Rolf Huisgen's Classic Studies of Cyclic Triene Diels–Alder Reactions Elaborated by Modern Computational Analysis

Rolf Huisgen explored the Diels–Alder reactions of 1,3,5‐cycloheptatriene (CHT) and cyclooctatetraene (COT) with the dienophiles maleic anhydride and 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione (PTAD) to determine the kinetics and mechanisms of various electrocyclizations and Diels–Alder reactions. These reactions have been examined with density functional theory. Modern computational chemistry has provided information not previously available by experiment. Transition states for all the reactions have been identified, and their Gibbs energies are used to explain the experimental reactivities. Zwitterionic intermediates were not found in the [4+2] cycloadditions of both CHT or COT with PTAD and are thus not involved in these reactions. [2+2+2] cycloadditions, as an alternative path to the Diels–Alder products, are highly disfavored. Rapid double nitrogen inversion was found for the cycloaddition products with PTAD.     

Rolf Huisgen's Classic Studies of Cyclic Triene Diels–Alder Reactions Elaborated by Modern Computational Analysis

Rolf Huisgen explored the Diels–Alder reactions of 1,3,5-cycloheptatriene (CHT) and cyclooctatetraene (COT) with the dienophiles maleic anhydride and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) to determine the kinetics and mechanisms of various electrocyclizations and Diels–Alder reactions. These reactions have been examined with density functional theory. Modern computational chemistry has provided information not previously available by experiment. Transition states for all the reactions have been identified, and their Gibbs energies are used to explain the experimental reactivities. Zwitterionic intermediates were not found in the [4+2] cycloadditions of both CHT or COT with PTAD and are thus not involved in these reactions. [2+2+2] cycloadditions, as an alternative path to the Diels–Alder products, are highly disfavored. Rapid double nitrogen inversion was found for the cycloaddition products with PTAD.     

DFT study on the Diels-Alder cycloaddition between alkenyl-M(0) (M = Cr, W) carbene complexes and neutral 1,3-dienes

The thermal Diels-Alder reaction between alkenylmetal(0) Fischer carbenes and 1,3-dienes (isoprene and cyclopentadiene) has been studied computationally within the density functional theory framework. The selectivity of the [4 + 2] cycloadditions between alkenyl-group 6 (Fischer) carbene complexes and isoprene is similar to the selectivity computed for the reactions involving Lewis acid complexed acrylates. The experimentally observed complete endo selectivity in the [4 + 2] cycloadditions of alkenyl-group 6 (Fischer) carbene complexes with cyclopentadiene, which takes place under kinetic control, may be due in part to the presence of stabilizing secondary orbital interactions. These interactions are stronger than the analogues in the metal-free processes. The [4 + 2] cycloadditions between alkenyl-group 6 (Fischer) carbene complexes and neutral dienes occur concertedly via transition structures which are more asynchronous and less aromatic than their non-organometallic analogues, a behavior which is extensible to the reactions between Lewis acid complexed acrylates.     

Air-stable platinum and palladium complexes featuring bis[2,4-bis(trifluoromethyl)phenyl]phosphinous acid ligands

Secondary phosphane oxides, R(2)P(O)H, are commonly used as preligands for transition-metal complexes of phosphinous acids, R(2)P-OH (R=alkyl, aryl), which are relevant as efficient catalysts in cross-coupling processes. In contrast to previous work by other groups, we are interested in the ligating properties of an electron-deficient phosphinous acid, (R(f))(2)P-OH, bearing the strongly electron-withdrawing and sterically demanding 2,4-bis(trifluoromethyl)phenyl group towards catalysis-relevant metals, such as palladium and platinum. The preligand bis[2,4-bis(trifluoromethyl)phenyl]phosphane oxide, (R(f))(2)P(O)H, reacts smoothly with solid platinum(II) dichloride yielding the trans-configured phosphinous acid platinum complex trans-[PtCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)POH)(2)]. The deprotonation of one phosphinous acid ligand with an appropriate base leads to the cis-configured monoanion complex cis-[PtCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)H](-), featuring the quasi-chelating phosphinous acid phosphinito unit, (R(f))(2)P-O-H···O=P(R(f))(2), which exhibits a strong hydrogen bridge substantiated by an O···O distance of 245.1(4) pm. The second deprotonation step is accompanied by a rearrangement to afford the trans-configured dianion trans-[PtCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)](2-). The reaction of (R(f))(2)P(O)H with solid palladium(II) dichloride initially yields a mononuclear palladium complex [PdCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)POH)(2)], which condenses under liberation of HCl to the neutral dinuclear palladium complex [Pd(2)(μ-Cl)(2){({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)H}(2)]. The equilibrium between the mononuclear [PdCl(2)({2,4-(CF(3))(2)C(6)H(3)}(2)POH)(2)] and dinuclear [Pd(2)(μ-Cl)(2){({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)H}(2)] palladium complexes is reversible and can be shifted in each direction by the addition of base or HCl, respectively. Treatment of palladium(II) hexafluoroacetylacetonate, [Pd(F(6)acac)(2)], with a slight excess of (R(f))(2)P(O)H yields the complex [Pd(F(6)acac)({2,4-(CF(3))(2)C(6)H(3)}(2)PO)(2)H]. The quasi-chelating phosphinous acid phosphinito unit, which is formed by the liberation of HF(6)acac, is characterized by a O···O distance of 244.1(3) pm. These transition metal complexes are stable towards air and moisture and can be stored for months without any evidence of decomposition.     

Utilizing Vinylcyclopropane Reactivity: Palladium‐Catalyzed Asymmetric [5+2] Dipolar Cycloadditions

Vinylcyclopropanes (VCPs) are commonly used in transition‐metal‐catalyzed cycloadditions, and the utilization of their recently realized reactivities to construct new cyclic architectures is of great significance in modern synthetic chemistry. Herein, a palladium‐catalyzed, visible‐light‐driven, asymmetric [5+2] cycloaddition of VCPs with α‐diazoketones is accomplished by switching the reactivity of the Pd‐containing dipolar intermediate from an all‐carbon 1,3‐dipole to an oxo‐1,5‐dipole. Enantioenriched seven‐membered lactones were produced with good reaction efficiencies and selectivities (23 examples, 52–92 % yields with up to 99:1 er and 12.5:1 dr). In addition, computational investigations were performed to rationalize the observed high chemo‐ and periselectivities.     

The chemistry of fluorine containing phosphaalkenes, arsaalkenes and selenocarbonyls

This review covers our extensive research activities in the area of fluorine containing phospha- and arsaalkenes as well as selenocarbonyls, which differ considerably in their properties and reactivities from their alkyl and aryl counterparts and thus contribute in a gratifying manner to the still growing field of unsaturated element-carbon compounds of 3rd and 4th row main group elements E. Of particular interest is the influence of the fluorine substituents and other small groups (OR, NR₂) with either inductive and/or mesomeric effects on the polarity and reactivity of the EC bond. Addition reactions of proton acidic and hydridic polar HX reactants as well as [2+2], [3+2] and [4+2] cycloadditions have been thoroughly studied. The results obtained allow a classification of the EC systems within five different types, A to E, and prove a change from “normal” to “inverse” heteroalkenes in this sequence. The ligand properties of some derivatives have also been investigated in some detail.     

RhII‐Catalyzed [3+2] Cycloaddition of 2 H‐Azirines with N‐Sulfonyl‐1,2,3‐Triazoles

Rh^II‐catalyzed intermolecular [3+2] cycloaddition of 2 H‐azirines with N‐sulfonyl‐1,2,3‐triazoles is disclosed, in which a series of fully functionalized pyrroles is produced via rhodium azavinyl carbene intermediates. A distinct feature of this reaction is that the azavinyl carbene serves as a [2 C] equivalent, instead of as [1 C] or aza‐[3 C] synthons, which have been reported previously in cyclopropanations and [3+n] cycloadditions. Moreover, this methodology has also been successfully applied in the total synthesis of URB447 as well as the formal synthesis of Atorvastatin (Lipitor).     

The synthesis and chemoselective reactivity of 3-aminocyclopentadienones

Iron and cobalt complexes of 3-aminocyclopentadienones have been synthesized from the [2 + 2 + 1] cycloadditions of nitrogen acetylenes and pendant alkynes. Following decomplexation, the resulting 3-aminocyclopentadienones have been subjected to chemo- and regioselective cycloadditions with dienophiles and heterodienes.     

The Divergent Synthesis of Nitrogen Heterocycles by Rhodium(II)‐Catalyzed Cycloadditions of 1‐Sulfonyl 1,2,3‐Triazoles with 1,3‐Dienes

The first rhodium(II)‐catalyzed aza‐[4+3] cycloadditions of 1‐sulfonyl 1,2,3‐triazoles with 1,3‐dienes have been developed, and enable the efficient synthesis of highly functionalized 2,5‐dihydroazepines from readily available precursors. In some cases, the reaction pathway could divert to formal aza‐[3+2] cycloadditions, thus leading to 2,3‐dihydropyrroles. In this context, the titled reaction represents a capable tool for the divergent synthesis of two types of synthetically valuable aza‐heterocycles from common rhodium(II) iminocarbene intermediates.     

Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Cyclization–[4+3] Annulation Cascades between 2‐(1‐Alkynyl)‐2‐alken‐1‐ones and Anthranils

This work reports gold‐catalyzed [4+3]‐annulations of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with anthranils to yield epoxybenzoazepine products with excellent exo‐diastereoselectivity (dr>25:1). The utility of this new gold catalysis is manifested by applicable substrates over a broad scope. More importantly, the enantioselective versions of these [4+3]‐cycloadditions have been developed satisfactorily with chiral gold catalysts under ambient conditions (DCM, 0 °C); the ee levels range from 88.0–99.9 %. With DFT calculations, we postulate a stepwise pathway to rationalize the preferable exo‐stereoselection.     

Recent topics of Cp1RuCl-catalyzed annulation reactions

A wide variety of annulation reactions have been developed using Cp¹RuCl(cod) and related complexes as precatalysts. This digest highlights recent progress in Cp¹RuCl-catalyzed annulation reactions. State-of-the-art examples are outlined as follows: [2+2+2] cycloadditions, [2+2] cycloadditions, cyclizations of enynes, and other annulation reactions.     

Competitive [4 + 2] cycloadditions in equimolar mixtures of 1‐arylphosphole oxides

Four different [4 + 2] cycloadditions were observed to take place in the equimolar mixtures of two different arylphosphole oxides 2a + 2b or 2b + 2c . In addition to the phosphole oxide dimers 3a‐a and 3b‐b , or 3b‐b and 3c‐c , the crossed cycloadducts 3a‐b and 3b‐a , or 3b‐c and 3c‐b were also formed in considerable portions. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:633–635, 2001     

Unmasking the Action of Phosphinous Acid Ligands in Nitrile Hydration Reactions Catalyzed by Arene–Ruthenium(II) Complexes

The catalytic hydration of benzonitrile and acetonitrile has been studied by employing different arene–ruthenium(II) complexes with phosphinous (PR₂OH) and phosphorous acid (P(OR)₂OH) ligands as catalysts. Marked differences in activity were found, depending on the nature of both the P‐donor and η⁶‐coordinated arene ligand. Faster transformations were always observed with the phosphinous acids. DFT computations unveiled the intriguing mechanism of acetonitrile hydration catalyzed by these arene–ruthenium(II) complexes. The process starts with attack on the nitrile carbon atom of the hydroxyl group of the P‐donor ligand instead of on a solvent water molecule, as previously suggested. The experimental results presented herein for acetonitrile and benzonitrile hydration catalyzed by different arene–ruthenium(II) complexes could be rationalized in terms of such a mechanism.     

Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions

Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the C_β‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.     

Palladium‐Catalyzed Asymmetric [8+2] Dipolar Cycloadditions of Vinyl Carbamates and Photogenerated Ketenes

Higher‐order cycloadditions, particularly [8+2] cycloadditions, are a straightforward and efficient strategy for constructing significant medium‐sized architectures. Typically, configuration‐restrained conjugated systems are utilized as 8π‐components for higher‐order concerted cycloadditions. However, for this reason, 10‐membered monocyclic skeletons have never been constructed via catalytic asymmetric [8+2] cycloaddition with high peri‐ and stereoselectivity. Here, we accomplished an enantioselective [8+2] dipolar cycloaddition via the merger of visible‐light activation and asymmetric palladium catalysis. This protocol provides a new route to 10‐membered monocyclic architectures bearing chiral quaternary stereocenters with high chemo‐, peri‐, and enantioselectivity. The success of this strategy relied on the facile in situ generation of Pd‐containing 1,8‐dipoles and their enantioselective trapping by ketene dipolarophiles, which were formed in situ via a photo‐Wolff rearrangement.     

π‐Electron Systems That Form Planar and Interlocked Anion Complexes and Their Ion‐Pairing Assemblies

Interactions between designed charged species are important for the ordered arrangements of π‐electron systems in assembled structures. As precursors of π‐electron anion units, new arylethynyl‐substituted dipyrrolyldiketone boron complexes, which showed anion‐responsive behavior, were synthesized. They formed a variety of receptor–anion complexes ([1+1] and [2+1] types) in solution, and the stabilities of these complexes were discussed in terms of their thermodynamic parameters. Solid‐state ion‐pairing assemblies of [1+1]‐ and [2+1]‐type complexes with countercations were also revealed by single‐crystal X‐ray analysis. In particular, a totally charge‐segregated assembly was constructed based on negatively and positively charged layers fabricated from [2+1]‐type receptor–anion complexes and tetrabutylammonium cations, respectively. Furthermore, the [1+1]‐type anion complex of the receptor possessing long alkyl chains exhibited mesophases based on columnar assembled structures with contributions from charge‐by‐charge and charge‐segregated arrangements, which exhibited charge‐carrier transporting properties.     

Utilizing Vinylcyclopropane Reactivity: Palladium-Catalyzed Asymmetric [5+2] Dipolar Cycloadditions

Vinylcyclopropanes (VCPs) are commonly used in transition-metal-catalyzed cycloadditions, and the utilization of their recently realized reactivities to construct new cyclic architectures is of great significance in modern synthetic chemistry. Herein, a palladium-catalyzed, visible-light-driven, asymmetric [5+2] cycloaddition of VCPs with α-diazoketones is accomplished by switching the reactivity of the Pd-containing dipolar intermediate from an all-carbon 1,3-dipole to an oxo-1,5-dipole. Enantioenriched seven-membered lactones were produced with good reaction efficiencies and selectivities (23 examples, 52–92 % yields with up to 99:1 er and 12.5:1 dr). In addition, computational investigations were performed to rationalize the observed high chemo- and periselectivities.     

Co‐Conformational Isomerism in a Neutral Ion‐Paired Supramolecular System

Two different counter‐ion‐free host–guest complexes have been prepared and isolated. These compounds were formed from two equally and opposite doubly‐charged species, the viologen guests 1 a ²⁺ and 1 b ²⁺ and the anti‐disulfodibenzo[24]crown‐8 [ DSDB24C8] ^2? host, which gave rise to the 1:1 neutral complexes [ 1 a?DSDB24C8 ] and [ 1 b?DSDB24C8 ]. These species are held together by hydrogen bonding and π stacking, as well as strong electrostatic interactions. The investigation of these neutral ion‐paired supramolecular systems in solution and in the solid state allowed us to establish their co‐conformational preferences. Compound [ 1 a?DSDB24C8 ], with small methyl groups as substituents on the viologen unit, may adopt three different geometries, 1) an exo nonthreaded, 2) a partially threaded, and 3) a threaded arrangement, depending on the relative spatial orientation between the host and guest: The partially‐threaded structure is preferred in solution and in the solid state. The presence of bulky tert‐butylbenzyl groups in the viologen moiety in compound [ 1 b?DSDB24C8 ] restricts the possible geometrical arrangements to one: The exo nonthreaded arrangement. This structure was confirmed in the solid state by X‐ray crystallography. The stability of the neutral complexes in solution was determined by UV/Vis spectrophotometry. The stoichiometry of the complexes was established by continuous variation experiments, and overall equilibrium constants and ΔG° values were determined on the basis of dilution experiments. The results observed are a consequence of only the intrinsic stability of the complexes as there are no additional contributions from counter ions.     

Lead‐enhanced gas‐phase stability of multiply charged EDTA anions: a combined experimental and theoretical study

Besides their fundamental importance, multiply charged anions (MCAs) are considered as promising molecular capacitors for which their intrinsic stabilities are of great significance. Herein, the gas‐phase stabilities of ethylenediaminetetraacetic acid (EDTA) anions (i.e. [EDTA‐nH]^n?, n = 1–4) and their Pb(II) complexes (i.e. [EDTA + Pb‐nH]^(2‐n)?, n = 3, 4) have been investigated using an approach that combines extractive electrospray ionization mass spectrometry (EESI‐MS) measurements, Car–Parrinello molecular dynamics simulations and density functional theory/Tao–Perdew–Staroverov–Scuseria calculations. The EESI‐MS data showed that the doubly charged EDTA anions in the form of [EDTA‐2H]^2? and [EDTA + Pb‐4H]^2? were much more abundantly observed than the singly charged species such as [EDTA‐H]^? and [EDTA + Pb‐3H]^?, respectively. The calculation results indicated that [EDTA‐2H]^2? and [EDTA + Pb‐4H]^2? anions were thermodynamically more stable than the [EDTA‐H]^? and [EDTA + Pb‐3H]^? species in the gas phase, respectively. The [EDTA + Pb‐3H]^? anions preferred five‐coordinated structure, whereas [EDTA + Pb‐4H]^2? anions formed either five‐coordinated or six‐coordinated structures. The calculations further revealed that significant electron clouds drifting from the ligand EDTA to the metal Pb(II) ions and the large distances between the carboxylic groups reduced the Coulomb repulsion among the excess electrons of these MCAs. Our data demonstrated that EESI‐MS combined with theoretic calculations were able to provide a deep insight into the fundamental behavior of stability of MCAs in the gas phase and, thus, might be useful tools for studying MCAs for potential molecular capacitors. Copyright © 2012 John Wiley & Sons, Ltd.     

Reversible Single‐Crystal‐to‐Single‐Crystal Photochemical Formation and Thermal Cleavage of a Cyclobutane Ring

A [2+2] cycloaddition reaction has been observed in a number of solids. The cyclobutane ring in a photodimerized material can be cleaved into olefins by UV light and heat. The high thermal stability of the metal–organic salt K₂SDC (H₂SDC=4,4’‐stilbenedicarboxylic acid) has been successfully utilized to investigate the reversible cleavage of a cyclobutane ring. The two polymorphs of K₂SDC undergo reversible cyclobutane formation by UV light and cleavage by heat in cycles. Of these, one polymorph retains its single‐crystal nature during the reversible processes. Polymorphs are known to show different physical properties and chemical reactivities. This work reveals that the retention of single‐crystal nature is strongly associated with the packing of molecules, which is controlled by kinetics and thermodynamics. The photoemissive nature of the products makes this as a promising material for photoswitches and optical data storage devices.