Showing papers on "Annulation published in 2006"
TL;DR: A palladium catalyzed C-H bond functionalization system that operates under ambient and aerobic conditions can be used to alkenylate pyrroles with control of regioselectivty with diverse pyrrole products.
Abstract: A palladium catalyzed C−H bond functionalization system that operates under ambient and aerobic conditions can be used to alkenylate pyrroles with control of regioselectivty. A steric and electronic control strategy can be used to influence positional control in the C−H bond functionalization process that results in either the C2 or C3 alkenylated products. Air, molecular oxygen, or tBuOOBz can be used as reoxidant in this mild process, and the reaction works on a range of substrates. Finally a catalytic aerobic annulation strategy is described that can be controlled to produce cyclization at either the C2 or C3 positions, thus forming diverse pyrrole products.
325 citations
TL;DR: It is conceivable that the spiroannulation protocol reported herein will be applicable to the synthesis of important natural products that are endowed with a spiro γ-butyrolactone motif, especially oxindoles and norsesquiterpenoids.
217 citations
171 citations
TL;DR: An enantioselective total synthesis of (-)-rhazinilam highlights the potential utility of this reaction technology in target-oriented synthesis.
Abstract: Highly stereoselective Au(I)-catalyzed pyrrole additions to enantioenriched allenes afford a unique entry to optically active heterocycles. Asymmetric quaternary carbons can be installed with concurrent heterocycle annulation utilizing this methodology. The enantioenriched allenes are conveniently obtained by catalytic asymmetric acyl halide−aldehyde cyclocondensations and SN2‘ ring opening of the resulting enantioenriched β-lactones. An enantioselective total synthesis of (−)-rhazinilam highlights the potential utility of this reaction technology in target-oriented synthesis.
168 citations
TL;DR: A mild and efficient route for the synthesis of quinolines and polycyclic quinOLines via Friedländer annulation, utilizing molecular iodine (1 mol%) as a new catalyst, is described.
Abstract: A mild and efficient route for the synthesis of quinolines and polycyclic quinolines via Friedlander annulation, utilizing molecular iodine (1 mol%) as a new catalyst, is described.
150 citations
TL;DR: A formal [4 + 3]-annulation of vinyl arenes and diynyl propargyl esters is described and a mechanism involving cationic phosphinegold(I)-catalyzed tandem cyclopropanation/hydroarylation to produce the benzonorcaradiene products is proposed.
Abstract: A formal [4 + 3]-annulation of vinyl arenes and diynyl propargyl esters is described. A mechanism involving cationic phosphinegold(I)-catalyzed tandem cyclopropanation/hydroarylation to produce the benzonorcaradiene products is proposed. In accord with this mechanism, the alkynyl cyclopropane can also be prepared with excellent regio- and diastereocontrol.
146 citations
TL;DR: This reaction employing cyclobutanones as a C4 unit constructs cyclooctadienone cores in one synthetic step and forms a nine-membered nickelacycle.
Abstract: Cyclobutanones underwent a formal [4 + 2 + 2] annulation reaction with 1,6- and 1,7-diynes in the presence of nickel(0) catalysts to provide bicyclic eight-membered ring ketones. The annulation reaction proceeds through a ring-expansion of oxanickelacycloheptadiene via β-carbon elimination to form a nine-membered nickelacycle. This reaction employing cyclobutanones as a C4 unit constructs cyclooctadienone cores in one synthetic step.
138 citations
TL;DR: The 1,2-nitrogen shift in the formation of indole is catalyzed by Zn(OTf)2, and its mechanism has been elucidated, and this catalytic cyclization is also applicable to the synthesis of oxazoles through the cyclization of propargyl alcohols and amides without a 1-2- Nitrogen shift.
Abstract: Zn(OTf)2 (10 mol %) catalyzed the cyclization of propargyl alcohols with PhXH (X = O, NH) in hot toluene (100 degrees C) without additive and gave indole and benzofuran products with different structures. In such transformations, alpha-carbonyl intermediates A and C were isolated as reaction intermediates. The 1,2-nitrogen shift in the formation of indole is catalyzed by Zn(OTf)2, and its mechanism has been elucidated. This catalytic cyclization is also applicable to the synthesis of oxazoles through the cyclization of propargyl alcohols and amides without a 1,2-nitrogen shift.
138 citations
122 citations
TL;DR: Coupling of (S)-2-N,N-di-tert-butoxycarbonyl-5-oxopentanoate, derived from L-glutamic acid, with ortho-haloanilines provides a rapid access to the ring-A-substituted tryptophans in good to excellent yields.
Abstract: One-pot synthesis of indoles by a palladium-catalyzed annulation of ortho-haloanilines and aldehydes has been developed. Coupling of ortho-iodoaniline with aldehyde is realized under mild ligandless conditions [Pd(OAc)2, DABCO, DMF, 85 °C], whereas X-Phos is found to be the ligand of choice for coupling reactions involving ortho-chloroanilines/ortho-bromoanilines and aldehydes. A variety of ortho-haloanilines with different electronic properties are suitable substrates, and aldehydes including chiral ones participated in this reaction without racemization. Coupling of (S)-2-N,N-di-tert-butoxycarbonyl-5-oxopentanoate, derived from l-glutamic acid, with ortho-haloanilines provides a rapid access to the ring-A-substituted tryptophans in good to excellent yields.
118 citations
TL;DR: The first total synthesis of the highly complex and potent anticancer agent haouamine A is reported through an eight-step sequence through a cascade annulation proceeding via a hitherto unknown chemical entity for the indeno-tetrahydropyridine ring system.
Abstract: The first total synthesis of the highly complex and potent anticancer agent haouamine A is reported through an eight-step sequence. Brevity of the sequence and complete control of chemo-, position-, and stereoselectivity (both planar and axial chirality) were possible through the invention of chemistry specifically tailored for the problems at hand, namely a cascade annulation proceeding via a hitherto unknown chemical entity for the indeno-tetrahydropyridine ring system as well as a pyrone-assisted stitching of the daunting bent-aromatic ring.
TL;DR: This work calculated mPW1PW91/6-311+G(2d,p)//B3LYP/ 6-31G* energies to establish the first comprehensive energy profiles for the cationic cyclization of oxidosqualene to lanosterol, lupeol, and hopen-3beta-ol to reveal systematic errors in DFT cyclization energies.
Abstract: Most quantum mechanical studies of triterpene synthesis have been done on small models. We calculated mPW1PW91/6-311+G(2d,p)//B3LYP/6-31G* energies for many C30H51O+ intermediates to establish the first comprehensive energy profiles for the cationic cyclization of oxidosqualene to lanosterol, lupeol, and hopen-3β-ol. Differences among these 3 profiles were attributed to ring strain, steric effects, and proton affinity. Modest activation energy barriers and the ample exothermicity of most annulations indicated that the cationic intermediates rarely need enzymatic stabilization. The course of reaction is guided by hyperconjugation of the carbocationic 2p orbital with parallel C–C and C–H bonds. Hyperconjugation for cations with a horizontal 2p orbital (in the plane of the ABCD ring system) leads to annulation and ring expansion. If the 2p orbital becomes vertical, hyperconjugation fosters 1,2-methyl and hydride shifts. Transition states leading to rings D and E were bridged cyclopropane/carbonium ions, which allow ring expansion/annulation to bypass formation of undesirable anti-Markovnikov cations. Similar bridged species are also involved in many cation rearrangements. Our calculations revealed systematic errors in DFT cyclization energies. A spectacular example was the B3LYP/6-311+G(2d,p)//B3LYP/6-31G* prediction of endothermicity for the strongly exothermic cyclization of squalene to hopene. DFT cyclization energies for the 6-311+G(2d,p) basis set ranged from reasonable accuracy (mPW1PW91, TPSSh with 25% HF exchange) to underestimation (B3LYP, HCTH, TPSS, O3LYP) or overestimation (MP2, MPW1K, PBE1PBE). Despite minor inaccuracies, B3LYP/6-31G* geometries usually gave credible mPW1PW91 single-point energies. Nevertheless, DFT energies should be used cautiously until broadly reliable methods are established.
TL;DR: In this article, a series of novel coplanar chromophores were synthesized in which heteroarenes, namely, thiophene, benzothiophene and carbazole, were fused to neighboring phenylene ring(s) through intramolecular annulation via sp3-hybridized carbon atoms bearing two p-tolyl groups as peripheral substituents.
TL;DR: An unexpected tetrahydrothiophene-catalyzed ylide annulation reaction, via tandem Michael addition/elimination/substitution, for the controllable synthesis of 2H-chromenes and 4H- chromenes has been developed.
TL;DR: A highly efficient annulation of phenols and naphthols with dienes was developed by using a combination of AuCl(3)/AgOTf as catalyst, which generated various benzofuran derivatives under mild conditions rapidly.
TL;DR: The Yb(OTf)3-catalyzed annulation reactions of phenols with 5-alkylidene Meldrum's acids enabled the synthesis of structurally diverse heterocycles in high isolated yields.
Abstract: The Yb(OTf)3-catalyzed annulation reactions of phenols with 5-alkylidene Meldrum's acids enabled the synthesis of structurally diverse heterocycles in high isolated yields. A series of 4-substituted 3,4-dihydrocoumarins, 2,2-disubstituted 4-chromanones, coumarins, and 2-substituted chromones were readily and efficiently assembled, including the naturally occurring coumarins citropten, scoparone, and ayapin. Addition of phenols to biselectrophilic 5-alkylidene Meldrum's acids proceeded through two distinct multibond-forming modes: Friedel−Crafts C-alkylation/O-acylation and Friedel−Crafts C-acylation/O-alkylation. The regioselectivity of the catalytic annulation reaction was controlled by the degree of substitution on the alkylidene moiety.
TL;DR: A novel and selective palladium-catalyzed annulation of 2-alkynylphenols method for the synthesis of2-substituted 3-halobenzo[b]furans is presented and selectively obtained as the major products.
TL;DR: A novel protocol for the annulation of tropone to enals involving nucleophilic heterocyclic carbene (NHC) catalyzed homoenolate formation has been developed and led to bicyclic delta-lactones instead of the expected gamma-spirolactones, presumably by the uncommon [8 + 3] annulation pathway.
Abstract: A novel protocol for the annulation of tropone to enals involving nucleophilic heterocyclic carbene (NHC) catalyzed homoenolate formation has been developed. Interestingly, the reaction led to bicyclic δ-lactones instead of the expected γ-spirolactones, presumably by the uncommon [8 + 3] annulation pathway. The strategy works well with a variety of enals.
TL;DR: A recently developed MgI(2)-mediated ring-expansion reaction of spiro[cyclopropan-1,3'-oxindole] with a cyclic disubstituted aldimine results in a single diastereoisomer, possessing the same stereochemical pattern found in strychnofoline.
Abstract: Studies aimed at preparing (+/-)-strychnofoline by total synthesis are detailed. The route described makes use of a recently developed MgI(2)-mediated ring-expansion reaction of spiro[cyclopropan-1,3'-oxindole] with a cyclic disubstituted aldimine. The ring-expansion product was formed as a single diastereoisomer in 55 % yield, possessing the same stereochemical pattern found in strychnofoline. In addition, our synthetic effort has led to the development of new reaction methodology to access 3,4-disubstituted cyclic aldimines.
TL;DR: Application of this strategy, together with additional key steps such as long-range directed hydrogenation and diastereoselective intramolecular iodo-amination, led to highly convergent total syntheses of (-)-batzelladine D and (+)-batzin A with excellent stereocontrol.
Abstract: A diastereoselective [4 + 2]-annulation of vinyl carbodiimides with chiral N-alkyl imines has been developed to access the stereochemically rich polycyclic guanidine cores of the batzelladine alkaloids. Application of this strategy, together with additional key steps such as long-range directed hydrogenation and diastereoselective intramolecular iodo-amination, led to highly convergent total syntheses of (-)-batzelladine D and (+)-batzelladine A with excellent stereocontrol.
TL;DR: A convergent and highly stereocontrolled synthesis of amphidinolide E (1) has been accomplished as discussed by the authors, which features a highly diastereoselective BF3·Et2O promoted [3+2] annulation reaction between aldehyde 3 and allylsilane 4 to afford substituted tetrahydrofuran 2.
Abstract: A convergent and highly stereocontrolled synthesis of amphidinolide E (1) has been accomplished. The synthesis features a highly diastereoselective (>20:1) BF3·Et2O promoted [3+2] annulation reaction between aldehyde 3 and allylsilane 4 to afford substituted tetrahydrofuran 2.
TL;DR: A planar-chiral DMAP derivative catalyzes an intriguing [3 + 2] annulation reaction of silylated indenes to produce diquinanes that bear three contiguous stereocenters (one quaternary and two tertiary).
TL;DR: In this paper, a highly diastereoselective Lewis acid (BF3·Et2O or TiCl4) induced cycloaddition of substituted and unsubstituted indoles with 2-arylcyclopropyl ketones/diesters yielding cyclopenta[b]indoles in high yields is reported.
TL;DR: In this paper, a mild and efficient method was developed for the condensation of 2-aminoaryl ketones with α-methylene ketones in the presence of a catalytic amount of reusable catalyst CeCl 3 ·7H 2 O (25m) at ambient temperature to afford the corresponding poly-substituted quinolines in high yields under mild conditions.
TL;DR: From certain substrates, the direct annulation is observed in the titanium-mediated step, which is likely to occur through an olefin metathesis-intramolecular olefination sequence.
Abstract: The dimethyltitanocene methylenation of N-acylamides derived from ortho-vinylanilines, ortho-allylaniline, and ortho-vinylbenzylamine provides the corresponding enamides, which upon exposure to the second generation Grubbs ruthenium catalyst give access to indoles, 1,4-dihydroquinolines, and 1,2-dihydroisoquinolines, respectively. This sequential protocol also allows the synthesis of dihydrobenzoazepines, although the ring-closing metathesis (RCM) step is complicated by the alkene isomerization processes. From certain substrates, the direct annulation is observed in the titanium-mediated step, which is likely to occur through an olefin metathesis−intramolecular olefination sequence.
TL;DR: A platinum-catalyzed domino process with intermediate benzopyrylium cations reaches its optimum utility in the formation of 7- and 8-membered rings.
TL;DR: In this article, the formal [3+2] dipolar cycloaddition of donor-acceptor cyclopropanoate esters with pyridines and 5-nitroquinoline is reported.
Abstract: The formal [3+2] dipolar cycloaddition (or annulation) of donor-acceptor cyclopropanoate esters with pyridines and 5-nitroquinoline is reported. Electron-deficient pyridine dipolarophiles (R=CN, CO2Et, COMe) participate in the annulation whereas electron rich species do not. The product 2,3-dihydroindolizines undergo rapid autooxidation, and the X-ray structures for two of the aromatic products are reported.
TL;DR: The syntheses of dodecamethoxytricyclobutabenzene (TCBB) 1 and hexaoxo-TCBB 2, a class of molecules with structural and theoretical interest, are reported, allowing rapid and regioselective annulation of fully functionalized four-membered rings.
Abstract: We report herein the syntheses of dodecamethoxytricyclobutabenzene (TCBB) 1 and hexaoxo-TCBB 2, a class of molecules with structural and theoretical interest. The preparation is based on the 3-fold [2 + 2] cycloadditions of benzyne and ketene silyl acetals (KSAs), where the selectively protected 2-iodophloroglucinol derivative served as a synthetic equivalent of benztriyne I, allowing rapid and regioselective annulation of fully functionalized four-membered rings. Structural study on the former compound showed that the C−C bond lengths in the central benzene ring were essentially the same.
TL;DR: In this article, a double annulation strategy was proposed to synthesize highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1]-annulation strategy starting from easily available α-alkenoyl-α-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3).
Abstract: A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available α-alkenoyl-α-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were created in high to excellent yields by a formal [5C + 1N] annulation reaction of ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step of the double annulation strategy, the highly functionalized dihydropyrido[2,3-d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1 = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were constructed, respectively, in fair to good yields by reacting 2 with excessive Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1] annulation step, including a formal [5 + 1] annulation and accompanied chlorovinylation, chlorofor...