Indole 3-alkylated

L//-Indole, 3<2-phenyl-l, 3-dithian-2-yl), 10 Indoles, 34 Indoles, 3-acyl-, 8 Indoles, 3 -alkyl, 8 Isocyanate, chlorosulfonyl [Sulfuryl chlonde isocyanate], 41 Isocyanate,2-propyl- [Propane, 2-iso-cyanato-], 96... 

Pharmacokinetic studies of Ai-pyridinyl-indole-3-(alkyl)carboxamides and derivatives 95... 

Rad-Moghadam K, Sharifi-Kiasaraie M (2009) Indole 3-alkylation/vinylation under catalysis of the guanidinium ionic liquids. Tetrahedron 65 8816-8820... 

Care must also be taken when choosing the reaction partners within reactions. Nucleophiles that have been reported to be effective in conjugate addition processes can also undergo 1,2-addition reactions and these possibilities must be addressed in reaction design. For example, aldehydes and ketones have been shown to undergo a bis-indole alkylation sequence in the presence of achiral amine 139 (42-84% yield 1-10 mol% catalyst) [189]. This additional reactivity was exploited in the... 

Using this information in conjunction with a study into the preferred conformations of iminium ions generated from catalysts 12 and 21, Houk suggests that the additional steric bulk of the ferf-butyl group causes the benzyl arm of the catalyst to shield better the Si face of the C=C double bond - a requirement for high ees in an open transition state. For both the Diels-Alder and pyrrole/indole alkylation... 

Indole, 2-acyl-1-benzenesulfonyl-intramolecular nucleophilic reactions, 4, 244 Indole, 1-acyloxy-synthesis, 4, 364 Indole, alkoxy-synthesis, 4, 367 Indole, 1-alkoxy-synthesis, 4, 364 Indole, 4-alkoxy-synthesis, 4, 328 Indole, 2-alkoxycarbonyl synthesis, 4, 337 Indole, alkyl-... 

Enantioselective additions of a,f)-unsaturated 2-acyl imidazoles, catalyzed by bis(oxazolinyl)pyridine-scandium(III)triflate complex, were used for the asymmetric synthesis of 3-substituted indoles. The complex 114 was one of the most promising catalysts. The choice of acetonitrile as the solvent and the use of 4 A molecular sieves were also found to be advantageous. The 2-acyl imidazole residue in the alkylation products of u,(i-unsaturated 2-acyl imidazoles could be transformed into synthetically useful amides, esters, carboxylic acid, ketones, and aldehydes (Scheme 32) [105]. Moreover, the catalyst 114 produced both the intramolecular indole alkylation and the 2-substituted indoles in good yield and enantioselectivity (Scheme 33) [106]. The complex... 

As a parallel to the rapid growth of asymmetric catalysis, chiral imida-zolidinon-HX salts 124a-c were used as catalysts for Michael-type alkylations between indoles and a,(3-unsaturated aldehydes with high levels of enan-tioselectivity and reaction efficiency. This chiral catalyst system is the first reported nonchelating catalyst for indole alkylation. It was assumed that the catalyst reacts with the unsaturated aldehydes to yield the chiral and highly reactive imimum intermediate, which influences both the LUMO-lowering... 

Jorgensen and co-workers employed chiral bis-sulfonamide catalyst 27, a proven ligand for metal-based asymmetric catalysis, for the Friedel-Crafts alkylations of N-methylindoles (24) using -substituted nitroolefins [52]. Using optimized conditions, 2 mol% 27 gave the desired indole alkylation products of substituted aryl and heteroaryl nitroolefins in moderate to high yields (20-91%) and moderate enantiopurities (13-63% ee Scheme 6.3). Aliphatic -substitution... 

Imino esters—Continued preparation, 483, 634 preparations listed in table 76, 637 pyrolysis to amides, 376 Imino ethers, see Imino esters Imino ketones, preparation, 730 jS-Iminonitriles, hydrolysis, 351 preparation, 730 Indoles, alkylation, 836... 

Of the five alkaloids with known structures, physostigmine (1), esera-mine (3), and physovenine (4) have been synthesized 1-4). Since the conversion of physostigmine (1), a principal alkaloid, to physovenine (4) (6) and geneserine (S) 7,8) has also been established, synthesis of the former implies acquisition of the latter two alkaloids in a formal sense. Up to 1970, the synthesis of geneserine (5) was not reported because its structure had been considered to be the /V-oxide of physostigmine (1) until 1969 9-II) since its first isolation in 1915 (72), The four approaches to the synthesis of physostigmine (1) may be classified into four types based on the key step employed (i) the Fischer indolization route, (ii) the indole alkylation route, (iii) the oxindole alkylation route [including synthesis of physovenine (4)], and (iv) the oxidative indolization route 1-4) (Scheme I). 

Lithio-indoles are equally useful again, the position of attack depends on both solvent and the nature of the electrophile. It is important to note that when an iV-metallated 3-substituted indole alkylates at carbon, necessarily a 3,3-disubstituted-3//-indole is formed, which cannot re-aromatise to form an indole (see 20.1.1.6 for rearrangements of 3,3-disubstituted indolenines). 

Due to the ambident reactivity of pyrroles and indoles, alkylations of such jt-excessive heterocycles can provide a mixture of N- and C-alkylated products. It is therefore of note that Bogdal has been able to achieve the regioselective N-alkylation of a number of azaheterocycles (i.e., pyrrole, imidazole, pyrazole, indole and carbazole) in "dry" media under microwave irradiation <97H(45)715>. The reactions were carried out by simply adsorbing a mixture of the heterocyclic compound, an alkyl halide and a catalytic amount of tetrabutylammonium bromide on a solid support (e.g., KOH, K2CO3), followed by irradiation in an open vessel for 1-10 min. Alternatively, the direct benzylation of pyrrole by the thermal decomposition of N-benzyl-N-nitrosobenzamide, which is believed to proceed by an essentially free carbocation, afforded only the C-2 and C-3 substituted pyrroles <97JOC8091>. 

Examples of direct alkylation of indoles under classical Friedel-Crafts conditions with strong Lewis acids are sparse. This fact probably reflects the tendency of indole to undergo oligomerization with such reagents (Sect. 2.2). The successful conditions for direct indole alkylation usually involve reagents that can generate carbocations under mild conditions, such as benzylic and allylic systems. Palladium-mediated allylations provide another approach. 

Interactive mechanism for enantioselective organocatalytic indole alkylation... 

There is one more way for conversion of ort/to-nitroarylacetonitriles into indoles. Alkylation of such nitriles with allyl or benzyl halides followed by treatment of the compounds obtained with basic agents results in a multistep transformation, which is likely to proceed via intermediate nitrosoarenes, to produce 1-hydroxyindoles. For instance, alkylation of ort/io-nitroarylacetonitriles with 3-phenylallyl bromide gives the compounds that in the presence of chlorotri-methylsilane and triethylamine undergo cyclization into 3-cyano-l-hydroxy-2-vinylindoles (Scheme 70) [188]. Presumably, this reaction proceeds via 0-silylation of the nitronate anion and 1,5-elimination of trimethylsilanol from the intermediate trimethylsilyl nitronate, followed by cyclization and a hydrogen shift. 

Austin JF, MacMillan DWC (2002) Enantioselective Organocatalytic Indole Alkylations. Design of a New and Highly Effective Chiral Amine Pot Iminium Catalysis. J Am Chem Soc 124 1172... 

Austin, J. E, and MacMillan, D. W. C. "Enantioselective Organocataly tic Indole Alkylations. Design of a New and Highly Efeclive Chiral Amine for Iminium Catalysis." /. Am. Chem. Soc., 124,11 (2002). 

N-benzylindoles (Scheme 12.58). It is noted that the enantiomeric excesses of the products were inversely proportional to the molne percent of the catalyst employed. 2-Methoxyfuran and pyrrole were also shown to be good nucleophiles, and intramolecular indole alkylation was successfully conducted. The 2-acyl imidazole moiety was transformed into the corresponding esters, amides, carboxylic acids, ketones and aldehydes. 

In their green catalytic method for the C—H alkylation of alkenes with alcohols, Yi and co-workers employed ruthenium complex 114 to alkylate Af-methylindole (113) in almost quantitative yields (116-117) whilst only generating water as the by-product (Scheme 10.38). Mechanistic experiments led the authors to propose a cationic Ru-indole-alkyl intermediate (115) that would arise from C2—H activation the exact mechanism of the C—O cleavage step is unknown. A related example with A-methoxycarbonyl-L-tryptophan methyl ester demonstrated that an indole protecting group was not necessary. 

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