Tetra-substituted alkenes, hydrogenation

For tetra-substituted alkenes [107], it was necessary to rely on the more reactive cationic Zr equivalent generated from [(EBTHI)ZrMe2] and either methyla-luminoxane or [PhMe2NH]+[Co(C2B9H11)2] developed earlier by Waymouth et al. [104]. Using H2 pressure ranging between 5 and 133 bar, it was possible to obtain the hydrogenated products with 80-98% ee in most cases (Table 6.3). 

Table 6.3 Enantioselective hydrogenation of tetra-substituted alkenes catalyzed by [(S,S)-(EBTHI)ZrMe2]/[PhMe2NH+B(C6F5)4V)...

Ionic hydrogenations of C=C bonds generally work well only in cases where a tertiary or aryl-substituted carbenium ion can be formed through protonation of the C=C bond. Alkenes that give a tertiary carbenium ion upon protonation include 1,1-disubstituted, tri-substituted and tetra-substituted alkenes, and each of these are usually hydrogenated by ionic hydrogenation methods in high yields. 

The rate-determining step in the ionic hydrogenation reaction of carbon-carbon double bonds involves protonation of the C==C to form a carbocation intermediate, followed by the rapid abstraction of hydride from the hydride source (equation 45). ° There is a very sensitive balance between several factors in order for this reaction to be successful. The proton source must be sufficiently acidic to protonate the C—C to form the intermediate carbocation, yet not so acidic or electrophilic as to react with the hydride source to produce hydrogen. In addition, the carbocation must be sufficiently electrophilic to abstract the hydride from the hydride source, yet not react with any other nucleophile source present, i.e. the conjugate anion of the proton source. This balance is accomplished by the use of trifluoroacetic acid as the proton source, and an alkylsilane as the hydride source. The alkene must be capable of undergoing protonation by trifluoroacetic acid, which effectively limits the reaction to those alkenes capable of forming a tertiary or aryl-substituted carbocation. This essentially limits the application of this reaction to the reduction of tri- and tetra-substituted alkenes, and aryl-substituted alkenes. 

We must remember that branched alkenes may contain centres of optical activity an example is (—)3,7-dimethyl-l-octene, which when hydrogenated on platinum shows little racemlsation, but on palladium this happens extensively, to an extent depending upon the form of catalyst and reaction conditions. - Isomerisation of the double bond to the 2-position negates the optical activity, so that it may return to the terminal position in either the (-1-)- or (—) form. When tetra-substituted alkenes of the type RR C=CCRR are hydrogenated, two centres of optical activity are created the fi-form gives the meso product, while the Z-form gives a racemic mixture. ... 

Birch also illustrated tire difference in selectivity between Wilkinson s catalyst and typical heterogeneous catalysts. Hydrogenation of 1,4-dihydrobenzenes (derived from the "Birch reductions" of arenes) in the presence of Wilkinson s catalyst forms the tetra-substituted alkene product, whereas hydrogenation with classic platinum and palladium heterogeneous catalysts causes disproportionation to form arene byproducts (Equation 15.6). Like the (3-keto alcohol in Equation 15.5, the ester in Equation 15.6 is not reduced. 

Although the [Ir(COD)(py)2]+ complex is inactive as a catalyst, because it fails to add hydrogen, the mixed-ligand complexes [Ir(COD)(py)(PR3)]+ are very active catalysts for the reduction of a variety of substrates, particularly tetra-substituted alkenes. Thus, in dichloromethane as solvent, [Ir(COD)(py)(PCy3)]+, usually known as Crabtree s catalyst, is a very active and selective catalyst, insensitive to oxidizing or other sensitive functionality. Figure 17 shows comparative rates of iridium cationic complexes of the formula [Ir(COD)(L)(PR3)]+ and Wilkinson s catalyst (52,53). 

Regarding the scope of the reaction, it was found that electron-rich substrates like di-, tri- and tetra-substituted alkenes were giving moderate to good yields of their corresponding epoxides. Styrene and styrene derivatives were also demonstrated to react smoothly, whereas mono-alkyl-substituted substrates were completely un-reactive under these conditions. The basic reaction medium used was very beneficial for product protection, and hence acid sensitive epoxides were formed in good yields. Different additives were screened in order to improve this epoxidation system, and it was found that the addition of sodium acetate was beneficial for reactions performed in t-BuOH. Similarly, the addition of salicylic acid improved the outcome of the reaction performed in DMF. The use of these additives efficiently reduced the number of hydrogen peroxide equivalents necessary for a productive epoxidation (Table 2.5). The reaction is not completely stereospecific, since the epoxidation of as-4-octene yielded a cis/trans mixture ofthe product (1 1.45 without additive and 1 1.1 in the presence of 4mol% salicylic acid). 

In general, the rate of alkene hydrogenation is typically ordered as follows terminal>di-substituted>tri-substituted >tetra-substituted. In fact, this allows terminal or di-substituted olefins to be hydrogenated selectively in the presence of tri- or tetra-substituted ones. Additionally, the rate of hydrogenation of al-kynes is much slower than that of alkenes, although the cis-alkene intermediate... 

All of the olefins discussed so far contain a functional group, other than the C=C bond, that binds to the metal to create a defined structure. The asymmetric hydrogenation of olefins that lack this second functional group has been a major challenge. Few complexes of any type catalyze the hydrogenation of tri-substituted and tetra-substituted olefins, let alone catalyze asymmetric hydrogenation of these olefins. Recall from Section 15.3 on achiral catalysts for olefin hydrogenation that Wilkinson s catalyst and ruthenium-hydride complexes display little reactivity for the reduction of tri-substituted alkenes, and no reactivity for... 

One of the most important transformations catalysed by palladium is the Heck reaction. Oxidative addition of palladium(O) into an unsaturated halide (or tri-flate), followed by reaction with an alkene, leads to overall substitution of a vinylic (or allylic) hydrogen atom with the unsaturated group. For example, formation of cinnamic acid derivatives from aromatic halides and acrylic acid or acrylate esters is possible (1.209). Unsaturated iodides react faster than the corresponding bromides and do not require a phosphine ligand. With an aryl bromide, the ligand tri-o-tolylphosphine is effective (1.210). The addition of a metal halide or tetra-alkylammonium halide can promote the Heck reaction. Acceleration of the coupling can also be achieved in the presence of silver(I) or thallium(I) salts, or by using electron-rich phosphines such as tri-tert-butylphosphine. ... 

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