Evolution of Routes for Asymmetric Total Synthesis of Cyclocitrinol Enabled by Type Ⅱ [5+2] Cycloaddition

Main observation and conclusion The asymmetric total synthesis of an unusual C25 steroid containing a unique bicyclo[4.4.1]undecene A/B ring system,resulting in...     

Construction of the Core of Pseudolaric Acid A and Mechanistic Studies on Intramolecular [4+3] Cycloaddition

Pseudolaric acid A (1), which exhibits antifungal activity, cytotoxicity against several tumor cell lines in vitro, as well as contraceptive effects in mice, is a diterpenoid compound isolated from Pseudolarix Kaemferi1. The unusual structural feature in this molecule is a trans arrangement of the lactone and acetoxy group at the fused junction of 5, 7-fused ring skeleton bearing four contiguous stereogenic centers. The synthetic challenges posed by these structural elements in a rather compa…     

Catalytic Enantioselective [2+2] Cycloaddition of α-Halo Acroleins: Construction of Cyclobutanes Containing Two Tetrasubstituted Stereocenters

A catalytic enantioselective formal [2+2] cycloaddition between α-halo acroleins and electronically diverse arylalkenes is described. In the presence of (S)-oxazaborolidinium cation as the catalyst, densely functionalized cyclobutanes containing two vicinal tetrasubstituted stereocenters were produced in high yields and high diastereoselectivities with excellent enantioselectivities. Mechanistic studies revealed that the cis isomer could be transformed into the trans isomer via an enantiocontrolled process. A gram-scale reaction of this catalytic method was used to demonstrate its synthetic potential.     

Asymmetric Construction of Alkaloids by Employing a Key ω-Transaminase Cascade

An ω-transaminase-triggered intramolecular aza-Michael reaction has been employed for the preparation of cyclic β-enaminones in good yield and excellent enantio- and diastereoselectivity, starting from easily accessible prochiral ketoynones and commercially available enzymes. The powerful thermodynamic driving force associated with the spontaneous aza-Michael reaction effectively displaces the transaminase reaction equilibrium towards product formation, using only two equivalents of isopropylamine. To demonstrate the potential of this methodology, this biocatalytic aza-Michael step was combined with annulation chemistry, affording unique stereo-defined fused alkaloid architectures.     

Intermolecular [4+3] Cycloaddition of Cyclic Oxyallyl

The[4+3]cycloaddihonreachonofatlyliCcationsanddienesisavodemeIhalfortheconstwhonofseven-memberedrings1.AkCyvariantofemPlOyingacyclicoxyalll,i.e.,anoxyallylembeinring,wouldPrOvidCaconvenientroutetofunctiotaledmdri-eddsyClesandheteIDCycles.Inaddihon,theketobridgeinthecycloadductwouldbeusefulnotonlyinProvthegasultablefUnchonalityforfurtherebohonbutalsoinrigmpingthefiechemedium-edring.Chaandhisco-workershaveemployedthesaPPrOaChtOthesynthesisofnandProductS2.AtpesenLonlyafewexamplesofthisre…     

Enantioselective Synthesis of Distorted π-Extended Chiral Triptycenes Consisting of Three Distinct Aromatic Rings by Rhodium-Catalyzed [2+2+2] Cycloaddition

The enantioselective synthesis of distorted π-extended chiral triptycenes, consisting of three distinct aromatic rings, has been achieved with high ee value of 87 % by the cationic rhodium(I)/segphos complex-catalyzed enantioselective [2+2+2] cycloaddition of 2,2′-di(prop-1-yn-1-yl)-5,5′-bis(trifluoromethyl)-1,1′-biphenyl with 6-methoxy-1,2-dihydronaphthalene followed by the diastereoselective Diels–Alder reaction and aromatization. Demethoxy derivatives were also synthesized by the C−O bond cleavage. In this synthesis, the use of the electron-deficient diyne and the electron-rich alkene is crucial to suppress the undesired strain-relieving carbocation rearrangement and stabilize the distorted triptycene structure.     

Why Is the Spontaneous Deprotonation of [Cu(uracil)2]2+ Complexes Accompanied by Enolization of the System?

The reaction‐force formalism is applied to carry out a detailed analysis of the mechanisms behind the enolization processes undergone by the complexes formed on interaction of uracil dimers with Cu²⁺ ions after spontaneous deprotonation of the resulting complexes. These enolization processes apparently involve a single proton transfer (PT) from an NH group to a carbonyl group of the same uracil moiety, which should involve a rather high activation barrier that prevents the process occurring. However, the reaction‐force, chemical‐potential, and electronic‐flux profiles unambiguously indicate that the actual mechanism involves three low‐barrier elementary steps, and this explains why enolization of the [Cu(uracil?H)(uracil)]⁺ complexes is a highly facile, assisted PT process. All of the observed PT processes show a typical profile for both the chemical potential and the electronic flux associated with the bond‐breaking and the bond‐formation processes.     

Donor–Acceptor Interactions Induced Interfacial Synthesis of an Ultrathin Fluoric 2D Polymer by Photochemical [2+2] Cycloaddition

Two-dimensional polymers (2DPs) have attracted much interest due to their unique 2D atomic-thick covalent network with periodically linked monomers. The preparation of mono- or few-layered 2DPs with highly ordered structures is still a big challenge. Herein, we report a preparation of ultrathin 2DP film based on photo-triggered [2+2] cycloaddition at the air/water interface. The pre-assembly process induced by the D–A interactions before the polymerization plays a key role in constructing the highly ordered structure. The precise structure and chemical compositions of the continuous 2DP films were proved by selected area electron diffraction (SAED), Tip-Enhanced Raman Spectroscopy (TERS) and molecular-mechanics-based structural simulation.     

A Density Functional Theory Investigation of the Cobalt-Mediated η(5) -Pentadienyl/Alkyne [5+2] Cycloaddition Reaction: Mechanistic Insight and Substituent Effects

Alkyl-substituted η(5) -pentadienyl half-sandwich complexes of cobalt have been reported to undergo [5+2] cycloaddition reactions with alkynes to provide η(2) ,η(3) -cycloheptadienyl complexes under kinetic control. DFT studies have been used to elucidate the mechanism of the cyclization reaction as well as that of the subsequent isomerization to the final η(5) -cycloheptadienyl product. The initial cyclization is a stepwise process of olefin decoordination/alkyne capture, C?C bond formation, olefin arm capture, and a second C?C bond formation; the initial decoordination/capture step is rate-limiting. Once the η(2) ,η(3) -cycloheptadienyl complex has been formed, isomerization to η(5) -cycloheptadienyl again involves several steps: olefin decoordination, β-hydride elimination, reinsertion, and olefin coordination; also here the initial decoordination step is rate limiting. Substituents strongly affect the ease of reaction. Pentadienyl substituents in the 1- and 5-positions assist pentadienyl opening and hence accelerate the reaction, while substituents at the 3-position have a strongly retarding effect on the same step. Substituents at the alkyne (2-butyne vs. ethyne) result in much faster isomerization due to easier olefin decoordination. Paths involving triplet states do not appear to be competitive.     

Synthesis of 4‐Methyl Pyrrolo[2,3‐b]xanthone,a Novel Ring System

A short, high yielding synthesis of a novel substituted pyrrolo[2,3-b]xanthone has been developed. The synthesis begins with a copper catalyzed Ullmann coupling reaction followed by and intramolecular Friedel-Crafts acylation reaction to establish the xanthone core structure. After a regioselective nitration, a Leimgruber-Batcho synthesis establishes the final pyrrole ring.     

π-Extended Pleiadienes by [5+2] Annulation of 1-Boraphenalenes and ortho-Dihaloarenes

Palladium-catalyzed [5+2] annulation of 1-boraphenalenes with ortho-dihaloarenes afforded negatively curved π-extended pleiadienes. Two benzo[1,2-i:4,5-i’]dipleiadienes (BDPs) featuring a seven-six-seven-membered ring arrangement were synthesized and investigated. Their crystal structure revealed a unique packing arrangement and theoretical calculations were employed to shed light onto the dynamic behavior of the BDP moiety and its aromaticity. Further, a naphthalene-fused pleiadiene was stitched together by oxidative cyclodehydrogenation to yield an additional five-membered ring. This formal azulene moiety led to distinct changes in optical and redox properties and increased perturbation of the aromatic system.     

Oxidation of Enones for Regioselective [3+2] Cycloaddition through γ-Enone Radical Intermediates

Herein, an oxidization reaction of enones with a Cu^II complex that leads to a new type of regioselective [3+2] cycloaddition is reported. Highly functionalized cyclopentenes and spirocyclic compounds are obtained in moderate-to-good yields. This cycloaddition reaction occurred through the formation of γ-enone radicals, providing a rarely explored reactivity pattern for enones.     

Supramolecular Photocatalysis by Utilizing the Host–Guest Charge-Transfer Interaction: Visible-Light-Induced Generation of Triplet Anthracenes for [4+2] Cycloaddition Reactions

Supramolecular photocatalysis via charge-transfer excitation of a host–guest complex was developed by use of the macrocyclic boronic ester [2+2]_BTH-F containing highly electron-deficient difluorobenzothiadiazole moieties. In the presence of a catalytic amount of [2+2]_BTH-F, the triplet excited state of anthracene was generated from the charge-transfer excited state of anthracene@[2+2]_BTH-F by visible-light irradiation, and cycloaddition of the excited anthracene with several dienes and alkenes proceeded in a [4+2] manner in high yields.     

[3 + 2] Cycloaddition of Diazomethane Derivatives to Perfluoro-2-phosphapropene

Perfluoro-2-phosphapropene ( 1 ) reacts with diazo compounds R(H)C=N₂ (R = H ( 2 a ), Ph ( 2 b ), CO₂Et ( 2 c ), Me₃Si ( 2 d )) at low temperatures regioselectively yielding via 1,3-H shift the novel 1,2,3-diazaphospholes 4 a – d . The mesomerically stabilized compounds 4 b and 4 c were characterized by NMR spectroscopy and single crystal X-ray diffraction studies. Using diphenyldiazomethane 5 as partner for 1 , the cycloaddition is spontaneously followed by N₂ elimination to give the crystalline phosphirane derivative 7 . The analogous reaction of 1 with 9-diazofluorene 9 unexpectedly leads to the so-far unknown 1,2-diphosphinane compound 11 . Quantum chemical calculations for the gas phase on DFT and RHF level prove that for both the perhydro- and the perfluoro-2-phosphapropene the [3 + 2]-cycloaddition is kinetically determined and that, due to high stability of the products, the thermodynamic equilibrium with the slightly more stable isomers is not accessible.     

Synthesis of the Bis-Tetrahydropyrano[2,3-b:2′,3′-e] Piperazine Ring System: A New Tricyclic Heterocycle from D-Glucosamine

ABSTRACT

2-Amino-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose was transformed into its bis(tetrahydropyranyl)piperazine dimer (4) by reaction with 1,1′-thionyldiimidazole or 1,1′-sulfonyldiimidazole. This dimeric form of glucosamine is the first representative of this previously unknown heterocyclic ring system.     

Catalytic Formal [2π+2σ] Cycloaddition of Aldehydes with Bicyclobutanes: Expedient Access to Polysubstituted 2-Oxabicyclo[2.1.1]hexanes

Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres of benzenoids in modern drug discovery. Here, we report a BF₃-catalyzed [2π+2σ] cycloaddition of aldehydes with bicyclo[1.1.0]butanes (BCBs) to access polysubstituted 2-oxabicyclo[2.1.1]hexanes. A new kind of BCB containing an acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve as a handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides can also be utilized as substrates which undergo cycloaddition with BCBs after in situ rearrangement to aldehydes. We anticipate that our results will promote access to challenging sp³-rich bicyclic frameworks and the exploration of BCB-based cycloaddition chemistry.     

Synthesis of Functionalized Tetrahydropyridines by SnCl4-Mediated [4+2] Cycloaddition between Donor–Acceptor Cyclobutanes and Nitriles

Cycloadditions of strained carbocycles promoted by Lewis acids are powerful methods to construct heterocyclic frameworks. In fact, the formal [3+2] cycloadditions of donor–acceptor (DA) cyclopropanes with nitriles has seen particular success in synthesis. In this work, we report on the first [4+2] cycloaddition of nitriles with DA cyclobutanes by Lewis acid activation. Tetrahydropyridine derivatives were obtained in up to 91 % yield from various aryl-activated cyclobutane diesters and aliphatic or aromatic nitriles.     

Synthesis and structure of bismuth-containing complexes [Ph3PMe] 2 + [BiI5]2− and [Ph3PMe] 2 + [BiI5 · C5H5N]2− · C5H5N

The complexes [Ph₃PMe] ₂ ⁺ [BiI₅]^2? (I) and [Ph₃PMe] ₂ ⁺ [BiI₅ · C ₅H₅N]^2? · C ₅H₅N (II) were synthesized by the reaction of bismuth triiodide with triphenylmethylphosphonium iodide, and their structures were determined by X-ray diffraction analysis. The P atom in cation I has slightly distorted tetragonal coordination polyhedron (the CPC angles 109.42(4)° and 109.52(4)°, the bond lengths P-C_Ph 1.779(2), P-C_Me 1.793(1) Å. The Bi atom in the anion of complex I has an ideal trigonal-bipyramidal coordination polyhedron (Bi-I_eq 3.0031(4), Bi-I_eq 3.0485(5) Å). The crystal of complex II consists of the anions [BiI₅ · C ₅H₅N]^2?, solvated pyridine molecules, and two types of crystallographically independent tetrahedral triphenylmethylphosphonium cations (the angles CPC 106.9(1)°–111.7(1)°, the distances P-C_Ph 1.785(3)–1.792(3), P-C_Me 1.793(3), 1.786(3) Å). The Bi atoms in the anion of complex II have a distorted octahedral coordination polyhedron (Bi-I 3.0878(4)–3.1240(3), Bi-N(1) 2.628(3) Å).     

Unexpected Direct Synthesis of N-Vinyl Amides through Vinyl Azide–Enolate [3+2] Cycloaddition

The unexpected synthesis of industrially important N-vinyl amides directly from aldehydes and α,β-unsaturated N-vinyl amides from esters is reported. This reaction probably proceeds through an initial [3+2] azide–enolate cycloaddition involving a vinyl azide generated in situ. A survey of the reaction scope and preliminary mechanistic findings supported by quantum computational analysis are reported, with implications for the future development of atom-efficient amide synthesis. Intriguingly, this study suggests that (cautious) reevaluation of azidoethene as a synthetic reagent may be warranted.     

Rhodium-Catalyzed Chemo-, Regio-, Diastereo-, and Enantioselective Intermolecular [2+2+2] Cycloaddition of Three Unsymmetric 2π Components

We have developed the Rh⁺/H₈-binap-catalyzed chemo-, regio-, diastereo-, and enantioselective intermolecular [2+2+2] cycloaddition of three unsymmetric 2π components. Thus, two arylacetylenes react with a cis-enamide to yield a protected chiral cyclohexadienylamine. Moreover, replacing one arylacetylene with a silylacetylene enables the [2+2+2] cycloaddition of three distinct unsymmetric 2π components. These transformations proceed with excellent selectivity (complete regio- and diastereoselectivity and up to >99 % yield and >99 % ee). Mechanistic studies suggest the chemo- and regioselective formation of a rhodacyclopentadiene intermediate from the two terminal alkynes.