An efficient and clean Michael addition of indoles to electron‐deficient olefins under solvent‐ and catalyst‐free condition

Liu, Xiong‐Li; Duan, Xue; Zhang, Zunting

doi:10.1002/jhet.569

Cited by 9 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aromatic aldehydes substituted with halogens and electron‐withdrawing groups (entries 2–4, 6, 8 and 11) reacted faster and gave higher product yields than those with electron‐donating groups (entries 5, 9, 10 and 14). A mixture of 2‐methylindole/indole/5‐cyanoindole with benzaldehyde and ethyl cyanoacetate under the identical conditions, however, provided the products 4l , 4m and 4u as an inseparable diastereomeric mixture (entries 12, 13 and 21) 20. It is interesting to mention that the reaction with salicylaldehyde did not provide the expected product, rather we were confronted with the formation of 2‐amino‐4‐(indol‐3‐yl)‐4 H ‐chromenes via a Knoevenagel/Pinner reaction proceeding in accordance with the earlier reports using an N,N′ ‐dioxide‐Zn(II) complex and InCl 3 21.…”

Section: Resultsmentioning

confidence: 99%

N‐Sulfanylethylanilide Peptide as a Crypto‐Thioester Peptide

et al. 2011

View full text Add to dashboard Cite

Native chemical ligation (NCL) has shown great utility in protein chemistry and has yielded impressive success in the preparation of a wide variety of proteins.[1] This methodology requires peptide thioesters that serve as chemoselective acylating agents for N-terminal cysteinyl peptides to afford ligated peptides through a sequence of reactions consisting of S-S and S-N acyl transfers. The susceptibility of the thioester moiety to basic reagents has necessitated the preparation of the key intermediate by Boc-based solid-phase peptide synthesis (Boc-SPPS) without requiring a nucleophile-mediated deprotection procedure.[2] However, the preferred use of Fmoc-based SPPS with piperidine treatment demands the development of a synthetic methodology using peptide thioesters that are compatible with Fmoc chemistry.In this context, many research groups, including ours, have explored an Fmoc-based synthetic protocol for thioesters. [3][4][5] Among the reported studies, N-S acyl-transfer-mediated procedures have great potential in Fmoc chemistry.[5] We have also developed an N-sulfanylethylaniline linker that can be used for the acyl-transfer-mediated synthesis of peptide thioesters.[5g]Standard Fmoc-SPPS on the sulfanylethylaniline linker followed by N-S acyl transfer under acidic conditions (4 m HCl in DMF) efficiently yielded peptide thioesters (Scheme 1). On the basis of these experimental results, we attempted to utilize an N-terminal cysteinyl N-sulfanylethylanilide (SEAlide) peptide as the middle fragment(s) for sequential NCL, which features the use of more than one thioester fragment.[6] Here, involvement of the SEAlide peptide in the first NCL with a peptide thioester would seem to selectively afford the corresponding ligated SEAlide peptide, which can be used in the second NCL step after conversion of the anilide moiety to the thioester under acidic conditions. The first NCL doubtlessly proceeded; however, contrary to our expectations, a not insignificant amount of cyclic material resulting from the unanticipated intramolecular NCL of the cysteinyl SEAlide peptide was observed (Scheme 2). This unexpected result indicated that the SEAlide moiety could work as a thioester in the presence of an N-terminal cysteinyl residue even under neutral NCL conditions to afford the corresponding NCL product. [7] In this study, we first examined the feasibility of the SEAlide peptide as a crypto-thioester peptide, and discuss the utility of the cryptic thioester in a kinetically controlled NCL. [8] Initial evaluation of the utility of the SEAlide peptide under NCL conditions was attempted through model coupling reactions between peptide 1 and 2 (Table 1). After preliminary experiments, we first fixed the control coupling conditions (1 mm each peptide in 6 m guanidine·HCl (Gn·HCl)-0.2 m sodium phosphate in the presence of 100 mm (4-carboxymethyl)thiophenol (MPAA) [9,10] and 40 mm tris(2-carboxyethyl)phosphine (TCEP), pH 7.3, 37 8C). Under standard conditions, the attempted NCL between 1 a and 2 was almost complete in 48 h and ...

show abstract

Section: Resultsmentioning

confidence: 99%

N‐Sulfanylethylanilide Peptide as a Crypto‐Thioester Peptide

et al. 2011

View full text Add to dashboard Cite

show abstract

“…In the very recent literature, other examples of solvent free aza-Michael additions across unsaturated substrates have been reported. [39][40][41] In order to synthesize the target b-aminocyclobutanecarboxylic acid derivatives 9a and 9b, the acyclic b-amino esters 7a-d were treated with a base to enable ring closure. Treatment of 2-[3-bromo-2,2-dimethyl-1-(diphenylmethylideneamino)propyl]malonates 7a and 7c with 1.2 equiv of KOtBu in THF for three hours at reflux temperature afforded b-aminocyclobutanecarboxylic acid derivatives 9a and 9b in good to excellent yield (Scheme 2).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of novel β-aminocyclobutanecarboxylic acid derivatives by a solvent-free aza–Michael addition and subsequent ring closure

2011

View full text Add to dashboard Cite

Novel b-aminocyclobutanecarboxylic acid derivatives were prepared via a sequential solvent-free aza-Michael addition of benzophenone imine across 3-halopropylidenemalonates and base-induced ring closure. These highly substituted cyclobutanedicarboxylic acid derivatives were subjected to a reactivity study which demonstrated the tendency of these donor-acceptor substituted four-membered rings to be converted into their corresponding ring-opened products.

show abstract

“…After synthesizing hypervalent iodine (III) reagents (78), they used these reagents for the sulfonylation of 1,3-diketones and ketones. They synthesized a variety of compounds (79)(80)(81)(82)(83)(84) in moderate to high yields and the structures of these synthesized compounds are shown in Figure 2. In order to set various reaction parameters such as solvent, equivalent proportions of reactants, they selected a representative reaction by reacting benzyl chloride (85, 3 mmol), CS 2 (6 mmol) and diethyl amine (86, 3 mmol).…”

Section: Synthesis and Application Of Hypervalent Iodine Reagentsmentioning

confidence: 99%

“…82 Xue and co-workers, in 2010, developed a solvent and catalyst-free method for this suitable transformation. 83 According to their assumption indole has an acidic N-H proton which took part in catalysis. During their initial study, they reacted β-nitrostyrene (141) Under the optimized conditions β-nitrostyrene, vinyl ethyl cyanoacetates, and vinyl malononitriles were treated with indoles and in each case the 3-substituted indoles were produced in excellent yields (Scheme 40).…”

Section: Michael Addition Of Indoles To Electron Deficient Olefinsmentioning

confidence: 99%

A decade update on solvent and catalyst-free neat organic reactions: a step forward towards sustainability

Sarkar

Santra

Kundu³

et al. 2016

Green Chem.

204

View full text Add to dashboard Cite

The keen success has been achieved towards the synthesis of new product and process as the twelve principle of "Green Chemistry" was formulated in 1990s. These products and processes are more compatible with human health, society and the environment. In this review a collection of researches has been documented from the view point of green chemistry. The main theme of this review is neat reactions which are solvent and catalyst-free reactions. Neat reactions in absence of any solvents and catalysts with the concise forms of microwaves, ball milling neat reactions have been described.

show abstract

An efficient and clean Michael addition of indoles to electron‐deficient olefins under solvent‐ and catalyst‐free condition

Cited by 9 publications

References 30 publications

N‐Sulfanylethylanilide Peptide as a Crypto‐Thioester Peptide

N‐Sulfanylethylanilide Peptide as a Crypto‐Thioester Peptide

Synthesis of novel β-aminocyclobutanecarboxylic acid derivatives by a solvent-free aza–Michael addition and subsequent ring closure

A decade update on solvent and catalyst-free neat organic reactions: a step forward towards sustainability

Contact Info

Product

Resources

About