Indolines indoles, amino

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. 

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-... 

Kumar BA, Ramasree D, Parthasarathy T, et al. QSAR studies of amino propyl tetrahydro indole-based indolin-2-ones as potent inhibitor of Src tyrosine kinase. Journal of Teaching and Research in Chemistry 2004 1 1 20-24. 

Dihydroindoles are readily produced from tryptamine and tryptophan derivatives through cycli-zation of amino groups at the indole C-2. This process can be reversed to regenerate the indole after advantage has been taken of the indoline reactivity. For instance, the tryptophan ester (341) can be cyclized to the indoline (342), which can then be brominated at C-5 the product (343) can also be converted to 5-cyanotryptophan (344) (Scheme 108) <92TL29>. The related indoline (3 ) has been... 

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]. 

The Ichikawa indole synthesis is the base-induced 5-endo-trig cycUzation of nrtfto-amino-p,p-difluorostyrenes 1 to 2-fluoroindoles 2 (Scheme 1, equation 1) [1-3]. The method is applicable to indolines, which can be oxidized to indoles [4, 5]. This nice chemistry exploits the inherent favorable conversion of a difluorinated sp carbon to an sp carbon, which then expels fluoride to give the aromatic indole. Ichikawa also applied this method to the preparation of 2-fluoiobenzo[fc]furans and 2-fluorobenzo[h]thiophenes [1, 2]. 

A set of new two-carbon-tethered fused acridine/indoles 62 were synthesized via a AcOH-promoted domino reaction of indoline-2,3-dione 61 and C2-tethered indol-3-yl enaminones 57a (Scheme 12.22) [43]. The reaction was further expanded to prepare C-tethered fused acridine/pyridines pairs, N-substituted amino acids, N-cyclopropyl, and N-aryl-substituted fused acridine derivatives. In these domino processes, a fused acridine skeleton with concomitant formation of two new rings was readily achieved in good yields. 

The preparation of indolines by the closure of a ring onto an aromatic nucleus is another very attractive and hitherto difficult process. Two groups have published work in this area in 1980 both displaced halogen atoms, both used organometallic species, but one ° created a C—N bond, and the other a C—C bond. The former piece of work interestingly also used the acylated nitrogen in preference to a free amino-function, as in Clives work vide supra) i.e. 262 and 263). The second paper describes what would appear the more versatile of the two methods, permitting, as it did, the preparation of indoles (265) and benzazepines (266) as well as the indoline (264). 

They are easily prepared from dithiocarbamate and nickel(ll) salts, and examples including those derived from simple amines (587,1472) fluorinated amines (76) amines with (O-hydroxyl groups (1473) indole (341) indoline, carbazole, and imidazole (342) (72) together with those with heterocyclic (72,1116,1126,1424,1474) benzyl (346,1475) and aryl (95,1423,1425,1476, 1477) substituents. Others include examples prepared from Schiff bases (1121), 2-aryldecahydroquinolin-4-ones (1478), tetrahydroquinoline and tetrahydroiso-quinoline (1479), succinimide and phthalimide (49), l,4,7,10-tetraoxa-13-aza-cyclopetadecane (50), 1,3,4-thiazolyl (1426), and 3-dithiocarboxy-3-aza-5-aminopentanoate (343) (1480,1481). A wide range of amino acid derivatives have also been prepared (122,133-137), as have derivatives of glycine, DL-alanine and DL-valine peptide bonded to ethyl esters of a-amino acids (134). 

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