Ruthenium-catalyzed regioselective 1,3-methylene transfer by cleavage of two adjacent sigma-carbon-carbon bonds: an easy and selective synthesis of highly substituted benzenes

We report a new ruthenium-catalyzed 6-endo-dig cyclization of 6,6-cycloalkylidenyl-3,5-dien-1-ynes, which produces highly substituted benzenes with considerable structural reorganization. In this process, we observe a regioselective 1,3-methylene migration via extrusion from a cycloalkylidenyl ring, in addition to a regiocontrolled 1,2-alkyl migration. This cyclization provides an easy and convenient synthesis of complex benzenes bearing various different substituents.     

Rh(I)-catalyzed Pauson-Khand reaction and cycloisomerization of allenynes: selective preparation of monocyclic, bicyclo[m.3.0], and bicyclo[5.2.0] ring systems

[reaction: see text] Rhodium(I)-catalyzed PKR of allenynes was found to be applicable for constructing azabicyclo[5.3.0]decadienone as well as oxabicyclo[5.3.0]decadienone frameworks. In addition, a reliable procedure for constructing a 10-monosubstituted bicyclo[5.3.0]deca-1,7-dien-9-one ring system by the rhodium(I)-catalyzed PKR of allenynes was developed under the condition of 10 atm of CO. Investigation of the rhodium(I)-catalyzed cycloisomerization of 4-phenylsulfonylnona-2,3-dien-8-ynes under nitrogen atmosphere gave the corresponding cyclohexene derivatives, whereas the C1-homologated allenynes produced cycloheptene derivatives and/or bicyclo[5.2.0]nonene skeletons depending on the substitution pattern at the allenic terminus. Thus, proper choice of the starting allenynes and reaction conditions led to the selective formation of 2-phenylsulfonylbicyclo[5.3.0]deca-1,7-dien-9-ones (Pauson-Khand-type product), 3-alkylidene-1-phenylsulfonyl-2-vinylcycloheptene derivatives, and bicyclo[5.2.0]nonene frameworks.     

A heterocycle-forming double michael reaction. [5 + 1] annulation route to highly substituted and functionalized piperidines

[reaction: see text]. Nitrogen-containing tethered diacids, easily prepared by reductive alkylation of diethyl aminomalonate or ethyl cyanoglycinate, undergo double Michael reactions with 3-butyn-2-one to give highly functionalized and substituted piperidines (pipecolic acid derivatives) with surprisingly high stereoselectivity. The heterocyclic double Michael adducts can be induced to undergo further cyclizations to give a variety of azabicyclic and diazabicyclic compounds.     

1,2-联烯基酮的合成与反应

1,2-联烯基酮可以通过2-丙炔基酮异构化反应,相应有机金属试剂中间体与酯、酰氯或酰胺的反应,[2,3]或[3,3]迁移反应,Wittig反应,消除反应,2,3-联烯醇氧化等方法合成。由于联烯酮上含有吸电子基团羰基,它可发生亲核加成、环加成、环化反应。     

Palladium-catalyzed polycyclizations of substituted dienynes: Stereoselective routes to highly complex polycycles

12-Substituted 2-bromo-1,11-dien-6-ynes were found to undergo a palladium-catalyzed biscyclization followed by a diastereospecific 6π-electrocyclic rearrangement or a Diels-Alder reaction to give substituted angularly bisanellated cyclohexadienes or polycyclic bicyclo[4.1.0]hept-2-ene derivatives containing a three-membered ring, depending on the type and pattern of substituents.     

Thermal and metal-catalyzed cyclization of 1-substituted 3,5-dien-1-ynes via a [1,7]-hydrogen shift: development of a tandem aldol condensation-dehydration and aromatization catalysis between 3-en-1-yn-5-al units and cyclic ketones

This work investigates the feasibility of thermal and catalytic cyclization of 6,6-disubstituted 3,5-dien-1-ynes via a 1,7-hydrogen shift. Our strategy began with an understanding of a structural correlation of 3,5-dien-1-ynes with their thermal cyclization efficiency. Thermal cyclization proceeded only with 3,5-dien-1-ynes bearing an electron-withdrawing C(1)-phenyl or C(6)-carbonyl substituent, but the efficiencies were generally low (20-40% yields). On the basis of this structure-activity relationship, we conclude that such a [1,7]-hydrogen shift is characterized by a "protonic" hydrogen shift, which should be catalyzed by pi-alkyne activators. We prepared various 6,6-disubstituted 3,5-dien-1-ynes bearing either a phenyl or a carbonyl group, and we found their thermal cyclizations to be greatly enhanced by RuCl(3), PtCl(2), and TpRuPPh(3)(CH(3)CN)(2)PF(6) catalysts to confirm our hypothesis: the C(7)-H acidity of 3,5-dien-1-ynes is crucial for thermal cyclization. To achieve the atom economy, we have developed a tandem aldol condensation-dehydration and aromatization catalysis between cycloalkanones and special 3-en-1-yn-5-als using the weakly acidic catalyst CpRu(PPh(3))(2)Cl, which provided complex 1-indanones and alpha-tetralones with yields exceeding 65% in most cases. The deuterium-labeling experiments reveal two operable pathways for the metal-catalyzed [1,7]-hydrogen shift of 3,5-dien-1-ynes. Formation of alpha-tetralones d(4)-56 arises from a concerted [1,7]-hydrogen shift, whereas benzene derivative d(4)-9 proceeds through a proton dissociation and reprotonation process.     

Synthesis of Highly Functionalized Polycyclic Quinoxaline Derivatives Using Visible‐Light Photoredox Catalysis

A mild and facile method for preparing highly functionalized pyrrolo[1,2‐a]quinoxalines and other nitrogen‐rich heterocycles, each containing a quinoxaline core or an analogue thereof, has been developed. The novel method features a visible‐light‐induced decarboxylative radical coupling of ortho‐substituted arylisocyanides and radicals generated from phenyliodine(III) dicarboxylate reagents and exhibits excellent functional group compatibility. A wide range of quinoxaline heterocycles have been prepared. Finally, a telescoped preparation of these polycyclic compounds by integration of the in‐line isocyanide formation and photochemical cyclization has been established in a three‐step continuous‐flow system.     

Unlocking the 5-exo Pathway with the AuI-Catalyzed Alkoxycyclization of 1,3-Dien-5-ynes

The first general regio- and stereoselective 5-exo gold(I)-catalyzed alkoxycyclization of a specific class of 1,5-enynes such as 1,3-dien-5-ynes has been described, despite 1,5-enynes being known to almost invariably proceed via endo cyclizations under gold-catalysis. The configuration of the terminal alkene in the starting 1,3-dien-5-yne plays a crucial role on the regiochemical outcome of the reaction. A wide variety of interesting alkoxy-functionalized alkylidenecyclopentenes have been synthesized from 1-monosubstituted (E)-1,3-dien-5-ynes. On the contrary, the corresponding Z isomers evolve affording formal 6-endo cyclization products. In addition, mechanistic exploration supports a highly stabilized carbocation as a key intermediate instead of a highly constrained cyclopropyl gold carbene from E isomers, and also accounts for the well differentiated reactivity observed between both E/Z geometrical isomers as well as for the stereochemical outcome of the reaction.     

Ni- and Pd-catalyzed synthesis of substituted and functionalized allylic boronates

Two highly efficient and convenient methods for the synthesis of functionalized and substituted allylic boronates are described. In one procedure, readily available allylic acetates are converted to allylic boronates catalyzed by Ni/PCy(3) or Ni/PPh(3) complexes with high levels of stereoselectivity and in good yields. Alternatively, the borylation can be accomplished with commercially available Pd catalysts [e.g., Pd(2)(dba)(3), PdCl(2), Pd/C], starting with easily accessed allylic halides.     

Regio- and stereoselective synthesis of boryl-substituted allylsilanes via transition metal-catalyzed silaboration

Regio- and stereo-controlled synthesis of boryl-substituted allylsilanes via transition metal-catalyzed additions of silylboranes to unsaturated organic compounds is described. Nickel-catalyzed reactions of (dimethylphenylsilyl)pinacolborane with 1,3-dienes, vinylcyclopropanes, and vinylcyclobutanes yielded 4-, 5-, and 6-boryl-substituted allylsilanes, respectively. Palladium-catalyzed addition of the silylborane to allenes took place at the more substituted C=C bond to yield 2-borylallylsilane selectively. The 2-borylallylsilanes served as useful allylation reagents in Lewis acid-mediated reactions with acetals and aldehydes. In addition to the simple allylation reactions, a cascade reaction to form the trans-9-boryl-1,2-benzooxadecalin skeleton and a cyclization reaction to form cyclic alkenylboranes were achieved by the use of 2-borylallylsilanes as key reagents. Reactions of methylenecyclopropanes were catalyzed by palladium and platinum catalysts. The reaction course, however, depended upon the substrate structure and the catalyst employed. For instance, cycloalkylidenecyclopropanes yielded 2-cycloalkylidene-3-boryl-1-silylpropanes selectively in the presence of a palladium catalyst, while 3-cycloalkylidene-3-boryl-1-silylpropanes were obtained selectively in the corresponding platinum-catalyzed reactions.     

Novel aziridination of α-halo ketones: an efficient nucleophile-induced cyclization of phosphoramidates to functionalized aziridines

A novel and efficient aziridination of α-halo ketones is reported. The reaction of α-halo ketones with diethyl N-arylphosphoramidates affords diethyl N-aryl-N-(2-oxoalkyl)phosphoramidates which undergo reductive (H⁻-induced) cyclization with sodium borohydride followed by sodium hydride to give 1,2-disubstituted and 1,2,3-trisubstituted aziridines. The cyclization induced by NCS⁻ or PhS⁻ affords substituted aziridines functionalized at C-2. The reactions give excellent yields and are highly diastereoselective in favour of cis aziridines.     

Photooxygenation of 5-dialkylamino-4-pyrrolin-3-ones. Synthesis of highly functionalized ureas, 2-oxazolidinones, and 2-oxazolinones

5-Dialkylamino-4-pyrrolin-3-ones, available from cyclocondensation of amidines with dimethyl acetylenedicarboxylate (DMAD), undergo rapid singlet oxygenation to give highly functionalized ureas by way of a 1,2-dioxetane cleavage of the initially formed [2 + 2] cycloadducts. These latter compounds undergo cyclization to 2-oxazolidinones in MeOH. Catalytic hydrogenation of the ureas in EtOAc gives 2-oxazolinones. The DBU-DMAD adduct undergoes photooxygenation by an entirely different pathway to give a large ring heterocycle.     

Efficient Heterogeneous Palladium‐Catalyzed Oxidative Cascade Reactions of Enallenols to Furan and Oxaborole Derivatives

A heterogeneous palladium‐catalyzed oxidative cyclization of enallenols has been developed for the construction of highly substituted furan and oxaborole derivatives. The heterogeneous catalyst (Pd‐AmP‐MCF) exhibits high activity, high site‐ and stereoselectivity, and efficient palladium recyclability in the transformations.     

ortho-Bromo(propa-1,2-dien-1-yl)arenes: substrates for domino reactions

o-Bromo(propa-1,2-dien-1-yl)arenes exhibit novel and orthogonal reactivity under Pd catalysis in the presence of secondary amines to form enamines (concerted Pd insertion, intramolecular carbopalladation, and terminative Buchwald-Hartwig coupling) and of amides to form indoles (addition, Buchwald-Hartwig cyclization, and loss of the acetyl group). The substrates for these reactions can be accessed in a reliable and highly selective two-step process from 2-bromoaryl bromides.     

Chiral symmetric phosphoric acid esters as sources of optically active organophosphorus compounds

Chiral symmetric di- and trialkylphosphites, derivatives of (−)-borneol, (−)-menthol and (−)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose, were studied as starting reagents for the preparation of chiral organophosphorus compounds. The reaction occurs by asymmetric induction at the α-carbon atom of substituted α-alkylphosphonates. The stereoselectivity of the reaction depends on the structure of the starting compounds and the reaction conditions. The configuration of the alkylphosphonates was established by NMR spectroscopy, by transformation into α-hydroxyalkylphosphonic acids and by X-ray crystal structure analysis.     

Gold(I)‐Catalyzed Regiodivergent Rearrangements: 1,2‐ and 1,2′‐Alkyl Migration in Skipped Alkynyl Ketones

A series of 2‐alkynyl carbonyl compounds that contain a cyclopentene ring or a heterocycle can be transformed into various fused dihydrobenzofurans and tetrahydrofuro[2,3‐c]pyridines by means of a 1,2‐alkyl migration process. Both of these reactions proceed with excellent regioselectivity and stereospecificity when using a cationic gold(I) catalyst. Treatment of 4‐styrylcyclopent‐1‐enecarboxylates under different conditions affords a range of highly functionalized dihydrobenzofurans and dihydroisobenzofurans. A divergence in product selectivity, which depends on the anion of the silver salts used, was observed. Interestingly, ring‐fused tetrahydroquinolines undergo only 1,2′‐alkyl migration reaction by means of a C? C cleavage/cyclization sequence to provide tetrahydroazepine derivatives. Mechanistic studies suggest that the gold complexes catalyze 1,2‐alkyl migration reactions through a concerted reaction pathway and 1,2′‐alkyl migration reactions through a stepwise reaction pathway.     

Nickel catalyzed stereoselective conjugate addition of dimethylzinc upon aldimines across 1,3-dien-8-ynes and 1,3-dien-9-ynes

Ni(acac)2 catalyzes the five-component connection reaction of Me2Zn, alkynes, diene (of 1,3-dien-8-ynes and 1,3-dien-9-ynes), aldehydes and anisidine to furnish cyclic dienyl amines anti-2 with high remote 1,5-diastereoselectivity.     

Efficient entry to diversely functionalized spirocyclic oxindoles from isatins through carbonyl-addition/cyclization reaction sequences

A novel approach to diversely functionalized spirocyclic oxindoles has been developed by using different metal-mediated carbonyl-addition/cyclization reaction sequences. Spirocyclization precursors, 2-indolinone-tethered homoallylic alcohols, (buta-1,3-dien-2-yl)methanols, and alpha-allenols have been obtained by regioselective addition of stabilized organoindium reagents to isatins in aqueous environment. Ruthenium-, silver-, and palladium-catalyzed reactions of the above unsaturated alcohol derivatives provided oxaspiro oxindoles.     

Conjugate addition reactions of alpha-aminoalkylcuprates with alpha, beta-alkenyl-, alpha,beta-alkynyl-, alpha,beta-beta,gamma-allenyl-, and alpha,beta-gamma,delta-dienyl carboxylic acid derivatives, nitriles, and sulfoxides

alpha-Aminoalkylcuprates prepared from alpha-lithio carbamates and CuCN.2LiCl participate in 1,4-addition reactions with alpha, beta-unsaturated esters, thiol esters, imides, and nitriles in poor to excellent yields depending upon the electron-withdrawing substituent and the substitution pattern of the unsaturated substrate. These reagents also undergo conjugate addition reactions with alpha,beta-alkynyl esters, sulfoxides, and nitriles and with alpha,beta-beta,gamma-unsaturated allenyl esters. Excellent stereocontrol is achieved in the conjugate additions of alpha-aminoalkylcuprates to the allenyl esters, while poor stereoselectivity results in the conjugate additions to the alkynyl derivatives. Deprotection and cyclization of the alkynyl adducts affords pyrrolin-2-ones, while similar treatment of the allenyl adducts affords 4-alkylidine- pyrrolidin-2-ones and pyrrolizidinones.     

Synthesis of dibenzo[g,p]chrysenes from bis(biaryl)acetylenes via sequential ICl-induced cyclization and Mizoroki-Heck coupling

We report a facile synthesis of functionalized dibenzo[g,p]chrysenes via initial ICl-promoted cyclization of bis(biaryl)acetylenes, followed by the Mizoroki-Heck coupling reaction. This new approach works well for various bis(biaryl)acetylenes to afford dibenzo[g,p]chrysenes bearing various functionalities. With substrates of one special type including 4'-methoxy-2-ethynylbiphenyls, we found that the ICl treatment led to ipso cyclization to give bicyclic spirocyclohexadienones. In the presence of MeOH/H2SO4, these spiroketone products undergo rearrangement to give 9-iodophenanthrenes through a selective 1,2-alkenyl migration. We prepared various 4'-methoxy-2-ethynylbiphenyl compounds to show the generalization of such an ipso cyclization and 1,2-alkenyl shift. This ipso-cyclization approach can be extended to the preparation of dibenzo[g,p]chrysenes.