Dicyanometallates as Model Extended Frameworks

We report the structures of eight new dicyanometallate frameworks containing molecular extra-framework cations. These systems include a number of hybrid inorganic–organic analogues of conventional ceramics, such as Ruddlesden–Popper phases and perovskites. The structure types adopted are rationalized in the broader context of all known dicyanometallate framework structures. We show that the structural diversity of this family can be understood in terms of (i) the charge and coordination preferences of the particular metal cation acting as framework node, and (ii) the size, shape, and extent of incorporation of extra-framework cations. In this way, we suggest that dicyanometallates form a particularly attractive model family of extended frameworks in which to explore the interplay between molecular degrees of freedom, framework topology, and supramolecular interactions

Dicyanometallates as Model Extended Frameworks

We report the structures of eight new dicyanometallate frameworks containing molecular extra-framework cations. These systems include a number of hybrid inorganic–organic analogues of conventional ceramics, such as Ruddlesden–Popper phases and perovskites. The structure types adopted are rationalized in the broader context of all known dicyanometallate framework structures. We show that the structural diversity of this family can be understood in terms of (i) the charge and coordination preferences of the particular metal cation acting as framework node, and (ii) the size, shape, and extent of incorporation of extra-framework cations. In this way, we suggest that dicyanometallates form a particularly attractive model family of extended frameworks in which to explore the interplay between molecular degrees of freedom, framework topology, and supramolecular interactions

α‑Lithiation–Electrophile Trapping of <i>N</i>‑Thiopivaloylazetidin-3-ol: Stereoselective Synthesis of 2‑Substituted 3‑Hydroxyazetidines

α-Lithiation of <i>N</i>-thiopivaloylazetidin-3-ol and subsequent electrophile trapping provides access to a range of 2-substituted 3-hydroxyazetidines with generally good <i>trans</i>-diastereoselectivity, aside from deuteration, which gives the <i>cis</i>-diastereoisomer. Deuterium labeling studies indicate that the initial α-deprotonation occurs preferentially, but not exclusively, in a <i>trans</i>-selective manner. These studies also suggest that the stereochemical outcome of the electrophile trapping depends on the electrophile used but is independent of which α-proton (<i>cis</i> or <i>trans</i> to the hydroxyl group) is initially removed

α‑Lithiation–Electrophile Trapping of <i>N</i>‑Thiopivaloylazetidin-3-ol: Stereoselective Synthesis of 2‑Substituted 3‑Hydroxyazetidines

α-Lithiation of <i>N</i>-thiopivaloylazetidin-3-ol and subsequent electrophile trapping provides access to a range of 2-substituted 3-hydroxyazetidines with generally good <i>trans</i>-diastereoselectivity, aside from deuteration, which gives the <i>cis</i>-diastereoisomer. Deuterium labeling studies indicate that the initial α-deprotonation occurs preferentially, but not exclusively, in a <i>trans</i>-selective manner. These studies also suggest that the stereochemical outcome of the electrophile trapping depends on the electrophile used but is independent of which α-proton (<i>cis</i> or <i>trans</i> to the hydroxyl group) is initially removed

Synthesis of Stereoisomers of <i>Artemisia</i> and <i>Chrysanthemum</i> Bis(acetylenic) Enol Ether Spiroacetals

An 11-step synthesis is described of two diastereomeric candidates for a bis­(acetylenic) enol ether spiroacetal isolated from <i>Chrysanthemum boreale</i>. Key steps in the synthetic route include spiroacetal lactone alkylidenation and subseqent modified Cadiot–Chodkiewicz cross-coupling to install the bis­(acetylenic) enol ether functionality. From NMR comparisons, neither of the candidates, whose structures were confirmed by single-crystal X-ray diffraction, correspond to the natural product, and a proposal for the correct structure is put forward

Porphyrin–Polyyne [3]- and [5]Rotaxanes

Porphyrin–polyyne [3]- and [5]­rotaxanes have been synthesized by condensing aldehyde–rotaxanes with pyrrole or dipyrromethane. The crystal structure of a [3]­rotaxane shows that the macrocycles adopt compact conformations, holding the hexaynes near the porphyrin core, and that the phenanthroline units form intermolecular π-stacked dimers in the solid. Fluorescence spectra reveal singlet excited-state energy transfer from the threaded hexayne to the porphyrin, from the phenanthroline to the porphyrin, and from the phenanthroline to the hexayne

<i>C</i>‑Alkylation of Chiral Tropane- and Homotropane-Derived Enamines

The synthesis and alkylation of chiral, nonracemic tropane- and homotropane-derived enamines is examined as an approach to enantioenriched α-alkylated aldehydes. The two bicyclic N auxiliaries, which differ by a single methylene group, give opposite senses of asymmetric induction on alkylation with EtI and provide modestly enantioenriched 2-ethylhexanal (following hydrolysis of the alkylated iminium). The observed stereoselectivity is supported by density functional studies of ethylation for both enamines

<i>C</i>‑Alkylation of Chiral Tropane- and Homotropane-Derived Enamines

The synthesis and alkylation of chiral, nonracemic tropane- and homotropane-derived enamines is examined as an approach to enantioenriched α-alkylated aldehydes. The two bicyclic N auxiliaries, which differ by a single methylene group, give opposite senses of asymmetric induction on alkylation with EtI and provide modestly enantioenriched 2-ethylhexanal (following hydrolysis of the alkylated iminium). The observed stereoselectivity is supported by density functional studies of ethylation for both enamines

Enantioselective Michael Addition/Iminium Ion Cyclization Cascades of Tryptamine-Derived Ureas

A Michael addition/iminium ion cyclization cascade of enones with tryptamine-derived ureas under BINOL phosphoric acid (BPA) catalysis is reported. The cascade reaction tolerates a wide variety of easily synthesized tryptamine-derived ureas, including those bearing substituents on the distal nitrogen atom of the urea moiety, affording polyheterocyclic products in good yields and good to excellent enantioselectivities

Synthesis of Mimics of Pramanicin from Pyroglutamic Acid and Their Antibacterial Activity

Epoxypyrrolidinones are available by epoxidation of carboxamide-activated bicyclic lactam substrates derived from pyroglutamate using aqueous hydrogen peroxide and tertiary amine catalysis. In the case of an activating Weinreb carboxamide, further chemoselective elaboration leads to the efficient formation of libraries of epoxyketones. Deprotection may be achieved under acidic conditions to give epoxypyroglutaminols, although the ease of this process can be ameliorated by the presence of internal hydrogen bonding. Bioassay against <i>S. aureus</i> and <i>E. coli</i> indicated that some compounds exhibit antibacterial activity. These libraries may be considered to be structural mimics of the natural products pramanicin and epolactaene. More generally, this outcome suggests that interrogation of bioactive natural products is likely to permit the identification of “privileged” structural scaffolds, providing frameworks suitable for optimization in a short series of chemical steps that may accelerate the discovery of new antibiotic chemotypes. Further optimization of such systems may permit the rapid identification of novel systems suitable for antibacterial drug development