Catalysis cycloadditions

The potential for sequential copper-catalyzed processes can also be illustrated in the case of formation of fully substituted 1,2,3-triazoles. In this sequence, the same copper catalyst is promoting two distinct types of catalysis [3+2]-cycloaddition and arylation via C-H activation. Each reaction type tolerates both electron-rich and -poor substrates, as well as steric hindrance, adding noteworthy breadth to this scheme. A 4-component sequence using NaNs, rather than an alkyl azide, is shown below. The diamine DMEDA (W.W -dimethylethylenediamine) is used to stabilize the copper catalyst. 

R = pC8Hi7-CsH4 Ri = (CH2)4NMe3Br Rj = (CHaleNMesBr Micellar catalysis cycloaddition in aqueous media [72b]... 

Keywords Pauson-Khand reaction Homogeneous catalysis Cycloaddition ... 

Keywords Catalysis Cycloaddition Cyclopentenones Pauson-Khand reaction Transition metal complexes... 

Aldehydes take part in the cycloaddition to give the methylenetetrahydrofuran 178 by the co-catalysis of Pd and Sn compounds[115]. A similar product 180 is obtained by the reaction of the allyl acetate 179, which has a tributyltin group instead of a TMS group, with aldehydesfl 16]. The pyrrolidine derivative 182 is formed by the addition of the tosylimine 181 to 154[117]. 

Miscellaneous Reactions. Some hydantoin derivatives can serve as precursors of carbonium—immonium electrophiles (57). 5-Alkoxyhydantoins are useful precursors of dienophiles (17), which undergo Diels-Alder cycloadditions under thermal conditions or in the presence of acid catalysis (58). The pyridine ring of Streptonigrine has been constmcted on the basis of this reaction (59). 

The reaction of dihalocarbenes with isoprene yields exclusively the 1,2- (or 3,4-) addition product, eg, dichlorocarbene CI2C and isoprene react to give l,l-dichloro-2-methyl-2-vinylcyclopropane (63). The evidence for the presence of any 1,4 or much 3,4 addition is inconclusive (64). The cycloaddition reaction of l,l-dichloro-2,2-difluoroethylene to isoprene yields 1,2- and 3,4-cycloaddition products in a ratio of 5.4 1 (65). The main product is l,l-dichloro-2,2-difluoro-3-isopropenylcyclobutane, and the side product is l,l-dichloro-2,2-difluoro-3-methyl-3-vinylcyclobutane. When the dichlorocarbene is generated from CHCl plus aqueous base with a tertiary amine as a phase-transfer catalyst, the addition has a high selectivity that increases (for a series of diolefins) with a decrease in activity (66) (see Catalysis, phase-TRANSFEr). For isoprene, both mono-(l,2-) and diadducts (1,2- and 3,4-) could be obtained in various ratios depending on which amine is used. 

Perfluoropolyenes also can rearrange to four-membered ring products upon fluoride ron or Lewis acid catalysis [112, II3, 114] (equations 46 and 47) These intramolecular cycloadditions are multistep processes involving carbanion or carbocation intermediates... 

We are now standing in the middle of the next step of the development of cycloaddition reactions - catalytic and catalytic enantioselective versions. The last two decades have been important in catalysis - how can we increase the reaction rate, and the chemo-, regio, diastereo-, and enantioselectivity of cycloaddition reactions. Metal catalysis can meet all these requirements ... 

The author has been involved for quite a long time in the study of Lewis acid catalysis of 1,3-dipolar cycloaddition reactions. From his research group, a series of methodologies directed to the Lewis acid-mediated stereochemical and regiochem-ical control of 1,3-dipolar cycloaddition reactions has been reported this includes ... 

Honk et al. concluded that this FMO model imply increased asynchronicity in the bond-making processes, and if first-order effects (electrostatic interactions) were also considered, a two-step mechanisms, with cationic intermediates become possible in some cases. It was stated that the model proposed here shows that the phenomena generally observed on catalysis can be explained by the concerted mechanism, and allows predictions of the effect of Lewis acid on the rates, regioselectivity, and stereoselectivity of all concerted cycloadditions, including those of ketenes, 1,3-dipoles, and Diels-Alder reactions with inverse electron-demand [2],... 

The final class of reactions to be considered will be the [4 + 2]-cycloaddition reaction of nitroalkenes with alkenes which in principle can be considered as an inverse electron-demand hetero-Diels-Alder reaction. Domingo et al. have studied the influence of reactant polarity on the reaction course of this type of reactions using DFT calculation in order to understand the regio- and stereoselectivity for the reaction, and the role of Lewis acid catalysis [29]. The reaction of e.g. ni-troethene 15 with an electron-rich alkene 16 can take place in four different ways and the four different transition-state structures are depicted in Fig. 8.16. 

A novel use of a chlorofluorocarbon is in the synthesis of a pyrone (30) from 1,1,1-trichlorotrifluoroethane. The key step involves Cu(I) catalysis. Pyrone (30) is a useful CF3 aromatic synthon, as it readily underwent (4 + 2) cycloaddition followed by spontaneous elimination of C02 (85-TL3947). 

The most frequently encountered, and most useful, cycloaddition reactions of silyl enol ethers are Diels-Alder reactions involving silyloxybutadicncs (Chapter 18). Danishefsky (30) has reviewed his pioneering work in this area, and has extended his studies to include heterodienophiles, particularly aldehydes. Lewis acid catalysis is required in such cases, and substantial asymmetric induction can be achieved using either a chiral lanthanide catalyst or an a-chiral aldehyde. 

Recently, Akiyama et al. reported an enantiocontrolled [3+2] cycloaddition of chirally modified Fischer alkenylcarbene complexes 180 with aldimines 181 under Lewis-acid catalysis (Sn(OTf)2) to afford enantiomerically pure 1,2,5-trisubstituted 3-alkoxypyrrolines 182 (Scheme 40) [121]. The mode of formation of these products 182 was proposed to be a [4+2] cycloaddition, with the complexes 180 acting as a 1-metalla- 1,3-diene with subsequent reductive elimination. Upon hydrolysis under acidic conditions, the enol ethers give the enantiomerically pure 3-pyrrolidinones 183 (Table 9). 

Epoxidations of chiral allenamides lead to chiral nitrogen-stabilized oxyallyl catioins that undergo highly stereoselective (4 + 3) cycloaddition reactions with electron-rich dienes.6 These are the first examples of epoxidations of allenes, and the first examples of chiral nitrogen-stabilized oxyallyl cations. Further elaboration of the cycloadducts leads to interesting chiral amino alcohols that can be useful as ligands in asymmetric catalysis (Scheme 2). 

The cycloaddition of chiral, racemic and non-racemic alkoxybutadienes 109 with phenyltriazolinedione led to aza compounds [110] in high yield, with good facial selectivity (diastereomeric excess 87-92%) (Equation 2.31). The cycloadditions of the same dienes with N-phenylmaleimide require Lewis acid catalysis. 

The presence of the catalyst can also favor multiple Diels-Alder reactions of cycloalkenones. Two typical examples are reported in Schemes 3.6 and 3.7. When (E)-l-methoxy-1,3-butadiene (14) interacted with 2-cyclohexenone in the presence of Yb(fod)3 catalyst, a multiple Diels-Alder reaction occurred [21] and afforded a 1 1.5 mixture of the two tricyclic ketones 15 and 16 (Scheme 3.6). The sequence of events leading to the products includes the elimination of methanol from the primary cycloadduct to afford a bicyclic dienone that underwent a second cycloaddition. Similarly, 4-acetoxy-2-cyclopenten-l-one (17) (Scheme 3.7) has been shown to behave as a conjunctive reagent for a one-pot multiple Diels-Alder reaction with a variety of dienes under AICI3 catalysis, providing a mild and convenient methodology to synthesize hydrofluorenones [22]. The role of the Lewis acid is crucial to facilitate the elimination of acetic acid from the cycloadducts. The results of the reaction of 17 with diene... 

Sulfinylacrylate 41 has been successfully used in the enantioselective synthesis of pseudo-sugar [46, 47]. Cycloaddition of (S)-3-(2-pyridylsulfinylacrylate) (41) with furan and 3,4-dibenzyloxyfuran under Et2AlCl catalysis afforded cycloadducts 42, 43 and 44 (Equation 3.12) which were converted into pseudo-manno-pyranoses 45, 46 and 47 (Figure 3.5). 

Several aluminum- and titanium-based compounds have been supported on silica and alumina [53]. Although silica and alumina themselves catalyze cycloaddition reactions, their catalytic activity is greatly increased when they complex a Lewis acid. Some of these catalysts are among the most active described to date for heterogeneous catalysis of the Diels-Alder reactions of carbonyl-containing dienophiles. The Si02-Et2AlCl catalyst is the most efficient and can be... 

Dihydrothiopyrans have also been prepared by cycloaddition between a,jS-unsaturated thioketones and carbonyl-activated dienophiles under Lewis-acid catalysis [78]. A marked dependence of the reaction yield on the catalyst was observed. The results of the cycloaddition reaction of thioketone 77 with methyl metacrylate, catalyzed by different catalysts, are illustrated in Equation 3.24. 

The 2-pyrones can behave as dienes or dienophiles depending on the nature of their reaction partners. 3-Carbomethoxy-2-pyrone (84) underwent inverse Diels-Alder reaction with several vinylethers under lanthanide shift reagent-catalysis [84] (Equation 3.28). The use of strong traditional Lewis acids was precluded because of the sensitivity of the cycloadducts toward decarboxylation. It is noteworthy that whereas Yb(OTf)j does not catalyze the cycloaddition of 84 with enolethers, the addition of (R)-BINOL generates a new active ytterbium catalyst which promotes the reactions with a moderate to good level of enantio selection [85]. 

Lewis-acid catalysis is effective in intermolecular as well as intramolecular /zomo-Diels-Alder reactions. Thus, complex polycyclic compounds 93 have been obtained in good yield by the cycloaddition of norbornadiene-derived dienynes 92 by using cobalt catalyst, whereas no reaction occurred under thermal conditions [91] (Scheme 3.18). 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

The intramolecular Diels-Alder reaction of 78 was investigated during the synthesis of isoquinoline alkaloids [65ij. No reaction occurred when solid-phase conditions were used (Florosil in DCM and CaCli) or when a variety of Lewis acids were employed (SnCU, BF3, RAICI2, Ti(z — Pr)4-TiCl4). A 56 % yield of 79 was obtained by carrying out the cycloaddition in toluene in a sealed tube at 200 °C. jS-CD catalysis in water under milder conditions (Equation 4.11) improved the conversion to 84 %. 

The complex obtained from commercially available chiral a-amino acids (AA) with Cu + ion induces asymmetry in the Diels-Alder reaction of 31 (R = H) with 32. By using 10% Cu(II)-AA (AA = L-abrine) the cycloaddition occurs e/iJo-stereoselectively in 48 h at 0°C with high yield and with acceptable enantioselectivity ee = 1A%). This is the first example of enantioselective Lewis-acid catalysis of an organic reaction in water [9b]. 

Togni A., Pastor S. D. Cooperativity of Chirality in Homogeneous Catalysis The Gold(I)-Catalyzed Aldol Reaction and the Vanadium(IV)-Catalyzed Hetero-Diels-Alder Cycloaddition Chirality 1991 3 331-340... 

Kappe and co-workers proposed an application of a microwave-assisted Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides 70, imder Cu(I) catalysis, as an example of click chemistry to obtain a collection of... 

Other reactions not described here are formal [3 -i- 2] cycloadditions of a,p-unsaturated acyl-fluorides with allylsilanes [116], or the desymmetrization of meso epoxides [117]. For many of the reactions shown above, the planar chiral Fe-sandwich complexes are the first catalysts allowing for broad substrate scope in combination with high enantioselectivities and yields. Clearly, these milestones in asymmetric Lewis-base catalysis are stimulating the still ongoing design of improved catalysts. 

Berlin JM, Eu GC (2008) Enantioselective nucleophilic catalysis the synthesis of Aza-P-lactams through [2 -I- 2] cycloadditions of ketenes with azo compounds. Angew Chem Int Ed 120 7156-7158... 

Keywords Allylic substitution Catalysis Cross-coupling Cycloaddition Cycloisomerisation DNIC Ferrate Hydrogenase Iron... 

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