Hydrogenation 2,3-anti selective

In the hydrogenation of diketones by Ru-binap-type catalysts, the degree of anti-selectivity is different between a-diketones and / -diketones [Eqs (13) and (14)]. A variety of /1-diketones are reduced by Ru-atropisomeric diphosphine catalysts to indicate admirable anti-selectivity, and the enantiopurity of the obtained anti-diol is almost 100% (Table 21.17) [105, 106, 110-112]. In this two-step consecutive hydrogenation of diketones, the overall stereochemical outcome is determined by both the efficiency of the chirality transfer by the catalyst (catalyst-control) and the structure of the initially formed hydroxyketones having a stereogenic center (substrate-control). The hydrogenation of monohydrogenated product ((R)-hydroxy ketone) with the antipode catalyst ((S)-binap catalyst) (mis-... 

The most impressive anti selectivity is demonstrated in olefin 13, where only the trans methyl hydrogens react. This can be attributed to the fact that in TSi, apart from the 1,3 non-bonded interactions of the fert-butyl group with oxygen, in the newly forming double bond the methyl groups are cis to each other, which is unfavourable. 

The anti selectivity increases as the disubstituted side of the double bond becomes more crowded (Scheme 8). This is illustrated with the trisubstituted alkenes 16, 17 and 13. Alkene 16 shows the normal cis effect selectivity where only 10% of the anti ene adduct is formed. However, as the size of the cis alkyl substituent increases from methyl in 16, to isopropyl in 17 and ferf-butyl in 13, the anti selectivity increases from 10% to 42% and to >97%, respectively. The same trend is also noted in substrate 19. A substantial deviation from cis effect selectivity is observed by replacing one methyl group in 18 with a ferf-butyl group in 19. The totally unreactive methylene hydrogens in 18 (cis effect) become reactive in 19, producing the exo ene adduct in 38% yield. 

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. 

The factors that influence the diastereoselectivity for the class of monocyclic hydrocarbons, from which monoterpenes are the most studied group, are mainly steric and conformational. Monoterpenes, in general, show relatively low overall syn/anti selectivity, usually attributed to the availability of allylic hydrogen atoms in the right alignment for abstraction. 

A number of examples involving nitrile oxide cycloadditions to cyclic cis-disubstituted olefinic dipolarophiles was presented in the first edition of this treatise, notably to cyclobutene, cyclopentene, and to 2,5-dihydrofuran derivatives (15). The more recent examples discussed here also show, that the selectivity of the cycloaddition to 1,2-cis-disubstituted cyclobutenes depends on the type of substituent group present (Table 6.8 Scheme 6.41). The differences found can be explained in terms of the nonplanarity (i. e., pyramidalization) of the double bond in the transition state (15) and steric effects. In the cycloaddition to cis-3,4-diacetyl-(197) and cis-3,4-dichlorocyclobutene (198), the syn-pyramidalization of the carbon atoms of the double bond and the more facile anti deformability of the olefinic hydrogens have been invoked to rationalize the anti selectivity observed. 

Scheme 65 shows a reaction occurring with opposite 2,3-syn diaste-reoselection. Hydrogenation of racemic 2-acetyl-4-butanolide, in which the 2-substituent and directing group are linked, proceeds with 98 2 yn anti selectivity to form the diastereomeric hydroxyethyl lactones. 

Scheme 68 shows the fit of the computer simulation (lines) to the experimental observation (dots). In dichloromethane, the ee of the major product, decreases as the hydrogenation proceeds, while the enantiomeric purity of the first minor isomer, P, increases as the reaction proceeds. The anti selectivity tends to decrease slightly as the reaction approaches completion. Dichloromethane is a better solvent than methanol in terms of the SEL value, primarily because of the increase of rate of stereoinversion of the substrate relative to hydrogenation. 

In trisubstituted alkenes with the cis alkyl groups highly crowded, the site selectivity (Sec. II.C) does not apply. In those cases, usually only one allylic hydrogen is available in the more crowded side, not sufficient to stabilize the proper transition state that could produce syn products. Instead, the major product is now produced by abstraction of the allylic hydrogen in the less substituted side of the double-bond anti selectivity [69], These results are summarized in Scheme 9. Photo-oxygenation of trisubstituted acyclic 15-17 [69] and cyclic 18 [70] and 19 [9] alkenes illustrates impressively a strong preference for hydrogen abstraction on the less substituted side of the double bond. 

The alkylation of asymmetric acyclic ketones takes place regioselectively on the most-substituted carbon, thus affording the syn isomers as major products. a-Hydroxyketones showed anti selective additions similar to that observed in related aldol, and Mannich-type additions (Scheme 2.39). Such selectivity is due to the preferred formation of the Z-enamine intermediate, stabilized by intramolecular hydrogen bonding between the hydroxy group and the tertiary amine of the catalyst [23]. 

Two hydrogen atoms are transferred to the alkene, and they are often both added to the same face of the alkene. In Chapter 20 you met other reactions of alkenes some, like bromination, were anti-selective, but others like epoxidation were syrc-selective like hydrogenation. 

Although hydrosilanes reduce ketones, in trifluoroacetic acid, to the corresponding methylene compounds or dimeric ethers via ionic hydrogenation, the reduction of a-amino and a-oxy ketones and p-keto acid derivatives with hydrosilanes, particularly PhMe2SiH, under these conditions proceeded with high anti selectivity to the alcohols. No racemization was observed at the carbon a to the carbonyl group. Intramolecular hydrosilylation catalyzed by Lewis acids provided a highly stereoselective route to anti-1,3-diols from p-hydroxy ketones (Section 1.1.3. ). ... 

A highly anti-selective hydrocyanation of (7 )-jV-Boc-2, 2-dimethylthia-zolidine-4-carbaldehyde (Gamer s aldehyde) with hydrogen cyanide in the presence of a Lewis acid has been reported [78]. In the initial study, we applied the procedure to the synthesis of anti-O-TMS cyanohydrin 23. However, the cyanosilylation of 22 in the presence of Lewis acid such as zinc iodide (Znl2), zinc bromide (ZnBr2) or boron trifluoride (BFy) diethyl ethcrate was problematic, leading only to traces of 23. 

In contrast, a cyclic substrate, methyl 2-oxocyclopentanecarboxylate, exhibited a remarkable anti selectivity on hydrogenation. A 99 1 transicis mixture of methyl 2-hydroxycyclopen-tanecarboxylate was obtained, both isomers in high optical purity60. 

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