Switching Over of the Chemoselectivity: I₂-DMSO-Enabled α,α-Dichlorination of Functionalized Methyl Ketones

Abstract

Precise control of the chemoselectivity of the halogenation of a substrate equipped with multiple nucleophilic sites is highly demanding and challenging. Most reported chlorinations of methyl ketones show poor compatibility or even exclusive selectivity toward electron-rich arene, olefin, and alkyne residues. This is attributed to the direct or in situ employment of electrophilic Cl 2 /Cl + species. Here, we reported that, even bearing those competitive residues, methyl ketones can still undergo dichlorination to afford α,α-dichloroketones in a chemo-specific manner. Enabled by the I 2 -dimethyl sulfoxide catalytic system, in which hydrochloric acid only acts as a nucleophilic Cl − donor, this straightforward dichlorination reaction is safe and operatorfriendly and has high atomic economy, giving access to structurally diverse α,α-dichloroketones in good yields and with good functional-group tolerance.

Cu@CuFe2O4 nanoparticles catalyzed oxidative functionalization of alkynes: Access to α,α‐dichloro ketones

“…Based on the aforementioned results and literature, [22][23][24]29 a plausible mechanism for the Cu@Cu-Fe 2 O 4 -promoted oxydichloromination of arylalkynes is proposed (Scheme 3d). When the alkyne is initially activated by heating in TFE/H 2 O, the chlorine radical is added from the NCS to the alkyne and then afforded vinyl radical In-A.…”

“…Consequently, there has been a concerted effort to develop new synthetic methods by using α,α ‐dihaloketones as starting material in recent decades. Furthermore, traditional transformations such as oxidation, reduction, and C‐C bond formation, and innovative methods such as photocatalytic or electrocatalytic reactions have been explored 15–31 . For example, Madabhushi reported that the a,a ‐dichloro arylketones were obtained through the oxidation of terminal alkyne, respectively (Scheme a) 32,33 .…”

“…Furthermore, traditional transformations such as oxidation, reduction, and C-C bond formation, and innovative methods such as photocatalytic or electrocatalytic reactions have been explored. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] For example, Madabhushi reported that the a,a-dichloro arylketones were obtained through the oxidation of terminal alkyne, respectively (Scheme a). 32,33 In the realm of photocatalytic reactions, Handa and Jiang demonstrated the transformation of alkyne to a,adichloro arylketones under photocatalytic conditions (Scheme b).…”

An I2–DMSO catalytic manifold enabled aromatization for C-ring editing of podophyllotoxone

“…Indeed, the sterically inhibited 2-substituted α-tetralone skeleton has been reported to be unreactive in some palladium-catalyzed aromatization, 10 c and the electron-donating E-ring residue and its electrophilic benzyl site are also risky for single-electron oxidation. 12,14 On the basis of our research spotlight on lignan synthesis 15 as well as our long-standing interest in the I 2 –DMSO reaction system, 16 we speculated that it might be possible to take advantage of the special structural characteristics of podophyllotoxone to develop an I 2 –DMSO catalytic manifold that would fulfil our synthetic requirements. The working hypothesis is outlined in Scheme 1b.…”