Beckmann rearrangement for the synthesis of derivatives of β- and γ-carbolinones, dihydropyrrolopyridinone and tetrahydroisoquinolinone

Abstract

Beckmann rearrangement was used as a key step to synthesize six-membered lactams fused to a heteroaromatic or aromatic system. Derivatives of biologically active scaffolds like β-and γ-carbolinone, dihydropyrrolopyridinone and tetrahydroisoquinolinone were synthesized using this strategy.

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

“…The rearrangement in the presence of Brønsted-acidic H 2 SO 4 afforded only minor amounts of S-acylated γ-mercaptoalkylphosphine oxide 68, but the enantiomeric excess was even higher than in the substrate. This suggested that the [1,3]-rearrangement was stereospecific in the presence of Brønsted acid, whereas the [1,4]-rearrangement proceeded with additional partial enrichment of one enantiomer. The latter may have occurred through the preferential acylation of one of two diastereoisomers under the reaction conditions where the second chirality center at the phosphorus atom influenced the ratio of the acylation reaction.…”

“…Among all organic reactions, rearrangements are an exciting class of transformations where unusual or even unexpected products can be obtained. Many rearrangements are of practical use in synthetic organic chemistry, including Beckmann [1][2][3][4], Claisen [5][6][7][8], pinacol [9][10][11][12], Wagner-Meerwein [13][14][15][16], Curtius [17][18][19][20], Hofmann [21][22][23][24], Overmann [25][26][27][28] rearrangements, and many others. In organophosphorus chemistry, rearrangements are less developed transformations, however, some examples can be found in the literature (Scheme 1).…”

“…In organophosphorus chemistry, rearrangements are less developed transformations, however, some examples can be found in the literature (Scheme 1). These include the famous Arbuzov rearrangement [29][30][31][32] as well as phospha-Fries ( [1,3]-rearrangements) [33][34][35][36][37], phospha-Brook ( [1,2]-rearrangement) [38][39][40][41][42], and [2,3]-sigmatropic rearrangements of propargyl and allylphosphinites [43][44][45][46].…”

“…Other [1,2]-rearrangements include α,β-epoxyphosphonate opening [47], β-halo-α-hydroxyphosphonate rearrangement [48], phosphirene rearrangement [49], or the unusual phosphonate-phosphinate rearrangement of dimethyl phosphonates [50]. Other [1,3]-rearrangements of organophosphorus compounds include phosphoenolpyruvate formation from phosphonopyruvate [51], benzylphosphonium salt formation from the corresponding o-methylaryl-substituted precursors [52], or the formation of ketophosphonates from vinylphosphates [53]. [1,4]-Rearrangements include that of o-phosphorus-substituted benzyl carbanions [34], phosphorus group migration in O-phosphorylated 1,4-benzodiazepines [54], or phosphoryl group carbon-to-oxygen transfer [55].…”

“…Herein, we present the results concerning an unusual transformation of β-hydroxyalkylphosphine sulfides, which undergo [1,3]-or [1,4]-rearrangement in the presence of an acid, yielding the corresponding β/γ-mercaptoalkylphosphine oxides. In this rearrangement, a sulfur atom transfers from phosphorus to carbon, whereas the phosphorus-carbon bonds remain intact.…”