Bicyclic Alkenes Research Articles

Nickel-Catalyzed Reaction of Benzamides with Bicylic Alkenes: Cleavage of C-H and C-N Bonds.

The nickel-catalyzed reaction of aromatic amides that contain an 8-aminoquinoline as a directing group with bicyclic alkenes, such as norbornene and 1,4-dihydro-1,4-epoxynaphthalene, results in the cleavage of both the C-H bond at the ortho-position of the benzene ring and the C(O)-N bond to give methanofluoren-9-one and 1,4-epoxyfluoren-9-one derivatives. Both Ni(OTf)2 and Ni(cod)2 show a high catalytic activity. The presence of AgOAc is essential for the reaction to proceed. In the meta-substituted aromatic amides, a less hindered C-H bond is exclusively functionalized.

1,3-Dipolar cycloaddition of nitrones to oxa(aza)bicyclic alkenes

A new 1,3-dipolar cycloaddition of oxa(aza)bicyclic alkenes with nitrones has been developed without any catalyst and additive under mild conditions. The proposed concerted mechanism is investigated by DFT calculations of the reaction pathways.

Nickel-catalyzed syn-stereocontrolled ring-opening of oxa- and azabicyclic alkenes with dialkylzinc reagents.

A new nickel-catalyzed syn-stereocontrolled ring-opening of oxa- and azabicyclic alkenes with dialkylzinc reagents was developed, which afforded the corresponding cis-2-alkyl-1,2-dihydronaphthalen-1-ols and 1,2-alkyl amide derivatives in moderate to excellent yields (up to 99% yield) under mild conditions. In this work, we successfully avoided obtaining hydride addition byproducts arising from β-hydride elimination on an ethyl nickel species. Furthermore, a plausible mechanism for the ring-opening reaction was also proposed.

Rhenium(I)-Catalyzed ortho-C-H Addition to Bicyclic Alkenes.

Hydroarylation of bicyclic alkenes has been developed using a low-valent ReI -catalyzed, directing group-assisted C-H bond activation strategy. The addition of sodium acetate significantly improves the reaction efficiency; moreover, bicyclic alkenes such as 7-oxa and aza benzonorbornadienes worked efficiently under this reaction condition. Preliminary mechanistic studies suggest that, after the alkene insertion, the rhenacycle preferentially undergoes protonolysis rather than reductive elimination.

Water-promoted synthesis of fused bicyclic triazolines and naphthols from oxa(aza)bicyclic alkenes and transformation via a novel ring-opening/rearrangement reaction

A water-promoted approach to synthesize fused bicyclic triazolines and naphthols from the oxa(aza)bicyclic alkenes in water/ haloalkane system, and a cascade ring-opening/rearrangement to synthesize indenes has also been reported.

Rhodium(III)‐Catalyzed C−H Activation of O‐Acetyl Ketoximes/N‐Methoxybenzamides toward the Synthesis of Isoquinoline/Isoquinolone‐Fused Bicycles

AbstractAn efficient rhodium(III)‐catalyzed C−H activation approach for the construction of fused heterocyclic motifs with urea‐derived bicyclic olefins has been demonstrated. A rhodium‐catalyzed reaction of O‐acetyl ketoximes with these bicyclic motifs furnished isoquinoline derivatives, whereas isoquinolone‐fused bicyclic olefins were obtained with the reaction of N‐methoxybenzamides.

Formal total synthesis of stigmatellin A

An efficient and stereoselective approach for the formal total synthesis of Stigmatellin A has been described. The key steps involved in this synthesis are desymmetrization of the bicyclic olefin to introduce two methyl and two hydroxyl chiral centers, Friedel Crafts acylation, regioselective demethylation, Baker-Venkataraman rearrangement and Grubbs cross metathesis.

Divergent Asymmetric Synthesis of Polycyclic Compounds via Vinyl Triazenes.

Vinyl triazenes were obtained by enantioselective [2+2] cycloaddition reactions of bicyclic alkenes with 1-alkynyl triazenes in the presence of a RuII catalyst with a chiral cyclopentadienyl ligand. These triazenes serve as unique vinyl cation surrogates. Under acidic conditions, the triazene functionality can be replaced with a variety of groups, including halides, alkoxides, sulfoxides, amides, arenes, and heteroarenes, thus providing efficient access to a pool of chiral polycyclic compounds.

Divergent Asymmetric Synthesis of Polycyclic Compounds via Vinyl Triazenes

AbstractVinyl triazenes were obtained by enantioselective [2+2] cycloaddition reactions of bicyclic alkenes with 1‐alkynyl triazenes in the presence of a RuII catalyst with a chiral cyclopentadienyl ligand. These triazenes serve as unique vinyl cation surrogates. Under acidic conditions, the triazene functionality can be replaced with a variety of groups, including halides, alkoxides, sulfoxides, amides, arenes, and heteroarenes, thus providing efficient access to a pool of chiral polycyclic compounds.

Access to polysubstituted naphthalenes and anthracenes via a retro-Diels–Alder reaction

Naphthalene and anthracene nuclei are present in several natural and synthetic compounds. Due to their unique physical and chemical properties, access to functionalized naphthalenes and anthracenes has attracted the attention of both synthetic and medicinal chemists over the decades. In this study, successive Diels–Alder/retro-Diels–Alder reactions of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate with various bicyclic alkenes in one pot to yield naphthalene and anthracene derivatives are reported. Using anti- and syn-cyclotrimers derived from the cyclotrimerization of benzobarrelene as alkene partner enabled efficient synthesis of trinaphthylene.

Palladium‐Catalyzed Cross‐Coupling of Aryl Iodides with Heterobicyclic Olefins: Access to Hydroarylated and Heteroannulated Motifs

AbstractTransition metal catalyzed synthetic transformations of bicyclic olefins have acquired considerable attention towards the construction of biologically relevant carbocycles and heterocycles. In this regard, urea derived bicyclic olefins grabbed our attention due to its tremendous biological significance and synthetic potential. Herein, we report a palladium catalyzed reductive Heck reaction of urea‐derived bicyclic olefins toward the synthesis of hydroarylated and heteroannulated motifs using aryl iodides. The reaction of aryl iodides in the presence of a hydrogen donor such as formic acid furnished the hydroarylated products in moderate to excellent yields. Heteroannulated products such as dihydrobenzofuran derivatives were obtained in moderate to good yields with 2‐iodophenols in the absence of a hydrogen donor. We were also successful in extending this strategy to 2‐iodobenzylbromide and 2‐iodobenzonitrile towards the synthesis of ring fused indane and indanone derivatives. To our dismay, the reactions with 2‐iodoaniline to provide the expected indoline derivatives remained futile. The presence of biologically significant urea moieties coupled with naturally as well as pharmaceutically prevalent carbo/heterocyclic derivatives in the products authenticate the relevance of the current synthetic strategy.

Cp*Rh(III)/Bicyclic Olefin Cocatalyzed C–H Bond Amidation by Intramolecular Amide Transfer

A bicyclic olefin was discovered as a cocatalyst in a Cp*Rh(III)-catalyzed C-H bond amidation proceeding by an intramolecular amide transfer in N-phenoxyacetamide derivatives. Combining experimental and theoretical studies, we propose that the olefin promotes a Rh(III) intermediate to undergo oxidative addition into the O-N bond to form a Rh(V) nitrenoid species and subsequently direct the nitrenoid to add to the ortho position. The amide directing group plays a dual role as a cleavable coordinating moiety as well as an essential coupling partner for the C-H amidation. This methodology was successfully applied to the late-stage diversification of natural products and a marketed drug under mild conditions.

First Detection of a Ruthenium–Carbene–Resorc[4]arene Complex During the Progress of a Metathesis Reaction

For the first time we describe the detection of a ruthenium‐carbene‐resorc[4]arene complex produced, as a key intermediate, during an olefin metathesis reaction carried out on a resorc[4]arene bicyclic olefin with [Ru(=CHPh)Cl2(PCy3)2] Grubbs first‐generation (G1ST) catalyst. The complex was identified by using high‐resolution (600 MHz) 1H, 31P NMR and DOSY spectroscopy, in a non‐invasive fashion. The singlet at δ = 19.98 ppm (1H NMR), attributed to the alkylidene proton in the G1ST catalyst and that at δ = 53.37 ppm (31P NMR), attributed to the phosphorus atom coordinated with the metal, were selected as probes for a kinetic analysis. The intensity of these signals decreased at the expense of the singlets at 19.26 (1H NMR) and 52.68 ppm (31P NMR), diagnostic for the formation of the ruthenium‐carbene‐resorc[4]arene complex 3a[Ru]. The resorc[4]arene activated olefin proved to behave as a key propagating species leading to oligomers according to a ROMP pathway.

Asymmetric Ring-Opening Reactions of Aza- and Oxa-bicyclic Alkenes with Boronic Acids Using a Palladium/Zinc Co-catalytic System.

The asymmetric ring opening reactions of bicyclic alkenes with boronic acids were accomplished by using a highly active palladium/zinc co-catalytic system that was suitable for both azabenzonorbornadienes and oxabenzonorbornadienes, which were transformed to the corresponding chiral hydronaphthalene products in high yields (up to 99%) and high optical purities (up to 98% ee). The reaction protocol is general and mild and displays good functional group tolerance.

Neutral chiral cyclopentadienyl Ru(ii)Cl catalysts enable enantioselective [2+2]-cycloadditions.

Cyclopentadienyl ruthenium(ii) complexes with a large number of available coordination sites are frequently used catalysts for a broad range of transformations. To be able to render these transformations enantioselective, we have designed a chiral neutral CpxRu(ii)Cl complex basing on an atropchiral cyclopentadienyl (Cpx) ligand which is accessed in a streamlined C-H functionalisation approach. The catalyst displays excellent levels of reactivity and enantioselectivity for enantioselective [2+2]-cycloadditions leading to strained chiral cyclobutenes, allowing for catalyst loadings as low as 1 mol%. A very strong counterion effect of a bound chloride anion transforms the corresponding unselective cationic complex into a highly enantioselective neutral version. Moreover, by adding norbornadiene at the end of the reaction the catalyst can be recovered and subsequently reused.

イリジウム触媒による高原子効率型の不斉合成反応

This article summarizes our recent studies on iridium-catalyzed asymmetric reactions realizing the high atom efficiency. Iridium complexes efficiently catalyzed asymmetric functionalization of aromatic compounds via directed C-H activation. Formal [3+2] annulation of ketimines with 1,3-dienes or alkynes gave the corresponding annulation products in high yields with high enantioselectivity. Branch-selective alkylation of aromatic compounds with vinyl ethers was efficiently catalyzed by Ir(I)/chiral diene complexes. Hydroacylation of bicyclic alkenes with salicylaldehydes also proceeded via acyl C-H bond activation. Meanwhile, asymmetric synthesis of heterocycles via C-O and C-N bond formation were also achieved. Annulation of salicylimines and α-oxocarboxamides with 1,3-dienes proceeded to give chromane and pyrrolidone derivatives, respectively. Asymmetric cyclization of alkenoic acids and alkenamides took place to give γ-lactones and γ-lactams, respectively.

Ruthenium/Iridium-Catalyzed C-2 Activation of Indoles with Bicyclic Olefins: An Easy Access to Functionalized Heterocyclic Motifs

Selective C-2 functionalization of N-protected and free indoles is reported. The ruthenium-catalyzed C-2 activation of indoles provided an easy access to cyclopentenylated indoles. Hydroheteroarylated bicyclic motifs were synthesized via iridium-catalyzed C-2 activation of NH indoles. The methodology was extended to different bicyclic adducts such as diaza- or urea-derived bicyclic olefins.

ChemInform Abstract: An Easy Access to Fused Chromanones via Rhodium Catalyzed Oxidative Coupling of Salicylaldehydes with Heterobicyclic Olefins.

AbstractDiazabicyclic and urea‐derived bicyclic olefins react with salicylaldehydes to produce various types of fused chromanone systems of biological interest in a single step (mechanism).

1,2‐Annulated Sugars: Synthesis of Polyhydroxylated 2,10‐Dioxadecalins with β‐manno Configuration

A new synthetic route to 1,2‐pyran‐annulated O‐glycosides (pyranopyrans) with β‐manno configuration is presented. Starting from a benzyl‐protected allyl β‐2‐uloside obtained by C2‐oxidation from the corresponding allyl glucoside, vinylation and ring‐closing metathesis provided a bicyclic alkene as a key substrate. Optimized reaction conditions involving the 2‐uloside were required to circumvent the formation of the unwanted 3,2‐enolone. Subsequent stereoselective alkene dihydroxylations were investigated and are presented. Diastereoselective catalytic osmoylation afforded the bicyclic β‐mannoside with syn‐diol configuration. In contrast, a sequence featuring a directed vanadium‐catalyzed alkene epoxidation and epoxide opening provided the corresponding 2,10‐dioxadecalin target compound with trans‐diol configuration. X‐ray crystallography was employed to study the molecular structure of the target compound with syn‐diol configuration. In addition, the molecular packing and hydrogen‐bonding interactions of the hydroxy‐rich molecule were examined.

Noncovalent Dimerization after Enediyne Cyclization on Au(111)

We investigate the thermally induced cyclization of 1,2-bis(2-phenylethynyl)benzene on Au(111) using scanning tunneling microscopy and computer simulations. Cyclization of sterically hindered enediynes is known to proceed via two competing mechanisms in solution: a classic C(1)-C(6) (Bergman) or a C(1)-C(5) cyclization pathway. On Au(111), we find that the C(1)-C(5) cyclization is suppressed and that the C(1)-C(6) cyclization yields a highly strained bicyclic olefin whose surface chemistry was hitherto unknown. The C(1)-C(6) product self-assembles into discrete noncovalently bound dimers on the surface. The reaction mechanism and driving forces behind noncovalent association are discussed in light of density functional theory calculations.