Indole aldehyde, reduction

Since both 2-nitrophenyl ketones and 2-substituted-l-hydroxyindoles are far more stable than the corresponding aldehydes and 2-H indoles, respectively, reduction of these ketones to the 1-hydroxyindoles is relatively easy. 

Various reactions of the 7-substitutent have been carried out, all of which have their counterparts in indole chemistry." Reduction of the imino compound 13, obtained from DMF-phosphoryl chloride treatment of 11 (R = Me), with potassium borohydride gave the Mannich base 14 (R = Me). Reduction of the aldehyde 12 (R = H) with sodium borohydride in the presence of aqueous dimethylamine gave the amine 14 (R = H), whereas the analogous aldehyde 12 (R = Me) gave only the alcohol 15 (R = Me)." The related alcohol 15 (R = H) was obtained on reducing the aldehyde with sodium borohydride in the absence of dimethylamine. ... 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Contrary to an alkoxy benzene scaffold, secondary amides were generated via novel aldehyde linker 43 based upon an indole scaffold (Scheme 15) [52]. The indole resin was prepared from indole-3-carboxy-aldehyde in two steps and reacted with amines under reductive conditions to generate resin-bound secondary amines. Treatment of the resin with... 

Nitroalkenes prepared from aromatic aldehydes are especially useful for natural product synthesis. For example, the products are directly converted into ketones via the Nef reaction (Section 6.1) or indoles (Section 10.2) via the reduction to phenylethylamines (Section 6.3.2). The application of these transformations are discussed later here, some examples are presented to emphasize their utility. Schemes 3.3 and 3.4 present a synthesis of 5,6-dihydroxyindole66 and asperidophytine indole alkaloid,67 respectively. 

Kraus has reported the synthesis of a tricyclic indole related to the pyrroloiminoquinone marine natural products (Scheme 10.9), in which an intramolecular SNAr and the reductive cyclization of a nitro aldehyde are involved as key steps.94 Related target compounds have been prepared by Joule and coworkers via a similar strategy.95... 

The second method leads to the formation 3-alkyl- and 3-arylindoles from the reaction of indole with aldehydes in the presence of alkali metal tetra-carbonylhydridoferrate (Scheme 40).67 It is possible that this novel process may occur via reduction of intermediate 3-alkylidene- or 3-arylidene indolenines. 

The TFA-catalyzed triethylsilane reductive condensation of an aldehyde with indoles provides a convenient route to 3-substituted indoles in modest to good yields (Eq. 197).355... 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

Reduction of amides to aldehydes was accomplished mainly by complex hydrides. Not every amide is suitable for reduction to aldehyde. Good yields were obtained only with some tertiary amides and lithium aluminum hydride, lithium triethoxyaluminohydride or sodium bis 2-methoxyethoxy)aluminum hydride. The nature of the substituents on nitrogen plays a key role. Amides derived from aromatic amines such as JV-methylaniline [1103] and especially pyrrole, indole and carbazole were found most suitable for the preparation of aldehydes. By adding 0.25 mol of lithium aluminum hydride in ether to 1 mol of the amide in ethereal solution cooled to —10° to —15°, 37-60% yields of benzaldehyde were obtained from the benzoyl derivatives of the above heterocycles [1104] and 68% yield from N-methylbenzanilide [1103]. Similarly 4,4,4-trifluorobutanol was prepared in 83% yield by reduction of N-(4,4,4-trifluorobutanoyl)carbazole in ether at —10° [1105]. 

When the reactions of pyrroles and indoles with aldehydes are catalyzed by hydriodic acid, the initially formed carbinols or azafulvenes are reduced to yield the corresponding alkylpyrroles and alkylindoles (68CJC3291,70CJC139). The reductive alkylation of the pyrrole ring, using a range of aliphatic and aromatic aldehydes and ketones, may also be accomplished with phosphonium iodide, with hydrochloric acid and zinc amalgam, or with tin(II) bromide in hydrobromic acid. 

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