Homologation of Indole-3-carboxylic Acids and Amides

Buttery, Cheryl D.; Jones, Richard G.; Knight, David W.

doi:10.1055/s-1991-20713

Cited by 10 publications

(6 citation statements)

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“…N-Protected indole-3-carboxylic acids and amides are similarly silylated (Scheme 159). 288 Uridine derivatives lithiate at C6 and react with tin and silyl electrophiles (Scheme 160). 289 a-Methoxy acrylamides can be directly deprotonated and silylated (and sulfenylated), as well (Scheme 161).…”

Section: Scheme 158mentioning

confidence: 99%

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

Sommer¹

2004

Synthesis

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The replacement of a b-hydrogen on an a,b-unsaturated carbonyl system with a non-hydrogen, non-carbon atom amounts to either a net two electron oxidation or an isohypsic substitution at the b-carbon. The resulting compounds are the functional equivalents of b-dicarbonyl derivatives. Although many methods have been developed to effect this transformation, they lack generality and the process remains an underutilized one in organic synthesis.

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Section: Scheme 158mentioning

confidence: 99%

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

Sommer¹

2004

Synthesis

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“…DoM reactivity of the SO 2 N À R DMG in thiophenes. formation of indole 2,3-substituted products (Scheme 15) [27]. Access to 7-substituted indoles via metalation chemistry has been achieved via indolines [28] and, more recently, specially designed N-DMGs such as N-COC(Et) 3 [29], and N-P(O)(tBu) 2 (Scheme 16) [30].…”

Section: Indolesmentioning

confidence: 99%

The Directed ortho Metalation Reaction – A Point of Departure for New Synthetic Aromatic Chemistry

Hartung

Snieckus

2002

Modern Arene Chemistry

159

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After a brief allusion to the current status of synthetic aromatic chemistry, a tour based on the Directed ortho Metalation (DoM) strategy is provided with selections from recent literature which highlight a) the use of DoM for the regiospecific preparation of polysubstituted aromatics and heteroaromatics; b) the valuable symbiosis of DoM with transition metal catalyzed AraAr cross-coupling protocols; c) the extension of DoM to the Directed remote Metalation (DreM) concept in biaryls, which provides methodologies for the construction of condensed aromatics (fluorenones, phenanthrols) and heterocyclics (thioxanthones, xanthones, acridones, dibenzphosphorinones, dibenzthiepinone dioxides, dibenzoxepinones, dibenzazepinones, dibenzphosphinones); and d) the evolving links of DoM to other modern methodologies with a note on the DoM-Grubbs ring-closing metathesis connection. The presentation is solely methodologically rather than total synthesis oriented; dependable directed metalation groups (DMGs ¼ CONR 2 , OCONR 2 , SONR 2 , NHBoc), new and renewed, are emphasized; p-excessive (furan, thiophene, indole) and p-deficient (pyridine) heterocycle HetDoM chemistry is delineated. While definitely not comprehensive, this account attempts to give a flavor of current anionic aromatic chemistry in synthesis. 10.1Scheme 1. Synthetic approaches to substituted aromatics. 10.2 The DoM Reaction as a Methodological Tool 331 Scheme 3. DoM chemistry generalizations. 10.2 The DoM Reaction as a Methodological Tool 333 Scheme 5. The N-cumyl sulfonamide DMG. Scheme 6. The N-cumyl carbamate DMG. 10.2 The DoM Reaction as a Methodological Tool 335 Scheme 9. The di-tert-butyl phosphine oxide DMG. 10.3 Heteroaromatic Directed ortho Metalation (HetDoM) in Methodological Practice 337

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“…In fact, a search of the literature revealed that in 1964 Canton and co-workers lithiated 3-methylisothiazole-4-carboxylic acid in the C-5 position by treating the acid with 2 equivs of BuLi! Since then, a number of heteroaromatic carboxylic acids have been ortho -lithiated using either BuLi 48d, or LDA. 8e, More recently Mortier et al have shown that various benzoic acids will direct lithiation to the ortho position when treated with s -BuLi/TMEDA at −90 °C in THF . Their work indicated ortho -lithiation with carboxylic acids was a general reaction when the lithiation was performed at −90 °C.…”

Section: C-4 Lithiation Of 2-(tert-butyldimethylsilyl)-3-furoic Acid ...mentioning

confidence: 99%

Regioselective Preparation of 2,4-, 3,4-, and 2,3,4-Substituted Furan Rings. 2.¹ Regioselective Lithiation of 2-Silylated-3-substituted Furan Rings

Bures

Nieman

et al. 1997

J. Org. Chem.

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A new method for the preparation of 3,4-and 2,5-disubstituted furan rings is described. A variety of 2-silylated-3-(hydroxymethyl)furans and 2-silylated-3-furoic acids lithiate exclusively at C-4 when treated with 2.2 equivs of BuLi. The resulting dianions were quenched with a variety of electrophiles to provide 2-silylated-3-(hydroxymethyl)-4-substituted furans and 2-silylated-4-substituted 3-furoic acids in good to excellent yields. Removal of the silyl group (n-Bu 4 NF) provided a variety of 4-substituted-3-(hydroxymethyl)furans and methyl 4-substituted-3-furoates, respectively. The latter esters were prepared due to difficulties encountered in isolating 4-substituted-3-furoic acids. The site of lithiation was altered by protecting the 3-hydroxyl group with a triethylsilane. Lithiation of 2-silylated-3-(((triethylsilyl)oxy)methyl)furan with 1.2 equivs of BuLi followed by the addition of electrophiles provided 2-silylated-3-(((triethylsilyl)oxy)methyl)-5-substituted furan rings. Subsequent removal of both silyl groups provided 2,4-disubstituted furan rings in moderate to good yields. A rationale is provided to explain why protection of the hydroxyl group at C-3 leads to a change in lithiation from the C-4 to the C-5 position of the furan ring. In addition, an explanation for the observed effect of adding HMPA or LiCl to the solution during the lithiation of 2-(tertbutyldimethylsilyl)-3-(hydroxymethyl)furan is provided.In the preceding paper, 1 the difficulty in preparing 3,4and 2,4-disubstituted furan rings due to the preference for furan rings to lithiate 2 and add electrophiles 3 in the C-2 or C-5 positions was discussed. New synthetic routes toward the preparation of furan rings which contain groups in the 3 and/or 4 positions are useful, since many natural products incorporate furan rings with either a 3,4-or 2,4-disubstituted or 2,3,4-trisubstituted pattern. 4 This paper describes a full account of our work in this area.Some previous reports on the preparation of 3,4disubstituted furans have involved using Diels-Alder/ retro-Diels-Alder chemistry, 5 chemical modifications of 3,4-furandicarboxylic acid, 6 and the synthetic modification of acyclic precursors. 7 An alternative approach to the preparation of 3,4-disubstituted furans is the direct lithiation of substituted furan rings. The C-4 lithiation of a 3-substituted furan, however, has not been successful

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Homologation of Indole-3-carboxylic Acids and Amides

Cited by 10 publications

References 0 publications

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

The Directed ortho Metalation Reaction – A Point of Departure for New Synthetic Aromatic Chemistry

Regioselective Preparation of 2,4-, 3,4-, and 2,3,4-Substituted Furan Rings. 2.¹ Regioselective Lithiation of 2-Silylated-3-substituted Furan Rings

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Homologation of Indole-3-carboxylic Acids and Amides

Cited by 10 publications

References 0 publications

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

β-Oxidation of α,β-Unsaturated Carbonyl Compounds

The Directed ortho Metalation Reaction – A Point of Departure for New Synthetic Aromatic Chemistry

Regioselective Preparation of 2,4-, 3,4-, and 2,3,4-Substituted Furan Rings. 2.1 Regioselective Lithiation of 2-Silylated-3-substituted Furan Rings

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Regioselective Preparation of 2,4-, 3,4-, and 2,3,4-Substituted Furan Rings. 2.¹ Regioselective Lithiation of 2-Silylated-3-substituted Furan Rings