Showing papers on "Annulation published in 1996"

Efficient Reagents for the Synthesis of 5-, 7-, and 5,7-Substituted Indoles Starting from Aromatic Amines: Scope and Limitations

Abstract: Upon reaction with IPy2BF4, 4-substituted anilines give regioselectively the corresponding o-iodoanilines in nearly quantitative yield, in a process that can be carried out on a multigram scale. Palladium-catalyzed coupling of the resulting 2-iodoanilines with (trimethylsilyl)acetylene (TMSA), followed by efficient CuI-mediated nitrogen cyclization onto alkynes with concurrent elimination of the TMS substituent, allows a straightforward elaboration of 5-mono- and 5,7-disubstituted indoles from aromatic amines. This new approach to the aforementioned indoles does not requires protective groups on nitrogen at any step and can be adapted for preparing related 7-monosubstituted indoles. Moreover, examples iterating the process are given, allowing bisannulation and sequential double annulation and resulting in synthesis of benzodipyrroles. Additionally, suitable conditions for iodination of some of the target indoles with IPy2BF4 are discussed.

Asymmetric Synthesis of Highly Functionalized 8-Oxabicyclo[3.2.1]octene Derivatives

Abstract: Rhodium(II) carboxylate catalyzed decomposition of vinyldiazomethanes in the presence of furans results in a general synthesis of oxabicyclo[3.2.1]octa-2,6-diene derivatives. These oxabicyclic products are versatile intermediates in organic synthesis. The mechanism of the [3 + 4] annulation is considered to be a tandem cyclopropanation/Cope rearrangement. Such a mechanism is consistent with the excellent regio- and stereocontrol that is observed in these [3 + 4] annulations. Asymmetric synthesis of the oxabicyclic products is possible through utilization of rhodium(II) (S)-N-(tert-butylbenzene)sulfonylprolinate as catalyst or by using (S)-lactate or (R)-pantolactone as chiral auxiliaries on the carbenoid. The highest yields (69−95%) and asymmetric induction (82−95% de) were obtained using 3-siloxy-2-diazo-3-butenoate derivatives as the vinylcarbenoid precursors.

Total Synthesis of (+/-)-Deethylibophyllidine: Studies of a Fischer Indolization Route and a Successful Approach via a Pummerer Rearrangement/Thionium Ion-Mediated Indole Cyclization.

Abstract: The total synthesis of (±)-deethylibophyllidine is described, proceeding in eight steps from 4-(methoxyphenyl)ethylamine in 5% overall yield (Scheme 6). In terms of sequential annulation, the strategy involves the following operations: E → DE → ABDE → ABCDE (Scheme 1). The key steps in the synthesis are the stereoselective formation of octahydroindol-6-ones by acid treatment of dihydroanisole derivatives, the regioselective Fischer indolization to obtain octahydropyrrolo[3,2-c]carbazoles, and the tandem process consisting of Pummerer rearrangement upon a β-amino sulfoxide and thionium ion cyclization upon a β-indole position of a 2,3-disubstituted indole to generate the quaternary spiro center. Attempts to effect the construction of the pentacyclic framework by means of Fischer indolization of the octahydropyrrolo[3,2,1-hi]indol-6-one resulted in failure (Scheme 2).

Cyclopentannulation by an Iterative Process of Sequential Claisen Rearrangement and Enyne Radical Closure: Routes to Triquinane and Propellane Systems and Use in the Synthesis of (±)-Ceratopicanol

Abstract: Cycloalkenyl acetylenes 4, which are easily prepared from allylic alcohols by Claisen rearrangement and homologation (1 → 4), generally undergo radical cyclization (4 → 6) on treatment with stannyl radicals. The products (6) can themselves be converted into allylic alcohols, so that the annulation sequence can then be repeated. In certain cases enyne cyclization initiated by stannyl radicals does not work, but an alternative process (cf. Scheme 9) of epoxide opening with bis(cyclopentadienyl)titanium(III) chloride can then be used. Di- and triquinanes (Scheme 3) were made by the stannyl radical approach; the epoxide route was used to prepare a simple propellane (Scheme 4) and in a synthesis of (±)-ceratopicanol (Schemes 5 and 9).

Divergent Pathways in the Intramolecular Reactions between Rhodium-Stabilized Vinylcarbenoids and Pyrroles: Construction of Fused Tropanes and 7-Azabicyclo[4.2.0]octadienes

Abstract: The rhodium(II)-catalyzed intramolecular reaction between vinyldiazomethanes and pyrroles leads to a novel synthesis of fused tropanes. The reaction occurs by a stepwise 3 + 4 annulation mechanism between a rhodium-stabilized vinylcarbenoid intermediate and the pyrrole rather than by the typical tandem cyclopropanation/Cope rearrangement sequence. The outcome of the reaction is very sensitive to the vinylcarbenoid structure. In particular, the presence of a 2-siloxy substituent on the vinylcarbenoid strongly favors the formation of fused tropanes. In the absence of such functionality, the formation of fused 7-azabicyclo[4.2.0]octadienes becomes the dominant reaction pathway.

A Concise, Enantioselective Synthesis of (-)- and (+)-Hongconin.

Abstract: Optically pure enone 9c, available in three steps from known 6-deoxy D-galactal derivative 7b, reacts with cyanophthalide 6 to directly afford the natural product (-)-hongconin (1), a compound from traditional Chinese medicine recently shown to exhibit antianginal activity. The enantiomer of 1 and its (+)-cis-diastereomer were also synthesized in a parallel fashion from the L-sugar counterpart. The use of C-glycoside Michael acceptors, as opposed to their O-glycoside counterparts, represents a potentially useful simplification of phthalide annulation methodology in synthesizing numerous other such optically pure isochromanquinoids, since it obviates the inconvenience of additional steps late in the synthetic scheme associated with reductive manipulation of a remaining acetal moiety into the desired pyran ring substituent.

Addition of Transiently-Generated Methyl o-Lithiobenzoate to Imines. An Isoindolone Annulation.

Abstract: Addition of phenyllithium to a mixture of an imine, methyl o-iodobenzoate, and BF(3).etherate at -105 degrees C gives good to excellent yields of isoindolones. The transient formation of methyl o-lithiobenzoate is proposed, which is formed by a rapid lithium/iodide exchange reaction of the phenyllithium with methyl o-iodobenzoate in the presence of the imine. The transiently generated anions can then be captured by the BF(3)-activated imines to form the isoindolones in good to high yield. The reactions conditions are sufficiently mild, and selective, to permit functional groups such carbmethoxy and aryl bromide, which could otherwise react with the added PhLi, to be tolerated.

Selective organic synthesis via group 6 metal carbene complexes

Abstract: The first examples of asymmetric Michael addition of lithium reagents to chiral vinylalkoxycarbene chromium complexes 2 is reported. The (4+3) annulation of azadienes and 2-aminodienes is accomplished with complexes 2. Vinylaminocarbenes cyclopropanate alkenes and dienes and allows to isolate two new intermediates in the Dotz reaction. Some features of the (4+2) cycloaddition of chiral2-aminodienes with both s-cis and s-rrans Fischer vinylcarbene complexes are also presented. Fischer carbene complexes are proving to be increasingly attractive reagents in modern organic synthesis. Particularly useful are complexes of group 6 (chromium, molibdenum, tungsten) and, among them, vinyl carbenes have been reported to exhibit great and versatile reactivity (1). We have been for some time involved in developing synthetic methodologies using functionalized organolithium derivatives (2) as well as carbo- and aminoazadienes (3), which are in turn readily available from enynes and imines, respectively (Figure 1). Because of the electrophilic nature of vinyl carbenes we became interested in studying their behaviour towards electron-rich reagents, such as organolithium, hetero- and carbodiene derivatives.

Synthesis of 2-azetidiniminium salts. 1. diastereoselectivity in keteniminium triflate/imine cycloadditions

Abstract: A systematic study of the synthesis of 2-azetidiniminium triflates, by annulation of aldimines with iminium salts derived from tertiary carboxamides and trifluoromethanesulfonic anhydride, has been carried out. The stereochemical output of a number of 2-azetidiniminium triflates is compared with that of the corresponding chloride salts synthesized by reaction of the same imines with α-chloro iminium chlorides. As a general rule, the stereochemical output of the reactions involving α-chloro iminium chlorides is in stark contrast to that of the corresponding triflates: while the chloride salts are trans stereoselective, the triflates show a preference for the cis products. The stereochemistry of the reactions involving the triflates has been examined in light of the structure of the reagents. Clear trends for a preferential formation of cis or trans products with the steric and electronic demand of the imine have been observed. By contrast, no correlation of the product distribution with the steric demand ...

Novel method for the synthesis of α- and β-halogenonaphthalenes by regioselective benzannulation of aryl(gem-dihalogenocyclopropyl)methanols: application to the total synthesis of the lignan lactones, justicidin E and taiwanin C1

Abstract: Acid treatment of two types of aryl(gem-dihalogenocyclopropyl)methanols (ADCMs) 1 and 3 gives α- and β-halogenonaphthalenes in good yields with excellent selectivity. These alternative annulations involve two distinctive types of highly regioselective acid-induced cyclopropane ring cleavage, wherein the preferential formation of more stable cationic intermediates determines the selectivity. The stereochemical mode of both the preparation and the annulation between diastereoisomers of an ADCM has been checked. As a demonstration of this annulation, a total synthesis of each of the natural lignan lactones, justicidin E 19 and taiwanin C 20, has also been performed. Since these 4-arylnaphthalenes are expected to exhibit biological activity, the anti-platelet activating factor (anti-PAF) activity of justicidin E has been assayed.

Steroid-Like Ring Skeletons by Cyclohexadiene Annulation to Enamines with Alkynylcarbene Complexes of Chromium and Tungsten via Pyran-2-ylidene Complexes†

Abstract: A highly regioselective cyclohexadiene annulation to the CC(N) bond of an enamine is achieved in two steps involving the condensation of a 1-alkynylcarbene complex (CO)5MC(OEt)C⋮CPh 1 (M = Cr, W) with an enolizable carbonyl compound (2,4-pentanedione, 3-oxobutyric acid ester, 2-tetralones, and 1,3-cyclopentanedione) to give a pyran-2-ylidene complex 3, 5, and 17, which on subsequent reaction with cyclic enamines 6, 9, 13, and 16, generate a 5-amino-1,3-cyclohexadiene by elimination of M(CO)6 Thus, bicyclic ring skeletons 7 and 10, steroid-like molecules 8, 18, and 19, and tetracyclic compounds 11, 12, and 15 are obtained mostly in good chemical yields and under mild conditions Side reactions, such as base-induced self-condensation of 3 to give aryl pyran-2-ylidene complexes 20 become efficiently suppressed in hydrocarbon solvents

Photochemistry of n-phthaloylcysteine derivatives : multiplicity-directed regioselective ch activation

Abstract: The photochemistry of the methyl esters of N-phthaloylcysteine derivatives 1b–5b was studied. The results are remarkable, because they prove a pronounced, multiplicity-controlled regioselectivity of the initial CH activation step. From substrates 1b–4b the benzazepine-1,5-dione 6 was produced exclusively by the singlet path. The formation of compound 6 is initiated by a γ-H abstraction; this was demonstrated by deuterium labeling experiments. The penicillamine derivative 5b was unreactive in the singlet manifold. From substrates 1b–3b and 5b the thiazinoisoindoles 7–9 and 11 were produced exclusively by the triplet path. The sterically hindered S-isopropylcysteine derivative 4b also furnished this product type (10) as a proportion of the products in the singlet manifold. These annulation products result from a primary photoinduced electron-transfer (PET) step followed by heterolytic ϵ-H activation. The mechanistic scenario was elucidated by quenching and sensitization experiments. An interplay of CH activation steps and electron back-transfer is probably responsible for this type of spin selectivity.

Tungsten-Promoted Intramolecular Annulation of Propargyl Bromides with Ketones and Aldehydes for Synthesis of Fused 2,5-Dihydrofurans

Abstract: Metal carbonyl salts CpW(CO)3Na, Re(CO)5Na, and CpFe(CO)2Na were used for intramolecular cyclization of 1-(3-bromo-1-propynyl)-2-(3-oxopropyl)benzene. Among these salts, CpW(CO)3Na was found to be ...

A General Synthesis of Methylenecyclopentanes by a Stereoselective [3 + 2] Approach

Abstract: The [3 + 2] cyclopentanation involving 3-(phenylsulfonyl)-2-(bromomethyl)-1-propene (1) and representative (E) α,β-unsaturated acyclic esters and ketones has been studied. High yields and complete stereoselectivity were observed in all reactions leading to tri- or tetrasubstituted methylenecyclopentanes. The anti-diastereoselectivity in the first, Michael addition step is rationalized by a chelation-controlled transition state in which MO interactions of the two π systems are involved. The Michael reactions of methallyl sulfone 8 with (E) enoates in the absence and presence of HMPA confirms the influence of chelation on the diastereomeric ratio of adducts. Cyclopentanations involving 1 with cyclohexenone, 2(5H)-furanone, and 5,6-dihydro-2-pyranone, respectively, were also studied with emphasis on the factors influencing the stereochemical outcome of the annulation process.

Reactions of Complex Ligands, LXX. An Intramolecular Alkyne Insertion/Carbonylation/Cyclization Sequence of Chromium Aminocarbene Complexes: A Novel Access to Indole and Indenoindole Skeletons

Abstract: 2-Alkynylanilinocarbene chromium complexes 1–7 bearing a rigid arene C2 spacer between the aminocarbene and alkyne units were prepared from pentacarbonyl(aroyl)chromates(–I), acetyl bromide, and 2-alkynylanilines. They undergo intramolecular cyclization the course of which depends on the substitution pattern at the alkyne terminus. A tandem alkyne insertion into the metal–carbene bond/carbonylation sequence affords Cr(CO)3-coordinated 3-indolylketenes 8, 9, 12–14 by using a bulky substituent; the rate of the reaction increases with N-alkylation. Less bulky n-alkynylanilinocarbene complexes 4, 5 exhibit two competing carbene annulation sequences: Benzannulation leads to benzo[a]carbazoles 15, 16, whereas cyclopentannulation without prior carbonylation furnishes indeno[1,2-b]indoles 17, 18.