Highly enantioselective construction of a chiral spirocyclic structure by the [2 + 2 + 2] cycloaddition of diynes and exo-methylene cyclic compounds

The enantioselective [2 + 2 + 2] cycloaddition of 1,6-diynes with alpha-methylene lactones and cyclic ketones gave various chiral spirocyclic compounds. The reaction proceeded with high enantioselectivity when the rhodium-xylylBINAP complex was used as a chiral catalyst. Not only exo-methylene cyclic compounds but also exo-methylene acyclic compounds could be used as coupling partners for diynes. The present protocol provides access to a new chiral library possessing a quaternary carbon center, including a spirocyclic system.     

The use of d-glucose-based silyloxy dienes in anthracyclinone synthesis

We wish to report asymmetric Diels–Alder reactions using a d-glucose-based diene and quinol dienophile without requiring additional steps of preparing an oxirane dienophile typically used in the Stoodley group. A new d-glucose-based diene is also reported and its chemistry investigated.     

Biomimetic macrocycle-forming Diels-Alder reaction of an iminium dienophile: synthetic studies directed toward gymnodimine

The macrocyclic core of gymnodimine has been constructed via an intramolecular Diels-Alder reaction of an alpha,beta-unsaturated iminium dienophile in water. The cycloaddition furnished a single exo-product, along with two endo-products. Through X-ray analysis of a suitable derivative, the stereochemistry of the exo-product was established, thereby demonstrating that its stereochemistry matches that of gymnodimine. In contrast, macrocyclization of an analogous alpha,beta-unsaturated ketone dienophile gave only undesired endo-products. Interestingly, the imine dienophile shows remarkable stability in water. [reaction: see text]     

Triflic acid-catalyzed additions of 2-alkoxycarbonyl allylboronates to aldehydes. Study of scope and mechanistic investigation of the reaction stereochemistry

The substrate scope and the effect of substrate on the observed inversion of stereoselectivity in the triflic acid-catalyzed allylboration reaction between 2-alkoxycarbonyl allylboronates and aldehydes are presented. A mechanistic investigation is described so as to confirm the involvement of a carbocation intermediate as the source of stereochemical inversion. This methodology allows a facile access to beta,gamma-disubstituted five-membered ring lactones with an exo-methylene at the alpha-position.     

Remote electronic control in the LiAlH4 reduction of tricyclic p-tolylsulfonylmethyl enones

The LiAlH₄ reduction of 4-p-tolylsulfonylmethyl-oxatricyclo[5.2.1.0^2,6]decadienones 3 and 8 leads regioselectively and stereospecifically to exo-methylene tricyclo-decenols 6 and 11. The sulfone function is essential for this bis-hydride reduction process. Flash vacuum thermolysis of 6 and 11 affords quantitatively the exo-methylene cyclopentenols 13 and 14.     

Silver-catalyzed regioselective carbomagnesiation of alkynes with alkyl halides and Grignard reagents

A silver-catalyzed carbomagnesiation of alkynes with alkyl halides and Grignard reagents afforded alkenyl Grignard reagents regioselectively, where the alkyl group of the alkyl halide, but not that of the Grignard reagent, was introduced into the alkyne. Application to δ-haloalkylacetylenes yielded cyclopentanes or a tetrahydrofuran containing an exo-methylene substituent via 5-exo-dig cyclization.     

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.     

Synthesis of novel 2,6-disubstituted-3,4-dimethylidene tetrahydropyrans via Prins-type cyclization

Synthesis of novel substituted tetrahydropyrans with adjacent exo-methylene groups at the C3 and C4 positions via Prins-type cyclization has been described.     

Propellanes—XXXI : The diels-alder reaction of [4.4.2]propellanes with 4-phenyl-1,2,4-triazoline-3,5-dione

Attack of a number of [4.4.2]propellanes by the dienophile named in the title occurs, when one equivalent of dienophile is used, for the direction anti- to the 4-membered ring.     

Synthesis of dimethyl gloiosiphone a by way of palladium-catalyzed domino cyclization

The synthesis of a spiro[4.4]nonane skeleton by the palladium-catalyzed domino cyclization of a linear 7-methylene-2,10-undecadienyl acetate is described. The pi-allylpalladium intermediate underwent intramolecular alkene insertion with high intraannular diastereoselectivity, followed by intramolecular Heck-type cyclization, leading to a spiro[4.4]nonane system. Oxidation of the allylic ether moiety and transformation of the vinyl group to an exo-methylene unit provided 3, which is the known synthetic intermediate of dimethyl gloiosiphone A (2).     

One and two hydrogen atom migrations in the retro-diels-alder fragmentation of norbornene and bicyclo [2.2.2] octene derivatives under electron impact

Norbornene derivatives with one or two carbonyl-containing substituents at positions 5 and 6 (anhydrides, esters, amides, cyclic ketones) undergo an electron impact induced rerro-Diels-Alder fragmentation accompanied by the migration of one hydrogen atom (RDA + H) giving rise to the [dienophile + H]⁺ ions. Bicyclo[2.2.2]octene derivatives substituted at C(5) and C(6) by a ring with two carbonyl groups (anhydrides, imides, diketones) undergo an RDA fragmentation accompanied by the transfer of two hydrogen atoms (RDA + 2H). Bicyclo[2.2.2]octene 5,6-diesters undergo both the RDA + H and RDA + 2H fragmentations, and the relative abundance of the resulting [dienophile + H]⁺ and [dienophile + 2H]⁺˙ ions is strongly affected by configuration.     

Propellanes—XXXVII : Further testing of thesis regarding control by secondary orbital overlap during certain diels-alder reactions

We show again that compounds containing CO groups which are capable of secondary orbital interactions with the dienophile, 4-phenyl-1,2,4-triazoline-3,5-dione cause reaction to occur from above. However, in substrates which do not have capability for overlap with the dienophile nitrogen lone pairs and, on the contrary, exert steric hindrance to topside reaction, reaction with the first equivalent of dienophile occurs from below. When a second equivalent can react it reacts from above, again for relative steric reasons.     

Diverse Reactivity of Dienes with Pentaphenylborole and 1-Phenyl-2,3,4,5-Tetramethylborole Dimer

The reactions of a monomeric borole and a dimeric borole with 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene were investigated. The monomeric borole reacted at ambient temperature whereas heat was required to crack the dimer to form the monomer and induce reactivity. 2,3-Dimethyl-1,3-butadiene reacts to give diverse products resulting from a cycloaddition process with the B−C moiety of the boroles acting as a dienophile, followed by rearrangements to furnish bicyclic species. For 1,3-cyclohexadiene, a [4+2] process is observed in which 1,3-cyclohexadiene serves as the dienophile and the boroles as the diene partner. The experimental results are corroborated with mechanistic theoretical calculations that indicate boroles can serve as either a diene or dienophile in cycloaddition reactions with dienes.     

Catalysis of a Diels-Alder Reaction by Amidinium Ions

Amidines and guanidines are important functional groups in molecular recognition and host-guest chemistry. Here it is shown that lipophilic amidinium ions catalyze a cycloaddition reaction representing the key step of the Quinkert-Dane estrone synthesis. Hydrogen-bond-mediated association with the organic cation leads to an electrophilic activation of the dienophile and to enhanced rates of the Diels-Alder reaction. The observed effects are similar to those expected from mild Lewis acids. In competition experiments, amidinium catalysis favors the reaction of the less electron deficient dienophile.     

How Ionization Catalyzes Diels-Alder Reactions

The catalytic effect of ionization on the Diels-Alder reaction between 1,3-butadiene and acrylaldehyde has been studied using relativistic density functional theory (DFT). Removal of an electron from the dienophile, acrylaldehyde, significantly accelerates the Diels-Alder reaction and shifts the reaction mechanism from concerted asynchronous for the neutral Diels-Alder reaction to stepwise for the radical-cation Diels-Alder reaction. Our detailed activation strain and Kohn-Sham molecular orbital analyses reveal how ionization of the dienophile enhances the Diels-Alder reactivity via two mechanisms: (i) by amplifying the asymmetry in the dienophile's occupied π-orbitals to such an extent that the reaction goes from concerted asynchronous to stepwise and thus with substantially less steric (Pauli) repulsion per reaction step; (ii) by enhancing the stabilizing orbital interactions that result from the ability of the singly occupied molecular orbital of the radical-cation dienophile to engage in an additional three-electron bonding interaction with the highest occupied molecular orbital of the diene.     

Oxidative cycloamination of olefins with aziridines as a versatile route to saturated nitrogen-containing heterocycles

Highly reactive [5,3] and [6,3] bicyclic aziridines can be readily prepared from the corresponding NH aziridines and N-bromosuccinimide by intramolecular oxidative cycloamination of olefins. These compounds, including surprisingly stable exo-methylene bicyclic aziridines, provide versatile synthetic entries into a wide range of pyrrolidine- and piperidine-containing heterocycles.     

Enantiodivergent [4+2] Cycloaddition of Dienolates by Polyfunctional Lewis Acid/Zwitterion Catalysis

Diels–Alder reactions have become established as one of the most effective ways to prepare stereochemically complex six-membered rings. Different catalysis concepts have been reported, including dienophile activation by Lewis acids or H-bond donors and diene activation by bases. Herein we report a new concept, in which an acidic prodiene is acidified by a Lewis acid to facilitate deprotonation by an imidazolium–aryloxide entity within a polyfunctional catalyst. A metal dienolate is thus formed, while an imidazolium–ArOH moiety probably forms hydrogen bonds with the dienophile. The catalyst type, readily prepared in few steps in high overall yield, was applied to 3-hydroxy-2-pyrone and 3-hydroxy-2-pyridone as well as cyclopentenone prodienes. Maleimide, maleic anhydride, and nitroolefin dienophiles were employed. Kinetic, spectroscopic, and control experiments support a cooperative mode of action. High enantioselectivity was observed even with unprecedented TONs of up to 3680.     

Reactivity and stereoselectivity of the Diels-Alder reaction using cyclic dienophiles and siloxyaminobutadienes

Several bicyclic compounds were synthesized by the Diels-Alder reaction using aminodiene and a cyclic dienophile. The stereochemistries of the obtained adducts were determined by X-ray crystallography or NMR analysis. The stereoselectivity of this Diels-Alder reaction was based on the interaction of molecular orbitals between the diene and dienophile. The reactivities of these Diels-Alder reactions were estimated, and the generality of this reaction is discussed.     

Stereocontrolled IMDA reaction of styrene derivatives. A way to enantiopure 3a,4,9,9a-tetrahydrobenz[f]isoindolines

IMDA reactions on chiral perhydro-1,3-benzoxazines, derived from (-)-8-amino menthol, bearing a styrene substituent at C-2 acting as diene and an acryl amide acting as dienophile occur with high stereoselection and excellent chemical yields. After elimination of the chiral appendage, enantiopure 3a,4,9,9a-tetrahydrobenz[f]isoindolines are prepared in this way. The effect of the substituents at both diene and dienophile are studied, showing that a methyl group at C-1 in the diene inhibited the reaction, while the ene adduct, instead of the IMDA product, was obtained when a methyl group was at C-2.     

Enantioselective total synthesis of (-)-candelalide A, a novel blocker of the voltage-gated potassium channel Kv1.3 for an immunosuppressive agent

A convergent route to (-)-candelalide A involved the union of a trans-decalin portion (AB ring) and a gamma-pyrone moiety through the C16-C3' bond to assemble the whole carbon framework and subsequent formation of the dihydropyran ring (C ring) as the crucial steps. A strategic [2,3]-Wittig rearrangement was employed for establishing the stereogenic center at C9 and an exo-methylene function at C8 present in the decalin portion. [reaction: see text]