Indolines 3-amino

Complexes of 107 have been isolated for copper(II), cobalt(II), and nickel(II) cations103). Condensation of 2,6-diaminopyridine with 108 affords the dimeric macrocycle 111 (70%). No complexes have been reported for ligands 111l08) or 113104 106>. in addition, the reaction of l,3-6is[(l-imino-4,5,6,7-tetrahydro-3-iso-indoline)amino]benzene with 2,6-diaminopyridine gives 113 (70%) 104>107>. 

An enantioselective a-indoline amino acid protocol was also described using glycinyl imines but with varying loss of enantiomeric purity [40]. More recently, synthetic attempts towards the indole alkaloid ambiguine G, as seen in the synthesis of 49, have also utilized this chemistry [41]. 

Sulfamyl-4-chloro-benzoyl chloride N-Amino-2-methyl indoline... 

A total of 8.9 parts of 3-sulfamyl-4-chloro-benzoyl chloride In a solution of 50 parts of anhydrous tetrahydrofuran are added portionwise in the course of 60 minutes, while stirring, to a solution of 5.2 parts of N-amino-2-methyl indoline and 3.5 parts of triethylamine in 150 parts of anhydrous tetrahydrofuran. The reaction mixture is left to stand 3 hours at room temperature, then the precipitated chlorhydrate of triethylamine is filtered off. 

Alkali metal borohydrides are frequently used for the reduction of rc-electron-deficient heteroaromatic systems, but reduction of jt-electron-excessive arenes is generally possible only after protonation of the systems [e.g. 35-37]. The use of tetra-n-butylammonium borohydride under neutral conditions for the conversion of alkylindoles into indolines [38] is therefore somewhat unusual. Reduction of indoles by diborane under strongly alkaline conditions involves the initial interaction of the indolyl anion with the diborane to form an amino-borane which, under the basic conditions, reacts with a second molecule of diborane to produce the indoline [39]. The reaction of tetra-n-butylammonium borohydride with indoles could also proceed via the intermediate formation of diborane. 

Brassilexin 48 and sinalexin 49 are among the most potent phytoalexins produced by economically important cruciferous plants. The most efficient preparation of brassilexin 48, sinalexin 49, and analogues 52 reported uses a Vilsmeier formylation-amination of readily available indoline-2-thiones 50 followed by an aqueous ammonia work-up procedure with subsequent oxidation of the 3-(amino)methyleneindoline-2-thione intermediates 51 using iodine in pyridine (Scheme 10) <20010L1213, 2005JOC1828>. The reaction yields are dictated by the efficiency of the... 

Perindopril (A), an orally active pharmaceutical for the treatment of hypertension, is an important commercial target compound that has a cyclic a-amino acid as an intermediate in its synthetic route. The bicyclic a-amino acid building block is synthesized by reduction of the chiral indoline-2-carboxylic acid (B, R=R =H) shown in Figure 1.4. This chiral cyclic amino acid has so far proven very difficult to synthesize in a highly enantioselective manner using chiral hydrogenation. 

Many methods have been developed for the enantioselective synthesis of unnatural a-amino acids. Jeff Johnston of Indiana University reports (J. Am. Chem. Soc. 125 163,2003) coupling the asymmetric alkylation of O Donnell with intramolecular radical cyclization, leading to what appears to be a general method for the enantioselective construction of indolines. 

The optically active N-aminoindoline (265) has been applied to the asymmetric synthesis of a variety of a-amino acids (70JA2476, 2488). Starting from TV-benzoyl-1,2,3,4-tetrahy-droquinaldine (257), the chloro amide (258) was prepared by von Braun cleavage. Thermolysis converted (258) to the rrans-unsaturated amide (259) which was epoxidized. On base treatment the epoxide (260) underwent intramolecular nucleophilic displacement and amide hydrolysis to afford indoline (261) stereospecifically. Resolution of (261) was accomplished via the brucine salt of the N-o-carboxybenzoyl derivative (262). Alkaline hydrolysis, N-nitrosation and reduction yielded the levorotatory 1-aminoindoline (265). Reaction of... 

Reaction of (2-aminophenyl)-(4-bromophenyl)-methanone with methylsulfanylacetic acid ethyl ester and tert-butyl hypochlorite gives a corresponding sulfonium salt. This salt was transformed to initially to the betaine. Electrocyclic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid. Internal ester-amine interchange leads then to 4-bromophenyl-(3-(methylthio)indolin-7-yl)methanone. The thiomethyl group is then removed with Raney nickel to give 4-bromophenyl-(indolin-7-yl)methanone. Saponification of this intermediate affords the (2-amino-3-(4-bromobenzoyl)-phenyl)-acetic acid (Bromfenac). 

This reaction was exploited by Pass, Amit and Patchornik to directly couple two peptide fragments (Scheme 13.30) [117]. However, one of the main issues to date has been the preparation of such activable amino acids. Two approaches (which, unfortunately, are limited in their scope) are nitration of the parent indoline derivative after acylation with the amino acid, or use of the amino acid chloride prepared in situ. 

Indolines and indoles were prepared by a direct electrochemical reduction of arenediazonium salts. As a result, radical intermediates were generated from which 3,4-disubstituted tetrahydrofuran skeleta were constructed <02OL2735>. A short and stereoselective total synthesis of furano lignans was realized by radical cyclization of epoxides using a transition-metal radical source <02JOC3242>. Other preparations of tetrahydrofurans using radical cyclization include the synthesis of novel amino acids L-bis-... 

Ar-[l-(-Piperidylethyl)indolin-6-yl](2-[(4-pyridinylmethyl)amino](3-pyridyl)]carbox-amide, (IV), and other alkyl amine derivatives prepared by Chen (6) were effective as VEGF inhibitors and were used in the treatment of angiogenesis-mediated diseases. 

A series of 1-substituted indolines such as 79 has been synthesized via aryl radieal cyclizations of acetophenone imines 80, providing an enantioselective route to indoline a-amino acids <03JA163>. Aluminum chloride-induced cyclization of imine precursors derived by condensation of p-anisidine and a-phosphorylated-a-chloro aldehydes provided 3-phosphorylated 5-methoxyindoles <03CHE1521>. 

Compound (1) and its enantiomer provide a variation on the same theme of stereospecific reductive amination. In this case, reduction of a chiral cyclic hydrazone (derived from an a-keto acid and (1)) with Aluminum Amalgam in wet DME proceeds with high stereoselectivity. Reductive cleavage of the N-N bond and ester hydrolysis complete the procedure, which produces a-amino acids with high optical purity (eq 4). The source of chirality is recovered by conversion of the resulting indoline-2-methanol back into (1). ... 

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