Dearomative Indole [5+2] Cycloaddition Reactions: Stereoselective Synthesis of Highly Functionalized Cyclohepta[b]indoles

The first dearomative indole [5+2] cycloaddition reaction with an oxidopyrylium ylide resulted in efficient and diastereoselective construction of some highly functionalized and synthetically challenging oxacyclohepta[b]indoles. The protocol proceeds under very mild reaction conditions, thus enabling high functional‐group tolerance and unique endo selectivity.     

Intramolecular [2+2] photocycloaddition of substituted isoquinolones: enantioselectivity and kinetic resolution induced by a chiral template

From simple to complex: Starting from easily accessible isoquinolones 1 (X=Br, OH), complex cyclobutane photoproducts such as compound 2 can be obtained with high enantioselectivity (88-96?%?ee) through the use of a chiral template. Compound 3, which was isolated in 53?%?ee starting from a racemic substrate, is the product of a unique, unprecedented kinetic resolution process.     

Visible‐Light‐Induced Formal [3+2] Cycloaddition for Pyrrole Synthesis under Metal‐Free Conditions

A photocatalytic formal [3+2] cycloaddition of 2H‐azirines with alkynes has been achieved under irradiation by visible light in the presence of organic dye photocatalysts. This transformation provides efficient access to highly functionalized pyrroles in good yields and has been applied to the synthesis of drug analogues. A primary trial of photocascade catalysis merging energy transfer and redox neutral reactions was shown to be successful.     

Rhodium‐Catalyzed [3+2+2] and [2+2+2] Cycloadditions of Two Alkynes with Cyclopropylideneacetamides

It has been established that a cationic rhodium(I)/H₈‐binap complex catalyzes the [3+2+2] cycloaddition of 1,6‐diynes with cyclopropylideneacetamides to produce cycloheptadiene derivatives through cleavage of cyclopropane rings. In contrast, a cationic rhodium(I)/(S)‐binap complex catalyzes the enantioselective [2+2+2] cycloaddition of terminal alkynes, acetylenedicarboxylates, and cyclopropylideneacetamides to produce spiro‐cyclohexadiene derivatives which retain the cyclopropane rings.     

Studies towards the Synthesis of (+)-Dictyoxetane

The dolabellane-type diterpene dictyoxetane represents a significant challenge to synthetic organic chemistry. Methodology directed towards the total synthesis of naturally occurring (+)-dictyoxetane is reported. Catalytic asymmetric synthesis of the trans-hydrindane ring system is achieved through chemoselective deoxygenation of the Hajos-Parrish ketone. An alternative to the Garst-Spencer furan annulation is developed for the synthesis of a 2,5-dimethyl, tetrasubstituted furan, employing a tandem 5-exo-dig alcohol to alkyne cyclisation/aromatisation reaction as a key step. The (4+3) cycloaddition reaction of an oxyallyl cation with a tetrasubstituted furan is established on a cyclohexanone-derived model system, and a range of related (4+3) cycloadditions investigated on a homochiral, trans-hydrindane-fused furan, where regio- and diastereoselectivity is required for the natural product synthesis. In an alternative (4+2) Diels-Alder approach, a C₂-symmetric vinyl sulfoxide-based chiral ketene equivalent is used to prepare oxanorbornenes with the same oxygen bridge stereochemistry found in the 2,7-dioxatricyclo[4.2.1.0^3,8]nonane ring system of the natural product.     

Gold‐Catalyzed Oxa‐Povarov Reactions for the Synthesis of Highly Substituted Dihydrobenzopyrans from Diaryloxymethylarenes and Olefins

Oxa‐Povarov reactions involving readily available diaryloxymethylarenes and aryl‐substituted alkenes are reported. Their [4+2] cycloadditions were efficiently catalyzed by IPrAuSbF₆ (IPr=1,3‐bis(diisopropylphenyl)imidazol‐2‐ylidene) with high diastereoselectivity. Product analysis revealed that the reactions likely proceed by a stepwise ionic mechanism, because both E‐ and Z‐configured β‐methylstyrene gave the same cycloadducts in the same proportions.     

Brønsted Acid Catalysis in Visible‐Light‐Induced [2+2] Photocycloaddition Reactions of Enone Dithianes

1,3‐Dithiane‐protected enones (enone dithianes) were found to undergo an intramolecular [2+2] photocycloaddition under visible‐light irradiation (λ =405 nm) in the presence of a Brønsted acid (7.5–10 mol %). Key to the success of the reaction is presumably the formation of colored thionium ions, which are intermediates of the catalytic cycle. Cyclobutanes were thus obtained in very good yields (78–90 %). It is also shown that the dithiane moiety can be reductively or oxidatively removed without affecting the photochemically constructed ring skeleton.     

Syntheses of seven-membered rings: ruthenium-catalyzed intramolecular [5+2] cycloadditions

The Ru-catalyzed intramolecular [5+2] cycloaddition of cyclopropylenynes is investigated with respect to the regio- and diastereoselectivity as well as the functional group compatibility of the reaction. Evidence for the mechanism as occurring through a ruthenacyclopentene intermediate is elucidated from 1) the study of the diastereoselectivity of the cycloaddition; 2) the effect of variation of substituents on the regioselectivity of cyclopropyl bond cleavage in 1,2-trans- and 1,2-cis-disubstituted cyclopropanes and 3) examples that clearly do not involve ruthenacyclohexene as intermediates as products still incorporate the cyclopropyl moiety. The scope and limitations of the Ru-catalyzed cycloaddition are discussed and compared with the Rh-catalyzed reaction. The potential power of this methodology towards natural product total synthesis is demonstrated by the formation of several polycyclic systems with the chosen reaction conditions and readily available cyclopropylenyne substrates.     

Hexafluoroantimonic Acid Catalysis: Formal [3+2+2] Cycloaddition of Aziridines with Two Alkynes

A practical method for the synthesis of azepine derivatives, a typical seven‐membered heterocyclic ring system, was developed and involves the use of hexafluoroantimonic acid to catalyze a formal [3+2+2] cycloaddition of aziridines with two alkynes. This method was applicable to two of the same or different terminal alkynes for the [3+2+2] cycloaddition with unactivated aziridines, and furnished the corresponding azepine derivatives in good yields with good levels of chemo‐ and regioselectivity. The mechanism was also discussed according to the results of the in situ HRMS and ¹H NMR analysis.