Carbonyl compounds indole

Both o-aminobenzyl aldehydes and ketones rapidly cyclize and undergo dehydration to indoles. The generation of these carbonyl compounds therefore represents a quite reliable route to indoles. The complication is that while there... 

This reaction is also a key method for the formation of tetrahydro-P-carbolines 5 from indole bases 4 and aldehydes, ketones, or 1,2-di carbonyl compounds 2. These reactions are similarly acid-catalyzed or thermally-induced and have been utilized in the synthesis of numerous indole alkaloids. 

The Pictet-Spengler condensation of indole bases and carbonyl compounds to form 3-carbolines involves a slightly different mechanism than the isoquinoline... 

In order to allow further transformation to an indole, the carbonyl compound 8 must contain an a-methylene group. The hydrazone 1 needs not to be isolated. An equimolar mixture of arylhydrazine 7 and aldehyde or ketone 8 may be treated directly under the reaction conditions for the Fischer indole synthesis. ... 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

Thus far, we have discovered and demonstrated a new and effident method for the synthesis of indoles from various carbonyl compounds. This, in conjunction with the use of alkyries in the palladium-catalyzed indolization, widens the spectrum of indoles that can be prepared by these means. The simple procedure, mild reaction conditions, and ready availability of the starting materials render these methods valuable additions to indole chemistry. We next extended this method to the synthesis of the indole core of a PGD2 receptor antagonist, laropiprant 3. 

As discussed in Chapter 9, various nucleophiles can be introduced at the ortho position of nitroarenes via the VNS process. This provides a useful strategy for the synthesis of indoles. One of the most attractive and general methods of indoles and indolinones would be the reductive cyclization of a-nitroaryl carbonyl compounds (Eq. 10.54). The VNS and related reactions afford a-nitroaryl carbonyl compounds by a simple procedure. For example, alkylation of 4-fluoronitrobenzene with a lactone silyl enol ether followed by reductive cyclization leads to tryptophols (Eq. 10.55).73... 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

In terms of Michael additions at the indole C-3-position, montmorillonite KIO has been shown to be effective in promoting the conjugate addition of indoles to a,p-unsaturated carbonyl compounds <99MC929>. In what is also a Michael process, microwave irradiation has been shown to be effective in promoting the trimolecular condensation of substituted indoles 111 with... 

With an excess of the lithiating agent, 1-benzenesulfonylindoles form dilithiated derivatives, which may be dialkylated or dideuterated (81JHC807). Reaction with carbonyl compounds, however, may result in the formation of the 2-substituted indole with cleavage of the protecting group (Scheme 37), although the reaction with benzoyl chloride yields the sultam (134). 

In addition to preparation of arylhydrazones from the carbonyl compounds and an arylhydrazine, the Japp-Klingemann reaction of arenediazonium ions with enolates and enamines is an important method for preparation of arylhydrazones. This method provides a route to monoarylhydrazones of a-dicarbonyl compounds from /3-keto acids and to the hydrazones of pyruvate esters from / -keto esters. Enamines also give rise to monoarylhydrazones of a-diketones. Indolization of these arylhydrazones provides the expected 2-acyI-or 2-alkoxycarbonyl-indoles (equations 95-97). 

Toward carbonyl compounds, the behavior of nonstabilized arsonium ylides such as methylene or ethylidene triphenylarsorane is similar to that of sulfonium ylides (10, II, 13, 97). When an arsonium ylide was reacted with aminoketones in a cold 1 1 DMSO-THF solution a smooth reaction took place and the corresponding 3-substituted indoles were obtained in fair to good yields (II). 

The reaction of nitroarenes with silyl end ethers and ketene silyl acetals in MeCNATiF with 1 equiv. of TASF, followed by in situ oxidation with Br2 or DDQ, provides an easy route to a-nitroaryl carbonyl compounds (Scheme l).12 The use of these compounds as reagents for the synthesis of arylacetic acids, propionic acids, indoles, 2-indolinones and other heterocyclic compounds has recently been described.88... 

The reaction of carbonyl compounds with P(III) acid chlorides has been widely discussed in the literature. The most complete information on this subject was compiled in the review [42]. As far as the carbonyl derivatives of indole in such reactions are concerned the information here is sparse. 

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