Total Synthesis of Ceratopicanol through Tandem Cycloaddition Reaction of a Linear Substrate

Total synthesis of ceratopicanol ( 1 ) was achieved with a tandem cycloaddition reaction of allenyl diazo compound 6 via a trimethylenemethane (TMM) diyl intermediate. The TMM diyl mediated [2+3] cycloaddition reaction furnished the consecutive quaternary carbon centers and showed an unusual diastereoselectivity.     

Total Synthesis of (±)-Waihoensene

The first total synthesis of waihoensene, a tetracyclic diterpene containing an angular triquinane and a six-membered ring, with four contiguous quaternary carbon atoms, was achieved through the tandem cycloaddition reaction of an allenyl diazo substrate containing a six-membered ring via trimethylenemethane (TMM) diyl intermediate.     

Total Synthesis of (±)‐Waihoensene

The first total synthesis of waihoensene, a tetracyclic diterpene containing an angular triquinane and a six‐membered ring, with four contiguous quaternary carbon atoms, was achieved through the tandem cycloaddition reaction of an allenyl diazo substrate containing a six‐membered ring via trimethylenemethane (TMM) diyl intermediate.     

From dimerization, to cycloaddition, to atom transfer cyclization: the further chemistry of TMM diradicals

We describe [a] the first examples of intramolecular cycloaddition of a TMM diyl to a remotely tethered aldehyde, [b] the effect of a Lewis acid upon the course of TMM chemistry, [c] examples of exclusive intramolecular cycloaddition, competitive cycloaddition and ATC, and exclusive ATC, and [d] a set of predictive guidelines with which to assess whether cycloaddition or ATC will be the preferred path, and when the two processes will be competitive. Remarkably, a wide variety of structures can be obtained simply by varying the length of the tether within the diazenes investigated. DFT calculations were used to probe the energy surfaces for both atom transfer and cycloaddition. The transition structure for atom transfer involving the captodative system indicates that it occurs earlier along the reaction coordinate than for a system having only one radical stabilizing group. This is consistent with the existence of an exothermic process leading from the initial diyl to the captodatively stabilized distonic diyl. Gratifyingly, theory agrees with observation and provides substantial insight into the chemistry.     

Triquinanes from linear alkylidene carbenes via trimethylenemethane diyls

The intramolecular [2+3] cycloaddition reaction of the trimethylenemethane diyl generated from the intramolecular cyclopropanation reaction of alkylidene carbene produced linearly fused triquinanes regio- and stereoselectively. The current tandem cycloaddition reaction was applied to a 14-step total synthesis of hirsutene from methallyl alcohol.     

Recent advances in transition-metal-catalyzed asymmetric reactions of diazo compounds with electron-rich (hetero-) arenes

The transition-metal-catalyzed reaction of diazo compounds with arenes or heteroarenes is an efficient and straightforward approach to functionalize aromatic compounds. This digest summarizes recent progresses on transition-metal-catalyzed asymmetric reactions of diazo compounds with electron-rich (hetero-) arenes, including C–H functionalization, cascade reaction, cyclopropanation, cycloaddition, Buchner reaction and intramolecular dearomatization.     

Intramolecular diyl trapping reactions en route to the bicyclo [3.2.1] framework; an approach to aphidicolin

We describe an application of the intramolecular diyl trapping cycloaddition reaction to the assembly of the bicyclo [3.2.1] framework, and utilize the outcome to complete a formal total synthesis of aphidicolin.     

Characterization of the switch in the mechanism of an intramolecular Diels-Alder reaction

Changing the dienophile moiety of an intramolecular Diels-Alder (IMDA) cycloaddition from an allyl ether to an allenyl ether can dramatically change the regioselectivity. We hereby show by density functional theory computations that such unprecedented divergence is produced by an underlying change in the mechanism of the reaction. The allyl ether yields a fused tetrahydrofuran through a classical Diels-Alder reaction, whereas the allenyl ether yields a (methylidene)tetrahydropyran through a stepwise process. The latter reaction involves an extreme asynchronism in the bond-forming events with a diradicaloid intermediate that is stabilized by conjugation and synergistic (captodative) effects. Comparison with intermolecular model D-A reactions, which are concerted processes with various degrees of asynchrony, helps explain the change in regioselectivity for the IMDA reaction of allyl systems and the shift in mechanism for the IMDA reaction of the allenyl derivatives studied.     

Dirhodium(II) tetraacetate catalysed reactions of diazo thioamides: isolation and cycloaddition of anhydro-4-hydroxy-1,3-thiazolium hydroxides (thioisomünchnones), an approach to analogues of dehydrogliotoxin

Dirhodium(II) tetraacetate catalysed reaction of the indoline diazo thioamide 8 gives the thioisomünchnone 9, a stable characterisable solid. This masked thiocarbonyl ylide undergoes 1,3-dipolar cycloaddition with N-methylmaleimide and maleic anhydride to give the exo-cycloadducts 10 and 11, characterised by X-ray crystallography. The thioisomünchnone 18, derived from diazo thioamide 17, is an extremely stable crystalline mesoionic system which can be characterised by X-ray crystallography but fails to undergo intramolecular cycloaddition. The related thioisomünchnone 19 can be generated by reaction of indoline-2-thione 7 with bromoacetyl chloride in the presence of triethylamine, and undergoes cycloaddition to give adducts 20 and 21.     

Regioselective intramolecular [3+2] annulation of allene-nitrones

The regioselective intramolecular 1,3-dipolar cycloaddition of the phenylsulfonylallene-nitrone derivatives has been developed. This reaction showed that the distal double bond of the allene exclusively reacted with the nitrone group to produce the bicyclic isoxazolidine derivatives regardless of the substitution pattern on the allenyl moiety.     

A highly efficient synthesis of bicyclo[n.3.1] ring systems by allene intramolecular cycloaddition: Tandem intramolecular [2+2] cycloaddition-[3,3]-sigmatropic rearrangement

A novel one-step construction of bicyclo[5.3.1]undecane skeleton via intramolecular cycloaddition of allenyl ethers is described.     

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。     

Cyclization-cycloaddition casade of rhodium carbenoids using different carbonyl groups. Highlighting the position of interaction

A series of 3-diazoalkanediones, when treated with a catalytic quantity of a rhodium(II) carboxylate, were found to afford oxabicyclic dipolar cycloadducts derived by the trapping of a carbonyl ylide intermediate. The reaction involves generation of the 1,3-dipole by intramolecular cyclization of the keto carbenoid onto the oxygen atom of the neighboring keto group. Both five- and six-ring carbonyl ylides are formed with the same efficiency. A study of the tandem cyclization-cycloaddition cascade of several alpha-diazo ketoesters was also carried out, and the cascade sequence proceeded in high yield. When the interacting keto carbonyl group was replaced by an imido group, the rhodium(II)-catalyzed reaction proceeded uneventfully. In contrast, alpha-diazo amidoesters do not undergo nitrogen extrusion on treatment with a Rh(II) catalyst. Instead, the diazo portion of the molecule undergoes 1,3-dipolar cycloaddition with various dipolarophiles to give substituted pyrazoles as the final products.     

Cycloaddition chemistry of 2-vinyl-substituted indoles and related heteroaromatic systems

[reaction: see text] The intramolecular Diels-Alder cycloaddition reaction (IMDAF) of several N-phenylsulfonylindolyl-substituted furanyl carbamates containing a tethered pi-bond on the indole ring were examined as an approach to the iboga alkaloid catharanthine. Only in the case where the tethered pi-bond contained two carbomethoxy groups did the [4 + 2]-cycloaddition occur. Push-pull dipoles generated from the Rh(II)-catalyzed reaction of diazo imides, on the other hand, undergo successful intramolecular 1,3-dipolar cycloaddition across both alkenyl and heteroaromatic pi-bonds to provide novel pentacyclic compounds in good yield and in a stereocontrolled fashion. The facility of the cycloaddition was found to be critically dependent on conformational factors in the transition state. Ligand substitution in the rhodium(II) catalyst markedly altered the product ratio between [3 + 2]-cycloaddition and intramolecular C-H insertion. The variation in reactivity reflects the difference in electrophilicity between the various rhodium carbenoid intermediates. Intramolecular C-H insertion is enhanced with the more electrophilic carbene generated using Rh(II) perfluorobutyrate.     

Cascade cyclization, dipolar cycloaddition of azomethine imines for the synthesis of pyrazolidines

A tandem multi-step, one-pot reaction of aldehydes with hydrazines has been used for the preparation of tetrahydropyrazoles and dihydropyrazoles. The chemistry involves condensation then cyclization, followed by inter- or intramolecular dipolar cycloaddition of the resulting azomethine imine intermediates. The intramolecular cycloaddition gives fused tricyclic compounds as single diastereoisomers. The intermolecular cycloaddition was successful with a variety of activated alkene and alkyne dipolarophiles.     

Intramolecular Diels-Alder Reaction of Furans with Allenyl Ethers Followed by Phenylthio and Trialkylsilyl Groups Rearrangement

A new reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by phenylthio group rearrangement was discovered. Treatment of the propargyl ethers 2a-c with t-BuOK in t-BuOH at 85 ° C gave the phenylthio group rearrangement products 5a-c and 6a-c . A reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by trialkylsilyl group rearrangement is also demonstrated.     

Highly Enantioselective Intramolecular 1,3‐Dipolar Cycloaddition: A Route to Piperidino‐Pyrrolizidines

Enantioselective catalytic intermolecular 1,3‐dipolar cycloadditions are powerful methods for the synthesis of heterocycles. In contrast, intramolecular enantioselective 1,3‐dipolar cycloadditions are virtually unexplored. A highly enantioselective synthesis of natural‐product‐inspired pyrrolidino‐piperidines by means of an intramolecular 1,3‐dipolar cycloaddition with azomethine ylides is now reported. The method has a wide scope and yields the desired cycloadducts with four tertiary stereogenic centers with up to 99 % ee. Combining the enantioselective catalytic intramolecular 1,3‐dipolar cycloaddition with a subsequent diastereoselective intermolecular 1,3‐dipolar cycloaddition yielded complex piperidino‐pyrrolizidines with very high stereoselectivity in a one‐pot tandem reaction.     

Tandem hetero diels-alder reaction: synthesis of oxygenated macrocycles

[structure: see text]. C2-symmetric, oxygenated macrocycles have been synthesized from simple acyclic precursors in a single step by a tandem hetero Diels-Alder reaction. Thermolysis and Lewis acid catalysis can effect this novel transformation. The tandem reaction product is formed in preference to the intramolecular cycloaddition product, and an explanation for this result is proposed.     

Facile construction of novel polycyclic ring systems using a metallocarbenoid-induced cyclization of acetylenic diazo carbonyl compounds

The Rh(II)-catalyzed reaction of diazo 2-propynyl maolonamic acid ester derivatives produce furo[3,4-c]furans in excellent yield. The methodology was applied to the synthesis of several polyheterocyclic systems by first generating a 2-alkoxy-substituted furan and then allowing it to undergo a subsequent intramolecular Diels-Alder cycloaddition. Ring opening of the resulting cycloadduct is followed by deprotonation to furnish a rearranged keto lactone.     

Enantio‐ and Diastereoselective Synthesis of Chiral Allenes by Palladium‐Catalyzed Asymmetric [3+2] Cycloaddition Reactions

A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium‐catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio‐, enantio‐, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.