Hydrogenation trisubstituted olefins

Chiral phosphinodihydrooxazole iridium ligands are used to hydrogenate trisubstituted olefins in moderate yields and high enantioselectivity albeit of... 

The argument of the directing effect of lone pairs on the substiment [92] easily extends to the alkyl cases. The orbital interaction (Scheme 20) [103] in the pere-poxide quasi-intermediate suggests the stabilization occurs by the simultaneous interaction of O with two allylic hydrogens on the same side of the alkene. Photooxygenation of trisubstituted olefins revealed a strong preference for H-abstraction from disubstituted side of the double bond [104, 105],... 

As depicted in Scheme 21, subjection of 86 with 20 mol% of freshly prepared 2 after 4 h at 22 °C indeed afforded 87 in 92% yield after silica gel chromatography (>98% Z). Stereocontrolled hydrogenation of the trisubstituted olefin (72% yield) and removal of the acetate and trifluroacetate groups, effected by subjection of the hydrogenated adduct with hydrazine in MeOH, delivered Sch 38516 (1) in 96% yield to complete the total synthesis. 

In entries 10-13 (Table 21.8) of trisubstituted alkenes, very high diastereo-selectivity is realized by the use of a cationic rhodium catalyst under high hydrogen pressure, and the 1,3-syn- or 1,3-anti-configuration naturally corresponds to the ( )- or (Z)-geometry of the trisubstituted olefin unit [48, 49]. The facial selectivity is rationalized to be controlled by the A(l,3)-allylic strain at the intermediary complex stage (Scheme 21.2) [48]. 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

Pressure effects have been found to have a significant effect on the enantiose-lectivity of hydrogenation of terminal olefins with ThrePHOX catalysts, in contrast to trisubstituted olefins [17, 25]. For example, in the hydrogenation of 2 with catalyst 12b, 94% ee was obtained at 1 bar H2, compared to 58% ee at 50 bar H2 (Table 30.2). 

As discussed below, Ir complexes derived from chiral P,N ligands have become the catalysts of choice for the enantiomeric hydrogenation of unfunctionalized trisubstituted olefins. Therefore, the most important characteristics of these catalysts are briefly summarized here [30-32]. 

Tetrasubstituted alkenes are challenging substrates for enantioselective hydrogenation because of their inherently low reactivity. Crabtree showed that it was possible to hydrogenate unfunctionalized tetrasubstituted alkenes with iridium catalysts [46]. Among the iridium catalysts described in the previous section, several were found to be sufficiently reactive to achieve full conversion with al-kene 77 (Table 30.14). However, the enantioselectivities were significantly lower than with trisubstituted olefins, and higher catalyst loadings were necessary. 

Broene and Buchwald37 synthesized chiral titanocene compound 22 for the asymmetric hydrogenation of trisubstituted olefins. 

TABLE 6-3. Chiral Titanocene-Catalyzed Asymmetric Hydrogenation of Unfunctionalized Trisubstituted Olefins... 

Asymmetric Hydrogenation of Trisubstituted Olefins with Heteroatoms... 

Phosphinodihydroxazole (PHOX) compounds, L2-4, act as P/N bidentate ligands showing excellent enantioselectivity in Ir-catalyzed hydrogenation of simple a,a-disubstituted and trisubstituted olefins (Figure 1.12). " The use of tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArp) as a counter anion achieves high catalytic efficiency due to avoidance of an inert Ir trimer... 

Chiral l,T-diphosphetanylferrocene Et-FerroTANE serves as an effective ligand for the rhodium-catalyzed hydrogenation of y9-aryl- and /9-alkyl-substituted monoamido ita-conates (Eqs. 19 and 20) [54]. The Et-DuPhos-Rh catalyst was utihzed for the asymmetric hydrogenation of the trisubstituted olefin derivative in the preparation of an important intermediate for the drug candoxatril (>99% ee) [110]. 

In conclusion, the anti selectivity for hydrogen abstraction of the ene reaction of trisubstituted olefins is related (a) to the degree of crowdedness of the more substituted side of the olefin (b) to the non-bonded interactions during the new double bond formation and (c) to the lack of interaction of oxygen with two allylic hydrogens. 

In contrast with these results, catalytic cracking yields a much higher percentage of branched hydrocarbons. For example, the catalytic cracking of cetane yields 50-60 mol of isobutane and isobutylene per 100 mol of paraffin cracked. Alkenes crack more easily in catalytic cracking than do saturated hydrocarbons. Saturated hydrocarbons tend to crack near the center of the chain. Rapid carbon-carbon double-bond migration, hydrogen transfer to trisubstituted olefinic bonds, and extensive isomerization are characteristic.52 These features are in accord with a carbo-cationic mechanism initiated by hydride abstraction.43,55-62 Hydride is abstracted by the acidic centers of the silica-alumina catalysts or by already formed carbocations ... 

Dihydrogeranylacetone, though not a completely simple olefin, is chemoselectively hydrogenated at the C=C bond in the presence of a Ru complex with MeO-BIPHEP analogue containing four P-2-fury 1 groups to afford the saturated ketone with 91 % ee (Scheme 1.31) [86]. Examples of hydrogenation of a trisubstituted olefin with an oxo or oxy substituent in the p-position are unknown. 

Optically active aldehydes can be obtained by asymmetric hydroformylation of olefinic substrates when at least one asymmetric carbon atom is formed either by addition of a formyl group or of a hydrogen atom to an unsaturated carbon atom (Scheme 1, reactions (1) and (2)). In the case of trisubstituted olefins, two new asymmetric carbon atoms can form due to the cis stereochemistry of the reaction10), in the absence of isomerization, the formation of only one epimer is expected. 

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