Direct Use of Methanol as an Alternative to Formaldehyde for the Synthesis of 3,3′‐Bisindolylmethanes (3,3′‐BIMs)

Abstract

Red card for formaldehyde: The direct coupling of indoles with methanol to 3,3'-bisindolylmethanes with good to excellent yields was accomplished by using a commercially available iridium complex. This study demonstrates the potential of direct use of methanol as an alternative to formaldehyde for synthetic transformations.

Brønsted Acid Catalyzed Bisindolization of α‐Amido Acetals: Synthesis and Anticancer Activity of Bis(indolyl)ethanamino Derivatives

“…Yield: 92 mg (49 %); white solid. The chemical‐physical data are in agreement with those reported 22 . 1 H NMR (200 MHz, [D 6 ]acetone, 20 °C): δ = 4.20 (s, 2 H, CH 2 ), 7.09 (dd, J 1 = 2.0, J 2 = 8.5 Hz, 2 H, Ar‐H), 7.17 (d, J = 2.0 Hz, 2 H, Ar‐H), 7.49 (d, J = 8.5 Hz, 2 H, Ar‐H), 7.57 (d, J = 1.5 Hz, 2 H, Ar‐H), 10.17 (br.…”

One‐Pot Sequential Catalytic Hydration of Alkynes and α‐Alkylation with Alcohols for the Synthesis of α‐Alkylated Ketones

“…We have reported transition‐metal‐catalyzed regioselective N ‐alkylation with alcohols for the preparation of 2‐ ( N ‐alkylamino)azoles,7a–d 2‐( N ‐alkylamino)quinazolines,7e N,N ′‐alkylarylureas, and N,N′ ‐dialkylureas 7f. We also demonstrated the direct synthesis of N ‐alkylated amides from aldoximes and alcohols via tandem rearrangement/ N ‐alkylation reaction catalyzed by a Ru/Ir dual‐catalyst system,8 Ir‐catalyzed direct coupling of indoles with methanol to give 3,3′‐bisindoles (3,3′‐BIM’s),9 the N ‐alkylation of sulfonamides with alcohols to give N ‐alkylated sulfonamides in water catalyzed by the water‐soluble iridium complex [Cp*Ir(6,6′‐(OH) 2 bpy)(H 2 O)][OTf] 2 . (Cp*=η 5 ‐pentamethylcyclopentadienyl, bpy=2,2′‐bipyridine; Tf=trifluoromethanesulfonyl)10 As part of a continuing interest in the development of new reactions with the activation of alcohols, herein we report the direct synthesis of α‐alkylated ketones via one‐pot, sequential, catalytic hydration of alkynes and α‐alkylation with alcohols.…”

Methylene Surrogates for the Synthesis of 3,3’‐Diindolylmethanes

“…Li and so-workers reported the first ever method to get diindolylmethanes using methanol as the sole C-1 source. [46] They relied on the coupling of indole with methanol in the presence of the iridium complex [(Cp*)IrCl 2 ] 2 as catalyst and a suitable base. The bases tried for the purpose were Cs 2 CO 3 , K 2 CO 3, K 3 PO 4 and t BuOK, all used 1 equivalent.…”

“…Subsequent hydride transfer from [BH(C 6 F 5 )] À to the carboxyl carbon generates the disilyl acetal (45) which upon acidic hydrolysis generates formaldehyde. Friedel Crafts reaction between indole and in situ generated formaldehyde (46) in the presence of the borane gives rise to the 3,3'-diindolylmethane (Scheme 45).…”