Cyclopropanated norbornenes

To date, only double Heck reactions have been described, but triple Heck reactions are also possible [39]. Reaction of the alkynyl aryl iodide 6/1-55 with norbor-nene in the presence of Pd(OAc)2, triphenylphosphane and triethylamine as base led to the cyclopropanated norbornene derivate 6/1-59 as a single diastereomer in 40% yield (Scheme 6/1.13). It can be assumed that the alkenyl Pd-species 6/1-56 is first formed stereoselectively, and this undergoes a Heck reaction with norbornene... 

In an efficient diastereo-differentiative assembly of three components of norbornene, tv. v-alkenyl iodide, and KCN, the isomerization of the cis to the trans double bond takes place to give the coupled product 224. The isomerization is explained by the formation of the cyclopropane 222. its rearrangement to give a irans double bond in 223, and trapping with CN anion to give 224[168],... 

Section B gives some examples of metal-catalyzed cyclopropanations. In Entries 7 and 8, Cu(I) salts are used as catalysts for intermolecular cyclopropanation by ethyl diazoacetate. The exo approach to norbornene is anticipated on steric grounds. In both cases, the Cu(I) salts were used at a rather high ratio to the reactants. Entry 9 illustrates use of Rh2(02CCH3)4 as the catalyst at a much lower ratio. Entry 10 involves ethyl diazopyruvate, with copper acetylacetonate as the catalyst. The stereoselectivity of this reaction was not determined. Entry 11 shows that Pd(02CCH3) is also an active catalyst for cyclopropanation by diazomethane. 

Another unprecedented domino cycloaddition process of a chromium complex, namely a [2+2+l]/[2+l] cycloaddition, was observed by Barluenga and coworkers [316]. These authors treated norbornene 6/4-137 with the Fischer alkynyl Cr car-bene 6/4-138 and obtained, as the main product, not the expected cyclopropane derivative 6/4-139, but compound 6/4-140 (Scheme 6/4.35). 

Cyclopentenes behave differently and often act through radical mechanisms this can lead to photoreduction to cyclopentanes, or photoaddition of the kind exemplified by norborneneand propan-2-ol 12.57). The photoadduct in this process is linked through the carbon atom of the alcohol, and not the oxygen atom. A related addition to acetonitrile 12.58) takes place when norbornene is irradiated in the presence of a silver(i) compound. It is likely thal a metal complex of the alkene is the real irradiation substrate, and the same may be true for copper(i)-promoted additions of haloalkanes to electron-deficient alkenes (2.59). When dichloromelhane is used in such a reaction the product can be reduced electrochemically to a cyclopropane (2.60), which is of value because the related thermal addition of CH.I, to alkenes in the presence of copper does not succeed with electron-poor compounds. 

Palladium(O) catalysed cyclopropanation of electron-rich strained olefins using ketone a-carbonate or cyclic carbonates produce the corresponding cyclopropane adducts136-139. Two examples of this unusual cyclopropanation of norbornene are shown in equations 91 and 92. 

A few examples are available in which regiocontrol in the cyclopropanation of non-conjugated diene is catalyst-dependent. An early example is showed in equation 118. Copper(II) triflate catalysed cyclopropanation of diene 132 with diazomethane occurs preferentially at the less substituted double bond, whereas copper(II) acetylacetonate in contrast promotes cyclopropanation at the more substituted double bond (equation 118)13. Regiocontrol in the cyclopropanation of norbornene derivative 133 is strongly catalyst-dependent (equation 119). When diphenyldiazomethane is used as carbenoid precursor, the regioselectivity of this cyclopropanation is significantly enhanced165. 

Diels-Alder cycloadditions of the readily available spiro[2.4]heptadiene (15) are a useful entry to spiro(cyclopropane-l,7 -norbornene) and related polycyclic compounds (equation 17)38. 1,1 -Diacetylcyclopropane was found to undergo unusual base catalyzed cyclizations resulting in spiroannulated cyclopropanes (equation 18)3,-4°. 

An unusual rhodium-catalysed addition of a dienylboronate ester to highly strained alkenes, such as norbornene, has been reported, resulting in the formation of vinyl-cyclopropane-fused tricyclic products (Scheme 7). Preliminary mechanistic studies have been presented.246... 

Unexpectedly, norbornene derivatives can undergo a novel cyclopropana-tion reaction with propargyl alcohol in the presence of cationic [(/f-Cp)(CH3CN)3Ru]+X catalysts, which have an electron-withdrawing substituent on the Cp ligand. Cyclopropanation products, exo-acetyltricyclooctanes, were obtained in good yields [50] (Eq. 37). The reaction has been shown not to involve the expected allenylidene intermediate but rather to lead to a ruthena-cycle intermediate and to a /i-hydroxy elimination. 

With strained bicycloalkenes such as norbornene derivatives a ruthenium-catalyzed tandem cyclopropanation occurred together with common [2+2+2] cy-clotrimerization, showing a biscarbenoid hybride structure for the ruthenacyclopentadiene intermediate [92] (Eq. 72). 

Simple alkenes, norbornene and styrene do not undergo cyclopropanation or insertion reactions with cyclopropyl(methoxy)carbene chromium pentacarbonyl complex. However, the conjugated 1-vinylcyclopentene is cyclopropanated under the reaction conditions at the terminal double bond, affording an isomeric mixture trans.cis = 40 60), in 66% yield (equation 72). 

The strained bicydic structure of norbornene is essential for the tandem cyclopropanation. Less strained cyclopentene furnished the corresponding tandem cyclopropanation product only in 25% yield [38]. Similarly, 2,5-dihydrofuran gave 48 in low yield (18%), but in this case, a normal [2 -1- 2 -1- 2] cycloadduct 47 became a major product (23%) (Scheme 4.15). Employing Cp RuCl(cod) 17 in place of the indenyl... 

At about the same time Wiberg and Bartley found that the endo cyclopropane group of 27 brought about a shielding of the vinyl protons to 55.64 as compared with 55.94 in norbornene. 

With methyl 2-alkylcycloprop-2-enecarboxylates, on the other hand, only [2-1-1] cycloaddition to the tricyclic dimers of cyclopentadiene (18) occurs. Only the strained double bond in the norbornene substructure is cyclopropanated, and the exo-adducts are formed. The Z/E isomeric ratios (6 1 and 2.5 1) are comparable to the ratios obtained in the reactions with norbornadiene vide supra). A mechanism proposing ring opening of the cyclopropene and attack on the metal-coordinated alkene in a concerted way has been suggested in order to explain the stereoselectivity of the reaction. ... 

Cyclopropanation of Norbornene and Related Systems with (2-Siloxyallyl) Acetates Catalyzed by Pallad-ium(O) General Procedure ... 

Cyclopropanation of Norbornene with Ethyl (2-Oxo-2-phenylethyl) Carbonate Catalyzed by Palladium(O), Formation of 3b Typical Procedure ... 

The cyclopropanated products are not formed if phenylalkenes or norbornene are reacted with phenyliodonium bis(phenylsulfonyl)methylide either by photolysis or heating in the presence of a catalyst or by noncatalytic thermolyses instead, oxidation products and indane derivatives result. The meehanisms of these processes are described in detail in literature. ... 

A similar reaction pathway is discussed in other cases of palladium-mediated cyclopropane formation. Thus diastereoselective [2 + 1] cyclopropanation, instead of [3 + 2] cyclopentane formation, is observed if norbornene (3), norbornadiene (6), or dicyclopentadiene (9) is treated... 

Cyclopropanation of norbornene (9) with vinyl halides benzyl halides " or alkynes is also interpreted as proceeding via homoallylmetal complexes 10 and intramolecular alkene insertion to form the tricyclic product 11. 

Cyclopropane formation can compete with direct conversion of the homoallylmetal complex intermediate. Thus reaction of norbornene (9) with j3-bromostyrene in the presence of tetrakis(triphenylphosphane)palladium(0) and ammonium formate leads to 3-benzyl-la,2j6,3a,4, 5a-tricyclo[3.2.1.0 " ]octane (12 52%) and tra s -2-styrylnorbornane (13 ... 

The following reactions of norbornene and other nonfunctionalized alkenes with substituted methylenecyclopropanes illustrate these points. (1-Methylethylidene)- and (diphenyl-methylene)cyclopropane (1 R = Me, Ph) give rise to the same type of cycloadducts in the presence of either nickel(O) or palladium(O) catalysts. Even at temperatures as low as 40 "C with bis(> -cycloocta-l,5-diene)nickel(0) as catalyst, 2 may be isolated in 70% yield. The reaction can be extended to vinylbenzene and ethene at temperatures of between 40 and 60 °C, where it may be advantageous to use (cyclododeca-l,3,5-triene)nickel(0) ° as a source of the catalytically active nickel(O) species instead of bis(j7" -cycloocta-l,5-diene)nickel(0). ° This is because ligand dissociation from the former complex is more facile, especially at relatively low temperatures. 

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