B(C₆F₅)₃-Catalyzed Highly Chemoselective Reduction of Isatins: Synthesis of Indolin-3-ones and Indolines

Abstract

A chemo-and site-selective reduction reaction of isatin derivatives using catalyst B(C 6 F 5 ) 3 and hydrosilanes is described. This transformation is operationally simple, proceeds under mild conditions, and is resistant to various functional groups. Thus, this efficient reaction using a combination of B(C 6 F 5 ) 3 and BnMe 2 SiH or B(C 6 F 5 ) 3 and Et 2 SiH 2 could potentially be utilized to produce various indolin-3-ones and indolines, without the need for multistep procedures and metal catalysis conditions. Letter pubs.acs.org/OrgLett

Modified Chemoselective Reduction and Consecutive Regioselective Deuteration Reaction Catalyzed by B(C6F5)3

“…Similarly, the expected products 2c , and 2d , were prepared in good yields of 75 and 70%, respectively, from 5-chloro , and 5-bromo-1-tosylisatins . In contrast to other halo-substituted 1-tosylisatins, the reaction of 6-chloro, 5-fluoro, and 5-iodo gave rise the desired products: 2e , , 2f , , and 2g , in moderate yields of 59, 56, and 53%, respectively. When 6-methoxy-1-tosylisatin 1h was utilized as the substrate, a mixture of regioisomers, 2h and 2h′ with 2h / 2h′ = 0.6:1, was generated in a combined yield of 67%.…”

“…13 C{ 1 H} NMR (125 MHz,CDCl 3 ): δ 194.7,153.5,137.4,136.6,134.2,129.6,127.2,125.1,124.6,124.3,115.9,indolin-3-one (2k). 8 Compound 2k was synthesized according to general procedure F using 1-(naphthalen-2-ylsulfonyl)indoline-2,3-dione (1k, 68.0 mg, 0.2 mmol) and H 2 O (0.5 μL, 0.03 mmol) instead of H 2 O (4.0 μL, 0.24 mmol) as a purple solid in 74% yield (47.9 mg, 0.148 mmol). R f = 0.5 (EtOAc/hexane = 1/3).…”

“…6-Methoxy-1-tosylindolin-2-one (2h′). 8 Compound 2h′ was synthesized according to general procedure D for using 6-methoxy-1-tosylindoline-2,3-dione (1h, 65.0 mg, 0.2 mmol) as a pale yellow solid in 42% yield (26.7 mg, 0.084 mmol). R f = 0.5 (EtOAc/hexane = 1/2).…”

“…Pleasingly, desired product 2a 14,15 was obtained in 53% yield, and the reaction time was lower than that in our previous work. 8 Due to the presence of the tosyl protecting group, reversed reactivity of carbonyl groups in tosylisatin 1a was observed compared with that of the general isatin possessing electrophilic carbonyl group at C3. Additionally, the use of H 2 O ranging from 0.15 to 0.6 equiv was screened in DCB, where 2a was isolated in yields of 54, 67, and 65%, respectively (entries 2−4).…”

“…8 Additionally, 5-methoxy-1-tosylisatin 1i 8 reacted smoothly to deliver the anticipated product 2i 14,15 in a 63% yield. For other electronwithdrawing protecting groups (1j−1q), 8,12,13 the reaction led to the formation of the products (2j−2q) 8,10c,13,14,16 in moderate to excellent yields (69−92%). Significantly, trace amounts of water, which is a Lewis base, could increase the reactivity, accelerating the selective reduction of N-protected isatins because of its compatibility with B(C 6 F 5 ) 3 as a Lewis acid catalyst.…”