Pyrrolo indoles, formation

The methine chain is obtained by reacting ethyl o-formate (method A ) or ethylisoformanilide (method B) with a bis quaternary salt of bis-(2-thiazolyllbutane. Concerning dyes with fused thiazolo rings pyrrolo[2. lb]thiazoIe. thiazolo[2.3a]indole. thiazolo[2.3c]1.4-benzox-azine. the a carbon directly linked to the carbon 2 of the thiazoJe ring is also responsible for the classical syntheses giving trimethine or penta-methine dyes. 

SCHEME 7.18 Formation and fate of the pyrrolo[l,2-a]indole (w — 0) and the pyrido[l,2-a] indole-based ( = 1) quinone methides. 

Further studies into the constmction of pyrrolo[l,2-a]indoles, however, revealed that the presence of a nitrile functionahty was not essential to the reaction (3). Subjecting precursor 13 to yhde formation by AgF (it should be noted that this was the only reagent to induce cycloaddition to any extent) in the presence of N-phenyhnaleimide surprisingly furnished adduct 14 in which the nitrile functionality was stiU intact. The reaction pathway was therefore assumed to proceed via initial formation of the silver bonded cation 15, which after desilyation generated the requisite silver bound azomethine yhde. Cycloaddition followed by sequential loss of silver and a hydrogen delivered the observed products. Replacement of the nitrile moiety with alternative functionalities also generated the expected products in good isolated yields (Scheme 3.4). 

Studies in the synthesis of the immunosuppressant FR901483 tricyclic skeleton showed that by palladium- and radical-mediated cyclizations of azaspiro-decanes the formation of azatricyclic derivatives was possible. Depending on the reaction conditions, 7,10 -methanopyrrolo[l,2- ]azocine 292 could be obtained from iV-(2-bromoprop-2-enyl)-l-azaspiro[4.5]decane 291 (Scheme 121) <2007ARKIVOG320>. When the reaction was performed in the presence of Bu3SnH, pyrrolo[2,3-r ]indoles were obtained instead. 

A tandem carbonylation-cyclization radical process in heteroaromatic systems bearing electron-attracting substituents such as l-(2-iodoethyl)indoles and pyrroles 970 result in the formation of 2,3-dihydto-l//-pyrrolo[l,2- ]indol-1-ones and 2,3-dihydro-l//-pyrrolizin-l-ones 974 (Scheme 188). The AIBN-induced radical reaction of compounds 970 with Bu3SnH under pressure of CO suggests that the acyl radical 972, derived from radical 971 and CO, would undergo intramolecular addition to C-2 of heteroaromatic system, and the benzylic radical 973 so obtained, upon in situ oxidation would produce final product 974 <1999TL7153>. 

A novel A-annelation provided access to pyrrolo[l,2-c]oxazoles and oxazolo[3,4-a indoles. Specificially, treatment of acyl benzotriazole 58 with ketones in the presence of DBU led to the formation of pyrrolo[l,2-c]oxazoles 59 <04JOC9313>. 

After treatment of Boc-protected tryptophan methyl ester (20) with 1,1-dimethylpropargyl chloride (31) / NaH in DMF, we isolated the five products 35, 36, 37, 38 and 39 (Scheme 8) [54]. Both the indole nitrogen and C3 had reacted as nucleophiles towards Cl and C3 of the intermediate dimethylvinylidene carbene, followed by cychsation to the pyrrolo[2,3-b]indoles. Earlier, Hino and co-workers had obtained a similar result when starting from achiral A b tncthoxycarbonyl-tryptamin [55]. With 3-unsubstituted indoles, Wenkert and co-workers observed formation of quinolines as side products, presumably via cyclopropanation of the indole 2,3-double bond by dimethylvinylidenecarbene [56]. 

In connection with the synthesis of pyrrolo[l,2-a]indoles, intramolecular carbene insertion reactions have been developed. Although strictly involving interactions between two substituents, they will be considered here because of their chemical similarity. Thermal decomposition of the sodium salt of the tosylhydrazone (219) gives intramolecular cycloaddition followed by loss of nitrogen to yield the fused indole (220) (Equation (66)) <89JCS(Pi)2449>. This technique can be extended to include oxime ethers (221) in place of alkenes and thus provide formation of an aziridine (222) insertion into alkynes could not be achieved (Equation (67)) <9iJCS(Pi)i72i>. 

Wong and coworkers recently reported an interesting application of multicomponent synthesis to the preparatirMi of aryl-pyrrolo-tetrahydrocarbazoles, via the in situ formation of indolo-2,3-quinodimeihanes and subsequent [4+2] cycloadditions with maleimides [124], A variety of indoles were treated with aldehydes... 

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