Disubstituted Alkenes Research Articles

ChemInform Abstract: Rhodium‐Catalyzed Enantioselective Intermolecular Hydroacylation Reactions

AbstractReview: 55 refs.

ChemInform Abstract: NHC—NiH Reactions with Simple Olefins: Advances in Hydroalkenylation, Polymerization, and Ionic‐Liquid Synthesis

AbstractReview: 57 refs.

ChemInform Abstract: Synthesis of Peroxylactones Using Mn(III)‐Catalyzed Aerobic Oxidation.

AbstractThe reaction of tetronic acid (I) with disubstituted alkenes (II) in the presence of air affords the corresponding hydroperoxyethyl‐peroxylactones or an equilibrium mixture of these compounds with the corresponding bishydroxyperoxide in moderate to good yields, whereas a similar reaction using 3‐alkyl‐substituted tetronic acids (X) provides the stable crystalline peroxylactones (XI) in good to excellent yields.

Photoinduced Conjugation of Aldehyde Functional Polymers with Olefins via [2 + 2]-Cycloaddition

Polymer end group modifications via [2 + 2] Paterno–Büchi reactions were carried out. Polyisobornyl acrylate (PiBoA, 3100 g·mol–1) and polystyrene (PS, 2800 g·mol–1) was synthesized by atom transfer radical polymerization (ATRP) employing an aldehyde functional initiator. Good control over the polymerizations was achieved, and material with high aldehyde functionality was obtained. The terminal aldehyde was then reacted with alkenes under UV irradiation in [2 + 2] cycloaddition reactions. Good yields of the modification reaction was confirmed via NMR and by electrospray ionization mass spectrometry (ESI–MS) analysis and generally conversion of the aldehyde function into the respective oxetanes of 90% or higher was observed. With the oxetane, a variety of functional groups were introduced to the polymer chain ranging from multifunctional allyl-compounds to disubstituted alkenes and amino- or hydroxyl-functional alkenes. In the photoreaction, the integrity of the bromine end group of the ATRP polymers is retained. ATRP chain extensions can be performed after the cycloaddition, demonstrating the versatility of this newly introduced polymer modification reaction.

Terminal Enyne Ring-Closing Metathesis Catalyzed by Ruthenium Carbene Catalysts

Enyne ring-closing metathesis (RCM) has recently emerged as a powerful tool for the formation of 1,3conjugated dienes. Under the influence of its efficacy and reliability, the enyne RCM reaction with ruthenium (Ru)based catalysts has been elegantly applied toward the total synthesis of bioactive compounds or natural products. In spite of its usefulness, the enyne RCM has yet a problem which remains to be solved: endo/exo mode selectivity. The exo/endo-selectivity in the enyne RCM has been studied and the reported results have varied. Mori reported that RCM of enyne having an monoor di-substituted alkene and a terminal alkyne gave only the exo product, while that of enyne having a disubstituted alkene and an internal alkyne gave a mixture of both endo and exo products. Lee reported that a competitive cross metathesis (CM) of the alkyne moiety in enyne substrate with ethylene led to a triene, which then underwent ring closure offering selectively endo product in 9-11 membered macrocycles. In the investigation on the reactivity profile of catalysts, Grela observed that the use of Grubbs’ first-generation complexes containing PCy3 ligand such as A and C led to only an exo product, while the use of second-generation complexes containing N-heterocyclic carbene (NHC) ligand led to a mixture of endo and exo products in the RCM of enyne having a disubstituted alkene and a terminal alkyne. Schrock and Hoveyda reported their elegant results on endoselective enyne RCM reactions promoted by use of in situ generated molybdenum (Mo)-based complexes containing pyrrole ligand and later by both tungsten (W)and Mobased mono-aryloxide pyrrolide (MAP) imido alkylidene complexes. Therefore, we envisioned that the endo/exo selectivity of terminal enyne RCM with Ru carbene catalysts could lead us to the selective synthesis of medium-sized N-containing heterocycles as shown in Scheme 1. We examined the well-known Ru-based complexes A-D as well as pyridine-chelating Ru complex E (Fig. 1). It was expected that the NHC ligand along with pyridine moiety in complex E would have an effect on the endo/exo selectivity in enyne RCM reactions. Our study started from a simple representative substrate 1 bearing a terminal alkyne at one end and a terminal olefin at the other. Each of five catalysts (A-E, 5 mol %) was added to the solution of 1 in benzene and the solution was refluxed for 2 h under an atmosphere of Ar. RCM of enyne 1 mediated by catalysts A-D gave only the 5-membered exocyclized compound 3 (Entry 1-4, Table 1). On the other hand, pyridine chelating catalyst E produced a small but significant amount of 6-membered endo-cyclized product 2 with the endo: exo ratio of 27:73 (45% conversion, 6% isolated yield of combined exo/endo) (Entry 5, Table 1). It is the first example of the endo-cyclized product being formed in the terminal enyne RCM using Ru-based catalyst. Since we were interested in the determination of endo/exo selectivity in terminal enyne RCM with Ru carbene catalysts under various reaction conditions, the task of improving isolated yield in each reaction was beyond the scope of the work described in this paper. Subsequently, we tested enyne RCM of 1 using the catalyst E in several representative solvents (Table 2). Among suitable organic solvents, toluene, benzene, tetrahydrofuran (THF), 1,2-dimethoxyethane (DME) and 1,2-dichloroethane (DCE) were carefully selected and examined because catalyst E showed the activating This paper is dedicated to Professor Eun Lee on the occasion of his honourable retirement. Scheme 1. Terminal enyne RCM with ruthenium carbene catalysts.

Pyranoside Phosphite–Oxazoline Ligands for the Highly Versatile and Enantioselective Ir-Catalyzed Hydrogenation of Minimally Functionalized Olefins. A Combined Theoretical and Experimental Study

A modular set of phosphite-oxazoline (P,N) ligands has been applied to the title reaction. Excellent ligands have been identified for a range of substrates, including previously challenging terminally disubstituted olefins, where we now have reached enantioselectivities of 99% for a range of substrates. The selectivity is best for minimally functionalized substrates with at least a moderate size difference between geminal groups. A DFT study has allowed identification of the preferred pathway. Computational prediction of enantioselectivities gave very good accuracy.

NHC-NiH Reactions with Simple Olefins: Advances in Hydroalkenylation, Polymerization, and Ionic-Liquid Synthesis

Various NHC-NiH species have been developed as ­hydroalkenylation and polymerization catalysts and for ionic-liquid synthesis. This article outlines their key features and connections and highlights the opportunities for using NHC-NiH species in the selective preparation of new geminal disubstituted olefins and how they complement traditional P-NiH technology.

DFT interpretation of 1,3-dipolar cycloaddition reaction of C,N-diphenyl nitrone to methyl crotonate in terms of reactivity indices, interaction energy and activation parameters

The cycloaddition reaction between C,N-diphenyl nitrone and an unsymmetrically disubstituted olefin, methyl crotonate has been studied in terms of several theoretical approaches at DFT/B3LYP/6-31G(d) level of theory. The electronic populations have been computed from natural orbital based charges using natural population analysis and electrostatic potential driven atomic charges using Merz–Kollman and Chirlian–Francl algorithm. The regioselectivity has been predicted on the basis of DFT based reactivity indices. Calculations of the interaction energy have been performed during the study. The interaction energy is partitioned in two terms; one resulting from the chemical potential equalization principle at constant external potential and the other step (the reshuffling of charge distribution) resulting from the maximum hardness principle at constant chemical potential. The transition states corresponding to the feasible stereoisomeric pathways along the regioisomeric reaction channels have been successfully located. Trends in the selectivities are predicted in terms of energy, enthalpy and free energy changes. An analysis of Pauling’s bond order, Wiberg bond index and atom–atom overlap-weighted NAO bond order values has been done to get a balanced measure of the extent of bond formation or bond breaking. The cycloaddition is favored along the meta reaction channel affording the endo adduct as the major diastereoisomer in agreement with the experimental results.

One pot spiropyrazoline synthesis via intramolecular cyclization/methylation

Regioisomeric spiropyrazolines were synthesized through a tandem intramolecular cyclization/methylation reaction of a functionalized 5,5-disubstituted pyrazoline in one reaction vessel. The 5,5-pyrazolines were constructed through a 1,3-dipolar cycloaddition reaction of aromatic ring containing nitrile imines and a disubstituted geminal alkene. An evaluation of the relative location of the nucleophilic and electrophilic functional groups on the pyrazoline was performed in order to ascertain the best pyrazoline system for the intramolecular cyclization/methylation reaction. Higher spiropyrazoline isolated yields were realized from pyrazolines with the electrophilic ester located further away from the pyrazoline when compared to pyrazolines with a directly bonded ester.

Catalytic Z-selective olefin cross-metathesis for natural product synthesis

Alkenes are found in a great number of biologically active molecules and are employed in numerous transformations in organic chemistry. Many olefins exist as E or higher energy Z isomers. Catalytic procedures for stereoselective formation of alkenes are therefore valuable; nonetheless, methods for synthesis of 1,2-disubstituted Z olefins are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and allylic amides, employed thus far only in E-selective processes; the corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. Transformations, promoted by catalysts that contain the highly abundant and inexpensive molybdenum, are amenable to gram scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. Utility is demonstrated by syntheses of anti-oxidant C18 (plasm)-16:0 (PC), found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000.

ChemInform Abstract: Application of a Chiral Scaffolding Ligand in Catalytic Enantioselective Hydroformylation.

The synthesis of β-amino-aldehydes has been achieved through enantioselective hydroformylation of PMP-protected allylic amines. The reaction is accomplished by using a scalemic scaffolding ligand that covalently and reversibly binds to the substrate. These ligands behave like chiral auxiliaries because they are covalently attached to the substrate during hydroformylation; however, similar to traditional asymmetric ligands, they can be used in catalytic quantities. The directed hydroformylation of disubstituted olefins occurs under mild conditions (35 °C and 50 psi CO/H2), and Z-olefins afford excellent enantioselectivities (up to 93% ee).

Rhodium-catalyzed enantioselective intermolecular hydroacylation reactions

Rhodium-catalyzed enantioselective hydroacylation reactions allow rapid access to chiral substituted ketones. However, due to the low reactivity of disubstituted alkenes in intermolecular versions of this process, only a small number of asymmetric intermolecular reactions have been described. Strategies employed to avoid reactivity issues include the use of norbornadienes, linear dienes, acrylamides, and allenes as the alkene components. In addition, our laboratory has recently reported the rhodium-catalyzed enantioselective inter-molecular alkyne hydroacylation reaction, leading to the formation of enone products via a kinetic resolution procedure.

Recycling of osmium catalyst in oxidative olefin cleavage: a chemoentrapment approach

A new chemoentrapment strategy for recycling osmium in the catalytic olefin cleavage reaction is reported. The new strategy utilizes KOH/ i-PrOH to generate water-soluble Os(VI) species as a recyclable metal catalyst after the oxidative cleavage reaction. For the recycling of the catalyst, NaIO 4–NaClO 2 was found to be the best combination of secondary oxidants and acetonitrile–water was chosen as an optimal solvent for the best recycling results. The new method allows for an efficient recycling of osmium in the reactions involving mono- and di-substituted olefins with 1 mol % of OsO 4 without any significant side reactions and loss of yield.

Copper(ii) complexes incorporating poly/perfluorinated alkoxyaluminate-type weakly coordinating anions: Syntheses, characterization and catalytic application in stereoselective olefin aziridination

The synthesis and characterization of a series of cationic copper(II) complexes of the type [Cu(NCR)(6)][Al(OC(CF(3))(2)R')(4)](2) (R = CH(3), Ph; R' = CF(3), Ph, PhCH(3)), incorporating poly/perfluoronated alkoxyaluminates as weakly coordinating anions (WCAs) is presented. Aziridination of various olefins, such as the unreactive olefins e.g. ethylhex-2-enoate and 1-decene, with N-tosyliminophenyliodinane catalyzed by [Cu(NCR)(6)][Al(OC(CF(3))(2)R')(4)](2) affords very good yields (up to 96%) and high TOFs (up to 5000 h(-1)) under mild conditions. Using disubstituted olefins as substrates, high stereoselectivities are obtained at room temperature. The to date highest cis : trans ratio (98 : 2) of the obtained aziridines is achieved for cis-stilbene in good yield (85%) as well as promising TOF (> 2000 h(-1)). The investigation of the solvent effect on yield and selectivity reveals that for certain oleophilic substrates (1-decene), less polar solvents, such as dichloromethane are a better choice than acetonitrile, which is commonly considered as the best solvent for olefin aziridination. Accordingly, a mechanism involving a paramagnetic copper nitrene intermediate with both concerted and stepwise pathways is proposed.

Application of a chiral scaffolding ligand in catalytic enantioselective hydroformylation.

The synthesis of β-amino-aldehydes has been achieved through enantioselective hydroformylation of PMP-protected allylic amines. The reaction is accomplished by using a scalemic scaffolding ligand that covalently and reversibly binds to the substrate. These ligands behave like chiral auxiliaries because they are covalently attached to the substrate during hydroformylation; however, similar to traditional asymmetric ligands, they can be used in catalytic quantities. The directed hydroformylation of disubstituted olefins occurs under mild conditions (35 °C and 50 psi CO/H(2)), and Z-olefins afford excellent enantioselectivities (up to 93% ee).

ChemInform Abstract: Cyclic 1,2‐Diketones as Core Building Blocks: A Strategy for the Total Synthesis of (‐)‐Terpestacin.

We report a full account of our work towards the total synthesis of (−)-terpestacin (1), a sesterterpene originally isolated from fungal strain Arthrinium sp. FA1744. Its promising anti-HIV and anti-cancer activity, as well as its novel structure, make terpestacin an attractive synthetic target. A strategy based on the unique reactivity of cyclic 1,2-diketones (diosphenols) was developed and total synthesis of 1 was achieved in 20 steps, in the longest linear sequence, from commercially available 2-hydroxy-3-methyl-2-cyclopenten-1-one. The key feature of our synthesis is the double usage of a “Pd AAA-Claisen” protocol (AAA=asymmetric allylic alkylation), first in the early stages to generate the C1 quaternary center and then in the late stages to install the side chain. In addition, a rather unusual ene-1,2-dione moiety was synthesized and utilized as an excellent Michael acceptor to attach the C15 substituent. Several possible routes towards the total synthesis have been examined and carefully evaluated. During our exploration many interesting chemoselectivity issues have been addressed, such as a highly selective ring-closing metathesis and a challenging oxidation of a disubstituted olefin in the presence of three trisubstiuted ones.

Copper-Catalyzed Olefin Aminoacetoxylation

A new catalyst system for intramolecular olefin aminoacetoxylation is described. In contrast to previously reported palladium- and copper-catalyzed systems, the conditions outlined in this communication favor piperdine formation with terminal olefin substrates and induce cyclization with traditionally less reactive disubstituted olefins.

ChemInform Abstract: Tandem Vicinal Difunctionalization: β-Addition to α,β- Unsaturated Carbonyl Substrates Followed by α-Functionalization

Vicinal difunctionalization reactions play an important role in modern synthetic organic chemistry. They provide access to complex structures in a stereocontrolled fashion and act as powerful, attractive, convergent elements in synthetic strategy. Consequently, examples of these reactions are numerous. Among them may be cited the Diels–Alder reaction, which results in vicinal dialkylation of a dienophile; epoxidation–functionalization of alkenes which results in 2-substituted alkanols carbenoid additions to alkenes resulting in cyclopropanes; organometalation–functionalization of alkynes giving vicinally disubstituted alkenes, and the additions of halides and acyl halides to alkenes using Friedel–Crafts catalysts. [2 + 2] Photocycloadditions and 1,3-dipolar cycloadditions are but two of many more examples. New reactions are introduced regularly, such as radical cyclization–trapping, which recently has been applied to a synthesis of prostaglandin F2α. Keywords: tandem vicinal difunctionalization; β-addition; α,β-unsaturated carbonyl substrates; mechanisms; scope; limitations; copper reagents; stabilized reagents; unstabilized reagents; functionalizing reagents; experimental procedures; unsaturated compounds; aldehydes; ketones; esters; lactones; amides; thioamides; neutral intermediates

DFT Investigation of the Palladium‐Catalyzed Ene–Yne Coupling

The mechanism of the recently developed palladium-catalyzed ene-yne coupling has been evaluated by DFT methods. The calculations validate the previously proposed reaction mechanism and explain the stereoselectivity of the reaction (exclusive formation of the E isomer of the disubstituted alkene). Concerning chemoselectivity, the calculations also clarify why the ene-yne coupling is able to dominate over plausible alternative reaction pathways such as alkene homocoupling and alkyne polymerization. The role of the phosphine ligand at various stages of the catalytic cycle has also been delineated.

Regioselective transformation of 6/5-fused bicyclic isoxazolidines to second-generation cyclic aldonitrones

The cycloaddition reactions of 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide with mono- and di-substituted alkenes have been found to be highly stereo- as well as face-selective. In solution, the 6/5 fused bicyclic cycloadducts remain solely as the cis-fused invertomers in order to accommodate the bulky tertiary substituent 2-hydroxy-2-propyl in the equatorial orientation. The cycloadducts, upon peracid oxidation, leads to the exclusive formation of synthetically important second-generation cyclic aldonitrones. The stereo- and face-selectivity of the cycloaddition reactions of these second-generation nitrones bearing substituents at C(4) and C(6) have been briefly examined. One interesting finding was that treatment of the first generation nitrone i.e., 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide, with mercury(II) oxide afforded a novel bicyclic nitrone, 1-oxa-5,6-dehydro-6-azabicyclo[3,2,1]heptane 6-oxide.