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Journal ArticleDOI

Indole synthesis by controlled carbolithiation of o-aminostyrenes.

21 Oct 2004-Journal of Organic Chemistry (American Chemical Society)-Vol. 69, Iss: 23, pp 7836-7846
TL;DR: An effective synthesis of the functionalized indole ring system has been developed from substituted o-aminostyrene starting material using a novel cascade reaction sequence of alkyllithium addition to the styrene double bond and subsequent trapping of the intermediate organolithium with a suitable electrophile.
Abstract: An effective synthesis of the functionalized indole ring system has been developed from substituted o-aminostyrene starting material. Our methodology involves a novel cascade reaction sequence of alkyllithium addition to the styrene double bond and subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring closure and dehydration to generate the indole ring. This new reaction sequence allows for the introduction of molecular diversity at all positions on the indole scaffold. The procedure was shown to be successful with a range of both C and N substituents on the o-aminostyrenes. The reaction sequence was tolerant to the reactivity range of alkyllithiums such as tert-, sec-, and n-butyllithium. The electrophiles used were DMF, which generated indole products with C-2 unsubstituted, and nitriles, which incorporated the nitrile substituent at C-2. The o-aminostyrene starting materials were generated by a Pd-catalyzed cross-coupling reaction of a vinyl boronic acid equivalent with the readily available substituted o-bromoanilines.
Citations
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Journal ArticleDOI
TL;DR: The gold-catalyzed reaction of 2-alkynyl-phenylamines with α,β-enones represents a new general one-pot entry into C-3-alkyl-indoles by sequential reactions as discussed by the authors.
Abstract: The gold-catalyzed reaction of 2-alkynyl-phenylamines with α,β-enones represents a new general one-pot entry into C-3-alkyl-indoles by sequential reactions. Gold-catalyzed sequential cyclization/alkylation, N-alkylation/cyclization, or N-alkylation/cyclization/alkylation reactions leading to different indoles can be directed by changing the 2-alkynyl-phenylamine 1/α,β-enone 3 ratio and the reaction temperature. Unusual gold-catalyzed rearrangement reaction of indoles are observed at 140 °C. New gold-catalyzed formation of propargyl-alkyl ether under mild conditions and the hydration reaction of N-acetyl-2-ethynyl-phenylamine are reported.

154 citations

Journal ArticleDOI
TL;DR: A convergent approach has been developed to synthesize disubstituted 2,1-borazaronaphthalenes from N-substituting 2-aminostyrenes and potassium organotrifluoroborates, where the potassium organosorbent is converted to the active R-BX2 species in situ by addition of a fluorophile.
Abstract: Azaborines are an important class of compounds with applications in both medicinal chemistry and materials science. The first borazaronaphthalene, 2-chloro-2,1-borazaronaphthalene, was reported in 1959; however, access to more highly functionalized substructures has been limited because of the harsh reaction conditions required to displace the chloride on boron. A convergent approach has been developed to synthesize disubstituted 2,1-borazaronaphthalenes from N-substituted 2-aminostyrenes and potassium organotrifluoroborates, where the potassium organotrifluoroborate is converted to the active R–BX2 species (X = Cl or F) in situ by addition of a fluorophile. Starting from aryl-, heteroaryl-, alkynyl-, alkenyl-, and alkyltrifluoroborates, a library of highly functionalized 2,1-borazaronaphthalenes were synthesized in one step under mild, transition-metal-free conditions.

79 citations

Journal ArticleDOI
TL;DR: The application of the Carbolithiation of diphenylacetylene method for the stereoselective synthesis of (Z)-tamoxifen and related analogues is described.
Abstract: Carbolithiation of diphenylacetylene can be exploited to generate (E)-1-lithio-1,2-diphenylalkyl-1-enes which can be reacted in situ with triisopropylborate to stereoselectively provide (E)-1,2-diphenyl-1-alkylene boronic acids. These tetrasubstituted vinylboronic acids served as versatile intermediates for the generation of tetrasubstituted olefins with retention of stereochemistry. The application of this method for the stereoselective synthesis of (Z)-tamoxifen and related analogues is described.

74 citations

Journal ArticleDOI
TL;DR: This Feature Article provides the first comprehensive summary of the vinylation methods currently available along with a critical comparison of the efficiency, cost and scope of the methods.

74 citations

References
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Journal ArticleDOI
TL;DR: In the reductive amination of some aldehydes with primary amines where dialkylation is a problem, a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4) gave consistently higher yields and fewer side products.
Abstract: Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C−C multi...

1,419 citations

Book
01 Jan 2002
TL;DR: In this article, the authors present a comprehensive overview of the synthesis of organolithium compounds in solution, including stereoselective and stereospecific reactions of organomethane compounds.
Abstract: Introduction: scope and overview organolithiums in solution. Regioselective synthesis of organolithiums by deprotonation: general points lithiation alpha to heteroatoms ortholithiation lateral lithiation remote lithiation, and beta-lithiation of non-aromatic compounds superbases co-operation, competition and regioselectivity. Regioselective synthesis of organolithiums by X-Li exchange: halogen-lithium exchange tin-lithium exchange chalcogen-lithium exchange phosphorus-lithium exchange. Regioselective synthesis of organolithiums by C-X reduction: reductive lithiation of alkyl and aryl halides reductive lithiation of C-O bonds reductive lithiation of C-N bonds reductive lithiation of C-S bonds reductive lithiation of C-C bonds and pi-bonds. Stereoselective and stereospecific synthesis of organolithiums: configurational stability of organolithiums Stereospecific synthesis of organolithiums by X-Li exchange diastereoselective deprotonation enantioselective deprotonation. Stereospecific and stereoselective substitution reactions of organolithiums: stereospecific reactions of organolithium compounds stereoselective substitution in the presence of chiral ligands. Regio- and stereoselective addition reactions of organolithiums: intermolecular addition to pi bonds - carbolithiation intramolecular addition and substitution reactions - anionic cyclization. Organolithium rearrangements: Shapiro reaction Brook rearrangements [1,2]-Wittig rearrangements [2,3]-Wittig rearrangements. Organolithiums in synthesis: ochratoxin - ortholithiation and anionic Fries rearrangement corydalic acid methyl ester - lateral lithiation fredericamycin A - ortho, lateral and alpha-lithiation (?)-Atpenin B - metallation of an aromatic heterocycle flurbiprofen - metallation with LiCKOR superbases California red scale pheromone - alpha- and reductive lithiation C1-C9 of the Bryostatins - diastereoselective bromine-lithium exchange (S)-1-methyldodecyl acetate, a Drosophila pheromone - (-)-sparteine assisted enantioselective lithiation (-)-Paroxetine - (-)-sparteine-promoted asymmetric lithiation and substitution.

350 citations

Journal ArticleDOI
TL;DR: In reactions of aliphatic alcohols with BOC2O/DMAP, carbonic-carbonic anhydride intermediates are isolated for the first time, which helps explain the formation of symmetrical carbonates in addition to the O-BOC products.
Abstract: The reaction of BOC2O in the presence and absence of DMAP was examined with some amines, alcohols, diols, amino alcohols, and aminothiols. Often, unusual products were observed depending on the ratio of reagents, reaction time, polarity of solvent, pKa of alcohols, or type of amine (primary or secondary). In reactions of aliphatic alcohols with BOC2O/DMAP, we isolated for the first time carbonic-carbonic anhydride intermediates; this helps explain the formation of symmetrical carbonates in addition to the O-BOC products. In the case of secondary amines, we succeeded to isolate unstable carbamic-carbonic anhydride intermediates that in the presence of DMAP led to the final N-BOC product. The effect of N-methylimidazole in place of DMAP was also examined.

190 citations

Journal ArticleDOI
TL;DR: The synthesis of functionalized styrene derivatives can be readily achieved utilizing a Suzuki cross-coupling protocol between aryl halides and 2,4,6-trivinylcyclotriboroxane-pyridine complex.
Abstract: The synthesis of functionalized styrene derivatives can be readily achieved utilizing a Suzuki cross-coupling protocol between aryl halides and 2,4,6-trivinylcyclotriboroxane-pyridine complex. The scope and limitations of the procedure were demonstrated by investigation of an array of ortho-substituted aryl halides.

122 citations