted as the inter-ribbon angle (θ_IR). (B, C) Molecular structures of GS hosts and guest molecules.

Figure 2.

(A) Reaction of 2-chloro- and 2-bromopropiophenone with allylmagnesium chloride (B) Hyperconjugative interactions of σ_C-X → π*_C–O. (C) Newman projection showing the polar Felkin–Anh transition state in nucleophilic attack to α-halopropiophenones.

Figure 3.

(A) (GCHMS)₄⊃Cl. (B) GCHMS⊃F. The lime-colored ovals represent disordered guests that could not be refined. (C) G₂BPDS⊃Cl. (D) G₂BPDS⊃Cl. (E) G₂1,5-NDS⊃Cl. (F) G₂1,5-NDS⊃Br. The GS frameworks are depicted as ball-and-stick and the guest molecules as space-filling.

Figure 4.

Summary of the structural features for the host frameworks (rows) and their F, Cl, and Br guest molecules (columns). Each guest is portrayed in two orientations: (left) perpendicular to the plane of the phenyl ring, (right) along the C–C bond of the O–C–C– X dihedral angle. *The positions of the halogen and methyl group in these cases is ambiguous (see text), such that two conformations are possible in unspecified ratios. The anticlinal conformation can be ruled out in all cases, however.

Figure 5.

Four fragments used for the Cambridge Structural Database (CSD) surveys (i-iv) of acyclic α-halo-substituted ketones.

Figure 6.

The crystal structure of 2-chlorocyclooctanone guest encapsulated in GCHMS reveals two conformers (A) gauche (39% occupancy), and (B) synperiplanar (23% occupancy), and their respective O–C–C–Cl dihedral angles (φ). The remainder of the guests were disordered and could not be refined. The structures on the right correspond to their respective Newman projections.