1- Lithio-3-methylindole

Indol-2-ylcopper reagents can also be prepared from 2-lithioindoles and they have some potential for the preparation of 2-substituted indoles. 1-Methyl-indol-2-ylcopper can be prepared by reaction of 2-lithio-l-methylindole with CuBr[10]. It reacts with aryl iodides to give 2-aryl-1-methylindoles. Mixed cyanocuprate reagents can be prepared using CuCN[ll], The cyan-ocuprate from 1-methylindole reacts with allyl bromide to give 2-allyl-l-methylindole. 

The first proton to be removed from iV-methylpyrrole by w-butyllithium is from an a-position a second deprotonation occurs to give a mixture of 2,4- and 2,5-dilithiated derivatives. The formation of a 2,4-dilithio derivative is noteworthy since in the case of both furan and thiophene initial abstraction of a proton at C-2 is followed by proton abstraction from C-5 (77JCS(P1)887). iV-Methylindole, benzo[6]furan and benzo[6]thiophene are also deprotonated at C-2. Selenophene and benzo[6]selenophene and tellurophene and benzo[6]tellurophene similarly yield 2-lithio derivatives (77AHC(21)119). 

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). 

N-Methylindole-2-carboxaldehyde also undergoes /8-lithiation, after in situ conversion to its a-amino alkoxide with lithium A-methylpiperazide, and the resulting 3-lithio species has been successfully alkylated with methyl iodide (Scheme 22)(87JOC104). However, when the same reaction was repeated using N,A(,A -trimethylethylenediamine as the amine com-... 

The C-phosphorylation of alkylindoles was realized using the magnesium and lithium derivatives of indole. The ( -substituted compound 3e was obtained from 2-lithio-l-methylindole (le), and the C(3)-substituted compounds 4a,b were obtained by means of the indole Grignard reagent Id [11, 16, 17]. It was shown [17] that 3-indolylphosphonite 4b forms complexes with copper(I) halides. 

Animations in this area involve anions of both it-excessive and it-deficient heterocycles, which are generated from the halo compounds or by direct metalation. Most of the animating reagents seem to be applicable except that phenylthiomethyl azide (32) fails with the 2-lithium or 2-copper derivatives of furan, thiophene, N-methylpyrrolc, and (V-methylindole.274 Similarly, chloramine and O-methylhydroxylaminc, but not phenyl azide, fail to aminate 2-lithio-1-methylimidazole 66 and the MeN(Li)OMe nitrenoid does not react with 2-lithiothiophene.97 The reactions that appear to be most widely applicable to heterocyclic carbanions are shown in Eqs. 73,100,101 74,316 and 75.358... 

A tandem strategy for indole annulation has been developed from indolylborates. Initial b-annulation was effected by the following sequence hydroboration of a terminally imsaturated allylic acetate with 9-BBN, reaction with 2-lithio-l-methylindole to nerate the borate palladium-induced cyclization at C-3, migration from boron to carbon and aromatization (Scheme 49) <91CC1219>. A development of this uses the hydroboration derivative (156) of a 1-alkenylindole, followed by... 

N-Methylindole (180) and -butyllithium were mixed in flow over 15 min at room temperature. To newly formed lithio species 181 was added a stoichiometric amount of carbon dioxide via a mass flow controller. After less than 1 min, a solution of -butyllithium in diethyl ether was added the reaction flowed through the column for 10 min at room temperature and was quenched with 1 M HCl to afford the desired ketone in 79% yield. Of particular note is the observation that the organolithium in the second addition was found to be far more reactive as a solution in diethyl ether compared to THF (14AG(I)8416). 

One-pot intramolecular reaction between trialkyl-( 1 -methyl-2-indolyl)borate and allylpalladium intermediate has been reported [20]. This. simultaneous 1,2-alkylmigration from boron to carbon provides a novel pathway to afford [i>]-an-nelated indole derivatives in 10-56% yields (Scheme 32.8). Trialkylindolylbo-rate 14 is generated in situ by the hydroboration of diene 13 with 9-BBN in THF followed by treatment with 2-lithio-1 -methylindole. The THF solution ofborate 14 containing 10 mol% of Pd(Ph3P)4 was heated under reflux for 1-3 h to afford [fc]-annelated indole 15 [20]. 

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