Alkenes chemoselective

The oxidation of terminal alkenes with an EWG in alcohols or ethylene glycol affords acetals of aldehydes chemoselectively. Acrylonitrile is converted into l,3-dioxolan-2-ylacetonitrile (69) in ethylene glycol and to 3,3-dimetho.xy-propionitrile (70) in methanol[28j. 3,3-Dimethoxypropionitrile (70) is produced commercially in MeOH from acrylonitrile by use of methyl nitrite (71) as a unique leoxidant of Pd(0). Methyl nitrite (71) is regenerated by the oxidation of NO with oxygen in MeOH. Methyl nitrite is a gas, which can be separated easily from water formed in the oxidation[3]. 

With higher alkenes, three kinds of products, namely alkenyl acetates, allylic acetates and dioxygenated products are obtained[142]. The reaction of propylene gives two propenyl acetates (119 and 120) and allyl acetate (121) by the nucleophilic substitution and allylic oxidation. The chemoselective formation of allyl acetate takes place by the gas-phase reaction with the supported Pd(II) and Cu(II) catalyst. Allyl acetate (121) is produced commercially by this method[143]. Methallyl acetate (122) and 2-methylene-1,3-diacetoxypropane (123) are obtained in good yields by the gas-phase oxidation of isobutylene with the supported Pd catalyst[144]. 

Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

A catalyst, usually acid, is required to promote chemoselective and regioselective reduction under mild conditions. A variety of organosilanes can be used, but triethylsilane ia the presence of trifiuoroacetic acid is the most frequendy reported. Use of this reagent enables reduction of alkenes to alkanes. Branched alkenes are reduced more readily than unbranched ones. Selective hydrogenation of branched dienes is also possible. 

Epoxides are regio- and stereoselectively transformed into fluorohydrins by silicon tetrafluoride m the presence of a Lewis base, such as diisopropyleth-ylamme and, m certain instances, water or tetrabutylammonium fluoride The reactions proceed under very mild conditions (0 to 20 C in 1,2-diohloroethane or diethyl ether) and are highly chemoselective alkenes, ethers, long-chain internal oxiranes, and carbon-silicon bonds remain intact The stereochemical outcome of the epoxide ring opening with silicon tetrafluoride depends on an additive used, without addition of water or a quaternary ammonium fluoride, as fluorohydrins are formed, whereas m the presence of these additives, only anti opening leading to trans isomers is observed [17, 18] (Table 2)... 

A first evaluation of complex 71a by Blechert et al. revealed that its catalytic activity differs significantly from that of the monophosphine complex 56d [49b]. In particular, 71a appears to have a much stronger tendency to promote cross metathesis rather than RCM. Follow-up studies by the same group demonstrate that 71a allows the cross metathesis of electron-deficient alkenes with excellent yields and chemoselectivities [50]. For instance, alkene 72 undergoes selective cross metathesis with 3,3,3-trifluoropropene to give 73 in excellent yield and selectivity. Precatalyst 56d, under identical conditions, furnishes a mixture of 73 and the homodimer of 72 (Scheme 17) [50a]. While 56d was found to be active in the cross metathesis involving acrylates, it failed with acrylonitrile [51]. With 71a, this problem can be overcome, as illustrated for the conversion of 72—>74 (Scheme 17) [50b]. 

Chemoselective alkenylation in the C-3 position of N-substituted 3,5-dichloropyrazin-2(lH)-ones has been described by Van der Eycken et al. [27]. When a mixture of N-substituted 3,5-dichloropyrazin-2(lH)-one, ethyl acrylate, and NEts in DME, using Pd(OAc)2/DTPB [2-(di-f-butylphosphanyl)bi-phenyl] as a precatalyst, was irradiated for 15 min at 150 °C, the desired /1-fimctionabzed ethyl acrylates could be obtained in moderate yields (Scheme 81). When styrene was used as an alkene, a mixture of E and Z products was isolated. The type of catalyst used proved to be important to avoid competitive Diels-Alder reaction of ethyl acrylate with the hetero-diene system of 3,5-dichloro-l-benzylpyrazin-2(lH)-one. 

COMPLETELY REGIO- AND CHEMOSELECTIVE BROMINATION OF fflGHLY CONJUGATED ALKENES... 

The Markovnikov regioselectivity of the gem-alkenes is associated with a chemoselectivity. in favour of methanol attack, significantly greater than that observed for the other alkenes. If no sodium bromide is added to the reaction medium, no dibromide is observed for this series. Therefore, these alkenes behave as highly conjugated olefins, as regards their regio- and chemo-selectivity. In other words, the bromination intermediates of gem-alkenes resemble P-bromocarbocations, rather than bromonium ions. Theoretical calculations (ref. 8) but not kinetic data (ref. 14) support this conclusion. 

The chemoselectivity of the other alkenes of Table 1 is more variable. It appears that bulky substituents favour bromide over methanol attack of the bromonium ion, since dibromlde increases from 39 to 70 % on going from methyl to tert-butyl in the monosubstituted series. The same trend is observed in the disubstituted series with a contraction of the chemoselectivity span (37 to 43 % on going from methyl to teH-butyl) for the trans isomers. Since the solvated bromide ion can be viewed as a nucleophile larger than methanol, the influence of steric effects, important in determining the regioselectivity, does not seem very significant as regards the chemoselectivity. This result has been interpreted in terms of a different balance between polar and steric effects of the substituents on these two selectivities. 

The chemoselectivity of bromination going through bromocarbocations (highly conjugated olefins and also gem-alkenes ) is 100 % in favour of methanol, a nucleophile stronger than bromide ions. However, when the intermediates are bromonium ions, the chemoselectivity is poor. Branched substituents seem to favour the dibromide over the solvent-incorporated adduct, although the bromide ion is considered to be a bulkier nucleophile than methanol. 

Until recently, iron-catalyzed hydrogenation reactions of alkenes and alkynes required high pressure of hydrogen (250-300 atm) and high temperature (around 200°C) [21-23], which were unacceptable for industrial processes [24, 25]. In addition, these reactions showed low or no chemoselectivity presumably due to the harsh reaction conditions. Therefore, modifications of the iron catalysts were desired. 

The complexes [Cu(NHC)(MeCN)][BF ], NHC = IPr, SIPr, IMes, catalyse the diboration of styrene with (Bcat) in high conversions (5 mol%, THF, rt or reflux). The (BcaO /styrene ratio has also an important effect on chemoselectivity (mono-versus di-substituted borylated species). Use of equimolecular ratios or excess of BCcat) results in the diborylated product, while higher alkene B(cat)j ratios lead selectively to mono-borylated species. Alkynes (phenylacetylene, diphenylacety-lene) are converted selectively (90-95%) to the c/x-di-borylated products under the same conditions. The mechanism of the reaction possibly involves a-bond metathetical reactions, but no oxidative addition at the copper. This mechanistic model was supported by DFT calculations [68]. 

The chemoselectivity of Schwartz s reagent (1) toward alkynes, alkenes, nitriles, and carbonyl groups, and thus its general functional group compatibility, can be modulated. However, it is important to keep in mind that the presence of functional groups may have regiochemical consequences on the hydrozirconation reaction. 

As predicted from the comparative rates for C=C over C=C hydrozirconation cited earlier, a (poly)enyne is selectively hydrozirconated at the alkyne moiety, whatever the position of the alkene function [138, 210] in the molecule. It can be exempUfied by the chemoselective hydrozirconation of 1,3-butenyne. One exception to this chemoselectivity has been reported, which showed the terminal alkene to react with 1 but leaving the TMS-substituted alkyne function intact (Scheme 8-25). 

Hydroformylation of a range of 1,1-di- and 1,1,2-trisubstituted unsatur-ated esters yields quaternary aldehydes (Table 1, entries 1-8). Hence, the regiochemistry-directing influence of the electron-withdrawing ester function overcompensates Keuleman s rifle. Furthermore, hydroformylation of 1,2-disubstituted unsaturated esters occurred with high a-selectivity and chemoselectivity (Table 1, entries 9 and 10). As a side reaction hydrogenation of the alkene has been observed [41]. 

The reductive coupling/silylation reaction was extended to more complicated polyenes, such as the triene-substituted cyclopentanol 73, which cyclizes to provide 74 with a 72% yield and 6 1 dr after oxidation (Eq. 10) [44], The reaction is chemoselective the initial insertion occurs into the allyl substituent, which then inserts into the less hindered of the two remaining olefins, leaving the most hindered alkene unreacted. 

The synthesis of 2,3,5-trialkylpyrroles can be easily achieved by conjugate addition of nitroalkanes to 2-alken-l,4-dione (prepared by oxidative cleavage of 2,5-dialkylfuran) with DBU in acetonitrile, followed by chemoselective hydrogenation (10% Pd/C as catalyst) of the C-C- double bond of the enones obtained by elimination of HN02 from the Michael adduct. The Paal-Knorr reaction (Chapter 10) gives 2,3,5-trialkylpyrroles (Eq. 4.124).171... 

The solvent has no influence on the stereoselectivity of bromine addition to alkenes (Rolston and Yates, 1969b), but it could have some effect on the regioselectivity, since this latter depends not only on polar but also on steric effects. Obviously, it modified the chemoselectivity. For example, in acetic acid Rolston and Yates find that 2-butenes give 98% dibromides and 2% solvent-incorporated products whereas, in methanol with 0.2 m NaBr, dibromide is only about 40% and methoxybromide 60%. There are no extensive data, however, on the solvent effects on the regio- and chemoselectivity which would allow reliable predictions. 

Ruasse et al, 1978) is totally regioselective and shows X-dependent chemoselectivity. This is partly in agreement with the kinetic data, which indicate no primary carbocation but rather a competition between the benzylic carbocation and the bromonium ion, depending on X. According to the data of Table 6, bridged intermediates would lead to more dibromide than open ions do. From these results and from those on gem-, cis- or frans-disubstituted alkenes, empirical rules have been inferred for chemoselectivity (i) more solvent-incorporated product is formed from open than from bridged ions (ii) methanol competes with bromide ions more efficiently than acetic acid. 

There are important issues relating to chemoselectivity (aldehydes or alcohols may be the products and alkene isomerisation is a competing side reaction, which must be reduced to a minimum) and regioselectivity (linear aldehyde is much preferred over branched)... 

There are several guidelines that should be followed in order to increase the chemoselectivity of the monoadduct. Firstly, radical concentration must be low in order to suppress radical termination reactions (rate constant of activation [fcal and fca2] < < rate constant of deactivation kd t andfcd2]). Secondly, further activation of the monoadduct should be avoided ( al> >kd2). Lastly, formation of oligomers should be suppressed, indicating that the rate of deactivation (kd 2[Cu"LmX]) should be much larger than the rate of propagation ( [alkene]). Alkyl halides for copper-catalyzed ATRA are typically chosen such that if addition occurs, then the newly... 

Controlled single-stage carbometallation reactions of alkenes and alkynes with group 4—7 metals are discussed with emphasis on regio-, stereo-, and chemoselectivity including clarification and understanding of factors governing these synthetically important aspects. 

Palladium-catalyzed cyclization of alkenes and alkynes were reported by Balme and co-workers.143 144 Intramolecular carbopalladation occurs to give polycyclic compounds. It has been shown that the nucleophile type has a large influence on the cyclization process. Both 5-exo- and 6-endo-cyclization are observed for substrates with nitrile (116 and 118) and ester (120, 122, and 124) substituents, respectively (Scheme 36). When a mixed nucleophile (CN and C02Me) is used, a mixture of 5-exo and 6-endo products is obtained. The chemoselectivity is controlled by the size of the nucleophile used. The stereochemistry of the initial double bond plays an important role on the stereoselectivity of the cyclization. (Z)-olefins (118 and 120) and (/. )-olefins (116 and 124) afford as- (119 and 121) and trans-cyclization products (117 and 123), respectively. 

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