Recent Advances in Transition-Metal-Catalyzed/Mediated Transformations of Vinylidenecyclopropanes

ConspectusVinylidenecyclopropanes (VDCPs), having an allene moiety connected to a highly strained cyclopropyl group, have attracted a substantial amount of attention since they are fascinating building blocks for organic synthesis. During recent years, the reactions of VDCPs in the presence of a Lewis acid or a Brønsted acid and those induced by heat or light have experienced significant advancements due to the unique structural and electronic properties of VDCPs. Transition-metal-catalyzed reactions of VDCPs were not intensely investigated until the last 5 years. Recently, significant progress has been made in transition-metal-catalyzed transformations of VDCPs, and they have emerged as a new direction for the chemistry of strained small rings, especially when new types of functionalized vinylidenecyclopropanes (FVDCPs) are used as substrates. To date, many interesting transformations have been explored using these novel VDCPs under the catalysis of transition metals, such as gold, palladium, or rhodium, and various novel and useful heterocyclic or polycyclic compounds have been generated. These new findings have enriched the chemistry of strained small carbocycles.This Account will describe the transition-metal-catalyzed transformations of VDCPs recently developed in our laboratory and by other groups. The chemistry of Au-catalyzed VDCPs has been enriched and extensively developed by our group. In this respect, a new process for generating gold carbenes from VDCPs has been disclosed. The reactivity of these new gold carbenoid species was fully investigated, and many novel reaction modes based on these new gold carbenoid species were explored, including oxidation reactions, intramolecular cyclopropanations, C­(sp³)–H bond functionalizations, and C–O bond cleavage reactions. Rh-catalyzed reactions of VDCPs are another key field of transition-metal-catalyzed reactions of VDCPs. In particular, rhodium-catalyzed cycloadditions, Pauson–Khand reactions, and C–H bond activations of FVDCPs have been explored in detail by our group. A new trimethylenemethane rhodium (TMM–Rh) complex generated from VDCPs was discovered and utilized as an electrophilic Rh−π-allyl precursor. Moreover, some unprecedented highly regio- and enantioselective asymmetric allylic substitutions via this novel TMM–Rh complex were developed with different kinds of nucleophiles. This Account will also summarize the recent advances in palladium-, copper-, and iron-catalyzed cycloisomerization reactions of VDCPs reported by our group and others. These reactions always afford the desired products with excellent chemo-, regio-, diastereo-, and enantioselectivities, which will make them highly valuable for the synthesis of key scaffolds in natural products and pharmaceutical molecules in the future

Pd(II)-Catalyzed Cyclization–Oxidation of Urea-Tethered Alkylidenecyclopropanes

A Pd­(OAc)₂-catalyzed intramolecular oxidative cyclization of urea-tethered alkylidenecyclopropanes with urea as a nitrogen source through a Pd­(II)/Pd­(IV) catalytic cycle has been presented, giving the corresponding cyclobuta­[<i>b</i>]­indoline derivatives in moderate to good yields with a broad substrate scope. The reaction proceeds through a ring expansion of alkylidenecyclopropane along with the nucleophilic attack of nitrogen atom onto the in situ generated palladium carbenoid species as well as an oxidation process

Phosphine-Catalyzed [3 + 2] Cycloaddition of 4,4-Dicyano-2-methylenebut-3-enoates with Benzyl Buta-2,3-dienoate and Penta-3,4-dien-2-one

4,4-Dicyano-2-methylenebut-3-enoates are employed in the phosphine-catalyzed [3 + 2] cycloaddition with allenoates for the first time, affording regiospecific [3 + 2]-annulation products in moderate to good yields. The multifunctional chiral thiourea-phosphines having an axially chiral binaphthyl scaffold are effective catalysts for the asymmetric variant of this reaction, giving the α-regioisomers in good yields and moderate enantioselectivities

Phosphine-Catalyzed [3 + 2] Cycloaddition of 4,4-Dicyano-2-methylenebut-3-enoates with Benzyl Buta-2,3-dienoate and Penta-3,4-dien-2-one

4,4-Dicyano-2-methylenebut-3-enoates are employed in the phosphine-catalyzed [3 + 2] cycloaddition with allenoates for the first time, affording regiospecific [3 + 2]-annulation products in moderate to good yields. The multifunctional chiral thiourea-phosphines having an axially chiral binaphthyl scaffold are effective catalysts for the asymmetric variant of this reaction, giving the α-regioisomers in good yields and moderate enantioselectivities

Enantioselective Desymmetrization of Bicyclic Hydrazines using a <i>C</i>₂‑Symmetric N‑Heterocyclic Carbene (NHC) Palladium Complex as Catalyst

The first example of palladium-catalyzed enantioselective desymmetrization of 2,3-bicyclic hydrazines with arylboronic acids through a ring-opening process is described by using a chiral <i>C</i>₂-symmetric N-heterocyclic carbene (NHC) palladium complex as the catalyst. The reaction can be performed under convenient conditions to give <i>trans</i>-1,2-disubstituted 3-cyclopentenes <b>3</b> with high regioselectivity in good to excellent yields (up to 95%) and moderate to good enantioselectivities (up to 88% ee)

Pd(II)-Catalyzed Tandem Heterocyclization of 1‑(1-Alkynyl)cyclopropyl Oxime Derivatives for the Synthesis of Functionalized Pyrroles

An efficient approach for the synthesis of highly functionalized pyrroles has been developed by a Pd­(TFA)₂-catalyzed tandem heterocyclization of 1-(1-alkynyl)­cyclopropyl oxime derivatives under mild conditions. The reaction first proceeded via an intramolecular nucleophilic attack followed by a ring-opening process and then intermolecular nucleophilic attack as well as protonation to afford the desired products in moderate to excellent yields

Enantioselective Synthesis of Polycyclic Indole Derivatives Based on aza-Morita–Baylis–Hillman Reaction

A chiral phosphine-catalyzed asymmetric aza-Morita–Baylis–Hillman reaction between indole-derived sulfonyl imines and bis­(3-chlorophenyl)­methyl acrylate has been developed, giving the desired adducts in good yields and enantiomeric excess values along with the further transformations to polycyclic indoles such as dihydropyrido­[1,2-<i>a</i>]­indole and dihydropyrazino­[1,2-<i>a</i>]­indole skeleton

Rh(II)-Catalyzed Chemoselective Oxidative Amination and Nucleophilic Trapping of <i>gem</i>-Dimethyl Alkynyl-Tethered Sulfamates

A Rh­(II)-catalyzed chemoselective oxidative amination and nucleophilic trapping of <i>gem</i>-dimethyl sulfamates has been presented. For 2,2-dimethyl-4-arylbut-3-yn-1-yl sulfamates, the reactions underwent a metallonitrene-initiated alkyne oxidation along with nucleophilic trapping of H₂O upon oxidation, giving aroyl group containing heterocycles. For 2,2-dimethyl-4-arylpent-3-yn-1-yl sulfamates, the α-iminometal carbene intermediate was trapped by aryl group migration, delivering a styryl group containing heterocycles

Iron(II) Dihydrocarbyls Supported by a Biphenyl-Linked Bis(benzimidazol-2-ylidene) Ligand: Syntheses and Characterization

The use of a biphenyl-linked bis­(benzimidazol-2-ylidene) ligand enables the access of dialkyl-, diaryl-, and diallyliron­(II) species with bis­(NHC) ligation. Deprotonation of the biphenyl-linked bis­(benzimidazolium) salt (<b>1</b>) with 2 equiv of KH affords the biphenyl-linked dibenzotetraazafulvalene <b>2</b> in high yield. Treatment of <b>2</b> with 0.5 equiv of [(TMEDA)­FeCl₂]₂ leads to the formation of the biphenyl-linked bis­(benzimidazol-2-ylidene)­iron­(II) dichloride <b>3</b>. Further salt elimination reactions between <b>3</b> and 2 equiv of TMSCH₂Li, C₆H₅CH₂K, PhMgBr, 3,5-(CF₃)₂C₆H₃MgBr, C₃H₅MgCl, and 2-Me-C₃H₄MgCl yield the corresponding biphenyl-linked bis­(benzimidazol-2-ylidene)­iron­(II) dihydrocarbyls, denoted as [bis­(NHC)­FeR₂] (R = CH₂TMS (<b>4</b>), CH₂Ph (<b>5</b>), Ph (<b>6</b>), C₆H₃-3,5-(CF₃)₂ (<b>7</b>), η³-CH₂CHCH₂ (<b>8</b>), η³-CH₂C­(Me)­CH₂ (<b>9</b>)). Compounds <b>2</b>–<b>9</b> have been fully characterized by NMR spectroscopy, absorption spectroscopy, solution magnetic susceptibility measurements, elemental analysis, and X-ray crystallography, revealing that <b>3</b>–<b>7</b> are four-coordinate high-spin iron­(II) compounds with a formal 14-electron count and <b>8</b> and <b>9</b> are diamagnetic bis­(η³-allyl)­iron­(II) species with 18 valence electrons. Attempts to prepare the bis­(hydrocarbyl)­iron­(II) complexes of bulky allyls lead to the isolation of mono­(η¹-allyl)­iron­(II) chloride, denoted as [bis­(NHC)­FeCl­(η¹-TMSCHCHCHTMS)] (<b>10</b>), in low yield, whose structure has also been established by an single-crystal X-ray diffraction study. The achievement of the syntheses of these bis­(hydrocarbyl)­iron­(II) compounds proves the unique electronic and steric features of the biphenyl-linked bis­(benzimidazol-2-ylidene)

Nucleotide sequence and predicted amino acid sequence of <i>Apidaecin1</i> (GenBank Accession EU727255).

<p>The putative signal peptide is bolded, the proregion of the peptide indicated by a single line, the dipeptide indicated by double line, the spacer sequences indicated by dotted line, the mature indicated by an open box, the translational signal (TAA) indicated by the star symbol, restriction and poly(A) adenylation signals(AATAAA) indicated by a wavy line, and the ATTTA sequence is indicated by a double wavy line. The variant loci are boxed in red or indicated by a short red arrow, and numbered in red. The nucleotide substitution sites in the precursor sequences between <i>Apidaecin1</i> and other <i>Apidaecin</i> genes are boxed with a dotted line. “<i>Apidaecin1∼Apidaecin13</i>” is abbreviated to “<i>Abi1∼Api13</i>”.</p