Electron poor alkenes

The reaction was successfully applied to both electron-rich and electron-poor 4-nitrophenyl carboxylates among them, the conversion of the electron-deficient esters was found to be faster and more efficient. Many functional groups are tolerated on both the side of the carboxylic ester (halo, keto, formyl, ester, cyano, nitro and protected amino groups, heterocyclic and a,-unsaturated carboxylic esters) and of the alkene (electron-rich alkyl-substituted alkenes, electron-poor acrylate derivatives, trimethylvinylsilane as an ethylene surrogate). The cinnamate derivatives could become particularly useful substrates, since the availability of the synthetically equivalent vinyl halides is rather limited. In analogy to conventional Mizoroki-Heck chemistry, linear (Zi)-substituted alkenes are predominantly but not exclusively obtained. Selected examples are shown in Table 4.1. 

Electron-withdrawing groups are groups of atoms that attract the electrons of the tt bond, making the alkene electron poor and therefore more electrophilic toward the diene. 

The stabilization of chloromethoxycarbene (234) was intensively studied. It is formed from diazirine (233) in a first order reaction with fi/2 = 34h at 20 C. It reacts either as a nucleophile, adding to electron poor alkenes like acrylonitrile with cyclopropanation, or as an electrophile, giving diphenylcyclopropenone with the electron rich diphenylacetylene. In the absence of reaction partners (234) decomposes to carbon monoxide and methyl chloride (78TL1931, 1935). 

The Diels-Alder reaction,is a cycloaddition reaction of a conjugated diene with a double or triple bond (the dienophile) it is one of the most important reactions in organic chemistry. For instance an electron-rich diene 1 reacts with an electron-poor dienophile 2 (e.g. an alkene bearing an electron-withdrawing substituent Z) to yield the unsaturated six-membered ring product 3. An illustrative example is the reaction of butadiene 1 with maleic anhydride 4 ... 

For the ordinary Diels-Alder reaction the dienophile preferentially is of the electron-poor type electron-withdrawing substituents have a rate enhancing effect. Ethylene and simple alkenes are less reactive. Substituent Z in 2 can be e.g. CHO, COR, COOH, COOR, CN, Ar, NO2, halogen, C=C. Good dienophiles are for example maleic anhydride, acrolein, acrylonitrile, dehydrobenzene, tetracya-noethylene (TCNE), acetylene dicarboxylic esters. The diene preferentially is of the electron-rich type thus it should not bear an electron-withdrawing substituent. 

We saw in the preceding chapter that the carbon-ha]ogen bond in an alkyl halide is polar and that the carbon atom is electron-poor. Thus, alkyl halides are electrophiles, and much of their chemistry involves polar reactions with nucleophiles and bases. Alkyl halides do one of two things when they react with a nucleophile/base, such as hydroxide ion either they undergo substitution of the X group by the nucleophile, or they undergo elimination of HX to yield an alkene. 

The conjugate addition of a nucleophile to an a,fi-unsaturated aldehyde or ketone is caused by the same electronic factors that are responsible for direct addition. The electronegative oxygen atom of the a,/3-unsaturated carbonyl compound withdraws electrons from the /3 carbon, thereby making it electron-poor and more electrophilic than a typical alkene carbon. 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

The reaction of alkenylcarbene complexes and electron-poor alkenes normally leads to mixtures of the expected [2S+1C] vinylcyclopropane derivatives (see... 

One of the earliest reported thermal reactions of Fischer carbene complexes was the reaction with olefins to give cyclopropanes [127]. More recently it has been shown that photolysis accelerates inter molecular cydopropanation of electron-poor alkenes [128]. Photolysis of Group 6 imine carbenes with alkenes... 

The (TMS)3SiH mediated addition of phosphorus-centered radicals to a number of alkenes has been investigated in some detail. Reaction (73) is an example of phosphorous-carbon bond formation using four structurally different phenylseleno derivatives with 3 equiv of (TMSlsSiH and AIBN in refluxing benzene for 2h. Comparative studies on the reaction of the four phosphorus-centered radicals have been obtained. Although the reaction with 1-methylene cyclohexane is efficient with all four derivatives, different selectivity is observed with electron-rich or electron-poor alkenes. 

As the Br2 molecule gets closer to the alkene, this temporary effect becomes more pronounced. Now we can understand why Br2 functions as an electrophile in this reaction there is a temporary 5+ on the bromine atom that is closer to the pi bond of the alkene. When the electron-rich alkene attacks the electron-poor bromine, we get the following hrst step of our mechanism ... 

Iron porphyrins display pronounced substrate preferences for alkene cyclopro-panation with EDA. In general, electron-rich terminal alkenes in conjunction with aromatic moiety or heteroatoms can efficiently undergo cyclopropanation with high catalyst turnover and selectivity. In contrast, 1,2-disubstituted alkenes cannot undergo cyclopropanation with diazoesters. Alkyl alkenes are poor substrates, giving cyclopropanated products in low yields. In both cases, the dimerization product diethyl maleate was obtained in high yield [53]. 

The thermal decompositions are catalyzed by Bronsted and Lewis acids [68]. In general, when M is electron poor and Lewis acidic, the thermal decompositions occur efficiently and at low temperatures (typically between 100 and 200 °C, but sometimes at lower temperature). The addition of a catalytic amount of a Lewis or Bronsted acid (i.e., AICI3 or HCl) has been observed to accelerate the ehmination of isobutylene and the formation of three-dimensional network structures [64,124-126]. Pioneering studies on pyrolyses of various metal alkoxides by Bradley and others have also shown that alkene eliminations represent a primary decomposition pathway [104]. 

The photoadditions proceed through 1,4-diradical intermediates. Trapping experiments with hydrogen atom donors indicate that the initial bond formation can take place at either the a- or (3-carbon of the enone. The excited enone has its highest nucleophilic character at the (3-carbon. The initial bond formation occurs at the (3-carbon for electron-poor alkenes but at the a-carbon for electron-rich alkenes.191 Selectivity is low for alkenes without strong donor or acceptor substituents.192 The final product ratio also reflects the rate and efficiency of ring closure relative to fragmentation of the biradical.193... 

The rate of epoxidation of alkenes is increased by alkyl groups and other ERG substituents and the reactivity of the peroxy acids is increased by EWG substituents.72 These structure-reactivity relationships demonstrate that the peroxyacid acts as an electrophile in the reaction. Decreased reactivity is exhibited by double bonds that are conjugated with strongly electron-attracting substituents, and more reactive peroxyacids, such as trifluoroperoxyacetic acid, are required for oxidation of such compounds.73 Electron-poor alkenes can also be epoxidized by alkaline solutions of... 

Amouri and coworkers also demonstrated that the nucleophilic reactivity of the exocyclic carbon of Cp Ir(T 4-QM) complex 24 could be utilized to form carbon -carbon bonds with electron-poor alkenes and alkynes serving as electrophiles or cycloaddition partners (Scheme 3.17).29 For example, when complex 24 was treated with the electron-poor methyl propynoate, a new o-quinone methide complex 28 was formed. The authors suggest that the reaction could be initiated by nucleophilic attack of the terminal carbon of the exocyclic methylene group on the terminal carbon of the alkyne, generating a zwitterionic oxo-dienyl intermediate, followed by proton transfer... 

The coordinated quinone methide Jt-system of complex 24 can also undergo cycloaddition (Scheme 3.17). When 24 was reacted with /V-methylmaleimide, a [3+2] cycloaddition took place to give the tricyclic iridium complex 29. The closest example to this unprecedented reactivity pattern is a formal [3 + 2] cycloaddition of /)-quinone methides with alkenes catalyzed by Lewis acids, although in that reaction the QMs serve as electron-poor reagents. 36... 

Diazomethane is also decomposed by N O)40 -43 and Pd(0) complexes43 . Electron-poor alkenes such as methyl acrylate are cyclopropanated efficiently with Ni(0) catalysts, whereas with Pd(0) yields were much lower (Scheme 1)43). Cyclopropanes derived from styrene, cyclohexene or 1-hexene were formed only in trace yields. In the uncatalyzed reaction between diazomethane and methyl acrylate, methyl 2-pyrazoline-3-carboxylate and methyl crotonate are formed competitively, but the yield of the latter can be largely reduced by adding an appropriate amount of catalyst. It has been verified that cyclopropane formation does not result from metal-catalyzed ring contraction of the 2-pyrazoline, Instead, a nickel(0)-carbene complex is assumed to be involved in the direct cyclopropanation of the olefin. The preference of such an intermediate for an electron-poor alkene is in agreement with the view that nickel carbenoids are nucleophilic 44). 

Diazocarbonyl compounds readily undergo [3 + 2] cycloaddition to electron-poor alkenes 139). The 1-pyrazolines thus formed usually tautomerize to 2-pyrazolines if there is a hydrogen in an a-position to one of the nitrogen atoms otherwise, thermally induced ring contraction with evolution of nitrogen to give cyclopropanes can occur (Scheme 18). 

Based on a detailed investigation, it was concluded that the exceptional ability of the molybdenum compounds to promote cyclopropanation of electron-poor alkenes is not caused by intermediate nucleophilic metal carbenes, as one might assume at first glance. Rather, they seem to interfere with the reaction sequence of the uncatalyzed formation of 2-pyrazolines (Scheme 18) by preventing the 1-pyrazoline - 2-pyrazoline tautomerization from occurring. Thereby, the 1-pyrazoline has the opportunity to decompose purely thermally to cyclopropanes and formal vinylic C—H insertion products. This assumption is supported by the following facts a) Neither Mo(CO)6 nor Mo2(OAc)4 influence the rate of [3 + 2] cycloaddition of the diazocarbonyl compound to the alkene. b) Decomposition of ethyl diazoacetate is only weakly accelerated by the molybdenum compounds, c) The latter do not affect the decomposition rate of and product distribution from independently synthesized, representative 1-pyrazolines, and 2-pyrazolines are not at all decomposed in their presence at the given reaction temperature. 

Some remarks concerning the scope of the cobalt chelate catalysts 207 seem appropriate. Terminal double bonds in conjugation with vinyl, aryl and alkoxy-carbonyl groups are cyclopropanated selectively. No such reaction occurs with alkyl-substituted and cyclic olefins, cyclic and sterically hindered acyclic 1,3-dienes, vinyl ethers, allenes and phenylacetylene95). The cyclopropanation of electron-poor alkenes such as acrylonitrile and ethyl acrylate (optical yield in the presence of 207a r 33%) with ethyl diazoacetate deserve notice, as these components usually... 

Intramolecular thermal [4+2] cycloaddition occurs smoothly, though at a high temperature, upon heating of the appropriately substituted electron-poor oxadiazole containing electron-rich alkene fragment (Equation 1) <2002JOC7361>. 

A new entry to exocyclic dienes was reported by Sha who uncovered that a radical cyclization of the vinyl iodide 100 can lead to the formation of an exocyclic dienes fused with a tetrahydrofuran ring. The cyclization is proposed to proceed in a 5-(n-exo)-exo-dig fashion <00OL2011>. 3,4-Disubstituted tetrahydrofurans can also be constructed via the cyclization of O-stannyl ketyls and allylic 0-stannyI ketyls onto electron-rich or electron-poor alkenes <00TL8941>. 

Fig. 16 Comparison of intrazeolite and solution singlet oxygen ene reactions of electron poor alkenes.

Scheme 14.11 Stereoselective hydrogenation of alkynes to al-kenes by [Pd(Ar-bian)(alkene)] (26). In compound 26a the electron-poor alkene is dimethyl fumarate, E = C02Me in 26b the electron-poor alkene is maleic anhydride, E = C(0)0C(0).

Historically, the asymmetric synthesis of epoxides derived from electron-poor alkenes, for example a, (3-unsaturated ketones, has not received as much attention as the equivalent reaction for electron-rich alkenes (vide supra). However, a recent flurry of research activity in this area has uncovered several... 

As a, (3-unsaturated ketones are electron-poor alkenes, they do not generally give epoxides when treated with peracids. They can be epoxidized with hydrogen peroxide which involves nucleophilic attack by HOO- to give the epoxy ketone (Figure 4.1). 

When other acceptor systems such as tetracyanoethylene, ethyl propiolate, dibenzoylacetylene, or dimethyl azodicarboxylate were reacted with 41, no additional products were formed. Accordingly, the scope of the reaction for the nucleophilic addition of 41 to electron-poor alkenes, alkynes, and diazo compounds is quite narrow. 

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