An organic photochromic compound: (2S)‐2′‐ethoxy‐1,3,3‐trimethyl‐6′‐(piperidin‐1‐yl)spiro[indoline‐2,3′‐3′H‐naphtho[2,1‐b][1,4]oxazine]

In the course of our synthesis of hybrid photochromic compounds, the unexpected new organic photochromic title compound, C₂₉H₃₃N₃O₂, (I), was obtained. It is a derivative of the parent spirooxazine 1,3,3‐trimethyl‐6′‐(piperidin‐1‐yl)spiro[indoline‐2,3′‐3′H‐naphtho[2,1‐b][1,4]oxazine], (II). The 2′‐ethoxy group gives (I) different photochromic properties from its parent spirooxazine (II).     

An approach to novel fused triazole or tetrazole derivatives starting from benzimidazo[1,2‐a]quinazoline‐5(7H)‐one and 5,7‐dihydro‐5‐oxopyrido[3′,2′:5,6]pyrimido[1,2‐a]benzimidazole

The synthetic potential of the title compounds benzimidazo[1,2‐a]quinazoline‐5(7H)‐one 2a and 5,7‐dihydro‐5‐oxopyrido[3′,2′:5,6]pyrimido[1,2‐a]benzimidazole 2b for the construction of novel polyhetero‐cyclic frameworks is reported. Compounds 2a,b , by conversion into their thio analogues 3a,b , were used for the synthesis of tetrazole ( 5a,b ) and triazole ( 7a,b ) derivatives, as well as for an unexpected synthesis of tri‐azoles 8a,b , isomers of 7a,b , resulting from the occurrence of a Dimroth rearrangement.     

Structure and Reactivity of Late Transition Metal η3‐Benzyl Complexes

The coordination of transition metals to organic fragments can yield complexes with fascinating and unexpected binding patterns. The study of metal‐benzyl complexes has demonstrated the feasibility of η³‐coordination, which results in a dearomatized ring. These complexes also offer insight into reaction mechanisms as proposed intermediates in catalytic cycles. In this Review we discuss the synthesis and characterization of these complexes with late transition metals and the subsequent development of catalytic benzylic functionalization methods, including asymmetric variants.     

Bioinspired Synthesis of (−)‐PF‐1018

The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF‐1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels–Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4‐exo‐trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.     

Synthesis and Cytotoxicity of 1,4‐Dihydropyridines and an Unexpected 1,3‐Oxazin‐6‐one

Eight heterocycles have been prepared in a one‐pot reaction manner based on the Hantzsch dihydropyridine synthesis. The synthesis afforded seven dihydropyridines (DHP) and one unexpected 1,3‐oxazin‐6‐one. Their structures were confirmed based on NMR spectroscopy and mass spectrometry. The obtained products have been evaluated for their cytotoxicity against eight cancer cell lines and one normal cell line. Two halogenated DHPs ( 7 and 8 ) displayed cytotoxicity toward all the nine tested cancer cell lines with IC₅₀ values from 4.10 to 58.90 μm, while others showed selective activities. DHPs ( 7 and 8 ) bearing a Me group at C(2) and C(6) as well as a halogenated substituent at C(4′) were more antiproliferative than the others.     

From an α‐Functionalized Silicon‐Stereogenic N,O‐Silane to a Monomeric and Tetracoordinate tBuLi Adduct with Lithium‐Centered Chirality

Donor‐functionalized silanes with stereogenic silicon centers are extremely rare. A convenient stereocontrolled route to a nitrogen‐oxygen‐functionalized silicon‐chiral compound with an additional aminomethyl function is presented. This silane was directly achieved in stereochemically pure form by a simple nucleophilic substitution reaction. Owing to the unique asymmetry of this silane and the presence of three donor functions, the first monomeric butyllithium compound with lithium‐centered chirality could be isolated; the configuration was assigned by X‐ray crystallography. This [silane? tBuLi] complex undergoes an unexpected deprotonation/stereospecific substitution sequence in toluene, leading to the development of a convenient one‐pot synthesis of a functionalized silicon‐chiral benzylsilane, which proceeds with inversion of configuration and complete preservation of the stereochemical integrity at silicon.     

无溶剂条件下利用微波促进下的多组分反应对2,6-二芳基-4-苯乙烯基吡啶化合物进行非预期的绿色简易合成

在无溶剂条件下,通过微波促进下的3-芳基丙烯醛肟、1-芳基乙酮及醋酸铵的多组分反应,非预期地实现了2,6-二芳基-4-苯乙烯基吡啶化合物的绿色简易合成。该方法具有环境友好、反应时间短、产率高、成本低、操作简便以及适用范围广等优点。     

A Short Scalable Route to (−)‐α‐Kainic Acid Using Pt‐Catalyzed Direct Allylic Amination

An increased supply of scarce or inaccessible natural products is essential for the development of more sophisticated pharmaceutical agents and biological tools, and thus the development of atom‐economical, step‐economical and scalable processes to access these natural products is in high demand. Herein we report the development of a short, scalable total synthesis of (?)‐α‐kainic acid, a useful compound in neuropharmacology that is, however, limited in supply from natural resources. The synthesis features sequential platinum‐catalyzed direct allylic aminations and thermal ene‐cyclization, enabling the gram‐scale synthesis of (?)‐α‐kainic acid in six steps and 34 % overall yield.     

Unexpected Michael Additions on the Way to 2.3,8.9‐Dibenzanthanthrenes with Interesting Structural Properties

The synthesis and properties of a new polycyclic aromatic hydrocarbon containing eight annulated rings and based on the anthanthrene core is described. An unexpected, nucleophile‐dependent Michael addition to a dibenzanthanthrene‐1,7‐dione is found, giving a product with three triisopropylsilylacetylene units and a remarkable solid‐state structure (as determined by X‐ray crystallography).     

An unexpected synthesis of an α,β,γ,δ-unsaturated ketone due to an abnormal opening of benzylidene acetal by bromide anion

An unexpected synthesis of an α, β, γ,δ-unsaturated ketone, which embodies a new type of oxy-carbon cyclic structure, was achieved, while we tried to construct the taxane CB-ring system. Also, a series of abnormal reaction phenomena was found to be related to the formation and reaction of seven membered cyclic benzylidene acetal.     

A Fluorescent Blue Phosphazene Dye: Synthesis,Structure and Optical Properties of 1,6‐Bis(Dimethylamino)‐2,5,7,10‐Tetraazo‐1,6λ5‐Diphosphapyrene

Herein we report on the synthesis, structure, and optical properties of the fluorescent blue phosphazene dye 1,6‐bis(dimethylamino)‐2,5,7,10‐tetraazo‐1,6λ⁵‐diphosphapyrene, which was isolated as the unexpected product of the reaction between 1,4,5,8‐(tetraamino)naphthalene and [P(NMe₂)₃Br]Br. This dye, which turned out to be soluble in water and a range of organic solvents (including hexane, tetrahydrofuran / petroleum ether, acetonitrile, and ethanol), was structurally characterized by XRD. Its absorption as well as emission spectra and their sensitivity to pH variations were analyzed. The experimental work is complemented by quantum chemical calculations on the possible intermediate on the way to the isolated product and on its pK_a value.     

Enantioselective Synthesis of Medium‐Sized Lactams via Chiral α,β‐Unsaturated Acylammonium Salts

Medium‐sized lactams are important structural motifs found in a variety of bioactive compounds and natural products but are challenging to prepare, especially in optically active form. A Michael addition/proton transfer/lactamization organocascade process is described that delivers medium‐sized lactams, including azepanones, benzazepinones, azocanones, and benzazocinones, in high enantiopurity through the intermediacy of chiral α,β‐unsaturated acylammonium salts. An unexpected indoline synthesis was also uncovered, and the benzazocinone skeleton was transformed into other complex heterocyclic derivatives, including spiroglutarimides, isoquinolinones, and δ‐lactones.     

Crystallographic identification of an unexpected by‐product in an Ullman's reaction toward biphenyls: 1‐(4‐hexyloxy‐3‐hydroxyphenyl)ethanone

The synthesis of 3,3′‐diacetoxy‐4,4′‐bis(hexyloxy)biphenyl following the nickel‐modified Ullmann reaction yielded a by‐product which was identified successfully by crystallographic analysis as 1‐(4‐hexyloxy‐3‐hydroxyphenyl)ethanone, C₁₄H₂₀O₃. This unexpected nonbiphenyl by‐product exhibited IR, ¹H NMR, ¹³C NMR and COSY (correlation spectroscopy) spectra fully consistent with the proposed structure. The compound crystallized in the orthorombic Pbca space group, with two independent formula units in the asymmetric unit (one of which was slightly disordered), and showed a supramolecular architecture in which molecules linked by hydroxy–ethanone O—H...O interactions are organized in columns separated by the aliphatic tails.     

Synthesis of Triazolo[1,5‐a]triazin‐7‐one Derivatives and Highly Functionalized [1,2,4]Triazoles

The synthesis of novel triazolo[1,5‐a]triazin‐7‐ones is presented. Starting from 3‐amino‐5‐sulfanyl‐1,2,4‐triazole, the synthetic sequence involved alkylation with benzyl bromide, reaction with p‐nitrophenyl chloroformate followed by treatment with a primary amine, and condensation with diethoxymethyl acetate. Final oxidation of the thioether moiety with 3‐chloroperbenzoic acid provided 2‐(benzylsulfonyl)[1,2,4]triazolo[1,5‐a][1,3,5]triazin‐7‐ones 5a and 5b in good overall yields. Treatment of 5a and 5b with secondary amines provided highly functionalized [1,2,4]triazoles through an unexpected triazinone ring opening. A mechanism for this transformation is proposed.     

A Novel One Pot Synthesis of o‐Nitrophenylacetic Acid and Unexpected p‐Nitrobenzoic Acid by HNO3‐Mediated CH2 Extrusion Reaction of Phenylacetic Acid

The HNO₃‐mediated CH₂ extrusion reactions of phenylacetic acid lead to one pot synthesis of unexpected commercially important product 4‐nitrobenzoic acid through the formation of 4‐nitrophenylacetic acid and 2‐nitrophenylacetic acid.     

Synthesis of pyridazine derivatives through the unexpected intermediate 5‐amino‐ 4‐cyano ‐2,3‐dihydro‐furan‐2,3‐disulfonic acid disodium salt

An unexpected compound (5‐amino‐4‐cyano‐2,3‐dihydrofuran‐2,3‐disulfonic acid disodium salt, 4 ) was isolated from the reaction of glyoxale bis hydrogen sulfite disodium salt with malononitrile. Its structure was undoubtly identified through crystal structure analysis. Compound 4 was highly stable and it was isolated easily and in a very high yield. Its reactivity was studied in the reactions with some hydrazine derivatives in order to obtain different pyridazine analogs.     

Multistep Flow Synthesis of 5‐Amino‐2‐aryl‐2H‐[1,2,3]‐triazole‐4‐carbonitriles

1,2,3‐Triazole has become one of the most important heterocycles in contemporary medicinal chemistry. The development of the copper‐catalyzed Huisgen cycloaddition has allowed the efficient synthesis of 1‐substituted 1,2,3‐triazoles. However, only a few methods are available for the selective preparation of 2‐substituted 1,2,3‐triazole isomers. In this context, we decided to develop an efficient flow synthesis for the preparation of various 2‐aryl‐1,2,3‐triazoles. Our strategy involves a three‐step synthesis under continuous‐flow conditions that starts from the diazotization of anilines and subsequent reaction with malononitrile, followed by nucleophilic addition of amines, and finally employs a catalytic copper(II) cyclization. Potential safety hazards associated with the formation of reactive diazonium species have been addressed by inline quenching. The use of flow equipment allows reliable scale up processes with precise control of the reaction conditions. Synthesis of 2‐substituted 1,2,3‐triazoles has been achieved in good yields with excellent selectivities, thus providing a wide range of 1,2,3‐triazoles.     

Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward Astellatol and the Total Synthesis of (−)‐Nitidasin

Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans‐hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems, posing significant challenges for chemical synthesis. Herein, the evolution of our stereoselective strategy for isopropyl trans‐hydrindane sesterterpenoids is detailed. These endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second‐generation and a third‐generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (?)‐nitidasin. In particular, a series of substrate‐controlled transformations to install the ten stereogenic centers of the target molecule was orchestrated and the carbocyclic backbone was forged in a convergent fashion. Furthermore, the progress toward the synthesis of astellatol is disclosed and insights into some observed yet unexpected diastereoselectivities by detailed quantum‐mechanical calculations are provided.     

Copper‐Free Huisgen Cycloaddition for the 14‐3‐3‐Templated Synthesis of Fusicoccin‐Peptide Conjugates

Mid‐sized molecules have emerged as an attractive chemical space and potentially provide a robust basis for the development of synthetic agents to control intracellular protein interactions. However, the limited cell permeability and chemical tractability of such agents remain to be addressed. We envisioned that target‐templated synthesis of such mid‐sized molecules might provide a solution. Here, we exploited a copper‐free Huisgen cycloaddition for template synthesis using a peptide fragment containing a 4,8‐diazacyclononyne (DACN) moiety and an azide‐containing fusicoccin derivative in the presence or absence of recombinant 14‐3‐3ζ protein in vitro. Time‐course changes in the yield of products demonstrated that the reaction was accelerated in the presence of 14‐3‐3 and one of the regioisomers was generated predominantly, supporting the template effect.     

FeCl3‐Mediated Three‐Component Cascade Reaction: An Effective Approach to the Construction of Highly Functionalized Pyrrolo[1,2‐c]quinazolinones

An unexpected FeCl₃‐mediated three‐component cascade reaction has been used to construct structurally diverse pyrrolo[1,2‐c]quinazolinone derivatives with potential biological activities. This method has advantages of mild conditions, simple work‐up, as well as wide substrate scope, which makes it a powerful approach to the synthesis of diverse pyrrolo[1,2‐c]quinazolinones. This cascade reaction involves 1,3‐dipolar cycloaddition between azomethine ylides and allenoates, followed by intramolecular nucleophilic addition in the presence of FeCl₃. The obtained products could be easily transformed into derivatives with the pyrrolo[2,3‐c]quinazoline alkaloid skeleton.