1 //-Indole-2-carbaldehydes, formation

The possibility of activating the indole nucleus to nucleophilic substitution has been realized by formation of chromium tricarbonyl complexes. For example, the complex from TV-methylindole (215) undergoes nucleophilic substitution with 2-lithio-l,3-dithiane to give a product (216) which can be transformed into l-methylindole-7-carbaldehyde (217) (78CC1076). 

Except for 3-bromoindole, it is necessary to proceed via the indoline, because treatment of indole with 1,1-dimethyIpropargyl chloride (31) in the presence of base leads to product mixtures resulting from reaction of in situ formed dimethyl-vinylidene carbene. Sheu and co-workers isolated the three products 32, 33 and 34 on reaction of indole-3-carbaldehyde (30) (Scheme 7) [53]. In the main reaction, indole C3 attacks at dimethylvinylidene carbene forming a vinyl anion, which is protonated to give the 3-allenylindolenine. Hydroxide then attacks the carbal-dehyde moiety with loss of formic acid and formation of a 3-allenylindole. Addition of a second equivalent of indole-3-carbaldehyde (30) affords 32 and 33. 

Organometallic intermediates continue to be important in the synthetic methodology for substitution of pyrroles and indoles. Numerous lithiation techniques have been reported and provide a range of useful reaction conditions. The pyrrolyl dimer (120) (really a dimeric equivalent of pyrrole-2-carbaldehyde) can be lithiated at the 5- and 5 -positions. Electrophilic substitution then yields 5-substituted pyrrole-2-carbaldehydes (121) (Scheme 34) <88TL777>. The related monomeric ald-iminium salts (122) yield similar products after anion formation, bromination, lithiation, and electrophilic attack (Scheme 35) <88HCA2053>. In a similar process, the dimer (120) can be brominated at C-4 and converted into 4-substituted pyrrole-2-carbaldehydes <88TL3215>. 

Nelson AC, Kalinowski ES, Jacobson TL, Grundt P. Formation of byptanthrin compounds upon Oxone-induced dimerization of indole-3-carbaldehydes. Tet. Lett. 2013 54 6804-6806. 

A study of the preparation of ocimene by isomerization of a-pinene has been reported. a-Azidoacetophenones have been converted to 2-aryl-l,3-oxazole-4-carbaldehydes by rearrangement of the carbon framework on exposure to DMF/POCI3. The rearrangement occurs via alkenyl azides and 2//-azirines. Enamine rearrangement of pyridinium salts to indoles has been studied.Kinetic stabilization and reactivity of a series of singlet 2,2-dialkoxy-l,3-diphenyloctahydropentalene-l,3-diyls enable cis-selective formation of the ring-closed compounds (Scheme 105). ... 

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