Sequential Cyclization Reactions Research Articles

Syntheses of imidazo-, oxa-, and thiazepine ring systems via ring-opening of aziridines/Cu-catalyzed C-N/C-C bond formation.

A simple and unpredicted synthetic pathway toward racemic and scalemic tetrahydrodibenzoimidazoazepines has been invented serendipitously proceeding through an S(N)2-type ring-opening of N-activated aziridines with 2-bromobenzylamine followed by a hitherto unprecedented cascade cyclization reaction sequence comprising a Cu-catalyzed cross dehydrogenation C-N coupling and an Ullmann C-C bond formation reaction. The tetrahydrobenzoxazepine and the tetrahydrobenzothiazepine derivatives have also been synthesized via the ring-opening of aziridines with 2-bromobenzyl alcohols and -mercaptan, respectively, followed by Cu-catalyzed N-arylation reaction.

Synthesis of 2‐Hydroxy‐7‐methylcarbazole, Glycozolicine, Mukoline, Mukolidine, Sansoakamine, Clausine‐H, and Clausine‐K and Structural Revision of Clausine‐TY

AbstractA Buchwald–Hartwig amination and palladium(II)‐catalyzed oxidative cyclization reaction sequence provided efficient access to a series of oxygenated tricyclic carbazoles. In the present work, this approach was applied to the total syntheses of the naturally occurring carbazole alkaloids 2‐hydroxy‐7‐methylcarbazole, glycozolicine, mukoline, mukolidine, sansoakamine, glycozolidine, clausine‐H (clauszoline‐C), clausine‐K (clauszoline‐J), and methyl 2‐hydroxy‐7‐methoxycarbazole‐3‐carboxylate, which was originally proposed as the structure of clausine‐TY. The synthesis of the latter led to the structural reassignment of clausine‐TY.

Reactions of Aromatic S- and O-Enynes with Two Methyl Substituents on the Olefinic Unit Assisted by a Ruthenium Complex: Tandem Cyclization and Product Selectivity

Ruthenium-assisted cyclizations of two enynes, HC≡CCH(OH)(C6H4)X-CH2CH=CMe2 (X=S (1a), O (1b)), each of which contains two terminal methyl substituents on the olefinic parts, are explored. The reaction of 1a in CH2Cl2 gives the vinylidene complex 2a from the first cyclization and two side products, 3a and the carbene complex 4a with a benzothiophene ligand. The same reaction in the presence of HBF4 affords 4a exclusively. Air oxidation of 4a in the presence of Et3N readily gives an aldehyde product. In MeOH, tandem cyclizations of 1a generate a mixture of the benzothiochromene compound 10a and the carbene complex 7a also with a benzothiochromene ligand. First, cyclization of 1b likewise proceeds in CH2Cl2 to give 2b. Tandem cyclization of 1b in MeOH yields comparable products 10b and 7b with benzochromene moieties, yet with no other side product. The reaction of [Ru]Cl with HC≡CCH(OH)(C6H4)S-CH2CH=CH2 (1c), which contains no methyl substituent in the olefinic part, in MeOH gives the carbene complex 15c with an unsubstituted thiochromene by means of a C-S bond formation. Structures of 3a and 15c are confirmed by X-ray diffraction analysis. The presence of methyl groups of enynes 1a and 1b promotes sequential cyclization reactions that involve C-C bond formation through carbocationic species.

Uncatalyzed One-Pot Synthesis of Highly Substituted Pyridazines and Pyrazoline-Spirooxindoles via Domino SN/Condensation/Aza-ene Addition Cyclization Reaction Sequence

A previously unknown class of highly substituted pyridazines and pyrazoline-spirooxinoles are easily prepared by an uncatalyzed one-pot three-component approach incorporating a domino SN/condensation/aza-ene addition cyclization reaction sequence. 1,1-Dihydrazino-2-nitroethylene (DHNE) which is generated in situ from the nucleophilic substitution (SN) reaction of hydrazine and 1,1-bis(methylthio)-2-nitroethylene (BMTNE), allowed to be condensed with active 1,2-dicarbonyl compounds followed by an intramolecular aza-ene addition cyclization to obtain the titled products depending on the type of 1,2-dicarbonyl. All reactions are easily performed and proceed with high efficiency under very simple and mild conditions without any catalyst and give good yields avoiding time-consuming, costly syntheses, and tedious workup and purification of products.

One-Pot Asymmetric Synthesis of 2- and 2,3-Disubstituted Tetrahydrofuran Derivatives

A novel and convenient one-pot asymmetric synthesis of 2- and 2,3-disubstituted tetrahydrofurans has been achieved in 56-81% yields and 86-99% ee from aliphatic and aromatic aldehydes via an allyl/crotyl/alkoxyallylboration-hydroboration-iodination-cyclization reaction sequence.

A Practical Asymmetric Synthesis of Enantiopure Spiro[4,4]nonane‐1,6‐dione

AbstractA practical asymmetric synthesis of enantiopure spiro[4,4]nonane‐1,6‐dione, a valuable precursor for chiral ligand development, is reported. This synthetic strategy includes a kinetic resolution of the readily synthesized ketone precursor with a chiral quaternary carbon center by bioreduction with baker’s yeast as the key step, followed by a hydroformylation, oxidation, esterification and Dieckmann cyclization reaction sequence to generate the spiro five‐membered ring. It was found that the masking of the β‐ketone carbonyl group of enantiopure ethyl 1‐allyl‐2‐oxocyclopentanecarboxylate via formation of a ketal with 1,3‐diol derivative is necessary during the process of Dieckmann condensation in order to prevent its racemization under basic conditions. This method allows the gram‐scale preparation of both enantiomers of spiro[4,4]nonane‐1,6‐dione (1) with excellent enantiopurities (up to >99% ee) in the overall yields of 54% [(R)‐1] and 42% [(S)‐1], respectively. The practicality of the present synthetic procedure has provided a fundamental platform for the development of spiro[4,4]nonane‐1,6‐dione‐based chiral chemistry.

Synthesis of the FG ring fragment of pectenotoxins 1– 9

The synthesis of the FG ring fragment common to pectenotoxins 1– 9 is reported. The successful, convergent synthesis relied on high yielding routes to access two key intermediates; aldehyde 1 and phosphonium salt 2. A Z-selective Wittig reaction gave access to advanced linear precursor 3, which was converted to FG ring fragment 4 using two sequential cyclization reactions.

Asymmetric synthesis of synthetic alkaloids by a tandem biocatalysis/Ugi/Pictet–Spengler-type cyclization sequence

We have combined the biocatalytic desymmetrization of 3,4-cis-substituted meso-pyrrolidines with an Ugi-type multicomponent reaction followed in situ by a Pictet-Spengler-type cyclization reaction sequence for the rapid asymmetric synthesis of alkaloid-like polycyclic compounds.

A Short Biomimetic Approach to the Fully Functionalized Bicyclic Framework of Type A Acylphloroglucinols

A biomimetic approach toward type A polyprenylated acylphloroglucinols (PPAPs) is described. The method is based on a C-alkylation-cation cyclization reaction sequence, leading to a convenient buildup of molecular complexity, employing the simple and readily available deoxycohumulone and an appropriately functionalized hydroxy halide. Thus, a versatile construction of the fully functionalized bicyclic framework of type A PPAPs (5) was achieved.

Gold(I) Iodide Catalyzed Sonogashira Reactions

AbstractGold(I) iodide catalyzed Sonogashira reactions have been developed. Terminal alkynes reacted with aryl iodides and bromides smoothly in the presence of AuI (1 mol‐%) and dppf (1 mol‐%) in toluene to generate the corresponding cross‐coupling products in good to excellent yields. Furthermore, aromatic terminal alkynes could also react with 2‐iodoaniline to form substituted indoles in excellent yields through a coupling–cyclization reaction sequence under the present reaction conditions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis of the FG Fragment of the Pectenotoxins

Correction to: Synthesis of the FG Fragment of the PectenotoxinsSynlett 2007; 2007(15): 2359-2362DOI: 10.1055/s-2007-985600

Facile formation of acenaphtho[1,2- a]pyrene structures by thermal isomerization of bis(8-ethynyl-1-naphthyl)ethynes

The title 1,8-naphthylene–ethynylene compounds underwent thermal isomerization into acenaphtho[1,2- a]pyrene derivatives, and the structure of the new polycyclic aromatic system was established by X-ray analysis. The mechanism of the isomerization is explained in terms of sequential cyclization reactions via biradical intermediates followed by hydrogen migration.

Facile and Versatile Annulation of the Imidazole Ring: Single and Sequential Cyclization Reactions of Fischer Carbene Complexes with 1,4‐Diazafulvenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Facile and Versatile Annulation of the Imidazole Ring: Single and Sequential Cyclization Reactions of Fischer Carbene Complexes with 1,4‐Diazafulvenes

We examined the reactivity of dimethylaminodiazafulvene 1 toward Fischer alkenylcarbene 2 and alkynylcarbene 3 complexes. Diazafulvene 1 reacts with alkenylcarbenes 2 through a formal [6+3] heterocyclization in a regio- and stereoselective manner to afford dihydroimidazo[1,2-a]pyridines 4. Acid-promoted dimethylamine elimination in compound 4 c gives rise to the aromatic imidazo pyridine 5. A likely mechanism for this reaction is a 1,2-nucleophilic addition/[1,2]-shift metal-promoted cyclization sequence. On the other hand, diazafulvene 1 and alkynyl carbenes 3 undergo a [6+2] cyclization to afford pyrrolo[1,2-a]imidazole carbene complex 6 that can be readily oxidized to the corresponding esters 7. When enynylcarbenes 3 e-i are treated with diazafulvene 1, consecutive and diastereoselective [6+2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 8, 9, and 12 that can be appropriately demetallated to the corresponding imidazole-based polyfused systems 10, 11, and 13 respectively. Finally, enynylcarbenes 3 d,f undergo consecutive [6+2]/[5+1] cyclization reactions with diazafulvene 1 and tBuNC, respectively, to yield tetracyclic adducts 14 and 15. All these processes result in high yields and provide a route to the preparation of imidazopyridines and pyrroloimidazoles as well as other polycyclic molecules that contain imidazole groups, which are interesting from a pharmacological and biological point of view.

A Tandem Radical Cyclization Route to Tricyclo[4.3.n.01,5]alkanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A tandem radical cyclization route to tricyclo[4.3. n.0 1,5]alkanes

A facile route to tricyclo[4.3. n.0 1,5]alkane skeletons from conjugated cyclic enones was developed through tandem free radical cyclization reaction sequence involving the cyclopropylmethyl radical mediated rearrangement. The scope and limitation of the reaction was investigated.

Development of an Efficient Procedure for Indole Ring Synthesis from 2‐Ethynylaniline Derivatives Catalyzed by Cu(II) Salts and Its Application to Natural Product Synthesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Development of an Efficient Procedure for Indole Ring Synthesis from 2-Ethynylaniline Derivatives Catalyzed by Cu(II) Salts and Its Application to Natural Product Synthesis

The development of efficient methods for the indole synthesis catalyzed by Cu(II) salts and its applications were investigated. Cu(OAc)(2) has been proved to be the best catalyst for the synthesis of various 1-p-tolylsulfonyl or 1-methylsulfonylindoles, which have both electron-withdrawing and electron-donating groups on the aromatic ring and C2 position of indoles. For the primary aniline derivatives, Cu(OCOCF(3))(2) showed good activities, while Cu(OAc)(2) was a good catalyst for the cyclization of secondary anilines. This methodology could be applied to the sequential cyclization reaction for the compounds which have the electrophilic part in the same molecule. By prior treatment with KH, the sequential cyclization was realized to provide the tricyclic ring systems, but it was limited to five- and six-membered rings for the second cyclization. Finally, formal and total synthesis of hippadine with the Cu(II)-promoted indole synthesis as the key step was accomplished.

Synthesis of a trans-fused perhydroindan analog of hispidospermidin

A reductive alkylation–halolactonization–free radical cyclization reaction sequence plays a pivotal role in a synthesis of the hispidospermidin analog 3 from m-toluic acid.

Novel intramolecular (4 + 1) and (4 + 2) annulations of halopolyenes by cascade radical reaction

Free radical reaction of vinyl iodides having dinenoate function in the presence of tributyltin hydride or tris(trimethylsilyl)silane caused a sequential cyclization reaction to produce (4 + 1) and (4 + 2) annulated compounds by means of a cascade radical reaction. Stereogenic centers of the cascade reaction were highly controlled. On the contrary, the cathodic electrolysis of the vinyl iodides afforded monocyclic compounds.