Efficient Syntheses of Substituted Carbazoles and Cyclopent[b]indoles from 1-Methyl-3-(benzotriazol-1-ylmethyl)indole

Abstract

1-Methyl-3-(benzotriazol-1-ylmethyl)indole (1) undergoes lithiation and 1,4-addition with a variety of alpha,beta-unsaturated ketones and aldehydes. Subsequent treatment with an acidic resin in refluxing 1,4-dioxane causes intramolecular cyclization followed by aromatization to furnish a wide range of 1,3-di-, 2,3-di-, and 1,2,3-trisubstituted carbazoles 6a-j and 8 in moderate to excellent yields. NMR study is described to discriminate between structures of types 6 and 8 on the basis of (1)H-(13)C long-range correlation. Treatment of 1 with styrenes in the presence of zinc bromide results in formal [3 + 2] cycloaddition to give cyclopent[b]indoles 14a-c in good yields. When 1 is first lithiated and reacts with electrophiles, the resulting alkylation products undergo similar [3 + 2] additions with styrenes to give 1-functionalized cyclopent[b]indoles 15 and 16with a high degree of stereoselectivity.

1,2,3-Triazoles

“…To replace the benzotriazolyl group with hydrogen, derivatives 397 are treated with zinc in refluxing acetic acid <1997JOC6215> . Similar benzotriazole-assisted side-chain transformations are reported for benzene <1997JOC721> , pyrrole 1996JOC1624 , 1996TL5641 , and indole 1995JOC3401 , 1995SC539 , 1996JOC7558 .

Scheme 64

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“…Substitution of one of the α protons in compound 400 with an alkyl group allows the introduction of substituents to C-4 of naphthalene. Analogous reactions of 1-[(1-methylindol-3-yl)methyl]benzotriazole lead to corresponding carbazoles <1996JOC7558> . Similar [3+3] benzannulation reactions are occur for furans <1997JOC8205> , indolizines <2000JOC8059> , pyrroles 1996TL5641 , 1997JOC4148 , thiazoles <2000JOC8059> , and thiophenes <1997JOC6215> ; several examples of which can be found in review articles 1999T8263 , 1998CCC599 .…”

“…Following treatment with ZnBr 2 cleaves the bond with benzotriazole to generate the corresponding benzyl cation which is then trapped by styrene to give a new cation that finally cyclizes on to the aromatic ring at its ortho position to furnish indan 443 <1997SC2467> . A similar process converts 1-methyl-3-[(benzotriazole-1-yl)methyl]indole 444 into tricyclic system 446 , via intermediate 445 <1996JOC7558> .

Scheme 72

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(5,6‐Dihydro‐1,4‐dithiin‐2‐yl)methanol as a Versatile Allyl‐Cation Equivalent in (3+2) Cycloaddition Reactions

“…To the best of our knowledge, dehydrative heterocyclic‐carbinol (3+2) cycloadditions have so far only been observed in indolecarbinols by Moody and co‐workers, as well as in some follow‐up studies,, including a very recent three‐component reaction reported by Wu and co‐workers . Furthermore, some benzyl alcohols can undergo similar reactions that resemble the classical cationic styrene‐dimerization process, as in the cyclopentannulation of styrenes with quinone methides or benzyl alcohols, as described by Angle et al .…”

α‐Substituted Chalcones: A Key Review

“…Katritzky and coworkers [69] published a paper dealing with the synthesis of a carbazole from the reaction of an indole with α‐CN‐chalcone (reaction 7, Figure 16). Moreover, α‐cyanochalcones can be converted to furans as shown earlier in Figure 7 above [22] .…”