Total synthesis of two naturally occurring bicyclo[3.2.1]octanoid neolignans

The first total syntheses of the racemates of naturally occurring macrophyllin-type bicyclo[3.2.1]octanoid neolignans, kadsurenin C 3 and kadsurenin L 4, were accomplished starting from vanillin and resorcinol. The acid-catalyzed rearrangement of hydrobenzofuranoid neolignans into bicyclo[3.2.1]octanoid neolignans was used as the key step.     

Total synthesis of (+/-)-clavubicyclone

[reaction: see text] The total synthesis of racemic clavubicyclone (1), which was isolated from Okinawan soft coral by our group, is described. The bicyclo[3.2.1]octane skeleton was prepared by Cope rearrangement of a divinylcyclopropane derivative. Three functional groups on the skeleton were constructed by Barton decarboxylation, Wittig reaction, and alkylation.     

Rhodium complexes of some cyclo-olefins

Dicarbonyl(pentane-2,4-dionato)rhodium(I) does not form a complex with, or induce a skeletal rearrangement in, cycloheptatriene. 5-Exo-methylene-2-norbornene is present as an impurity in cycloheptatriene and is complexed by Rh(I) complexes as its endocyclic tautomer. Rhodium complexes of 1,3,5-cyclooctatriene, bicyclo [3.2.1] octa-2,6-diene, cyclooctatetraene, cyclooctatetraene epoxide, bicyclo [6.1.0] nonatriene and 9,9-dimethyl bicyclo [6.1.0] nonatriene are also reported.     

Trimethylsilyl group directed wagner-meerwein rearrangement of bicyclo[2.2.2]octan-2-ol derivatives

Trimethylsilyl group substituted bicyclo[2.2.2]octane derivatives were synthesized and subjected to TMS group directed Wagner-Meerwein rearrangement to give bicyclo[3.2.1]octene derivatives in high yields.     

Enantioselective synthesis of bicyclo[3.n.1]alkanes by chiral phosphoric acid-catalyzed desymmetrizing Michael cyclizations

2,2-Disubstituted cyclic 1,3-diketones containing a tethered electron-deficient alkene undergo chiral phosphoric acid-catalyzed desymmetrizing Michael cyclizations to give bridged bicyclic products in high enantioselectivities. Both bicyclo[3.2.1]octanes and bicyclo[3.3.1]nonanes are accessible using this methodology.     

Oxabicyclo[3.2.1]octane derivatives as highly reactive dienophiles: synthesis of bicyclo[5.n.0] systems

[reaction: see text] We have developed highly versatile, homochiral oxabicyclo[3.2.1]octadiene building blocks for the synthesis of natural products. We have found that these bridged alkenes undergo exceptionally facile Diels-Alder reactions and react faster than several well studied bicyclo[2.2.1]heptene dienophiles. The reaction proceeds with high levels of stereochemical control and in very good to excellent yields, providing access to bicyclo[5.4.0]undecane and bicyclo[5.3.0]decane systems. This reactivity is attributed to strain and homoconjugation effects.     

Enantioselective Synthesis of Bicyclo[3.2.1]octadienes via Palladium-Catalyzed Intramolecular Alkene-Alkyne Coupling Reaction

Bicyclo[3.2.1]octadiene compounds and derivatives exist in a number of natural products and bioactive compounds. Nevertheless, catalytic enantioselective protocols for the synthesis of these skeletons have not been disclosed. Herein we reported a palladium-catalyzed asymmetric intramolecular alkene-alkyne coupling of alkyne-tethered cyclopentenes, affording a library of enantionenriched bicyclo[3.2.1]octadienes in excellent yields and enantioselectivities (mostly >99 % ee). Moreover, the products could undergo an unusual iodination-induced 1,2-acyl migration, forming iodinated bicyclo[3.2.1]octadienes with three vicinal stereocenters. The enone and isolated olefin motifs embedded in the products provide useful handles for downstream elaboration.     

萜品油烯的DeMayo光环加成产物的反应研究

通过萜品油烯和2，6-二氧代戊酸甲酯的de Mayo反应，使[2 + 2]环加成产物 3-6经retro-aldol重排，开环生成取代环己烯7和12。在不同反应介质中对开环产 物进行再环合，并对其反应机理进行研究。在碱性条件下，经分子内Claisen缩合 反应形成螺环化合物；以对甲本碘酸为催化剂的环合，除生成正常的Claisen缩合 产物以外，7和12均发生烯键亲核加成反应，生成具有二环[3.3.1]结构的桥环化合 物9-11和二环[3.2.1]结构的桥环化合物16-18。所得新化合物的化学结构均经IR, ~1H NMR，~(13)C NMR及元素分析予以确定。     

Rearrangements and Hydration of 2-Ethynylisoborneol and 2-Ethynylisocamphanol

The reaction of 2-ethynylisoborneol with acetic acid in the presence of boron trifluoride-diethyl ether complex gave 4-ethynylisobornyl acetate as a result of successive skeletal rearrangements. Under the Kucherov reaction conditions 2-ethynylisoborneol underwent Meyer—Schuster rearrangement leading to (2-bornylidene)acetaldehyde. The hydration product of 2-ethynylisoborneol, 2-acetylisoborneol, was obtained by the action of mercury(II) acetate in dioxane under mild conditions. The Nieuwland reaction of 2-ethynylisoborneol afforded 4-acetylisoborneol acetate. 2-Ethynylisocamphanol in the presence of formic acid gave rise to a mixture of Rupe and Meyer—Schuster rearrangement products, stereoisomeric 2-(isocamphylidene)acetaldehydes and 2-acetylisocamphene. Mixtures of acetyl-substituted acetates having a camphane, isocamphane, and bicyclo[3.2.1]octane skeleton were obtained in the reaction with acetic acid in the presence of BF₃-Et₂O. Under the Nieuwland reaction conditions 2-ethynylisocamphanol underwent hydration and rearrangement with ring expansion, yielding a mixture of endo-2-hydroxy-2,6,6,7-tetramethylbicyclo[3.2.1]octan-3-one and the corresponding acetate.     

Differential Bridging in the Solvolysis of Epimeric Bicyclic Sulfonates,Norbornanes, Part 17

The solvolysis rates and products of the 2-exo- norbornyl, bicyclo[3.2.1]oct-8-yl, bicyclo[3.3.1]non-2-yl, bicyclo[3.2.1]oct-6-yl, bicyclo[3.2.1]oct-2-yl and bicyclo[3.2.2]non-6-yl p-toluenesulfonates 10–15 , respectively, are reported. The exo/endo rate ratios for these epimeric secondary tosylates in 80% EtOH varied from 1125 for 11 to 1.6 for 15 . The relative rates varied between 2278 for exo- 10 and 4 ·10^?3 for endo- 11 . The hydrolysis products were mainly rearranged alcohols and olefins. The unrearranged alcohols from the exo-tosylates were formed with complete or predominant retention of configuration, whereas those derived from the endo-tosylates were mostly inverted. These results confirm the hypothesis that relative rates, as well as products, are largely determined by the degree of bridging between the cationic center and a dorsal C-atom in the transition state and in the resulting ion pairs. Since bridging is a directed bonding interaction, it is subject to the same angle and conformational strains as ordinary covalent bonds. But bridging requires less geometrical change than the formation of normal bonds and of nonclassical ions.     

An approach to the synthesis of gelsemine: the intramolecular reaction of an allylsilane with an acyliminium ion for the synthesis of one of the quaternary centres

We describe an efficient synthesis (summarised in Schemes 8 and 10) of an advanced intermediate (34) suitable for the synthesis of gelsemine. The key steps in the synthesis are (i) the Diels-Alder reaction between 1-tetrahydropyranyloxycyclohexa-1,3-diene (10) and methyl β-nitroacrylate (11) giving an adduct (12), in which the chiral centre in the tetrahydropyranyl ring is produced substantially in only one sense, (ii) the rearrangement of a bicyclo [2.2.2] octane (23) into a bicyclo[ 3.2.1] octane (24), where control of which bridge migrates is achieved by a choice of the counterion in the Lewis acid, and (iii) the efficient formation of the quaternary centre by an intramolecular reaction between an allylsilane group and an acyliminium ion (33 → 34).     

Bicyclo[3.2.1]octenones As Building Blocks in Natural Products Synthesis (III). Total Synthesis of (±)-10-Deoxygeniposide Aglucone

The title compound was synthesized from bicyclo[3.2.1]octenone 1 in six steps and in overall yield 59%. Photochemical rearrangement of β,γ-unsaturated enone 1 is the key step.     

Chiral synthons from α-pinene: enantioselective syntheses of bicyclo[3.3.0] and [3.2.1]octanones

Enantioselective syntheses of bicyclo[3.3.0]octan-3-one, bicyclo[3.2.1]octan-3-one and bicyclo[3.2.1]octan-2-one derivatives were accomplished by employing a chiron based approach, using intramolecular rhodium carbenoid C–H insertion, acid catalysed cyclisation of α-diazo ketone and intramolecular type II carbonyl ene reactions as key steps.     

Carbon-13 chemical shifts of bicyclo[3.2.1]octane and bicyclo[2.2.1]heptane derivatives

¹³C chemical shifts of more than fifty bicyclo[3.2.1]octane and bicyclo[2.2.1]heptane derivatives (hydrocarbons, alcohols, ketones and esters) have been determined. The usefulness of ethyl derivatives for the assignment of close ¹³C chemical shifts in bicyclic methyl derivatives is shown both for the bicyclo[3.2.1]octane and bicyclo[2.2.1]heptane series. Comparison of substituent effects on α-, β-, γ- and δ-carbons in both series of compounds shows remarkable differences in steric interactions. In contrast to the rigid bicyclo[2.2.1]heptane system, both chair and boat conformations can be predominant in the bicyclo[3.2.1]octane series with the conformationally flexible 6-membered ring.     

Synthesis and reactivity of bicyclo[3.2.1]octanoid-derived cyclopropanes

Photochemical oxa-di-π-methane rearrangement of bicyclo[3.2.1]octanoid scaffolds affords multifunctional, donor-acceptor cyclopropanes. A related photochemical reaction of an iminium ether substrate uncovered an unprecedented aza-di-π-methane rearrangement of a β,γ-unsaturated iminium. Donor-acceptor cyclopropanes have been evaluated as substrates for reactions generating several new chemotypes.     

Enantioselective Total Synthesis of (+)‐Jungermatrobrunin A

A concise and enantioselective total synthesis of (+)‐jungermatrobrunin A ( 1 ), which features a unique bicyclo[3.2.1]octene ring skeleton with an unprecedented peroxide bridge, was accomplished in 13 steps by making use of a late‐stage visible‐light‐mediated Schenck ene reaction of (?)‐1α,6α‐diacetoxyjungermannenone C ( 2 ). Along the way, a UV‐light‐induced bicyclo[3.2.1]octene ring rearrangement afforded (+)‐12‐hydroxy‐1α,6α‐diacetoxy‐ent‐kaura‐9(11),16‐dien‐15‐one ( 4 ). These divergent photo‐induced skeletal rearrangements support a possible biogenetic relationship between (+)‐ 1 , (?)‐ 2 , and (+)‐ 4 .     

Conformations and reactions of bicyclo[3.2.1]oct-6-en-8-ylidene

Bicyclo[3.2.1]oct-6-en-8-ylidene (1) can assume either the conformation of "classical" carbene 1a or that of foiled carbene 1b in which the divalent carbon bends toward the double bond. Oxadiazoline precursors for the generation of 1 were prepared, followed by photochemical and thermal decomposition as well as flash vacuum pyrolysis (FVP) of a tosyl hydrazone sodium salt precursor, to give a number of rearrangement products. Matrix isolation experiments demonstrate the presence of a diazo intermediate and methyl acetate in all photochemical and thermal precursor reactions. The major product from rearrangements of "classical" bridged carbene 1a is bicyclo[3.3.0]octa-1,3-diene as a result of an alkyl shift, while dihydrosemibullvalene formed from a 1,3-C-H insertion. In contrast, thus far unknown strained bicyclo[4.2.0]octa-1,7-diene formed by a vinyl shift in foiled carbene 1b. The experimental results are corroborated by density functional theory (DFT), MP2, and G4 computations.     

A formal [3+2] cycloaddition for the synthesis of bicyclo[3.2.1]octanes

A new and a direct synthetic method for the construction of the bicyclo[3.2.1]octane system is envisioned by assembling cyclic allylsilanes with electron-deficient double bonds in a single step via a formal diastereoselective Lewis acid-promoted [3+2] cycloaddition.     

Acid-catalyzed synthesis of bicyclo[3.n.1]alkenediones

An acid-catalyzed Dieckmann-type reaction has been developed to access functionalized bicyclo[3.2.1]alkenediones. This methodology has been successfully extended to more substituted and larger ring homologues, providing a new and efficient route to the core of numerous attractive natural products and their analogues.     

A facile synthesis of a polyhydroxylated 2-azabicyclo[3.2.1]octane

Synthetic or natural aza-sugars have shown promise as a therapeutic approach to a variety of disease states by acting as transition state mimics to sugar processing enzymes. Although the synthesis of functionalized bicyclo[3.2.1]octanes has been reported, the procedures are relatively long and low yielding. Herein, we report the facile synthesis of polyhydroxylated 2-azabicyclo[3.2.1]octane that can be selectively functionalized.