Batch versus Flow Photochemistry: A Revealing Comparison of Yield and Productivity

The use of flow photochemistry and its apparent superiority over batch has been reported by a number of groups in recent years. To rigorously determine whether flow does indeed have an advantage over batch, a broad range of synthetic photochemical transformations were optimized in both reactor modes and their yields and productivities compared. Surprisingly, yields were essentially identical in all comparative cases. Even more revealing was the observation that the productivity of flow reactors varied very little to that of their batch counterparts when the key reaction parameters were matched. Those with a single layer of fluorinated ethylene propylene (FEP) had an average productivity 20 % lower than that of batch, whereas three‐layer reactors were 20 % more productive. Finally, the utility of flow chemistry was demonstrated in the scale‐up of the ring‐opening reaction of a potentially explosive [1.1.1] propellane with butane‐2,3‐dione.     

An Aluminophosphate Molecular Sieve with 36 Crystallographically Distinct Tetrahedral Sites

The structure of the new medium‐pore aluminophosphate molecular sieve PST‐6 is determined by the combined use of rotation electron diffraction tomography, synchrotron X‐ray powder diffraction, and computer modeling. PST‐6 was prepared by calcination of another new aluminophosphate material with an unknown structure synthesized using diethylamine as a structure‐directing agent, which is thought to contain bridging hydroxy groups. PST‐6 has 36 crystallographically distinct tetrahedral sites in the asymmetric unit and is thus crystallographically the most complex zeolitic structure ever solved.     

B-MWW Zeolite: The Case Against Single-Site Catalysis

Boron-containing materials have recently been identified as highly selective catalysts for the oxidative dehydrogenation (ODH) of alkanes to olefins. It has previously been demonstrated by several spectroscopic characterization techniques that the surface of these boron-containing ODH catalysts oxidize and hydrolyze under reaction conditions, forming an amorphous B₂(OH)_xO_(3−x/2) (x=0–6) layer. Yet, the precise nature of the active site(s) remains elusive. In this Communication, we provide a detailed characterization of zeolite MCM-22 isomorphously substituted with boron (B-MWW). Using ¹¹B solid-state NMR spectroscopy, we show that the majority of boron species in B-MWW exist as isolated BO₃ units, fully incorporated into the zeolite framework. However, this material shows no catalytic activity for ODH of propane to propene. The catalytic inactivity of B-MWW for ODH of propane falsifies the hypothesis that site-isolated BO₃ units are the active site in boron-based catalysts. This observation is at odds with other traditionally studied catalysts like vanadium-based catalysts and provides an important piece of the mechanistic puzzle.     

Diversely Functionalised Cytochalasins through Mutasynthesis and Semi-Synthesis

Mutasynthesis of pyrichalasin H from Magnaporthe grisea NI980 yielded a series of unprecedented 4′-substituted cytochalasin analogues in titres as high as the wild-type system (≈60 mg L⁻¹). Halogenated, O-alkyl, O-allyl and O-propargyl examples were formed, as well as a 4′-azido analogue. 4′-O-Propargyl and 4′-azido analogues reacted smoothly in Huisgen cycloaddition reactions, whereas p-Br and p-I compounds reacted in Pd-catalysed cross-coupling reactions. A series of examples of biotin-linked, dye-linked and dimeric cytochalasins was rapidly created. In vitro and in vivo bioassays of these compounds showed that the 4′-halogenated and azido derivatives retained their cytotoxicity and antifungal activities; but a unique 4′-amino analogue was inactive. Attachment of larger substituents attenuated the bioactivities. In vivo actin-binding studies with adherent mammalian cells showed that actin remains the likely intracellular target. Dye-linked compounds revealed visualisation of intracellular actin structures even in the absence of phalloidin, thus constituting a potential new class of actin-visualisation tools with filament-barbed end-binding specificity.     

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids

As a key element in the construction of complex organic scaffolds, the formation of C?C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single‐electron chemistry have enabled new methods for the formation of various C?C bonds. Disclosed herein is the development of a novel single‐electron reduction of acyl azoliums for the formation of ketones from carboxylic acids. Facile construction of the acyl azolium in situ followed by a radical–radical coupling was made possible merging N‐heterocyclic carbene (NHC) and photoredox catalysis. The utility of this protocol in synthesis was showcased in the late‐stage functionalization of a variety of pharmaceutical compounds. Preliminary investigations using chiral NHCs demonstrate that enantioselectivity can be achieved, showcasing the advantages of this protocol over alternative methodologies.     

B‐MWW Zeolite: The Case Against Single‐Site Catalysis

Boron‐containing materials have recently been identified as highly selective catalysts for the oxidative dehydrogenation (ODH) of alkanes to olefins. It has previously been demonstrated by several spectroscopic characterization techniques that the surface of these boron‐containing ODH catalysts oxidize and hydrolyze under reaction conditions, forming an amorphous B₂(OH)_xO_(3?x/2) (x=0–6) layer. Yet, the precise nature of the active site(s) remains elusive. In this Communication, we provide a detailed characterization of zeolite MCM‐22 isomorphously substituted with boron (B‐MWW). Using ¹¹B solid‐state NMR spectroscopy, we show that the majority of boron species in B‐MWW exist as isolated BO₃ units, fully incorporated into the zeolite framework. However, this material shows no catalytic activity for ODH of propane to propene. The catalytic inactivity of B‐MWW for ODH of propane falsifies the hypothesis that site‐isolated BO₃ units are the active site in boron‐based catalysts. This observation is at odds with other traditionally studied catalysts like vanadium‐based catalysts and provides an important piece of the mechanistic puzzle.     

Total Synthesis of (±)‐Phyllantidine: Development and Mechanistic Evaluation of a Ring Expansion for Installation of Embedded Nitrogen‐Oxygen Bonds

The development of a concise total synthesis of (±)‐phyllantidine ( 1 ), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen‐oxygen (N?O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early‐stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N?O bond cleavage, and the rapid assembly of the butenolide found in ( 1 ) via use of the Bestmann ylide.     

Copper(I) halide complexes with 2,2′-bis(diphenylphosphano)-1,1′-binaphthyl (rac-binap) and heterocyclic thiones. Racemic compounds in chiral and achiral crystal space groups

Reactions of copper(I) halides with racemic 2,2′-bis(diphenylphosphano)-1,1′-binaphthyl (rac-binap) in 1:1 molar ratio afforded mononuclear complexes of the type [CuX(rac-binap)] (X = Cl, Br, I) which, on further treatment with 1 equiv. of pyridine-2-thione (py2SH), pyrimidine-2-thione (pymtH) or 4,6-dimethyl-pyrimidine-2-thione (dmpymtH) gave rise to the formation of mixed-ligand complexes of the formula [CuX(rac-binap)(thione)]. The molecular structures of [CuBr(rac-binap)(py2SH)] · 2CH₂Cl₂, [CuBr(rac-binap)(py2SH)] · CH₂Cl₂ and [CuBr(rac-binap)(dmpymtH)] · CH₂Cl₂ have been established by single-crystal X-ray diffraction. Each of the complexes features a distorted tetrahedral copper(I) center with the phosphane acting in a chelating fashion. The complexes are strongly luminescent in the solid state at ambient temperature. Unusually, the [CuBr(rac-binap)(py2SH)] · 2CH₂Cl₂ molecules crystallise in a chiral space group with independent S- and R-enantiomers in the asymmetric unit.