Cooperative Polar/Steric Strategy in Achieving Site‐Selective Photocatalyzed C(sp³)−H Functionalization

Abstract

Synergistic control over the S 2 transition states of hydrogen abstraction exploiting polar and steric effects provides a promising cooperative strategy for site-selective C(sp )-H functionalization using decatungstate anion photocatalysis. By using this photocatalytic approach, the C-H bonds of substituted lactones and cyclic ketones were functionalized selectively. In the remarkable case of 2-isoamyl 4-tert-butyl cyclohexanone (1 t) bearing five methyl, five methylene, and three methine C-H bonds, one methine C-H bond in the isoamyl tether was selectively functionalized.

Site-selectivity in TBADT-photocatalyzed C(sp3)–H Functionalization of Saturated Alcohols and Alkanes

“…5 Consequently, we were able to find notable site-selectivity for a variety of ketones, 6,7 esters, 7 nitriles, 8 and alkylpyridines, 9 in which the S H 2 (bimolecular homolytic substitution) transition states between CH bond and decatungstate anion are highly influenced by radical polar and steric effects, rendering the functionalization of C(sp 3 )H bonds site-selective in each case. For example, β-selective CH to CC conversion of 3,3-dimethylcyclohexanone was achieved using TBADT as a photocatalyst (Scheme 1), 7 in which the lack of any α-CH functionalization was rationalized by the mismatched polar S H 2 transition state for α-CH cleavage, while the lack of γ-CH functionalization was due to the steric hindrance by the two methyl groups attached at the adjacent carbon of the targeted methylene group. Since little information on site-selectivity is available in TBADT-catalyzed C(sp 3 )H functionalization of aliphatic alcohols 10 and alkanes, 4a,1113 we decided to embark on a systematic study using structurally varied alcohols and alkanes.…”

Selective C(sp3)−H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow

“…Biologically active compounds, such as eucalyptol (product 27 , 66 %) and (1 R )‐(+)‐camphor (product 28 , 63 %) were also successfully oxidized. In the case of eucalyptol, the less sterically hindered position was selectively targeted, which can probably be attributed to the large size of the tungstate cluster 31. Another proof of this steric‐hindrance‐driven selectivity was observed in the oxidation of (+)‐sclareolide, in which the oxidation occurred preferentially at the C2 position (product 29 , 44 %) 3d, 32.…”

Selective C(sp3)−H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow

“…In the case of eucalyptol, the less sterically hindered position was selectively targeted, which can probably be attributed to the large size of the tungstate cluster. [31] Another proof of this steric-hindrance-driven selectivity was observed in the oxidation of (+ +)-sclareolide, in which the oxidation occurred preferentially at the C2 position (product 29,4 4%). [3d,32] Finally,t he utility of our oxidation protocol was convincingly demonstrated by the scalable oxidation of another complex compound, artemisinin, to its natural derivative artemisitone-9 (30)ingood yield (59 %, 5mmol scale).…”