Electron-rich alkene

Well-known is the cyclopropanation of various alkenes. As shown by 329, cyclopropanation starts by electrophilic attack to the alkene. Electron-rich alkenes have higher reactivity. Numerous applications of intramolecular cyclopropanation to syntheses of natural products have been reported. Optically active cyclopropanes are prepared by enantioselective cyclopropanation [100], As the first successful example, asymmetric synthesis of chrysanthemic acid (331) was carried out by cyclopropanation of 2,5-dimethyl-2,4-hexadiene (330) with diazoacetate, catalysed by the chiral... 

Careful product and kinetic studies for selected electron-deficient alkenes, electron-rich dienes and vinyl-substituted aromatic systems have provided some clarification of the [2 + 2] versus [2 + 2] cycloaddition issue. The thermodynamically favored product can often be anticipated on structural grounds. Reactions of TCNE with vinyl-substituted benzenoid aromatics, protoporphorins or heteroaromaticsgive [2 + 2] products, but for some styrenes the [2 + 4] addition may be kinetically favored. p-Methoxystyrene and TCNE react to form a charge-transfer complex which leads reversibly to the Diels-Alder product, and eventually to the finally isolated [2 + 2] adduct. An isomer of di-cyclopentadiene shows the same pattern, with the initially formed Diels-Alder adduct giving rise to a [2 + 2] adduct. 

Ti(Cp)2(CO)2l is a catalyst for the hydrogenation of phenylacetylene to ethylbenzene, while alkyl-substituted terminal alkynes are reduced to alkenes. Electron rich titanium(II) complexes, [Cp2Ti(PhC OPh)(PMe3)], [(MeCp)2Ti(PhC=CPh)(PMe3)] and [CpCp Ti(PhCsCPh)] are also catalyst precursors for the hydrogenation of alkynes to alkanes at 20 C under atmospheric pressure of hydrogen. "... 

Studies on the stability of nitrile oxides [299] bound to Wang resin revealed that decomposition started to be detectable only after 3 days of storage in a dry box at r. t. The authors also demonstrated that cleaner products were obtained by generating the 1,3-dipole prior to addition of the dipolarophile. Mono-substituted electron-poor alkenes represent better dipolarophiles (in terms of both yield and regiose-lectivity) than 1,2-substituted electron-poor alkenes. Electron-rich alkenes gave good results vstith electron-poor (carboxy-substituted) nitrile oxides. The latter were more reactive than the corresponding alkoxy-substituted nitrile oxides. 

The photoaddition of simple aldehydes and ketones to alkenes, electron-deficient alkenes, electron-rich alkenes, and carbohydrate-... 

The asymmetric dihydroxylation is much less fussy about the alkenes it will oxidize than Sharpless asymmetric epoxidation. Osmium tetroxide itself is a remarkable reagent, since it oxidizes more or less any sort of alkene, electron-rich or electron-poor, and the same is true of the asymmetric dihydroxylation reagent. The following example illustrates both this and a synthetic use for the diol product. 

Pd-catalyzed hydroarylation of alkynes via aromatic C—bond activation has been reported by Fujiwara. The reaction offers a good synthetic method of arylalkenes, which are usually prepared by Heck reaction of alkenes. Electron-rich arenes bearing more than one OH, OMe, and alkyl groups react with electron-deficient alkynes [6], The reaction proceeds with a catalytic amount of Pd(OAc)2 in trifluoroacetic acid (TEA) at room temperature. Hydroarylation of ethyl propiolate (15) with / -dimethoxybenzene yielded ethyl (Z)-3-(2,5-dimethoxyphenyl)-2-propenoate (16). Mesitylene (17) is an active arene and the reaction of 17 with 3-butyn-2-one (18) afforded the imsaturated ketone 19 which has f-form [7]. 

The Mizoroki-Heck reaction is a subtle and complex reaction which involves a great variety of intermediate palladium complexes. The four main steps proposed by Heck (oxidative addition, alkene insertion, )3-hydride elimination and reductive elimination) have been confirmed. However, they involved a considerable number of different Pd(0) and Pd(Il) intermediates whose structure and reactivity depend on the experimental conditions, namely the catalytic precursor (Pd(0) complexes, Pd(OAc)2, palladacycles), the Ugand (mono- or bis-phosphines, carbenes, bulky monophosphines), the additives (hahdes, acetates), the aryl derivatives (ArX, ArOTf), the alkenes (electron-rich versus electron-deficient ones), which may also be ligands for Pd(0) complexes, and at least the base, which can play a... 

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. 

A major difficulty with the Diels-Alder reaction is its sensitivity to sterical hindrance. Tri- and tetrasubstituted olefins or dienes with bulky substituents at the terminal carbons react only very slowly. Therefore bicyclic compounds with polar reactions are more suitable for such target molecules, e.g. steroids. There exist, however, several exceptions, e. g. a reaction of a tetrasubstituted alkene with a 1,1-disubstituted diene to produce a cyclohexene intermediate containing three contiguous quaternary carbon atoms (S. Danishefsky, 1979). This reaction was assisted by large polarity differences between the electron rich diene and the electron deficient ene component. 

The alkylpalladium intermediate 198 cyclizes on to an aromatic ring, rather than forming a three-membered ring by alkene insertion[161], Spirocyclic compounds are easily prepared[l62]. Various spiroindolines such as 200 were prepared. In this synthesis, the second ring formation involves attack of an alkylpalladium species 199 on an aromatic ring, including electron-rich or -poor heteroaromatic rings[l6.5]. 

Both parts of the Lapworth mechanism enol formation and enol halogenation are new to us Let s examine them m reverse order We can understand enol halogenation by analogy to halogen addition to alkenes An enol is a very reactive kind of alkene Its carbon-carbon double bond bears an electron releasing hydroxyl group which makes it electron rich and activates it toward attack by electrophiles... 

AUylic organoboranes react via cyclic transition states not only with aldehydes and ketones, but also with alkynes, aHenes, and electron-rich or strained alkenes. Bicyclic stmctures, which can be further transformed into boraadamantanes, are obtained from triaHyl- or tricrotylborane and alkynes (323,438,439). 

The addition proceeds in three discrete steps and the intermediates can be isolated. Simple alkenes are less reactive than alkynes and do not undergo the addition to aHylic boranes, but electron-rich alkyl vinyl ethers react at moderate temperatures to give 1,4-dienes or dienyl alcohols (440). 

The initial bond formation between the -> ir excited carbonyl compound and an alkene can occur by interaction of the half-filled n -orbital of the [I CO] with the ir-system of the alkene, in a sense transferring a tt-electron to the -orbital and making a bond between an alkene carbon and the carbonyl oxygen. In this process (common for electron rich olefins) the plane formed by the alkene carbons and their four substituents is perpendicular to the plane of the carbonyl groups and its two substituents (Figure 1). In the... 

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). 

Other isocyanates undergo [2 + 2] cycloaddition, but only with very electron rich alkenes. Thus phenyl isocyanate gives /3-lactams with ketene acetals and tetramethoxyethylene. With enamines, unstable /3-lactams are formed if the enamine has a /3-H atom, ring opened amides are produced 2 1 adducts are also found. Photochemical addition of cis- and traH5-stilbene to phenyl isocyanate has also been reported (72CC362). 

Photochemical [2 + 2] cycloaddition of benzonitrile and of 1- and 2-naphthonitriles to electron-rich alkenes such as 2,3-dimethyIbut-2-ene gives the corresponding 2-aryl-l-azetines in poor yield 72JA5929,76CC729, 77JOC4238). This does not appear to be a versatile route to 1-azetines. 

Reaction of triethylsilyl hydrotrfoxide with electron-rich olefins to gh/e dioxetanes that react IntrarTMlecularly with a keto group in the presence of t-txrtyidimethyl silyl triflateto afford 1,2,4 Inoxanes also oxydatnre cleavage ol alkenes Also used in cleavage ol olefins... 

Small shift values for CH or CHr protons may indicate cyclopropane units. Proton shifts distinguish between alkyne CH (generally Sh = 2.5 - 3.2), alkene CH (generally 4, = 4.5-6) and aro-matic/heteroaromatic CH (Sh = 6 - 9.5), and also between rr-electron-rich (pyrrole, fiiran, thiophene, 4/ = d - 7) and Tt-electron-deficient heteroaromatic compounds (pyridine, Sh= 7.5 - 9.5). 

The pyrolysis of sodium chlorodinuoroacetate is still a widely used, classical method for generating difluorocarbene, especially with enol and allyl acetates [48, 49, 50, 51] (equation 21) A convenient alternative that avoids the hygroscopic salt uses methyl chlorodifluoroacetate with 2 equivalents of a lithium chlonde-hexa-methylphosphoric triamide complex at 75-80 °C in triglyme [52], Yields are excellent with electron-rich olefins but are less satisfactory with moderately nucleophilic alkenes (4-5% yields for 2-bulenes)... 

Simultaneous elimination of chloride ion and carbon dioxide occurs dunng heating of methyl chlorodifluoroacetate with lithium chloride in hexamethyl-phosphoric tnamide (HMPA) The difluorocarbene generated in this way is trapped by electron-rich alkenes to form 1,1-difluorocyclopropanes [26] (equation 24)... 

Early work established that S4N4 forms di-adducts with alkenes such as norbornene or norbomadiene. Subsequently, structural and spectroscopic studies established that cycloaddition occurs in a 1,3-S,S"-fashion. The regiochemistry of addition can be rationalized in frontier orbital terms the interaction of the alkene HOMO with the low-lying LUMO of S4N4 exerts kinetic control. Consistently, only electron-rich alkenes add to S4N4. 

Is the stable cation that formed as a result of protonation of the more electron-rich end of the alkene Examine electrostatic potential maps for propene, 2-methylpropene and 2-methyl-2-butene. For each, can you tell whether one end of the 7t bond is more electron rich than the other end If so, does protonation on the more electron-rich end lead to the more stable carbocation ... 

Examine the eleetrostatic potential map of eaeh nueleophile (enamine, silyl enol ether, lithium enolate and enol) with emphasis on the face of the nucleophilic alkene carbon. Rank the nucleophiles from most electron rich to least electron rich. What factors are responsible for this order (Hint For each molecule, consider an alternative Lewis structure to that given above that places a negative charge on the nucleophilic carbon.)... 

Reaction of 2-[(benzotriazol-l-yl)alkylamino]pyridines 341 with open-chain electron-rich alkenes 342 in the presence of BF3-Et20 gave 4-substituted 1,2,3,4-tetrahydropyrido[l, 2-n]pyrimidinium tetrafluorobo-rates 343 (98S704). 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

The reactions of nitrones constitute the absolute majority of metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions. Boron, aluminum, titanium, copper and palladium catalysts have been tested for the inverse electron-demand 1,3-dipolar cycloaddition reaction of nitrones with electron-rich alkenes. Fair enantioselectivities of up to 79% ee were obtained with oxazaborolidinone catalysts. However, the AlMe-3,3 -Ar-BINOL complexes proved to be superior for reactions of both acyclic and cyclic nitrones and more than >99% ee was obtained in some reactions. The Cu(OTf)2-BOX catalyst was efficient for reactions of the glyoxylate-derived nitrones with vinyl ethers and enantioselectivities of up to 93% ee were obtained. 

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