Showing papers on "Intramolecular reaction published in 2007"
TL;DR: The reaction of silylaryl triflates, CsF, and ortho-heteroatom-substituted benzoates affords a general and efficient way to prepare biologically interesting xanthones, thioxanthone, and acridones.
Abstract: The reaction of silylaryl triflates, CsF, and ortho-heteroatom-substituted benzoates affords a general and efficient way to prepare biologically interesting xanthones, thioxanthones, and acridones. This chemistry presumably proceeds by a tandem intermolecular nucleophilic coupling of the benzoate with an aryne and a subsequent intramolecular electrophilic cyclization.
166 citations
TL;DR: An efficient intramolecular palladium-catalyzed, asymmetric reductive-Heck reaction has been developed, which allowed for the synthesis of either enantiomerically enriched 3-substituted indanones or alpha-exo-methylene indanone depending on the base used.
Abstract: An efficient intramolecular palladium-catalyzed, asymmetric reductive-Heck reaction has been developed, which allowed for the synthesis of either enantiomerically enriched 3-substituted indanones or alpha-exo-methylene indanones depending on the base used.
134 citations
TL;DR: Evidence supports a mechanism wherein the N-C bond is formed via intramolecular syn aminocupration and the C-C Bond is formed through intramolescular addition of a primary carbon radical to an aromatic ring.
Abstract: An expanded substrate scope and in-depth analysis of the reaction mechanism of the copper(II) carboxylate-promoted intramolecular carboamination of unactivated alkenes is described. This method pro...
129 citations
TL;DR: CuI-catalyzed coupling of 1-bromo-2-iodobenzenes with beta-keto esters in THF at 100 degrees C leads to 2,3-disubstituted benzofurans, a domino transformation that involves an intermolecular C-C bond formation and a subsequent intramolecularC-O bond formation process.
Abstract: CuI-catalyzed coupling of 1-bromo-2-iodobenzenes with β-keto esters in THF at 100 °C leads to 2,3-disubstituted benzofurans. This domino transformation involves an intermolecular C−C bond formation and a subsequent intramolecular C−O bond formation process. Benzofurans with different substituents at the 5- and 6-position are accessible by employing the corresponding 1-bromo-2-iodobenzenes.
122 citations
TL;DR: A tandem cyclization/nucleophilic addition procedure involving reaction of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient approach to C3-substituted indole derivatives when an excess of Et2Zn was used.
Abstract: Intramolecular hydroamination of alkynyl amides was effected by a catalytic amount of Et2Zn (20 mol %) to form indole derivatives, and a tandem cyclization/nucleophilic addition procedure involving reaction of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient approach to C3-substituted indole derivatives when an excess of Et2Zn (120 mol %) was used.
121 citations
TL;DR: A short, two-step approach to the synthesis of diazepane or diazocane systems, based on a Ugi multicomponent reaction followed by a subsequent intramolecular SN2 reaction was studied and a mechanistic explanation of the observed outcomes is proposed.
Abstract: A short, two-step approach to the synthesis of diazepane or diazocane systems, based on a Ugi multicomponent reaction followed by a subsequent intramolecular SN2 reaction was studied. 1-Sulfonyl tetrahydrobenzo[e]-1,4-diazepin-1-ones 1 were obtained in very high yield through a Ugi multicomponent reaction followed by Mitsunobu cyclization. On the other hand, aliphatic 1-sulfonyl 1,4-diazepan-5-ones 2 could be obtained employing different cyclization conditions (sulfuryl diimidazole). A similar approach toward diazocane rings using hydroxamates as nucleophiles was less successful, affording only O-cyclized adducts or unexpected side products. A mechanistic explanation of the observed outcomes is proposed.
107 citations
TL;DR: A novel multicomponent reaction of arynes, beta-keto sulfones, and Michael-type acceptors is presented, providing an efficient method for the synthesis of polysubstituted naphthols and polysubstantial naphthalenes.
Abstract: A novel multicomponent reaction of arynes, beta-keto sulfones, and Michael-type acceptors is presented, providing an efficient method for the synthesis of polysubstituted naphthols and polysubstituted naphthalenes. Further investigation suggests that the tandem reaction may proceed via a sequential nucleophilic attack to arynes, intramolecular nucleophilic substitution followed by a Michael addition, and a ring closure-elimination process.
96 citations
TL;DR: A palladium-catalyzed reaction of gem-dichloroolefins and a boronic acid via a tandem intramolecular C-N and intermolecular Suzuki coupling process gave corresponding substituted azaindoles or thienopyrroles.
Abstract: A palladium-catalyzed reaction of gem-dichloroolefins and a boronic acid via a tandem intramolecular C-N and intermolecular Suzuki coupling process gave corresponding substituted azaindoles or thienopyrroles. This method is a very modular protocol to synthesize all four isomers of azaindole and two isomers of thienopyrroles in good to excellent yield.
94 citations
TL;DR: Based on the spectroscopic evidence, conformations and dynamics of 1, arising from the hindered rotation of the major axis, are proposed.
Abstract: Synthesis of a tetrakis(1-pyrenylethynyl)-substituted rigid hinge-like molecule (1) is described. The intramolecular π-stacking interaction of the pyrene units is studied by 1H NMR and fluorescence spectroscopy. Due to intramolecular π-stacking interactions, chemical shifts of the pyrene protons in 1 are highly shielded in the NMR spectrum. Fluorescence from the static excimer state is observed due to π-stacking interactions among the pyrene units in the ground state of 1. Based on the spectroscopic evidence, conformations and dynamics of 1, arising from the hindered rotation of the major axis, are proposed.
89 citations
TL;DR: The hypervalent iodine reagent PIFA promotes the intramolecular electrophilic cyclization of easily accessible alkynylamides and alkynyl carboxylic acids, leading to the formation of pyrrolidinone and lactone skeletons in a very efficient way.
Abstract: The hypervalent iodine reagent PIFA promotes the intramolecular electrophilic cyclization of easily accessible alkynylamides and alkynyl carboxylic acids, leading to the formation of pyrrolidinone and lactone skeletons, respectively, in a very efficient way. A synthetic study and a mechanistic proposal for these transformations are presented.
85 citations
TL;DR: The total synthesis of several members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family has been carried out and the stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered vinyl group oriented exo with respect to the oxygen bridge.
Abstract: The total synthesis of several members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family has been carried out. (±)-Lycoricidine and (±)-7-deoxypancratistatin were assembled through a one-pot Stille/intramolecular Diels−Alder cycloaddition cascade to construct the core skeleton. The initially formed [4 + 2]-cycloadduct undergoes nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone on further heating at 160 °C. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered vinyl group oriented exo with respect to the oxygen bridge. The resulting cycloadduct was used for the stereocontrolled installation of the remaining functionality present in the C-ring of the target molecules. Key features of the synthetic strategy include (1) a lithium hydroxide induced tandem hydrolysis/decarboxylation/elimination sequence to introduce the required π-bond in the C-ring of (±)-...
TL;DR: In this article, the combination of 5 with NaB[3,5-C6H3(CF3)2]4 (denoted as NaBArF4) provides a potent catalytic system for both intra-and intermolecular hydroamination of alkynes.
TL;DR: The cyclization of amino-alkynes 1 in which an amino group is attached to the aromatic ring, proceeded smoothly using a catalytic amount of Pd(PPh3)4 and benzoic acid in toluene at 120 degrees C, leading to the formation of the 2-substituted tetrahydroquinolines 2.
Abstract: The cyclization of amino-alkynes 1 in which an amino group is attached to the aromatic ring, proceeded smoothly using a catalytic amount of Pd(PPh3)4 and benzoic acid in toluene at 120 °C, leading to the formation of the 2-substituted tetrahydroquinolines 2. An asymmetric variant of the reaction using the chiral palladium catalyst (prepared in situ by mixing Pd2(dba)3·CHCl3 and (R,R)-RENORPHOS) was also explored. The absolute configuration of the enantiomerically enriched tetrahydroquinolines, obtained in this way, was determined by converting them to the known compounds and was found to be R. The alkaloids such as (±)-galipinine, (±)-angustureine, and their optically active form were synthesized by using this reaction as a key step.
TL;DR: Construction of the pyrrolidine and piperidine ring of each alkaloid was achieved by using an intramolecular 1,3-dipolar cycloaddition of an azide onto an alkene and subsequent reduction of the resulting imine and aziridine.
Abstract: The practical and expedient total syntheses of the representative phenanthroindolizidine and phenanthroquinolizidine alkaloids, antofine and cryptopleurine, are described. Construction of the pyrrolidine and piperidine ring of each alkaloid was achieved by using an intramolecular 1,3-dipolar cycloaddition of an azide onto an alkene and subsequent reduction of the resulting imine and aziridine.
TL;DR: This methodology has been used to demonstrate its utility in the regio- and stereoselective synthesis of a 1,2-diamino-3-hydroxycyclohexane and is found in natural products such as Tamiflu.
Abstract: Aziridines were formed by copper-catalyzed intramolecular nitrene addition to alkenes. The carbamate group was used as the tether between the alkene and the nitrene. Subsequent nucleophilic attack of the aziridine was accomplished using RSH, R2NH, N3-, or ROH as the nucleophile. This addition was found to be regio- and stereoselective. This methodology has been used to demonstrate its utility in the regio- and stereoselective synthesis of a 1,2-diamino-3-hydroxycyclohexane. This substitution pattern is found in natural products such as Tamiflu.
TL;DR: It was revealed that increasing the size of the alkyl substituents of the acetal unit resulted in improving the stereoselectivity of the anomeric position, and the desired ribosides 21b and 22b were obtained in 80% yield when the ribosyl fluoride 16 possessing a more sterically hindered 3-pentylidene group was used.
Abstract: Full details of the total synthesis of (+)-caprazol are described. The key elements of our approach include the early stage introduction of the aminoribose in a highly β-selective manner, using the steric hindrance in the transition state and the construction of the diazepanone by a modified intramolecular reductive amination. The 5‘-C-glycyluridine derivative 9, which was prepared stereoselectively via Sharpless asymmetric aminohydroxylation, was ribosylated with 2,3-O-alkylidene ribofuranosyl donors. It was revealed that increasing the size of the alkyl substituents of the acetal unit resulted in improving the stereoselectivity of the anomeric position, and the desired ribosides 21b (1‘ ‘-β) and 22b (1‘ ‘-α) were obtained in 80% yield (21b/22b = 24.0/1) when the ribosyl fluoride 16 possessing a more sterically hindered 3-pentylidene group was used. The origin of the stereoselectivity of the ribosylation was also discussed. Construction of the diazepanone system was optimized with the model aldehyde 37, ...
TL;DR: The total syntheses of (-)-magellanine, (+-magellaninone, and (+)-paniculatine were completed from diethyl l-tartrate via the common intermediate in a stereoselective manner, and involved two intramolecular Pauson-Khand reactions of enynes.
Abstract: The total syntheses of (−)-magellanine, (+)-magellaninone, and (+)-paniculatine were completed from diethyl l-tartrate via the common intermediate in a stereoselective manner. The crucial steps in these syntheses involved two intramolecular Pauson−Khand reactions of enynes: the first Pauson−Khand reaction constructed the bicyclo[4.3.0] carbon framework, the corresponding A and B rings of these alkaloids in a highly stereoselective manner, whereas the second Pauson−Khand reaction stereoselectively produced the bicyclo[3.3.0]skeleton, which could be converted into the C and D rings of the target natural products.
TL;DR: While the reaction of terminal allenes afforded bicyclic cyclobutane derivatives as a single isomer, the cycloaddition of some internal allenes with axial chirality yielded a diastereomeric mixture of cycloadducts.
Abstract: Thermal [2 + 2] cycloaddition of allenes with an additional multiple bond is described. By simply heating the allenenes or allenynes having a three-atom tether in an appropriate solvent such as dioxane or DMF, the distal double bond of the allenic moiety regioselectively participates in the cycloaddition to form bicyclo[4.2.0]oct-5-ene derivatives in good to excellent yields. In all the reactions of allenenes, the olefin geometry was completely transferred to the cycloadducts. While the reaction of terminal allenes afforded bicyclic cyclobutane derivatives as a single isomer, the cycloaddition of some internal allenes with axial chirality yielded a diastereomeric mixture of cycloadducts. These results are in good accordance with the stepwise mechanism through a biradical intermediate with a coplanar allyl radical.
TL;DR: Starting from appropriate alkynoic acid derivatives, either enol lactones or 1,2,3-triazole click products can be obtained selectively by Cu(I) catalysis in aqueous media.
Abstract: Alkynoic acids, in particular, 4-pentynoic acid derivatives, undergo intramolecular cyclizations to enol lactones under reaction conditions typically applied for the Cu(I)-catalyzed cycloaddition of terminal alkynes and azides (click chemistry). Starting from appropriate alkynoic acid derivatives, either enol lactones or 1,2,3-triazole click products can be obtained selectively by Cu(I) catalysis in aqueous media.
TL;DR: Starting from a monoformylated indolocarbazole, novel benzimidazolyl-substituted derivatives were synthesized, while Suzuki cross-couplings on a monobrominated building block afforded a novel pathway toward functionally arylated ICZs.
Abstract: A facile three-stage, one-pot approach for the synthesis of a variety of novel 6-monosubstituted and 6,12-disubstituted 5,11-dihydroindolo[3,2-b]carbazoles, in moderate to good yields (20−50%), has been developed, based on the condensation of an indole and an aldehyde with a catalytic amount of iodine, followed by an acid-catalyzed intramolecular cyclization with an ortho ester. The parent indolo[3,2-b]carbazoles (ICZs) could be converted to various functional derivatives. Both N-alkylation and N-arylation were successfully accomplished, and azo-coupling, formylation, as well as bromination were performed in a regioselective way leading to the formation of novel functional 6,12-disubstituted indolo[3,2-b]carbazoles. Starting from a monoformylated indolocarbazole, novel benzimidazolyl-substituted derivatives were synthesized, while Suzuki cross-couplings on a monobrominated building block afforded a novel pathway toward functionally arylated ICZs.
TL;DR: The alpha-amidoalkylation process seems to be effective in intermolecular and intramolecular manners leading to alpha-substituted lactams and heterocyclic systems containing azacycles, respectively, and having diastereoselectivity comparable to protocols using classical Lewis acids.
Abstract: Bismuth(III) triflate was found to promote the formation of stable cyclic N-acyliminium species in remarkable catalytic amounts (1 mol %). The alpha-amidoalkylation process seems to be effective in intermolecular and intramolecular manners leading to alpha-substituted lactams and heterocyclic systems containing azacycles, respectively. By comparing our results with those obtained with the classical Lewis acids as catalysts, it was evidenced clearly that the use of bismuth(III) triflate had been efficient for nearly all alpha-acetoxy lactams we used, except for N-acyliminium precursors bearing a sulfur atom. Also, the process seems to be easy, general, and clean, having diastereoselectivity comparable to protocols using classical Lewis acids and resulting in the formation of polyheterocyclic systems in good to excellent yields (64-99% in acetonitrile as solvent).
TL;DR: N-Protected amino aldehydes can be converted into allylic alcohols by the classical Morita-Baylis-Hillman reaction or by condensation with selenium-stabilized carbanions, followed by oxidation.
Abstract: N-Protected amino aldehydes can be converted into allylic alcohols by the classical Morita−Baylis−Hillman reaction (cf. 2 → 3) or by condensation with selenium-stabilized carbanions, followed by oxidation (cf. 2 → 8 → 3). The derived acetates undergo cyclization when the nitrogen protecting group is removed, affording [m,n,0]-bicyclic structures with nitrogen at a bridgehead (cf. 4 → 5 → 6). Formation of bicyclic structures via the reactions of Schemes 1 and 2 is general, and the stereochemistry of the starting amino aldehyde is preserved.
TL;DR: The first total synthesis of the 15-membered ring cyclopeptide alkaloid abyssenine A 1 has been achieved with a longest linear sequence of 15 steps with the synthetic utility of copper-catalyzed coupling reactions.
Abstract: The first total synthesis of the 15-membered ring cyclopeptide alkaloid abyssenine A 1 has been achieved with a longest linear sequence of 15 steps. Central to the synthetic approach was an efficient copper-mediated Ullmann coupling/Claisen rearrangement sequence allowing for both ipso and ortho functionalization of aromatic iodide 4. This sequence was used for the synthesis of the aromatic core. The synthetic utility of copper-catalyzed coupling reactions was further demonstrated to install the enamide with a concomitant straightforward macrocyclization starting from acyclic alpha-amido-omega-vinyl iodide 13.
TL;DR: A concise and highly enantioselective route has been developed for the synthesis of angucyclinone-type natural products having the benz[a]anthraquinone skeleton based on a sequential intramolecular enyne metathesis, intermolecular Diels-Alder reaction (DAR), and aromatization.
Abstract: A concise and highly enantioselective route has been developed for the synthesis of angucyclinone-type natural products. Utilizing this strategy, total syntheses of five natural products YM-181741, (+)-ochromycinone, (+)-rubiginone B2, (-)-tetrangomycin, and MM-47755 have been accomplished in 22%, 23%, 19%, 18%, and 12% overall yields, respectively. Our approach for the synthesis of these natural products having the benz[a]anthraquinone skeleton is based on a sequential intramolecular enyne metathesis, intermolecular Diels-Alder reaction (DAR), and aromatization. The intramolecular enyne metathesis reaction was employed for the synthesis of enantiopure 1,3-dienes in excellent yields. Furthermore, the synthesis of YM-181741 as well as structurally similar angucyclinones such as (+)-ochromycinone and (+)-rubiginone B2 was achieved via asymmetric enolate alkylation of an oxazolidinone in excellent de. The related angucyclinones (-)-tetrangomycin and MM-47755, bearing a labile tertiary alcohol, were synthesized via Sharpless asymmetric epoxidation of a known allylic alcohol followed by opening the epoxide with Red-Al. The introduction of oxygen functionality at C-1 in all these natural products was accomplished by photooxygenation under a positive pressure of oxygen.
TL;DR: The complex bioactive natural and unnatural benzopyran congeners have been synthesized using one-/two-step approaches in very good yields from the reactions of two different dihydroxyphthalides, natural resorcyclic acid derivative, and trihydroxybenzophenone through the phenol-driven intramolecular diastereoselective thermal/base-catalyzed dipolar [2+2] cycloaddition reactions.
Abstract: The complex bioactive natural and unnatural benzopyran congeners have been synthesized using one-/two-step approaches in very good yields from the reactions of two different dihydroxyphthalides, natural resorcyclic acid derivative, and trihydroxybenzophenone with citral and/or farnesal, via the phenol-driven intramolecular diastereoselective thermal/base-catalyzed dipolar [2 + 2] cycloaddition reactions and three different thermal intramolecular cyclization reactions. The effects of the nature and the position of phenolic groups in the starting materials on the course of these cycloaddition reactions have also been described. Depending upon the absence or presence of intramolecular hydrogen bonding of the phenolic group with the carbonyl moiety in the starting materials, these phenol-driven intramolecular thermal/base-catalyzed dipolar [2 + 2] cycloaddition reactions either furnished the kinetically controlled products or directly formed the thermodynamically controlled rearranged products, respectively.
TL;DR: In aldol condensation, i-Pr-substituted bimorpholine is the most stereoselective catalyst affording products in high yield with enantioselectivities up to 95% ee.
Abstract: Monosalts of N-substituted bimorpholine derivatives are efficient organocatalysts in intramolecular and intermolecular aldol reactions. The properties of the catalysts can be tuned either by the selection of an appropriate acid for the salt formation or by the change of a substituent at the nitrogen atom. In aldol condensation, i-Pr-substituted bimorpholine is the most stereoselective catalyst affording products in high yield with enantioselectivities up to 95% ee.
TL;DR: A facile and efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones was developed via Vilsmeier-Haack reactions of readily available enaminones, 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.
Abstract: A facile and efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones was developed via Vilsmeier−Haack reactions of readily available enaminones, 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.
TL;DR: A detailed study to assess the enantioselectivity of the amino acid mediated intramolecular asymmetric aldol reaction of 1,3-cycloheptanedione bearing a C-2 methyl substituent has been undertaken.
Abstract: A detailed study to assess the enantioselectivity of the amino acid mediated intramolecular asymmetric aldol reaction of 1,3-cycloheptanedione bearing a C-2 methyl substituent has been undertaken. The cyclizations were mediated by a series of l-amino acids in the presence of an acid cocatalyst. Strikingly, the process is characterized by an inversion of enantioselectivity when compared to a similar reaction involving the 1,3-cyclohexanedione counterpart.
TL;DR: An enantioselective synthetic method for (-)-cis-clavicipitic acid was reported, obtained in 10 steps (99% ee and 20% overall yield) from 1H-indole-3-carboxylic acid methyl ester via asymmetric phase-transfer catalytic alkylation and diastereoselectives Pd(II)-catalyzed intramolecular aminocyclization as key steps.
Abstract: An enantioselective synthetic method for (−)-cis-clavicipitic acid (1) was reported. 1 was obtained in 10 steps (99% ee and 20% overall yield) from 1H-indole-3-carboxylic acid methyl ester (9) via asymmetric phase-transfer catalytic alkylation and diastereoselective Pd(II)-catalyzed intramolecular aminocyclization as key steps.
TL;DR: The enantioselective intramolecular [2 + 2 + 2] cycloaddition of various enediynes, where two acetylenic moieties are connected by a trans-olefinic moiety, gave chiral tricyclic cyclohexa-1,3-dienes using Rh-H8-BINAP catalyst.
Abstract: The enantioselective intramolecular [2 + 2 + 2] cycloaddition of various enediynes, where two acetylenic moieties are connected by a trans-olefinic moiety, gave chiral tricyclic cyclohexa-1,3-dienes using Rh-H8-BINAP catalyst. In the case of carbon-atom-tethered enediynes, enantioselectivity was generally good-to-high regardless of the substituents on their alkyne termini. In contrast, with heteroatom-tethered enediynes, appropriate substituents were required to induce the oxidative coupling of alkyne and alkene moieties before that of two alkyne moieties, which would be important for highly enantioselective intramolecular cycloaddition.