Copper(I)‐Catalyzed 3‐Position Methylation of Coumarins by Using Di‐tert‐butyl Peroxide as the Methylation Reagents

Abstract

The copper-catalyzed methylation of coumarin by using di-tert-butyl peroxide (DTBP) has been described. The reaction provides direct access to a wide range of 3-methylcoumarins in moderate to good yields. In this procedure, it is noteworthy that DTBP was employed not only as the oxidant, but also as the methyl source.

Installing the “magic methyl” – C–H methylation in synthesis

“…They employed a Cu(I)/Cu(II) catalytic cycle to enable the methylation of coumarins utilising DTBP as the methyl source. 110 A distinct approach from Gu & Xia used a Na 2 SO 3 /I 2 couple to act as an external oxidant, via the gradual release of I-radicals capable of triggering rearomatisation of the Minisci adduct. 111 In a 2017 report from Bao, this approach has found further application in the methylation of styrene derivatives (Scheme 37C).…”

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

“…The application of DTBP in Scheme is summarized here: 1) synthesis of 144 is demonstrated by an iron‐catalyzed decarboxylative methylation of α,β‐unsaturated acids in the absence of ligands; 2) by using Cu(OAc) 2 as the catalyst, N‐methylation of sulfoximines 145 was developed with good functional group tolerance; 3) a facile and straightforward route to the synthesis of 3‐methylcoumarins 146 was achieved through the radical reaction of coumarins with DTBP catalyzed by CuCl; 4) two different methods of amidic N‐methylation of amides 147 and sulfonamides 148 were developed by Li and Cai. Under the conditions, the methylation selectively occurs on the amidic nitrogen .…”

Di-tert-butyl peroxide as an effective two-carbon unit in oxidative radical cyclization toward 7-methylazolo[1,5-a]pyrimidines

“…In fact, the oxygen-centered radical from DTBP can undergo further β-scission to provide a by-product acetone along with a methyl radical. 12 However, acetone with a rather low boiling point was invariably discarded in these reactions. Accidentally, DTBP exceptionally emerges as an unprecedented C2 cyclic unit and undergoes formal [3 + 2 + 1] cyclization with 3(5)-aminoazoles and aromatic aldehydes to afford 7-methylazolo[1,5- a ]pyrimidines with excellent regioselectivities and good yields (Scheme 1e).…”