Iron-catalyzed oxidative sp³ carbon–hydrogen bond functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones

Abstract

A novel and efficient iron-catalyzed sp carbon-hydrogen bond functionalization of benzoxazinone derivatives has been developed. For the first time, benzoxazin-2-ones were used as substrates in an oxidative dehydrogenative coupling reaction. The experiments were performed under mild reaction conditions to construct alkyl-aryl C(sp)-C(sp) bonds. The application of this method to the gram-scale synthesis of natural product cephalandole A has been accomplished in a 3-step sequence. A plausible one electron oxidation involved mechanism is proposed.

Oxidative Cross‐Dehydrogenative‐Coupling Reaction of 3,4‐Dihydro‐1,4‐Benzoxazin‐2‐ones through Visible‐Light Photoredox Catalysis

“…It can be seen that the corresponding products were obtained in good yields, except for the 2-methyland 4-methyl-substituted indoles. 4-Benzyl-3,4-dihydro-1,4-benzoxazin-2ones with various substituents on the benzyl moiety participated smoothly in the reaction, but the substrate with a substituent at the 2-position of the benzyl moiety gave a lower yield than those with substituents at the 3-or 4-positions (Table 3, entries [13][14][15][16], possibly due to steric hindrance. Next, a variety of 3,4-dihydro-1,4-benzoxazin-2-ones 1 were tested (Table 3, entries 11-18).…”

“…Based on previous literature reports [13,18] and the control experiments, a possible mechanism for the reaction is proposed (Scheme 3). Firstly, under the irradiation of visible light, Ru II is excited to Ru II *.…”

“…: [13] [13] [13] Yellow solid (9.8 mg, 13 % [13] 1, 135.8, 134.6, 130.9, 128.9, 128.1, 127.8, 125.4, 124.9, 122.8, 122.6, 122.5, 119.8, 116.6, 113.4, 110.3, 109.2, 55.4, 51.1, 20.5 ppm. [13] White solid (44.9 mg, 61 % 6, 142.0, 136.2, 134.3, 134.2, 129.8, 128.8, 127.9, 127.8, 126.5, 125.3, 124.5, 123.0, 119.9, 118.8, 116.6, 114.0, 110.9, 108.4, 55.9, 51.7, 21.4 ppm.…”

“…[13] White solid (44.9 mg, 61 % 6, 142.0, 136.2, 134.3, 134.2, 129.8, 128.8, 127.9, 127.8, 126.5, 125.3, 124.5, 123.0, 119.9, 118.8, 116.6, 114.0, 110.9, 108.4, 55.9, 51.7, 21.4 ppm. [13] 5, 142.0, 136.4, 136.2, 134.2, 132.8, 128.8, 127.8, 127.8, 125.3, 124.0, 122.3, 122.3, 119.8, 118.9, 116.6, 113.9, 111.1, 108.8, 56.0, 51.7, 21.6 ppm. [13] 4, 142.0, 136.2, 135.5, 134.2, 128.8, 127.8, 127.8, 125.8, 125.3, 123.4, 122.5, 120.7, 120.4, 119.9, 116.9, 116.6, 114.0, 109.5, 56.1, 51.7, 16.4 ppm.…”

“…It is an efficient strategy for molecular construction in synthetic organic chemistry, [10] because the prefunctionalization of starting materials is avoided, and the number of synthetic steps is decreased. [13] Thus, the CDC reaction is one of the most common and useful methods for the direct functionalization of the α-C(sp 3 )-H of amines, and it has received significant attention in the field of visible-light photoredox catalysis. [12] These intermediates can then be attacked by various nucleophiles to form different structures, including natural products and pharmaceuticals.…”