Catalyst Hindrance

It has been generally accepted that the orientation of adsorption of an unsaturated molecule onto the catalyst is controlled by a steric interaction or hindrance between the substrate and the catalyst in other words, the adsorption at a less hindered side of the substrate is more favored.149 The stereochemical outcomes of many hydrogenations have thus been explained by syn addition of hydrogen (from the catalyst) to the substrate at a less hindered side. Unless isomerization or some other opposing factors are concerned, such a theory may be successfully applied to those cases where the adsorption of substrate or the formation of half-hydrogenated state is the key step that 

TABLE 3.16 Percent Cis Isomer in Saturated Product from Hydrogenation of Disubstituted Cyclopentenes and Related Cyclopentylidenes , gf 

Hydrogenation of L-ascorbic acid (vitamin C) takes place stereoselctively to give l-gluco-1,4-lactone in high yield over Pd-C,156 or better, over Rh-C in water at temperature below 45°C and 0.38 MPa H2 (eq. 3.29).157 It is noted that hydrogen adds preferentially from the least hindered side opposite the side chain. 

In contrast to the case with 65a, the hydrogenation of dimethyl bicyclo[2.2.2]oct-2-ene-2,3-dicarboxylate (69) yields the syn-endo-addition product 70 over Rh-C and Pt-C in heptane at 25°C and 1 atmH2 (eq. 3.31).161,162 The hydrogenation over Pt-C, however, was accompanied by 7.1% of apparent anri-addition product 71. The presence of small amounts of a strong acid, which had little effect on the hydrogenation with rhodium, greatly increased the formation of 71 over Pd-C, which amounted to as much as 60% in the presence of p-TsOH in methanol. 

The addition of hydrogen to (1- and a-pinenes (72 and 73) takes place preferentially from the methylene bridge side, rather than from the isopropylidene bridge side, as might be expected from the consideration of catalyst hindrance. Van Tamelene and Timmons obtained a 84 16 cis.trans mixture in the hydrogenation of 72 over platinum at unspecified conditions.160 The stereoselectivity for the cis isomer is even higher with 73 more than 90% yields of cA-pinane were obtained with platinum catalysts.160,163 

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Fig. 1. Catalyst hindrance according to Linstead et al. (/6) reproduced with permission of the publishers.

The location of hydroxy groups relative to the carbon-carbon double bond appears at times to direct the addition to the side of the molecule which presents the greater catalyst hindrance. ITiis has been noted by Dart and Henbest, " who termed it an anchor effect , and later by Nishimura and Mori for the hydrogenation of several steroid structures. ... 

Certain ortho substituted derivatives of aromatic amines are difficult to acetylate under the above conditions owing to steric hindrance. The process is facilitated by the addition of a few drops of concentrated sulphuric acid (compare Section IV,47), which acts as a catalyst, and the use of a large excess of acetic anhydride. 

The polyaddition reaction is influenced by the stmcture and functionaHty of the monomers, including the location of substituents in proximity to the reactive isocyanate group (steric hindrance) and the nature of the hydroxyl group (primary or secondary). Impurities also influence the reactivity of the system for example, acid impurities in PMDI require partial neutralization or larger amounts of the basic catalysts. The acidity in PMDI can be reduced by heat or epoxy treatment, which is best conducted in the plant. Addition of small amounts of carboxyHc acid chlorides lowers the reactivity of PMDI or stabilizes isocyanate terrninated prepolymers. 

Since regular helices with the inner layer matching the catalyst particle size have been observed[4,5], we propose a steric hindrance model to explain the possible formation of regular and tightly wound helices. 

From the observation of the early stage of nanotube production by the catalytic decomposition of acetylene, it is concluded that steric hindrance arising from the surrounding nanotubes, graphite, amorphous carbon, catalyst support and catalyst particle itself could force bending of the growing tubules. 

In a situation where severe steric hindrance e.g., 16,16-dimethyl-20-keto-pregnanes) prevents enol acetate formation, an alternate scheme has been devised. Condensation of ethyl oxalate at C-21 produces, after hydrolysis, the 21-glyoxylic acid this on treatment with acetic anhydride and a strong acid catalyst such as perchloric acid gives both lactone acetates. 

A syn-selective asymmetiic nih o-aldol reaction has been reported for structurally simple aldehydes using a new catalyst generated from 6,6-bis[(tiiethylsilyl)ethynyl]BINOL (g in Scheme 3.18). The syn selectivity in the nitro-aldol reaction can be explained by steric hindrance in the bicyclic transition state as can be seen in Newman projection. In the favored h ansition state, the catalyst acts as a Lewis acid and as a Lewis base at different sites. In conbast, the nonchelation-controlled transition state affords anti product with lower ee. This stereoselective nitro-aldol reaction has been applied to simple synthesis of t/ireo-dihydrosphingosine by the reduction of the nitro-aldol product with H2 and Pd-C (Eq. 3.79). 

Steric hindrance around an allylic function will diminish its hydrogenolysis as access of the function to the catalyst surface is impeded. Reduction of 5-methylthebaine (32) proceeds smoothly over Pd-on-C in ethanol at 1 atm to afford 5-methyldihydrothebaine (33), whereas reduction of thebaine itself is less clean and gives dihydrothebainol, dihydrothebainone, and dihydro-thebaine (/b). 

Product composition can be controlled to a considerable extent by the molar ratio of reactants alkylation tends to become more extensive as the molar ratio of carbonyl to amine increases. Product distribution is influenced also by the catalyst and by steric hindrance with the amount of higher alkylate formed being inversely proportional to the steric hindrance in the neighborhood of the function (60 2). Cyclic ketones tend to alkylate ammonia or amines to a further extent than do linear ketones of comparable carbon number 36). 

The work of Greenfield and Malz (25) on the preparation of arylamines illustrates the sensitivity of yield to hindrance and an influence of catalyst. 

These side reactions may occur if the /V-acyliminium ion is not trapped quickly enough by a nucleophile. So problems may arise with relatively poor nucleophiles or if there is too much steric hindrance, while in the case of intramolecular reactions, unfavorable stereoelectronic factors or intended formation of medium- or large-sized rings may play a role. The reaction conditions, such as the nature of the (acidic) catalyst and the solvent, may also be of importance. 

A kinetic isotope effect, kH/kD = 1.4, has been observed in the bromination of 3-bromo-l,2,4,5-tetramethylbenzene and its 6-deuterated isomer by bromine in nitromethane at 30 °C, and this has been attributed to steric hindrance to the electrophile causing kLx to become significant relative to k 2 (see p. 8)268. A more extensive subsequent investigation304 of the isotope effects obtained for reaction in acetic acid and in nitromethane (in parentheses) revealed the following values mesitylene, 1.1 pentamethylbenzene 1.2 3-methoxy-1,2,4,5-tetramethyl-benzene 1.5 5-t-butyl-1,2,3-trimethylbenzene 1.6 (2.7) 3-bromo-1,2,4,5-tetra-methylbenzene 1.4 and for 1,3,5-tri-f-butylbenzene in acetic acid-dioxan, with silver ion catalyst, kH/kD = 3.6. All of these isotope effects are obtained with hindered compounds, and the larger the steric hindrance, the greater the isotope... 

Gallium bromide was used as the catalyst in a determination346 of the partial rate factors, by the competition method, for ethylation of some substituted benzenes in 1,2-dichloroethane at 25 °C. No direct rate measurements were made and the results, summarised in Table 80, show the low selectivity and high steric hindrance in the reaction. 

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