Transition Metal-catalyzed Cycloisomerization Research Articles

Sequencing palladium-catalyzed cycloisomerization cascades in a synthesis of the gelsemine core.

Transition metal-catalyzed cycloisomerization is a powerful strategy for the construction of cyclic organic molecules, and the use of palladium catalysts can deliver a wide range of monocyclic and bicyclic products. However, applications of cycloisomerizations in complex target synthesis in which more than one cycloisomerization process is deployed in a cascade context are rare. Here we report investigations of the relative rates of two different types of ene-ynamide cycloisomerization that form fused and spirocyclic rings, and use of these results to design a sequence-controlled cascade cycloisomerization that prepares the tetracyclic core of gelsemine in a single step. Crucial to this work was an evaluation of the kinetics of each cycloisomerization in competition experiments, which revealed a key influence of the ynamide electron-withdrawing group on the cycloisomerization reaction.

Synthesis of Proposed Structure of Aaptoline B via Transition Metal-Catalyzed Cycloisomerization and Evaluation of Its Neuroprotective Properties in C. Elegans

A concise synthesis of the proposed structure of aaptoline B, a pyrroloquinoline derived from a marine sponge, was accomplished. A key feature of this synthesis is the versatile transition metal-catalyzed cycloisomerization of N-propargylaniline to construct a quinoline skeleton. However, the spectral data of the synthesized aaptoline B did not agree with those of previous studies. The structure of the synthesized aaptoline B was confirmed using a combined 2D NMR analysis. Furthermore, we assessed the possible neuroprotective potential of aaptoline B using the C. elegans model system. In this study, aaptoline B significantly improved the viability and the morphology of dopaminergic neurons of nematodes under MPP+ exposure conditions. We also found that MPP+-induced motor deficits in nematodes were efficiently restored by aaptoline B treatment. Our findings demonstrate the neuroprotective effects of aaptoline B against MPP+-induced dopaminergic neuronal damage. Further studies are underway to explain its pharmacological mechanism.

Selectivity in Transition Metal-catalyzed Cyclizations: Insights from Experiment and Theory.

Transition metal-catalyzed cycloisomerization reactions offer a powerful tool for the synthesis of complex cyclic organic molecules from acyclic precursors. In addition to ring formation, these processes can result in the generation of new stereocentres at the site of ring formation; understanding the origins of stereoselectivity enables the use of cycloisomerization chemistry in synthesis, and promotes the design of new reactions. In this article, some recent developments from our groups in regio- and stereoselective cycloisomerization reactions are discussed. Alongside experimental observations, crucial to developing a robust understanding of selectivity has been the use of computation to explore theoretical reaction pathways, which provides an exceptional level of insight into selectivity. In its most valuable form, this correlation between experiment and theory enables the design of improved catalyst systems exhibiting both enhanced reactivity, and selectivity.

ChemInform Abstract: 1,2‐Boryl Migration Empowers Regiodivergent Synthesis of Borylated Furans.

A regioselective transition metal-catalyzed cycloisomerization reaction of boron-containing alkynyl epoxides toward C2- and C3-borylated furans has been developed. It was found that the copper catalyst as well as the gold catalyst with more basic triflate counterion favor boryl migration toward C3-borylated furans, whereas employment of the cationic gold hexafluoroantimonate affords C2-borylated furan via a formal 1,2-hydrogen shift.

ChemInform Abstract: A Versatile Synthetic Platform Based on Bicyclo[4.1.0]heptenes

AbstractReview: 79 refs.

1,2-boryl migration empowers regiodivergent synthesis of borylated furans.

A regioselective transition metal-catalyzed cycloisomerization reaction of boron-containing alkynyl epoxides toward C2- and C3-borylated furans has been developed. It was found that the copper catalyst as well as the gold catalyst with more basic triflate counterion favor boryl migration toward C3-borylated furans, whereas employment of the cationic gold hexafluoroantimonate affords C2-borylated furan via a formal 1,2-hydrogen shift.

A Versatile Synthetic Platform Based on Bicyclo[4.1.0]heptenes

Bicyclo[4.1.0]heptenes, which are readily accessible molecules via the transition metal-catalyzed cycloisomerization of 1,6-enynes, and have served as useful building blocks in organic synthesis. These molecules can undergo a variety of ring-opening reactions given that the release of the cyclopropyl ring strain (27.5 kcal/mol) may serve as a thermodynamic driving force for reactions, and the double bond within the skeleton can afford the kinetic opportunity to initiate the ring-opening via a coordination to a metal species. Even though the chemistry of the cyclopropyl group has been widely explored in organic chemistry, less attention has been paid to the chemistry of bicyclo[4.1.0]heptenes. However, during the past 5 years, we have been engaged in the exploration of the chemistry of bicyclo[4.1.0]heptenes. This review describes the chemistry developed in our laboratory. Depending upon the position, number, and identity of the substituent(s), the identity of the tether group, and the nature of the catalytic system, bicyclo[4.1.0]heptenes can undergo a variety of transformations. Our studies have revealed the reaction patterns of bicyclo[4.1.0]heptenes which include thermal reactions, nucleophilic addition, and rhodium-catalyzed reactions, that can proceed both with and without opening of the cyclopropyl ring. The chemistry described in this review can be used to produce a variety of new compounds such as 2,4-pentadienals, 3-methylene-4-vinylcyclohex-1-enes, bicyclo[3.2.2]nonadienes, 1,6,7,9a-tetrahydrocyclohepta[c] pyrans and -pyridines, hexahydroisoquinolines, 4-oxa-6-azatricyclo[3.3.0.02,8]octanes, and heterotricyclo[3.3.1.02,8]nonanes.

ChemInform Abstract: Transition Metal‐Catalyzed Carbocyclization of Nitrogen and Oxygen‐Tethered 1,n‐Enynes and Diynes: Synthesis of Five or Six‐Membered Heterocyclic Compounds

AbstractReview: 228 refs.

Transition metal-catalyzed carbocyclization of nitrogen and oxygen-tethered 1,n-enynes and diynes: synthesis of five or six-membered heterocyclic compounds

Cycloisomerization of 1,n-enynes and diynes is a powerful method in organic synthesis to access heterocyclic compounds and has drawn increasing attention from organic chemists. In this paper, we attempted to summarize our recent results on the transition metal-catalyzed cycloisomerization to synthesize five or six-membered heterocyclic compounds using 1,n-enynes and diynes having a propargylic ester moiety. First, we will describe the synthesis of 2,3-disubstituted 3-pyrrolines via gold catalyzed cycloisomerization of 1,6-diynes. In addition, we will also disclose a novel silver catalyzed tandem 1,3-acyloxy migration/Mannich-type addition/elimination of the sulfonyl group of N-sulfonylhydrazone-propargylic esters to 5,6-dihydropyridazin-4-one derivatives. Furthermore, we will introduce three interesting examples of the synthesis of bicyclic compounds via titanium or rhodium catalyzed carbocyclization of enynes. In this context, we have presented that 1,n-enynes and diynes containing propargylic esters are highly reactive and useful starting materials for the cycloisomerization catalyzed by a transition metal catalyst.

Multisubstituted N-fused heterocycles via transition metal-catalyzed cycloisomerization protocols

Two complementary protocols for assembly of multisubstituted N-fused heterocycles have been developed. It was demonstrated that 1,3-disubstituted N-fused heterocycles, including indolizines, pyrroloquinoxalines, and pyrrolothiazoles can easily be synthesized via an exceptionally mild and efficient method involving a novel silver-catalyzed cycloizomerization of propargyl-containing heterocycles. Alternatively, 1,2-disubstituted heterocycles can be accessed through the novel cascade transformation involving an alkyne–vinylidene isomerization with concomitant 1,2-shift of hydrogen, silyl, stannyl, or germyl groups. This mild and simple method allows for selective and highly efficient synthesis of indolizines, pyrroloisoquinolines, pyrroloquinoxalines, pyrrolopyrazines, and pyrrolothiazoles.

Base‐ and Ligand‐Free Room‐Temperature Synthesis of N‐Fused Heteroaromatic Compounds via the Transition Metal Catalyzed Cycloisomerization Protocol.

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.

Base- and ligand-free room-temperature synthesis of N-fused heteroaromatic compounds via the transition metal-catalyzed cycloisomerization protocol.

A new practical method for the synthesis of N-fused heterocycles via the transition metal-catalyzed cycloisomerization of heterocyles possessing a propagyl group has been developed. This very mild, base- and ligand-free method allows for the synthesis of diverse fused heterocyclic cores in good to excellent yields.

New Advances in Selected Transition Metal-Catalyzed Annulations

This account describes the recent advances on the Pd-catalyzed [4+2]-benzannulation reaction, development of chemo- and regiospecific formal [2+2+2]-cyclotrimerization of alkynes, as well as discovery and evolution of the transition metal-catalyzed cycloisomerization of alkynyl ketones and imines into five-membered heteroaromatics.