Electrophilic halogenations of propargyl alcohols: paths to α-haloenones, ß-haloenones and mixed ß,ß-dihaloenones.

The Meyer-Schuster rearrangement of propargyl alcohols or alkynols leading to α,ß-unsaturated carbonyl compounds is well known. Yet, electrophilic halogenations of the same alkynols and their alkoxy, ester and halo derivatives are inconspicuous. This review on the halogenation reactions of propargyl alcohols and derivatives intends to give a perspective from its humble direct halogenation beginning to the present involving metal catalysis. The halogenation products of propargyl alcohols include α-fluoroenones, α-chloroenones, α-bromoenones and α-iodoenones, as well as ß-haloenones and symmetrical and mixed ß,ß-dihaloenones. They are, in essence, tri and tetrasubstituted alkenes carrying halo-functionalization at the α- or ß-carbon. This is a potential stepping stone for further construction towards challenging substituted alkenones via Pd-catalysed coupling reactions.

Halogen bond-induced electrophilic aromatic halogenations.

In recent years, there has been increasing interest in utilising halogen bonds in organic synthesis, especially in aromatic halogenation reactions. N-Halosuccinimides and 1,3-dihalo-5,5-dimethylhydantoins are popular sources of halonium ions due to their ease of handling and low toxicities. Traditionally, these N-haloimides are activated by electrophiles, namely Brønsted and Lewis acids. The recent discovery of possible activation by nucleophilic Lewis base catalysts led to a paradigm shift in aromatic halogenation. Active functional motifs in Lewis base catalysts such as CS, R-S-R1, Ar-S-S-Ar, SO, Ar-NH2, and R2NH+Cl- form halogen bonds with the positively charged σ-hole of the halogen atoms: an essential interaction to produce halonium ions. This review highlights the evolution of the two modes of activation. Evidence of halogen bond formation from mechanistic studies of nucleophilic activation is also discussed herein.

Halogen bonding in (Z)-2-iodocinnamaldehyde.

Based on the bulkiness of the iodine atom, a non-planar conformation was expected for the title compound. Instead, its molecular structure is planar, as experimentally determined using single crystal X-ray diffraction, and confirmed theoretically by DFT calculations on the single molecule and the halogen pair paired molecules, therefore ruling out crystal packing forces as a principal factor leading to planarity. Indeed, planarity is ascribed to the carbonyl double bond, as when this bond is saturated on forming the related alcohol derivative, the molecule loses planarity. The X-ray molecular structure shows an intermolecular separation between the iodine and the oxygen of the carbonyl shorter than the corresponding van der Waals distance suggesting a weak halogen bond interaction. DFT minimization of this 2-molecule arrangement shows the iodine--oxygen distance much shorter than that observed in the crystal interaction and confirming its stronger halogen bond nature. A trend between increasing I•••O(carbonyl) separation and decreasing C-I•••O(carbonyl) angle is demonstrated, further confirming the existence of a halogen bond.

N-Acetyl-3,5-dibromo-l-tyrosine hemihydrate.

The title compound, C(11)H(11)Br(2)NO(4)·0.5H(2)O, was prepared by an electrophilic bromination of N-acetyl-l-tyrosine in acetonitrile at room temperature. The two independent mol-ecules do not differ substanti-ally and a mol-ecule of water completes the asymmetric unit. The synthesis of the title compound does not modify the stereochemical center, as shown by the absolute configuration found in this crystal structure. Comparison with the non-bromo starting material differs mainly by rotation features. For instance the H(methine)-C(chiral center)-C(methyl-ene)-C(ipso) is 173.0 (2)° torsion angle in one mol-ecule and 177.3 (2)° in the other, indicating a trans arrangement. This is in contrast with approximately 50° in the starting material. A short inter-molecular Br⋯Br separation is observed [3.2938 (3) Å]. The molecules in the crystal are connected via a network of hydrogen bonds through an N-H⋯O hydrogen bond between the hydroxy group of the phenol of the tyrosine and the N-H of the amide of the other molecule and an O-H⋯O hydrogen bond between the hydroxy group of the carboxylic acid and the oxygen of the carbonyl of the amide.

Novel Photochemical Hydrolysis of o-Acetylphenylacetonitriles to Amides.

Irradiation of o-acetylphenylacetonitriles 1a,b in methanol (lambda >280 nm) leads to essentially quantitative photohydrolysis with formation of the corresponding ketal amides 3a,b. The mechanism proposed for this novel reaction is supported by the qualitatively different photochemical behavior of 1c and by a labeling experiment with 1a-L that confirms transfer of the carbonyl oxygen atom of 1a to the amide oxygen atom of 3a.