N–H Insertion reactions of rhodium carbenoids. Part 3.1 The development of a modified Bischler indole synthesis and a new protecting-group strategy for indoles

Abstract

A modified version of the Bischler indole synthesis has been developed in which the key step is the N-H insertion reaction of rhodium carbene intermediates derived from α-diazo-β-ketoesters with anilines. Thus N-methylanilines 1 react with diazoketoesters 2 in the presence of dirhodium() acetate to give (N-arylamino)ketones 3, cyclisation of which using boron trifluoride-ethyl acetate or acidic ion exchange resin gives the indoles 4. In order to extend this method to the synthesis of N-unsubstituted indoles, a new protecting group strategy for indoles was developed. In this, anilines are reacted with α,β-unsaturated-esters or -sulfones to give the conjugate addition products 6 and 9, cyclisation of which gives indoles 8 and 11. The N-(2-ethoxycarbonylethyl)-and -(2-sulfonylethyl)-protecting groups are readily removed from indoles 8 and 11 by treatment with base.

The Epoxy‐Ramberg–Bäcklund Reaction (ERBR): A Sulfone‐Based Method for the Synthesis of Allylic Alcohols

“…Filtration through celite, washing with diethyl ether (2 × 50 mL), evaporation under reduced pressure followed by flash column chromatography (PE/EtOAc, 1:1) gave the epoxide 4n Preparation of 3-Phenyl-2-propen-1-ol (5p) and 5-Phenyl-2,4-pentadien-1-ol (5q): (a) 2-Benzylsulfanylethan-1-ol: Preparation according to a literature procedure. [67] (b) 2-Benzylsulfonylethan-1-ol: Preparation according to a literature procedure. [67] (c) 2-Benzylsulfonylethene: Preparation according to a literature procedure.…”

“…[67] (b) 2-Benzylsulfonylethan-1-ol: Preparation according to a literature procedure. [67] (c) 2-Benzylsulfonylethene: Preparation according to a literature procedure. [67] [68] (f) 2-(3-Phenyl-2-propen-1-sulfanyl)ethan-1-ol: Prepared according to a literature procedure.…”

One-pot synthesis of N-methylindoles from N-methylanilines and of benzofurans from phenols using transition-metal carbene X–H insertion reactions

“…In our previously described modification of the Bischler reaction, 14,15 the key a-(N-arylamino)ketone intermediate was obtained by the aforementioned rhodium carbene N-H insertion reaction, and, after isolation, was subsequently cyclized using protic or Lewis acids (Scheme 1).…”

“…4 Subsequently, reports of other reactions of anilines with diazocarbonyl compounds catalyzed by a range of transition-metal complexes, including copper, [5][6][7][8] rhodium, [9][10][11] rhenium 12 and ruthenium, 13 followed. We previously reported the rhodium carbene insertion reaction into the N-H bond of N-alkylanilines as a key step in a modified Bischler synthesis of indoles, 14,15 whilst subsequently Janda and co-workers have developed a solid-phase variant of this reaction, and applied it to the synthesis of an array of indoles. 16 In continuation of our own work on carbene N-H insertion reactions in synthesis, [17][18][19][20][21][22] we sought to develop a solution-phase, one-pot route to arrays of indoles, and we report our results herein.…”

Heterogeneous Synthesis of Indole-2-Carboxylic Esters Via Bischler Cyclization Under the Catalysis of Sulfonic Acid-Functionalized SBA-15 Silicas

“…Over the last century, the synthesis of indole and its derivatives has constantly been the blooming area both in organic synthesis and medicinal chemistry [41,42]. Among the massive works to construct indole ring, Bischler cyclization, which was based on the acid-promoted intramolecular electrophilic cyclization of a-(N-arylamino)-b-ketones [43][44][45] and its analogs, such as a-(N-arylamino)acetals [46][47][48][49] and a-(N-arylamino)-bketo esters [50][51][52][53], was one of the most efficient and attractive strategies. Traditionally, a large excessive amount of homogeneous strong acids were crucially required to promote the cyclizations, as the Bischler cyclization was a Friedel-Crafts type reaction (electrophilic attack on the phenyl ring).…”