Indole debenzylation

Indole was included with alkyl and arylamines in a study which demonstrated the potential of 2-pyridylsulfonyl as an /v -protecting group. The group is reductively removed using SmI,. <95JOC5969> A possible new means for indole debenzylation was uncovered l-Benzyl-2-phenylindole and several /V-benzylcarbazoles and tetrahydrocarbazoles were found to undergo debenzylation on reaction with methyllithium or LDA. An -elimination mechanism is proposed. <95TL1671>... 

A combined Fischer indolization, debenzylation and aromatization occurs when ketones of type (94.6) are heated for several hours with an arylhydrazine. Examples of reactions in which hydrazines exhibit dehydrogenative properties are given in this paper [3287]. 2,3-[>ihydrofuran behaves as would be expected... 

Tetrahydro-y-carbolines may be prepared by an internal Mannich-type reaction between 2-j8-aminoethyhndoles and formaldehyde. Kebrle et al. prepared 27 by the reaction of 2-lithio-l-methyl-indole with A-benzyl-A-ethylaminoacetone followed by debenzyl-ation treatment of 27 with formaldehyde led to the formation of the tetrahydro-y-carboline 28. Similarly, when the quaternary salts (30) of the Mannich bases (29) are heated at 100°, 1,2,3,4-tetrahydro-y-carbohnium salts (31) are formed. 

Vilsmeier-Haack and Friedel-Crafts reactions, bromination, debromination, debenzylation in indole series and their synthetic application 99YZ35. 

The final phase of our syntheses of vinblastine and analogous compounds required closure of the piperidine ring in the seco cleavamine part of the indole-indoline compounds 162 and 163. We had originally studied this reaction with the simple indolic C-16 and C-20 unsubstituted C-16 epimeric carbomethoxy seco cleavamines 164 and 165 and found that on cyclization they produced, through conformations 166 and 167, almost exclusively quaternary salts 168 and 169, which on debenzylation gave... 

Cycloaddition to an ot,p-unsaturated lactam. Ficini et al. have extended cycloaddition reactions of diethylaminoalkynes (5, 219 7,107-108) to include the a,j3-unsaturated lactam 1. N,N-Diethylaminobutyne condenses with lactam 1 in the presence of MgBr2 to afford enamine 2. This product is hydrolyzed and esterifled to afford 3 in 50% overall yield from 1. The intermediate 3 is converted into the indole alkaloid ( )-dihydroantirhine (4) by LiAlH4 reduction and debenzylation. 

The ring opening of epoxides with indole is accelerated by a combination of lanthanide catalysts and pressure, which was exploited in a synthesis of diolmycin A2 (35) (Scheme 7.8) [11]. Thus, reaction of epoxyalcohol 32 and indole (33) at 10 kbar in the presence of ytterbium(III) triflate and water gave rise to the adduct 34 in 51 % yield. Again, the application of pressure drastically decreased the reaction time. Subsequent debenzylation then provided the desired natural product 35. 

The two amines were efficiently debenzylated with Pd/C in acidic methanol at room temperature, and the remaining tryptamine bridge carbons inserted by double alkylation at the indole /3 -position and the secondary amine. Deprotonation of the resulting indolenine gives the / -anilinoacrylate, minovine (506 Scheme 27) (226, 227). 

Debenzylation. A new method for A(-debenzylation of substituted indoles consists of treatment with MeLi. 

A recent synthesis of tubulosine served to determine the position of the hydroxyl in the indole moiety as shown. The levorotatory ester LXXIV 201) was converted into its 5-benzyloxytryptamide which was cyclized and reduced with sodium borohydride. Two products, a crystalline one (mp 196°) and an amorphous one were obtained. Debenzylation of the former generated isotubulosine (mp 164° [ ]ff —78.7°) and debenzylation of the latter gave tubulosine (mp 283° [a]ff -62.7°) 202). 

Synthesis of [6]-annelated indoles by thermal electrocyclic reactions 95MI7. Transition metal-mediated syntheses of carbazole derivatives 95MI6. Vilsmeier-Haack and Friedel-Crafits reactions, bromination, debromination, debenzylation in indole series and their synthetic application 99YZ35. 

Fluorinated indoles reveal very similar properties in comparison to their non-fluorinated analogues. However, it should be noted that the chemistry of monofluori-nated indoles (with fluorine atom attached to both 2 and 3 position) is scarcely studied. For example, 3-fluoroindole derivative 19a was debenzylated to give indole carboxylic acid ester 157 quantitatively the latter one was converted into amide 159 by hydrolysis followed by reaction with the corresponding amine in the presence of BOP reagent [9a]. Nitrogen atom in case of 3-fluorosubstituted indole derivatives has usual nucleophilicity and can participate in standard indole reactions, for example reaction with tosyl chloride provided V-sulfonylation product in 61 % yield [15]. 

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