Indolines from enamines

Oxazines, which are readily prepared from enamines and a-bromokctoximes, are reductively converted to pyrroles in good yields by iron carbonyls (Scheme 116) (81CL869). The reductive conversion of cinnolines to indoles or indolines (71JCS(C)3088> and of phthalazines to isoindoles or phthalimidines (70ACS1867) may occasionally be of synthetic value. 

SCHEME 26 Synthesis of indolines from arynes and N-Boc enamines [50]. 

Pyrano[3,2 ]indolizines such as 120 can be prepared from the reaction of N-( 1 -benzotriazolylmethyl)indolines with 3,4-dihydro-2//-pyran under acidic or Lewis-acidic conditions (Equation 26) <2001T4933>, and a simpler analogue 122 is the end product of an annulation process starting from the enamine 121 and ethyl acrylate <1996H(43)1391> (Scheme 34). Pyrano[4,3-/]indolizinetriones, for example, 124, result from the hydrolysis of protected 2,3-dihydro-l//-indolizincdioncs 123 (Equation 27) <2000H(53)771>. 

The use of cyclic enamines" > " " b.436,441,443,446.447, 456.457,470-480 (-g g UQ o ) or dieneamines (e.g., 141 ) yields fused bicyclic systems, although the latter may also yield bis-thietane sulfones. Enamines derived from morpholine, piperidine, pyrrolidine, and dimethylamine are most commonly used, but derivatives of diethylamine, di- -propyl-amine, piperazine, 4-benzylpiperidine, methylpyrrolidines, hexahydroazepin, N-methylaniline, and indoline have also been treated with sulfenes to give thietane sulfones. Asymmetric induction has been observed with the optically active enamine, 142. ... 

Aniline derivatives have been used to synthesize the indoline system. A large variety of indoline alkaloid substructures are available in a very efficient way. Enamine derivatives such as 39 bearing electron withdrawing substituents on the olefinic double bond were transformed in high yields (Scheme 7). Two syn/anti isomers 41 and 42 were isolated. The isomeric ratio of the final products was influenced by a photostationary equilibrium between the substrates 39 and 40. The reaction was applied to the synthesis of a variety of derivatives of the alkaloid aspidospermidine." In this context, the cyclization products 43 were transformed into the polycyclic indole derivatives 44,45, and 46. Polycyclic indolone compounds 48 have been successfully produced by cyclization of enaminone derivatives 47 carrying a quinoline substituentIn these cases and contrary to the examples 41,42, and 43, the products 48 resulted from an oxidation of the cyclization product (also compare the formation of 30 in Scheme 5). 

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