Regioselective intramolecular Pauson-Khand reactions of C60: an electrochemical study and theoretical underpinning

Suitably functionalized fulleropyrrolidines endowed with one or two propargyl groups at the C-2 position of the pyrrolidine ring (1,6-enynes) react efficiently and regioselectively with [Co2(CO)8] to afford the respective Pauson-Khand products with an unprecedented three (5 a-d, 7, and 24) or five (25) pentagonal rings, respectively, fused onto the fullerene sphere. Fulleropyrrolidines with 1,7-, 1,9-, 1,10-, or 1,11-enyne moieties do not undergo the PK reaction and, instead, the intermediate dicobalt complexes formed with the alkynyl group are isolated in quantitative yields. These differences in reactivity have been studied by DFT calculations with a generalized gradient approximation (GGA) functional and several important energy and structural differences were found for the intermediates formed by the interaction between the coordinatively unsaturated Co atom and the pi system of C60 in 1,6- and 1,7-enynes. The different lengths of the alkyne chains are responsible for the observed reactivities. Cyclic voltammetry reveals that the presence of the cyclopentenone's carbonyl group connected directly to the C60 core results in PK compounds with remarkable electron-accepting ability.     

Mild and efficient molybdenum-mediated Pauson-Khand-type reaction

[reaction: see text] The molybdenum-mediated Pauson-Khand reaction promoted by Mo(CO)3(DMF)3 takes place under very mild conditions in the absence of any promoter. High yields in Pauson-Khand adducts are obtained in the cyclization of a wide variety of functionalized 1,6- and 1,7-enynes. Enynes bearing electron withdrawing groups at the alkene terminus are particularly good substrates.     

Catalytic annulation of 1-substituted-3-en-1-yn-5-als with cycloalkanones using acid-base dual catalysts

CpRu(PPh₃)₂Cl and DBU dual catalysts in combination enable a one-pot annulation of 1-R-3-en-1-yn-5-als (R = aryl, alkenyl, alkyl) and cycloalkanones to give highly substituted benzene products. This catalytic reaction consists of a tandem aldol condensation, dehydration and aromatization through a 1,7-hydrogen shift; the resulting 1-indanones and α-tetralones are obtained in moderate to good yields.     

Convergent and stereodivergent synthesis of complex 1-aza-7-oxabicyclo[2.2.1]heptanes

A convergent and stereodivergent pathway to highly substituted 1-aza-7-oxabicyclo[2.2.1]heptanes is described. It begins with a coupling reaction involving allylic alcohol, aldehyde, and LiHMDS to produce stereodefined primary homoallylic amines. Subsequent N-oxidation and condensation with formaldehyde or glyoxylate defines a convenient entry to densely functionalized homoallylic nitrones whose intramolecular annulation can be controlled to deliver one of two distinct heterocyclic skeletons, each with ≥20:1 stereoselection. Control of the stereochemistry in these reactions results from both control of the nitrone geometry and selective partitioning of the reaction pathway between direct [3 + 2] cycloaddition and tandem [3,3] rearrangement/[3 + 2] cycloaddition.     

Asymmetric Catalytic [4+5] Annulation of ortho-Quinone Methides with Vinylethylene Carbonates and its Extension to Stereoselective Tandem Rearrangement

Palladium-catalyzed asymmetric [4+5] annulation of ortho-quinone methides (o-QMs) with substituted vinylethylene carbonates (VECs) is described for the first time, giving a novel enantioselective approach to chiral nine-membered benzoheterocycles. Based on this designed [4+5] annulation, an unprecedented silica gel-promoted tandem rearrangement reaction featuring a unique asymmetric aromatic Claisen rearrangement is explored at room temperature, offering a new method for asymmetric construction of all-carbon quaternary stereocenters embedded in chiral functionalized homoallylic alcohols.     

Gold(III)-catalyzed tandem conjugate addition/annulation of 4-hydroxycoumarins with α,β-unsaturated ketones

An efficient and selective approach for the synthesis of functionalized pyranocoumarins has been developed via a gold(III)-catalyzed tandem conjugate addition/annulation reaction of 4-hydroxycoumarins with α,β-unsaturated ketones.     

Synthesis of tri- or tetrasubstituted pyrimidine derivatives through the [5+1] annulation of enamidines with either N,N-dimethylformamide dialkyl acetals or orthoesters and their application in a ring transformation of pyrimidines to pyrido[2,3-d]pyrimidin-5-one derivatives

The [5+1] annulation of enamidines, which were prepared from functionalized silanes, organolithium compounds and two nitriles, with N,N-dimethylformamide dialkyl acetals as the C1 unit is described, leading to the synthesis of tri- and tetrasubstituted pyrimidine derivatives under catalyst- and solvent-free reaction conditions. Furthermore, the [5+1] annulation of enamidines by using orthoesters as the C1 unit is described, in which catalytic amounts of ZnBr(2) catalyze the annulation to produce polysubstituted pyrimidines under toluene or xylene reflux conditions. Moreover, the combination of a reductive ring-opening reaction with [Mo(CO)(6)] and a subsequent intramolecular cyclization with tBuOK effectively causes a skeletal transformation from the pyrimidines containing an isoxazolyl and an ethoxy substituent to form pyrido[2,3-d]pyrimidin-5-one frameworks in excellent yield.     

Triflic acid-catalyzed cascade cyclization of arenyl enynes via acetylene-cation cyclization and Friedel-Crafts type reaction

A novel triflic acid-catalyzed cascade cyclization of arenyl 1,7-enynes through acetylene-cation cyclization followed by Friedel-Crafts reaction has been described. Various fused poly carbocycles can be obtained in good to high yields under mild reaction conditions.     

Eight-membered ring construction by [4 + 2 + 2] annulation involving beta-carbon elimination

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 beta-carbon elimination to form a nine-membered nickelacycle. This reaction employing cyclobutanones as a C4 unit constructs cyclooctadienone cores in one synthetic step.     

Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a double annulation strategy from alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals

A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available alpha-alkenoyl-alpha-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, chloroformylation, amination, and aromatization reactions, is proposed.     

Co2(CO)8-mediated cycloisomerization of arylene 1,7-enynes

Co₂(CO)₈ was found to be effective for cycloisomerization reaction of arylene 1,7-enynes to form 2,3-dihydroindene derivatives, and a catalytic version assisted by different Lewis base ligands was also studied.     

Au- and pt-catalyzed cycloisomerizations of 1,5-enynes to cyclohexadienes with a broad alkyne scope

We describe the development of gold- and platinum-catalyzed cycloisomerizations of 1,5-enynes. This catalytic process displays a wide alkyne scope and furnishes a range of highly functionalized 1,4- and 1,3-cyclohexadienes. In the case of 1-siloxy-1-yne-5-enes, the reactions are efficiently catalyzed by AuCl (1 mol %) at ambient temperature to afford siloxy cyclohexadienes or the corresponding 1,2- and 1,3-cyclohexenones upon subsequent protodesilylation. We propose that the reaction proceeds via a novel mechanism involving a series of 1,2-alkyl shifts. Elucidation of this unusual reaction mechanism enabled us, in turn, to significantly expand the scope of the cycloisomerization by incorporation of a quaternary center at the C(3) position of the enyne. Indeed, we established that PtCl(2) (5 mol %) efficiently catalyzed the cycloisomerizations of 1,5-enynes containing terminal, internal, and arene-conjugated alkynes. Since a variety of 1,5-enynes are readily accessible, the cycloisomerization provides a rapid approach to a wide range of highy substituted cyclohexadienes for many subsequent synthetic applications.     

Ruthenium-catalyzed enyne cycloisomerizations. Effect of allylic silyl ether on regioselectivity

The ruthenium-catalyzed cycloisomerization of 1,6- and 1,7-enynes substituted in the terminal allylic position with a tert-butyldimethylsilyl ether group emerges as an effective reaction to form unprecedented five- or six-membered rings possessing a geometrically defined enol silane. Straightforward synthetic access to a variety of achiral 1,6- and 1,7-enynes, as well as chiral ones, is presented. Ruthenium catalysts effect efficiently such single-step cycloisomerization at room temperature in acetone under neutral conditions. The cycloisomerization functions with (E) or (Z) 1,2-disubstituted alkenes. Parameters influencing the enol silane geometry are discussed. The level of selectivity depends on the alkyne substitution, the geometry of the double bond, and the nature of the catalyst. Furthermore, examples of stereoinduction are shown and lead to highly substituted carbo- and heterocycles with excellent diastereocontrol.     

Efficient one-pot preparation of bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-yl)benzenes based on an aza-Wittig/mediated annulation strategy

Aza-Wittig mediated annulation provides a highly facile and straightforward one-pot strategy for the synthesis of bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-yl)benzenes 5 and 7. A tandem aza-Wittig reaction of iminophosphorane 2 with 1,4- or 1,3-phenylene diisocyanate, followed by intramolecular heteroconjugate addition annulation after addition of a nucleophilic reagent (amine, phenol, thiophenol or ROH), in presence of catalytic K₂CO₃ or NaOR, gives selectively the functionalized bis(pyrazinothienopyrimidinones) 5 and 7.     

Room-temperature metal-free electrophilic 5-endo-selective iodocarbocyclization of 1,5-enynes

A highly efficient NIS-promoted iodocarbocyclization reaction of various functionalized 1,5-enynes is described via a 5-endo diastereoselective process. The cyclizations are conducted in the presence of 1.2 equiv of N-iodosuccinimide in dichloromethane at room temperature. The reaction conditions are compatible with several functional groups and lead to original iodo-functionalized carbocycles in good to excellent yields.     

Diastereoselective [2+2+1] Hydrative Annulation of Phenol-Linked 1,6-Enynes with Acetylenes Through Rhodium Catalysis: A Rapid Access to Cyclopenta[b]benzofuranols

An unprecedented [2+2+1] hydrative annulation of 1,6-enynes with terminal alkynes is achieved using catalytic cationic Rh(I). Thus, a modular assembly of cyclopenta[b]benzofuranols with two consecutive quarternary stereocenters is achieved from readily available alkynes. The reaction is proposed to go through a sequence of 5-membered rhoda-cycle formation, regioselective acetylene insertion, 1,5 H-shift, substrate controlled stereoselective addition of water molecule followed by 1,2-rhodium migration gave contracted rhoda-cycle D and reductive elimination. Necessary control/labelling experiments were conducted to gain insight in to the mechanism.     

1,7-Octadiene-Assisted Tandem Multicomponent Cross-Enyne Metathesis (CEYM)-Diels-Alder Reactions: A Useful Alternative to Mori's Conditions

The use of 1,7-octadiene as an in situ source of ethylene led us to develop a novel multicomponent tandem cross-enyne metathesis (CEYM)-Diels-Alder reaction. The process can be considered a relay metathesis, in which the ethylene liberated in the ring-closing metathesis (RCM) of 1,7-octadiene initiates the tandem sequence. Aliphatic, aromatic, and fluorinated alkynes and several dienophiles are compatible with the process, which is particularly efficient with aromatic alkynes. This methodology constitutes a useful variant of Mori's conditions in CEYM-related reactions.     

Cobalt-phosphite-catalyzed asymmetric Pauson-Khand reaction

A complex formed from dicobalt octacarbonyl and a chiral aryl bisphosphite served as a catalyst for the intramolecular asymmetric Pauson-Khand reaction. Bicyclic cyclopentenones were obtained in up to 75% enantiomeric excess. For a terminal 1,6-enyne, the incremental enantiomeric excess was found to increase from 4 to 26% over the course of the reaction. The scope of this process was examined for a variety of 1,6- and 1,7-enynes, and a moderate degree of enantioselectivity was maintained only in the case of aryl-substituted 1,6-enynes.     

Rhodium-catalyzed olefin isomerization/enantioselective intramolecular Alder-ene reaction cascade

The olefin isomerization/enantioselective intramolecular Alder-ene reaction cascade was achieved by using a cationic rhodium(I)/(R)-BINAP complex as a catalyst. A variety of substituted dihydrobenzofurans and dihydronaphthofurans were obtained from phenol- or naphthol-linked 1,7-enynes, respectively, with good yields and ee values.     

Selective construction of indeno[1,2-b]phenothiazine and indeno[2,1-c]phenothiazine via tandem annulation reaction

AcOH promoted annulation reaction of 2-arylideneindane-1,3-diones with methyl 2-(benzo[b][1,4]thiazin-3-ylidene)acetate in refluxing ethanol afforded pentacyclic tetrahydroindeno [1,2-b]phenothiazine in satisfactory yields and with high diastereoselectivity according to the unexpected tandem annulation process. When the above reaction was carried out in refluxing acetic acid, isomeric dihydroindeno [1,2-b]phenothiazines and dihydroindeno [2,1-c]phenothiazines were obtained in comparable yields according to alternate tandem annulation process.