Enzyme‐Mediated Preparation of (+)‐ and (−)‐β‐Irone and (+)‐ and (−)‐cis‐γ‐Irone from Irone alpha®

The (−)‐ and (+)‐β‐irones ((−)‐ and (+)‐ 2 , resp.), contaminated with ca. 7 – 9% of the (+)‐ and (−)‐trans‐α‐isomer, respectively, were obtained from racemic α‐irone via the 2,6‐trans‐epoxide (±)‐ 4 (Scheme 2). Relevant steps in the sequence were the LiAlH₄ reduction of the latter, to provide the diastereoisomeric‐4,5‐dihydro‐5‐hydroxy‐trans‐α‐irols (±)‐ 6 and (±)‐ 7 , resolved into the enantiomers by lipase‐PS‐mediated acetylation with vinyl acetate. The enantiomerically pure allylic acetate esters (+)‐ and (−)‐ 8 and (+)‐ and (−)‐ 9 , upon treatment with POCl₃/pyridine, were converted to the β‐irol acetate derivatives (+)‐ and (−)‐ 10 , and (+)‐ and (−)‐ 11 , respectively, eventually providing the desired ketones (+)‐ and (−)‐ 2 by base hydrolysis and MnO₂ oxidation. The 2,6‐cis‐epoxide (±)‐ 5 provided the 4,5‐dihydro‐4‐hydroxy‐cis‐α‐irols (±)‐ 13 and (±)‐ 14 in a 3 : 1 mixture with the isomeric 5‐hydroxy derivatives (±)‐ 15 and (±)‐ 16 on hydride treatment (Scheme 1). The POCl₃/pyridine treatment of the enantiomerically pure allylic acetate esters, obtained by enzymic resolution of (±)‐ 13 and (±)‐ 14 , provided enantiomerically pure cis‐α‐irol acetate esters, from which ketones (+)‐ and (−)‐ 22 were prepared (Scheme 4). The same materials were obtained from the (9S) alcohols (+)‐ 13 and (−)‐ 14 , treated first with MnO₂, then with POCl₃/pyridine (Scheme 4). Conversely, the dehydration with POCl₃/pyridine of the enantiomerically pure 2,6‐cis‐5‐hydroxy derivatives obtained from (±)‐ 15 and (±)‐ 16 gave rise to a mixture in which the γ‐irol acetates 25a and 25b and 26a and 26b prevailed over the α‐ and β‐isomers (Scheme 5). The (+)‐ and (−)‐cis‐γ‐irones ((+)‐ and (−)‐ 3 , resp.) were obtained from the latter mixture by a sequence involving as the key step the photochemical isomerization of the α‐double bond to the γ‐double bond. External panel olfactory evaluation assigned to (+)‐β‐irone ((+)‐ 2 ) and to (−)‐cis‐γ‐irone ((−)‐ 3 ) the strongest character and the possibility to be used as dry‐down note.     

Alternative synthetic strategies for Schiff base derived liquid crystal polymers: A comparative study

Semiflexible liquid crystalline polymers based on Schiff bases as mesogenic cores have been synthesized through different synthetic strategies. The mesogenic cores are derived from 1,5-naphthalenediamine linked to a polymethylenic spacer by means of ether or ester groups. The synthetic strategies differ in the disconnection of the molecules to design the synthesis of the repeating units. Polymers were synthesized either as polyazomethines, where imine bonds are formed in the polymer synthesis, or as polyethers or polyesters, where the ether or ester groups are formed at the polymer-forming stage. The influence of the synthetic method and the linking groups between mesogenic core and flexible spacer on the thermal and mesogenic properties has been analyzed by DSC, thermogravimetry, and optical microscopy. The possibility of obtaining hydroxy-functionalized polymers by different synthetic strategies has been studied as well as the influence of these groups on the thermal and mesogenic properties. © 1996 John Wiley & Sons, Inc.     

Synthesis of Functionalized Proline-Derived Azabicycloalkane Amino Acids and Their Applications in Drug Discovery: Recent Advances

After the first synthesis reported in 1994, azabicycloalkane amino acids have raised increasing interest, becoming one of the most important classes of constrained dipeptide mimics. Their incorporation into peptidomimetic structures allowed the obtainment of a wide range of biologically active compounds. Over the years, different research groups have worked at the development of synthetic strategies to gain these rigid dipeptide surrogates, nevertheless, methods affording functionalized and “easy-to-functionalize” derivatives are quite less described. The presence of a derivatizable azabicycloalkanone core could allow the introduction of chemical modifications aimed to improve the pharmaceutical properties of a biologically active compound without the need for redesigning its chemical synthesis. This account has collected and critically surveyed relevant approaches to the synthesis of functionalized azabicycloalkane amino acids, focusing the attention on the period of 2010 to the present. Moreover, recent applications of these compounds in drug discovery will be discussed.     

One-dimensional metal–organic frameworks built by coordinating 2,4,6-tris(4-pyridyl)-1,3,5-triazine linker with copper nodes: CO2 adsorption properties

The reaction between 2,4,6-tris(4-pyridyl)-1,3,5-triazine (4-tpt) and copper(II) hexafluoroacetylacetone (Cu(hfa)₂) yields two different 1D metal–organic frameworks (MOFs), [(Cu(hfa)₂)₂(4-tpt)]_n ( 1 ) and [Cu(hfa)₂(4-tpt)]_n ( 2 ). The Cu:4-tpt ratio in the new MOFs is determined by the reaction medium, particularly, the solvent used. The two compounds have been fully characterized, including crystal structure elucidation. [(Cu(hfa)₂)₂(4-tpt)]_n ( 1 ), with a 2:1 Cu:4-tpt ratio, could be precipitated in either 1,1,2-trichloroethane or supercritical CO₂. In ( 1 ), 4-tpt shows a tritopic coordination mode, but only half of the Cu(hfa)₂ subunits act as a node, thus connecting two 4-tpt and giving a 1D network. The other half of Cu(hfa)₂ subunits are connected only to one pyridine and thus protrude along the chains. The later Cu(hfa)₂ fragments show a labile character and can be dissolved in diethyl ether to give the second MOF [Cu(hfa)₂(4-tpt)]_n ( 2 ), with a 1:1 Cu:4-tpt ratio. The compound ( 2 ) has also a 1D structure, with all the incorporated copper atoms acting as nodes. In this case, the packing of the chains defines accessible channels, which are perpendicular to the chain axis. After activation, N₂ adsorption/desorption measurements at 77 K confirm the microporous character of ( 2 ) with an apparent surface area of 190 m² g⁻¹. Besides, at 273 K this material clearly shows a significant adsorption of CO₂ prompted by noncoordinated nitrogen in the triazine linker.     

Mechanistic Studies on the Bismuth-Catalyzed Transfer Hydrogenation of Azoarenes

Organobismuth-catalyzed transfer hydrogenation has recently been disclosed as an example of low-valent Bi redox catalysis. However, its mechanistic details have remained speculative. Herein, we report experimental and computational studies that provide mechanistic insights into a Bi-catalyzed transfer hydrogenation of azoarenes using p-trifluoromethylphenol ( 4 ) and pinacolborane ( 5 ) as hydrogen sources. A kinetic analysis elucidated the rate orders in all components in the catalytic reaction and determined that 1 a (2,6-bis[N-(tert-butyl)iminomethyl]phenylbismuth) is the resting state. In the transfer hydrogenation of azobenzene using 1 a and 4 , an equilibrium between 1 a and 1 a ⋅ [OAr]₂ (Ar=p-CF₃−C₆H₄) is observed, and its thermodynamic parameters are established through variable-temperature NMR studies. Additionally, pK_a-gated reactivity is observed, validating the proton-coupled nature of the transformation. The ensuing 1 a ⋅ [OAr]₂ is crystallographically characterized, and shown to be rapidly reduced to 1 a in the presence of 5 . DFT calculations indicate a rate-limiting transition state in which the initial N−H bond is formed via concerted proton transfer upon nucleophilic addition of 1 a to a hydrogen-bonded adduct of azobenzene and 4 . These studies guided the discovery of a second-generation Bi catalyst, the rate-limiting transition state of which is lower in energy, leading to catalytic transfer hydrogenation at lower catalyst loadings and at cryogenic temperature.     

Pushing Up the Size Limit of Boron-doped peri-Acenes: Modular Synthesis and Characterizations

Heteroatom-doped peri-acenes (PAs) have recently attracted considerable attention considering their fascinating physical properties and chemical stability. However, the precise sole addition of boron atoms along the zigzag edges of PAs remains challenging, primarily due to the limited synthetic approach. Herein, we present a novel one-pot modular synthetic strategy toward unprecedented boron-doped PAs (B-PAs), including B-[4,2]PA ( 1 a-2 ), B-[4,3]PA ( 1 b-2 ) and B-[7,2]PA ( 1 c-3 ) derivatives, through efficient intramolecular electrophilic borylation. Their chemical structures are unequivocally confirmed with a combination of mass spectrometry, NMR, and single-crystal X-ray diffraction analysis. Notably, 1 b-2 exhibits an almost planar geometry, whereas 1 a-2 displays a distinctive bowl-like distortion. Furthermore, the optoelectronic properties of this series of B-PAs are thoroughly investigated by UV/Vis absorption and fluorescence spectroscopy combined with DFT calculation. Compared with their parent all-carbon analogs, the obtained B-PAs exhibit high stability, wide energy gaps, and high photoluminescence quantum yields of up to 84 %. This study reveals the exceptional ability of boron doping to finely tune the physicochemical properties of PAs, showcasing their potential applications in optoelectronics.