4,7,11‐Triheterotrishomocubanes – Propeller‐Shaped Highly Symmetrical Chiral Molecules Derived from Barrelene

Abstract

Keywords: Barrelene / Chirality / Epoxidation / Rearrangement / Small ring systems / Structure elucidation Epoxidation of barrelene (3) with a neutralized solution of Oxone ® gave the barrelene trisepoxide 6 in 82 % isolated yield, while lead tetraacetate promoted aziridination of 3 with two equiv. of N-aminophthalimide gave a mixture of mono-7 and bis(aziridine) endo,exo-8, which were isolated in 67 and 8 % yield, respectively. Fourfold repetition of this aziridination gave the bis(aziridines) exo,exo-and endo,exo-8 along with the trisaziridine 9 in 21, 8 and 19 % yield, respectively. Epoxidation of 7 and endo,exo-8 with buffered m-chloroperbenzoic acid furnished the dioxaazatrishomobarrelene 10 and oxadiazatrishomobarrelene 11 in 36 and 62 % yield, respectively. The structures of triheteratrishomobarrelenes 6 and 9 were established by X-ray crystallography. Upon treatment with BF 3 ·Et 2 O at -20°C (for 6) or with the strongly acidic ion exchange resin Amberlyst 15 at ambient or elevated temperatures (for 9-11), these triheteratrishomobarrelenes rearrange to give the triheteratrishomocubanes rac-12 to rac-15, as proved by X-ray crystal structure analysis of rac-13, in 75-100 % yield. The enantiomeric pairs of trioxa-12 and triazatrishomocubane 13 were separated by prepara-

Structure Control of Polysaccharide Derivatives for Efficient Separation of Enantiomers by Chromatography

“…According to these statistics, the 3,5-dimethylphenylcarbamates of cellulose, 17ab (Chiralcel OD), and amylose, 18ab (Chiralpak AD), seem to be the most popular ones, followed by cellulose 4-methylbenzoate, 13b (Chiralcel OJ), and amylose ( S )-1-phenylethylcarbamate, ( S )- 30a (Chiralpak AS). Figure shows the recent examples of chiral compounds resolved by the polysaccharide-based CSPs, which include alcohols, amines, , carboxylic acids, ethers, carbonyl and cyano compounds, aromatic hydrocarbons, , nonaromatic compounds, metal-containing compounds, − chiral sulfur or phosphorus , compounds, and axially, − planar, and topologically − asymmetric compounds. For more examples of the available chiral compounds, see the reviews ,− and catalogs. , …”

The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery

“…[51] Further 3D-shaped chiral ring systems that are typical of GDB4c but are already known include twistane 24 obtained by intramolecular α-alkylation of a [2.2.2]bicyclooctanone 25 and deoxygenation of 26, [52] and tris-homocubane reported as the trioxa tris-homocubane 27 resulting from epoxidation of barrelene 28 followed by acid-catalyzed cyclization of the symmetrical triepoxide stereoisomer 29. [53]…”

Three-Membered-Ring-Based Molecular Architectures

“…A recent revisit to this area 582 showed that epoxidation of barrelene (892) with a neutralized solution of Oxone gave the trisepoxide 896 in 82% isolated yield, while aziridination of 892 with phthalimidonitrene generated in situ by lead tetraacetate oxidation of N-aminophthalimide (895) gave a mixture of mono-(897), bis-(898) and trisaziridine (899) in different proportions depending on the number of repeti- Epoxidation of 897 and endo,exo-898 with buffered m-chloroperbenzoic acid furnished the azadioxatrishomobarrelene 900 and diazaoxatrishomobarrelene 901 in 36% and 62% yield, respectively. Upon treatment with BF 3 ‚Et 2 O at -20°C (for 896) or with the strongly acidic ion-exchange resin Amberlyst 15 at ambient or elevated temperatures (for 899-901), these triheterotrishomobarrelenes rearrange to give the 4,7,11-triheterotrishomocubanes, propeller-shaped highly symmetrical chiral molecules rac-902-905 derived from barrelene, in 75-100% yields.…”

“…A recent revisit to this area 582 showed that epoxidation of barrelene (892) with a neutralized solution of Oxone gave the trisepoxide 896 in 82% isolated yield, while aziridination of 892 with phthalimidonitrene generated in situ by lead tetraacetate oxidation of N-aminophthalimide (895) gave a mixture of mono-(897), bis-(898) and trisaziridine (899) in different proportions depending on the number of repeti- The recently published π,σ-domino-Heck arylations, 584 which proceed cleanly with the endo,exo-(877a) but not with the exo,exo-bishomobarrelene (877b), convincingly demonstrate how important the relative configuration of such strained oligocyclic molecules with three-membered rings can be for their reactivity (Scheme 153). 585 Thus, treatment of 877a with aryl iodides under the optimized conditions for hydroarylations of bicyclic alkenes [Pd(OAc) 2 , AsPh 3 , NEt 3 , HCO 2 H, DMF, 65 °C] 585 surprisingly led to the formation of previously unknown 9-arylhomobarbaralanes 909 (barbaralane 570,572b ≡ tricyclo[3.3.1.0 2,8 ]nona-3,6-diene) in 50-86% yield; the straightforward product of a hydroarylation across the double bond in 877a was not even formed in traces.…”