Indole chromium complex

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Stereoselective chromium tricarbonyl migration was achieved in the sterically hindered A -aryl indole chromium complex 178b by refluxing in toluene (Equation 34) <20060L1097>. 

Complexation of indoles with chromium hexacarbonyl, which reduces the electron density of the heterocyclic system, promotes nucleophilic attack at the 7-position and, to a lesser extent, also at the 4-position of the indole ring and provides a viable synthetic route to 7-formyl-l-methylindole (78CC1076). Curiously, although the benzenoid ring is rendered susceptible to nucleophilic attack, the reaction of the chromium complex with butyllithium results in abstraction of the proton from the 2-position. However, if this position is... 

Arenes and heteroarenes which are particularly easy to metalate are tricarbo-nyl( 76-arene)chromium complexes [380, 381], ferrocenes [13, 382, 383], thiophenes [157, 158, 181, 370, 384], furans [370, 385], and most azoles [386-389]. Meta-lated oxazoles, indoles, or furans can, however, be unstable and undergo ring-opening reactions [179, 181, 388]. Pyridines and other six-membered, nitrogen-containing heterocycles can also be lithiated [59, 370, 390-398] or magnesiated [399], but because nucleophilic organometallic compounds readily add to electron-deficient heteroarenes, dimerization can occur, and alkylations of such metalated heteroarenes often require careful optimization of the reaction conditions [368, 400, 401] (Schemes 5.42 and 5.69). 

The synthesis of 2 -methylspiro[cyclohexane-l,3 -indole] chromium tricarbonyl 1179 was carried out by treatment of 3/7-indole 1178 with chromium hexacarbonyl in THF/dioxane (1 5), under rigorous dryness, argon atmosphere and sunlight coverture, in a Strohmeier-type system, in good yield (Scheme 227) <1996JOM(522)231>. Solvent mixture was very important for the complex formation, and when Bu"20/THF (9 1) was used, a brown oil was obtained which contained the free 3/7-indole 1178 and the C=N reduction product, while complex 1179 was not detected. 

A number of substituted benzenes, naphthalenes, indans, pyridmes, and indoles form arene(tricarbonyl)chromium complexes upon thermolysis under an inert atmosphere, usually in a high boiling ether, or by irradiation of the arenes in the presence of chromium hexacarbonyl. The complexes are relatively air-stable and can usually be stored for long periods in the absence of light. Somewhat milder conditions can be used by transfer of the chromium tricarbonyl group from preformed naphthalene(tricarbonyl)chromium, tris(L)tricarbonyl chromium (L = acetonitrile, ammonia, pyridine), or tricarbonyl( -l-methylpyrrole)chromium. Enan-tiomerically pure arene(tricarbonyl)chromium complexes having two different substituents, either ortho or meta can be prepared conveniently by classical resolution of racemic... 

Pyrroles 531 are formed from the chromium complex 529 and alkynes 530 (R = H, Me or Ph = Me, Ph or NEt2). The dicobaltoctacarbonyl-catalysed reaction of cyanotrimethylsilane with a variety of acetylenes R C=CR (R R = alkyl or Ph) furnishes pyrroles 532, in which the bulkier of the two substituents of unsymmetrical internal acetylenes appears at the position marked with an asterisk . An indole synthesis from o-iodo-aniline and alkynes R C=CR (R R =alkyl or Ph) in the presence of palladium(II) acetate, triphenylphosphine, lithium chloride and potassium carbonate has been described (equation 56). In the case of unsymmetrical alkynes, the bulkier substituent tends to be in position 2 of the indole. ... 

Functionalization of indoles at C-4 can be achieved by the addition of nucleophiles to indole tricarbonylchromium complexes, followed by oxidative removal of the chromium. A recent example, from 1992, shows the formation of the 4-allylindole (164) following carbanion addition (Scheme 54) <92AJC99>. This technique has also been applied to formation of a 4-indolylbutenone, a key intermediate in the synthesis of clavicipitic acid <93TL5051>. 7-Substitution of the indole ring can... 

Yamashita and colleagues reported an indole synthesis absence of Ac O. The pyrrole carbene complex was from pyrrole-carbene chromium complexes reacting with prepared from 2-Uthio-l-methylpyrrole and chromium... 

A number of miscellaneous methods for forming carbon-carbon bonds are of interest. Carbene-chromium complexes were involved in the synthesis of deoxyfrenolicin, the important step being conversion into the naphthoquinone (Scheme 32). Silylated tricarbonylarenechromium(0) complexes of indole may... 

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). 

As indicated in Scheme 27, indoles may be alkylated by their acid-catalyzed reaction with alcohols. Similarly, r-butylation of pyrroles has been effected by the acid-catalyzed reaction with t- butyl acetate (B-77MI30502), and the diarylmethylation of 1-methylpyrrole from the acid-catalyzed reaction with the chromium trichloride complex of the diarylcarbinol has been described (78JA4124). The alkylation of indoles by alcohols in the presence of the aluminum alkoxide and Raney nickel appears to be efficient for the synthesis of 3-substituted indoles, but is less successful in the alkylation of 2-methylindole (79JHC501). The corresponding isopropylation of pyrrole produces 2,5-diisopropylpyrrole and 1-isopropylpyrrolidine, as the major products (79JHC501). 

Chloroperoxidase catalysis by, 58, 302 in chlorination of pyrazoles, 57, 337 Chlorophyll, thioaldehyde synthetic intermediate to, 55, 3 Chlorosulfonyl isocyanate, reaction with 2-arylhydrazono-3-oxobutanoate, 59, 148 Chromatography, of [l,2,4]triazolo[l,5-a]-pyrimidines, 57, 106 Chrom-3-enes, see 2//-l-Benzopyrans Chromium tricarbonyl complexes of 3,5-diphenyl-l-(alkyl- or oxido-)-thiabenzenes, 59, 206, 227 indoles, lithiation of, 56, 181, 184 of pyridine, 58, 160 pyridines, lithiation of, 56, 230, 239 of 2f/-thiopyrans, 59, 227 Chromones, see l-Benzopyran-4-ones Cinnamonitrile, a-cyano-, condensations with thio-, seleno-amides, 59, 184, 186 Cinnoline, nitration, MO calculation, 59, 302... 

---