Hydrogenation of Alkenes

Scheme 3.16 Products of the hydrogenation of trans-1-methoxy-1,3-butadiene

3.7 STEREOCHEMISTRY OF THE HYDROGENATION OF CARBON–CARBON DOUBLE BONDS

3.7.1 Syn and Apparent Anti Addition of Hydrogen

With a few exceptions it has been generally accepted that two atoms of hydrogen are added syn to a carbon–carbon double bond from the catalyst surface. If such were the case, cis-tetrasubstituted ethylene I would give meso form and trans-tetrasubstituted ethylene II a racemic mixture, while the situations would be reversed if anti addition were the case (Scheme 3.17). The situation is also the same for disubstituted cy-cloalkenes. Syn addition of hydrogen gives the cis isomer (meso form) and anti addi-tion the trans isomer (d,l mixture). Actually, the mode of hydrogen addiaddi-tion is not so simple and depends on the catalyst, the substrate as well as the hydrogenation condi-tions (e.g., temperature and hydrogen pressure).

An excellent example of stereospecific syn addition is seen in the hydrogenation of cis- and trans-dimethylstilbene with palladium catalyst (eq. 3.24).13 Under the same conditions, diethylstilbestrol (50, R = H) and its dimethyl ether (50, R = Me) were hy-drogenated to the products containing, respectively, 90 and 97% of the corresponding racemic 3,4-diphenylhexane derivatives. Syn addition decreased to 86 and 70%,

re-1 g (2.3 m m ol)

0.2 g Adams Pt oxide*

75 ml EtOAc/0.1 ml AcOH 27°C, 98.8 ml H2 (97.0 ml for 2 mol)

AcO AcO

(3.23)

*Prereduced in the solvent.

+

Scheme 3.17 Stereochemistry of the hydrogenation of tetrasubstituted ethylenes. a—syn addition of H2; b—anti addition of H2.

spectively, with dimethylmaleic acid and dimethylfumaric acid when hydrogenated as their sodium salts over Pd–C in aqueous solution.12 With a Ni–C catalyst under simi-lar conditions, the syn addition product was exclusive with sodium dimethylfumarate and 86% with sodium dimethylmaleate. Dimethylmaleinimide was hydrogenated to nearly pure meso-dimethylsuccinimide in the hydrogenation over platinum oxide in ethanol.136

Siegel and Smith found that the hydrogenation of 1,2-dimethylcyclohexene (19) with Adams platinum in acetic acid at 25°C and 1 atm H2 gave a mixture of 81.8% cis- and 18.2% of trans-1,2-dimethylcyclohexane. The proportion of the cis isomer increased to 95.5% under a hydrogen pressure of 30 MPa.137 In contrast, the hydrogenation of 19 with 5% Pd–Al2O3 at 25°C and 1 atm H2 gave the trans isomer predominantly (74.7% trans and 25.3% cis). Hydrogenation of 1,6-dimethylcyclohexene (20) and 2-methylmethyle-necyclohexane (21) with the palladium catalyst also gave approximately the same com-position of the mixture of cis and trans isomers as that obtained with 1,2-dimethylcyclohexene.14 The hydrogenations over palladium were accompanied by extensive isomerization and the composition of the reaction mixtures at ~60% hydrogena-tion was almost the same as with any of the isomeric cyclohexenes as starting material.

The results were explained by assuming that the rate-controlling surface reaction is the conversion of the hydrogenated states to saturated products where reversal of the half-hydrogenated states to adsorbed olefins as well as desorption of adsorbed olefins are faster than the hydrogenation to give the saturated products. The predominant formation of trans-1,2-dimethylcyclohexane over palladium has thus been explained by assuming that the stability sequence among the half-hydrogenated states is 1t > 1c >> 2t > 2c >> 3c > 3t on the basis of decreasing stability of primary > secondary > tertiary half-hydrogenated states and considering their conformations (Scheme 3.18).14

Nishimura et al. studied the hydrogenation of 19–21 over the six unsupported plati-num group metals in t-butyl alcohol at 26°C and 1 atm H2.138 The hydrogenations of 19 over iridium and osmium have been found to be highly stereoselective, affording

98% dl (meso 1.7–2.4%) 99% meso (dl <1–2%)

MeCHPhCHPhMe MeCHPhCHPhMe

0.1 g Pd (Willstätter) 75 ml 0.0225M AcOH solution

18°C, 1 atm H2 18°C, 1 atm H2

75 ml 0.0225M AcOH solution 0.1 g Pd (Willstätter) Ph

Ph

Me Me

Me Ph

Me Ph

(3.24)

50

Et

Et RO

OR

3.7 STEREOCHEMISTRY OF THE HYDROGENATION OF CARBON–CARBON DOUBLE BONDS 101

99.2 and 98.7% yields of cis-1,2-dimethylcyclohexane, respectively (eq. 3.25). The order of the platinum metals in the formation of cis isomer for 19 (Ir > Os > Ru > Rh

> Pt >> Pd) also holds approximately for the hydrogenation of 20 and 21 (Table 3.14).

Iridium and osmium are always among the metals that give the highest yields of the cis isomer, and palladium always gives the trans isomer predominantly. In most cases ruthenium, rhodium, and platinum show the intermediate stereoselectivity between these extreme metals. In general, the tendency of the platinum metals for the formation of the cis isomer has been found to correlate inversely with their ability for isomeriz-ing 20 to 19 or 21 to 19 and 20 (see Table 3.14).

Scheme 3.18 Stereochemistry of the hydrogenation of 1,2- and 1,6-dimethylcyclohexenes and 2-methylmethylenecyclohexane over palladium catalyst.

Catalyst (mg)

Weitkamp studied the deuteration of ∆9,10-octalin over carbon-supported platinum metals in cyclohexane at 25°C and 2.45–2.72 MPa D2.139 The formation of cis-decalin decreased in the following order (proportions in parentheses): 5% Ir–C (97.8 %) > 5%

Ru–C (94.7%) > 5% Rh–C (84.9%) > 5% Pt–C (66.6%) > 5% Pd–C (15.6%).

In contrast to 1,2-dimethylcyclohexene, methyl cyclohexene-1,2-dicarboxylate was reported to yield only the cis saturated product in the hydrogenation over platinum oxide in acetic acid at 26–27°C, independently of the pressure of hydrogen (0.1–20 MPa) and the concentration of the substrate (0.05–1.0M).140 Hydrogenation of methyl cyclohexene-1,6-dicarboxylate also gave the same result at about 1 atm H2, but some of the trans isomer (6±2%) was formed at a pressure of 13 MPa H2.

Siegel et al. studied the effects of hydrogen pressure and the structure of the exo olefinic groups on the stereochemistry of hydrogenation of 1-alkylidene-4-t-butylcyclohexanes over platinum oxide in acetic acid.141,142 In contrast to the case with 4-t-butyl-1-methyl-cyclohexene, the percent cis isomer of the product from 4-t-buty-1-methylenecyclohexane decreased with increasing hydrogen pressure from 87% at 0.025 MPa H2 to 61% at 30 MPa. With respect to the structure of 1-alkylidene groups, the percent cis isomer decreased in the order 87% for 1-methylene-, 32% for 1-ethylidene-, and 21% for 1-isopropylidene-4-t-butylcyclohexane at low hydrogen pressure. In all the cases the formation of cis isomer decreased at high hydrogen pressure, compared with the corresponding values at low pres-sure. The results have been discussed on the basis of the increasing intramolecular non-bonded interactions from methylene to isopropylidene groups. Kamiyama et al. extended the studies to the hydrogenations over group VIII transition metals other than platinum.143 The similar effects of the exo alkene groups on the cis/trans isomer ratios of saturated prod-ucts were observed for all the catalysts investigated. The results by Siegel et al. and by Kamiyama et al. are summarized in Table 3.15.

TABLE 3.14 The Stereoselectivity and Isomerization Ability of the Platinum Metals in the Hydrogenation of 1,6-Dimethylcyclohexene and

2-Methylmethylenecyclohexanea,b

Proportion of cis Isomer in Saturate (%)

Proportion of Isomerized Product (%)c

Catalyst 20 21 20 → 19 21 → 19 + 20

Ir 89.0 85.4 0.8 0.0

Os 87.0 84.4 1.1 0.1

Pt 80.6 65.5 2.5 0.27

Ru 86.9 65.5 2.6 2.0

Rh 78.5 63.8 2.7 2.6

Pd 28.9 30.8 44.1 69.0

aData of Nishimura, S.; Sakamoto, H.; Ozawa, T. Chem. Lett. 1973, 855. Reprinted with permission from Chemical Society of Japan.

b20: 1,6-dimethylcyclohexene; 21: 2-methylmethylenecyclohexane; 19: 1,2-dimethylcyclohexene. For the reaction conditions, see eq. 3.25. The amounts of catalyst were reduced for the more reactive substrate 21.

cGiven by mol% 19 or 19 and 20 in the product, respectively. The values were obtained at initial stages of hydrogenation.

3.7 STEREOCHEMISTRY OF THE HYDROGENATION OF CARBON–CARBON DOUBLE BONDS 103

Siegel and Dmuchovsky also studied the stereochemistry of the hydrogenation of iso-meric dimethylcyclopentenes and 2-methylmethylenecyclopentane (51–55) over platinum and palladium catalysts.144 The hydrogenation of 1,2-(51) and 1,5-dimethyl-cyclopentene (52) over reduced platinum oxide in AcOH at 25°C and 1 atm H2 gives mixtures of cis- and trans-1,2-dimethylcyclopentanes in which the trans isomer is slightly more abundant than the cis isomer. Formation of the cis isomer from 51 in-creased from 43% at 0.1 MPa H2 to 69% at 8.1 MPa H2 but was almost independent of hydrogen pressure in the case of 52. Compared to the cyclohexene analogs, the rela-tive rate of isomerization (52 to 51) to hydrogenation was greater in the five-mem-bered ring than in the six-memfive-mem-bered ring. The isomerization of 51 to 52 was also much TABLE 3.15 Percent Cis Isomer from Hydrogenation of

1-Alkylidene-4-t-butylcyclohexanea

4-t-Butylcyclohexane

1-Methylene- 1-Ethylidene-

1-Isopropylidene-Catalyst Solvent Ref.

H2 pressure (MPa)

0.1 10 0.1 10 0.1 10

Pt AcOH 87 61 32 17 21 11 142

Cyclohexane 68 66 26 20 2 4 143

EtOH 74 70 22 35 5 7 143

Ru Cyclohexane 87 85 72 66 46 50 143

EtOH 92 85 66 72 46 55 143

Rh Cyclohexane 84 78 68 60 34 36 143

EtOH 90 85 64 69 34 35 143

Pd Cyclohexane 59b 72b 26b 35b tb tb 143

EtOH 36b 47b 17b 30b tb 3b 143

Os Cyclohexane 91 88 86 80 80 74 143

EtOH 87 84 85 86 78 78 143

Ir Cyclohexane 84 80 70 74 37 12 143

EtOH 87 85 65 70 42 16 143

Co Cyclohexane 33 46 25 44 NRc 24 143

Raney Co Cyclohexane — — 30 45 11 15 143

EtOH 32 47 — — — — 143

Ni Cyclohexane 47 47 33b 33b 8b 10 143

Raney Ni Cyclohexane — — 21b 22b 1 4 143

EtOH 46 47 — — — — 143

aHydrogenations at room temperature.

bThe products contained large amounts (14–76%) of isomerized cyclohexenes. Over the other metals, the amounts of isomerized product in the reaction mixture were rather small (mostly less than 7%).

cNo reaction.

51 52 53 54 55 56 57 58

Ph

more extensive than in the cyclohexene analogs. These results, together with the fact that 51 and 52 yield almost the same cis/trans ratios of 1,2-dimethylcyclopentane at low hydrogen pressures, suggested that the majority of the trans isomer formed in the hydrogenation of 51 resulted via prior isomerization to 52.145 The greater amount of trans saturated isomer formation from 52 than from the corresponding cyclohexene analog 20 at all hydrogen pressures has been explained by the increasing vicinal methyl interactions that accompany the changing geometry of the adsorbed molecule along the reaction path leading to cis-1,2-dimethylcyclopentane. Such interactions are expected to disappear in the hydrogenation of 1,3- and 1,4-dimethylcyclopentenes (54 and 55), both of which gave cis-1,3-dimethylcyclopentane in more than 90% propor-tions.144 The hydrogenation of 2-alkylmethylenecyclopentanes over platinum yields the products in which the cis isomers predominate. Hydrogenation of 2-methylcy-clopentylidenecyclopentane (56) over platinum oxide in AcOH gives more trans- than cis-2-methyl-1-cyclopentylcyclopentane (trans/cis = 77:23) at 1 atm H2. The trans:cis isomer ratio increased to 79:21 at 8 MPa H2. Hydrogenation of 2-methyl-1-cyclopen-tycyclopentene (57), an isomerization product of 56, gave more amounts of the cis product, which increased with increasing hydrogen pressure.146 From these results Siegel and Cozort suggested that the repulsive interactions between 2,2′ and 5,5′ ring positions in the transition state leading to the cis isomer become more important than the catalyst hindrance of the 2-methyl group at the species leading to the trans isomer, which might reduce at the transition state.146 As in the cases of the six-membered cy-cloalkenes, extensive isomerization and predominant formation of the more stable iso-mers resulted over palladium catalyst, as observed in the hydrogenations of 53, 56, and 57.144,145 Mitsui et al. investigated the stereochemistry of the hydrogenation of 2-al-kylmethylenecyclopentanes and 1,2- and 1,5-disubstituted cyclopentenes over Raney Ni as well as over platinum, palladium, and rhodium, mostly in ethanol as the solvent at room temperature and atmospheric pressure.147,148 In contrast to the cases with platinum and palladium, the hydrogenation of 1,2-disubstituted cyclopentenes over Raney Ni and Rh–C gave preferentially the cis saturated products, whereas the hydro-genation of 1,5-disubstituted cyclopentenes yielded the trans products in excess over all the catalysts investigated. Hydrogenation of 1-methyl-2-phenylcyclopentene (58) is characteristic in that the cis product was formed in high stereoselectivity (> 92%), irrespective of the kind of catalyst. The results by Siegel et al. and by Mitsui et al. on substituted cyclopentene and cyclopentane derivatives are summarized in Table 3.16.

In document Nishimura Sh. Handbook of heterogeneous catalytic hydrogenation for organic synthesis (Wiley, 2001)(ISBN 0471396982)(747s).pdf (Page 110-115)