Convergent Strategy for the Synthesis of Oxa-, Thia-, and Selena[5]helicenes by Acetylene-Activated SNAr Reactions.

A tandem acetylene-activated SNAr-anionic cyclization strategy is presented for the synthesis of chalcogen-containing hetero[5]helicenes. Oxa-, thia-, and selena[5]helicenes are accessed from common ortho-fluoro-ethynylarene precursors, allowing the heteroatoms to be installed at the 1-position or 1- and 12-positions of the hetero[5]helicene inner core surface.

An alternative role for acetylenes: activation of fluorobenzenes toward nucleophilic aromatic substitution.

Acetylenes are increasingly versatile functional groups for a range of complexity-building organic transformations and for the construction of desirable molecular architectures. Herein we disclose a previously underappreciated aspect of arylacetylene reactivity by utilizing alkynes as electron-withdrawing groups (EWG) for promoting nucleophilic aromatic substitution (S(N)Ar) reactions. Reaction rates for the substitution of 4-(fluoroethynyl)benzenes by p-cresol were determined by (1)H NMR spectroscopy, and these rate data were used to determine substituent (Hammett) constants for terminal and substituted ethynyl groups. The synthetic scope of acetylene-activated S(N)Ar reactions is broad; fluoroarenes bearing one or two ethynyl groups undergo high-yielding substitution with a variety of oxygen and arylamine nucleophiles.

Oxacalixarenes and oxacyclophanes containing 1,8-naphthyridines: a new class of molecular tweezers with concave-surface functionality.

The first examples of oxacalix[4]arenes and [1(4)]oxacyclophanes bearing 1,8-naphthyridine units are reported, and these systems function as molecular tweezers containing inner-cavity hydrogen bond acceptors.

Synthesis of oxacalixarenes incorporating nitrogen heterocycles: evidence for thermodynamic control.

[structure: see text] Oxacalix[2]arene[2]hetarenes are formed in a single step by cyclooligomerization of meta-diphenols with meta-dichlorinated azaheterocycles. The high selectivity for cyclic tetramer formation results from thermodynamic product control. Macrocycles as large as oxacalix[5]arene[5]hetarenes have been isolated under nonequilibrating conditions.

Single-step synthesis of D3h-symmetric bicyclooxacalixarenes.

Bicyclooxacalixarenes are obtained in up to 95% yield by condensation of phloroglucinol with electron-poor meta-dihalogenated benzenes or pyridines. Single-crystal X-ray analysis reveals that these compounds adopt highly symmetrical, all-1,3-alternate cage-like structures. [structure: see text]

Synthesis of functionalized oxacalix[4]arenes.

Tetranitrooxacalix[4]arenes are generated in high yield by the room-temperature S(N)Ar reaction of 1,3-dihydroxybenzenes with 1,5-difluoro-2,4-dinitrobenzene. The reaction is tolerant to a range of functionality on the nucleophilic component, including hydroxyl-substitution at the 2- and 5-positions, which yields previously unknown 26,28- and 5,17-dihydroxyoxacalix[4]arenes.

Total Syntheses of Vancomycin and Eremomycin Aglycons.

Controlling the elements of planar and axial chirality are the principal challenges in the synthesis of the aglycon of vancomycin. Vancomycin is the prototypical member of the glycopeptide family of antibiotics which are effective for the treatment of infections by methicillin-resistant Staphylococcus aureus. The first total syntheses of the vancomycin and eremomycin aglycons provide insight into the influence of structure on kinetic and thermodynamic control of atropselective macrocyclizations.

Nonconventional Stereochemical Issues in the Design of the Synthesis of the Vancomycin Antibiotics: Challenges Imposed by Axial and Nonplanar Chiral Elements in the Heptapeptide Aglycons.

Controlling the elements of planar and axial chirality are the principal challenges in the synthesis of the aglycon of vancomycin. Vancomycin is the prototypical member of the glycopeptide family of antibiotics which are effective for the treatment of infections by methicillin-resistant Staphylococcus aureus. The first total syntheses of the vancomycin and eremomycin aglycons provide insight into the influence of structure on kinetic and thermodynamic control of atropselective macrocyclizations.

Single step synthesis of acetylene-substituted oxacalix[4]arenes.

Oxacalixarenes bearing acetylene groups are synthesized in a single step by nucleophilic aromatic substitution reactions of orcinol with various 1,5-diethynyl-2,4-difluorobenzenes. Thermodynamic equilibration of the cyclooligomer mixtures was accomplished for arylethynyl activating groups, leading to increased yields of the corresponding oxacalix[4]arenes. A 1,3-alternate macrocycle conformation is observed in the solid state, presenting a large V-shaped π-surface.

Synthesis of inherently chiral azacalix[4]arenes and diazadioxacalix[4]arenes.

Described are nucleophilic aromatic substitution reactions for the synthesis of inherently chiral azacalix[4]arenes and diazadioxacalix[4]arenes comprised of two or three different aromatic monomers. A variety of functional groups are tolerated at the 2-, 4-, and 5-positions on the nucleophilic-component monomers; reactions are run under ambient atmosphere; and the macrocycles are constructed without isolation of intermediate linear species.