Examples of Selectivity Control

General Course of Olefin Oligomerization and Related Reactions 

The reversal of the insertion reaction [Eq. (10)] is not normally observed [in contrast to nickel hydride addition to olefins, Eq. (9)]. An exception is the skeletal isomerization of 1,4-dienes (88, 89). A side reaction—the allylhydrogen transfer reaction [Eq. (5)]—which results in the formation of allylnickel species such as 19 as well as alkanes should also be mentioned. This reaction accounts for the formation of small amounts of alkanes and dienes during the olefin oligomerization reactions (51). 

The nature and distribution of the products of an olefin oligomerization reaction will depend, inter alia, on the relative rate constants of the insertion step (ki)vs. the displacement step (fcd) [Eq. (11)]  

The nature and distribution of the products of the dimerization or oligomerization of unsymmetrical olefins, such as propene, will depend, among others, on the direction of addition of the hydrido- and alkylnickel species to the olefin, i.e., on the regioselectivity of the catalyst (see Section 1 V,E). In order to define the direction of addition of hydrido- or alkylnickel species to terminal olefins, we shall adopt the convention nickel-to-C, addition [Eq. (12)] (Ni — Cj)  

The reaction of ethylene at -20°C and 1 atm with the phosphine-free catalyst prepared from 77-allylnickel chloride and ethylaluminum dichloride in chlorobenzene results in the rapid formation of a mixture of ethylene dimers with lesser amounts of higher oligomers. The dimer fraction consists mainly of 2-butenes and the trimer fraction of 3-methylpentenes and 2-ethyl-1-butene as well as a minor amount of hexene (97). From the composition of the products it can be concluded that the displacement reaction predominates over the insertion reaction when using the phosphine-free catalyst and that the direction of addition of both the H—Ni and C2H5—Ni species is mainly of the Ni — C2 type. 

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Fig. 17. Examples of selective control strategy (a) reactor hot spot (b) level override (c) prioritized and (d) constraint controls, where...

A convincing example of selectivity control in isomerization reactions is the formation of cis-2-butene from the isomerization of 1-butene using the catalyst [(C6H5)3P]2NiX2-P(CeH5)3-Zn-SnCl2 a ratio of c/i-2-bu-tene /ra .s-2-butene as high as 98 2 has been observed. Isomerization to the thermodynamically more stable /ra ns-olefin occurs only after conversion of all the 1-butene (98). Further examples of selective olefin isomerization will be discussed in Section IV,D. 

In contrast to the examples of selectivity control discussed in the previous sections, the problem here is control of the regioselectivity of the individual reaction steps. This is evident from the Scheme 5. In the first reaction step the nickel-hydride species adds to propene forming a propyl- or isopropyl-nickel intermediate this step is reversible, and the ratio of the two species can be controlled both thermodynamically and kinetically. In the second step, a second molecule of propene reacts to give four alkylnickel intermediates from which, after j8-H elimination, 8 primary products are produced (Scheme 5). 2-Hexene and 4-methyl-2-pentene could be the products of either isomerization or the primary reaction. Isomerization leads to 3-hexene, 2-methyl-2-pentene (the common isomerization product of 2-methyl-1-pentene and 4-methyl-2-pen-tene), and 2.3-dimethyl-2-butene. It can be seen from the Scheme 5 that, if the isomerization to 2-methyl-2-pentene can be neglected, the distribution of the products enables an estimate to be made of the direction of... 

Hydrogenation of acetylenic to ethylenic is a classical example of selectivity control using an additive which can realise a competitive chemisorption. 

The use of high or low limits for process variables is another type of selective control, called an override. The feature of anti-reset windup in feedback controllers is a type of override. Another example is a distillation column with lower and upper limits on the heat input to the column reboiler. The minimum level ensures that liquid will remain... 

Exploitation of analytical selectivity. We have seen, in our discussion of the A —> B C series reaction (Scheme IX), that access to the concentration of A as a function of time is valuable because it permits to be easily evaluated. Modern analytical methods, particularly chromatography, constitute a powerful adjunct to kinetic investigations, and they render nearly obsolete some very difficult kinetic problems. For example, the freedom to make use of the pseudoorder technique is largely dependent upon the high sensitivity of analytical methods, which allows us to set one reactant concentration much lower than another. An interesting example of analytical control in the study of the Scheme IX system is the spectrophotometric observation of the reaction solution at an isosbestic point of species B and C, thus permitting the A to B step to be observed. 

Scheme 2.7 gives some examples of the control of stereoselectivity by use of additional Lewis acid and related methods. Entry 1 shows the effect of the use of excess TiCl4. Entry 2 demonstrates the ability of (C2H5)2A1C1 to shift the boron enolate toward formation of the 2,3-anti diastereomer. Entries 3 and 4 compare the use of one versus two equivalents of TiCl4 with an oxazoldine-2-thione auxiliary. There is a nearly complete shift of facial selectivity. Entry 5 shows a subsequent application of this methodology. Entries 6 and 7 show the effect of complexation of the aldehyde... 

Directed sp2 -C-H functionalizations enable the catalytic transformation to be controlled by a coordinating group, often leading to ort o-functionalized products. These are extremely popular processes, and a selection of these reactions have been reviewed in Section 10.03.3.2.60 In contrast, non-directed sp2-C-H functionalization processes are invariably less selective but synthetically more desirable since a directing group is not required. Examples of selective non-directed sp2-C-H functionalizations will be presented, where the regioselective outcome of the reaction is usually more difficult to control. 

Using this system, (Z)-hinokiresinol isolated from cultured cells of A. officinalis was determined to be the optically pure (75 )-isomer, while ( )-hinokiresinol isolated from cultured cells of C. japonica had 83.3% e.e. in favor of the (7S)-enantiomer (Table 12.1). The enzymatically formed (Z)-hinokiresinol obtained following incubation of p-coumaryl p-coumarate with a mixture of equal amounts of recZHRSa and recZHRSf) was found to be the optically pure (75)-isomer, which is identical to that isolated from A. officinalis cells (Table 12.1). A similar result was obtained with the crude plant protein from A. officinalis cultured cells, where the formed (Z)-hinokiresinol was almost optically pure, 97.2% e.e. in favor of the (75)-isomer (Table 12.1). In sharp contrast, when each subunit protein, recZHRSa or recZHRSP, was individually incubated with p-coumaryl p-coumarate, ( )-hinokiresinol was formed (Table 12.1). The enantiomeric compositions of ( )-hinokiresinol thus formed were 20.6% e.e. (with recZHRSa) and 9.0% e.e. (with recZHRSP) in favor of the (7S)-enantiomer (Table 12.1). Taken together, these results clearly indicate that the subunit composition of ZHRS controls not only cis/trans selectivity but also enantioselectivity in hinokiresinol formation (Fig. 12.3). This provides a novel example of enantiomeric control in the biosynthesis of natural products. Although the mechanism for the cis/trans selective and enantioselective reaction remains to be elucidated, for example by x-ray crystallography, the enantioselective mechanism totally differs from the enantioselectivity in biosynthesis of lignans, another class of phenylpropanoid compounds closely related to norlignans in terms of structure and biosynthesis. 

Dithioacetalization can be regarded as a combination of addition and elimination. A cogent example of electronic control by a remote substituent is the selective reaction of l,l,l-trifluoroalkane-2,4-diones at the 4-oxo site [142], Here, the three... 

The presence of solids such as clays, zeolites, silica or ion-exchange resins may allow catalysis or control of organic reactions. Often, yields are higher and work-up procedures simpler than for the corresponding homogeneous reactions, and product distributions may also be improved. Examples of selective substitution reactions in aromatic and heteroaromatic systems and of selective reactions of alkenes are discussed, and the wider potential for synthesis of fine chemicals is discussed. 

Several other examples of selective multicomponent glycosylation protocols have been designed based on steric and/or electronic control of reactivity between glyco-syl donors and acceptors [77]. In the context of this chapter, these MCR strategies will be exemplified with the synthesis of 147, which was initiated with the triflic... 

Another important example of coherent control introduces the possibility of quan- turn interference that arises through competitive optical routes in the excitation of a single bound state to an energy E. Specifically, we consider the photodissociation of a single state via two simultaneous pathways, an TV-photon and an M-photon disso- ciation route. As will become evident in our discussion of selection rules (Section 3,3.2), the N vs. M scenarios are of two types, N and M of the same parity (e.g., both N and M odd or both even) or of opposite parity (one of N, M being odd and ] the other being even). The latter allows for control over the photodissociation differ- ]... 

Although with the selective removal proecdurc the active component and the support are usually verv intimately mixed, it is difficult to control the porous structure and/or the mechanical strength ol the result ing eatalyst bodies Nonetheless the procedure is difficult to beat for the production ol highly loaded supports The most well known example of selective removal, the preparation of Raney metals, where alu minum is selectively removed, leaves behind almost exclusively the desired active metal... 

Selective enolate formation is straightforward if the protons on one side of the ketone are significantly more acidic than those on the other. This is what you have just seen with ethyl acetoacetate it is a ketone, but with weak bases (pKaH < 18) it only ever enolizes on the side where the protons are acidified by the second electron-withdrawing group. If two new substituents are introduced, in the manner you have just seen, they will always both be joined to the same carbon atom. This is an example of thermodynamic control only the more stable of the two possible enolates is formed. 

There is another example of selective protection using thermodynamic control In Chapter 49, p. 1361,... 

Fig. 27 Examples of thermodynamically controlled reactions employed in the near-quantitative synthesis of MIMs. (a) Disulfide-exchange reaction permits equilibration between a bis(ammo-nium) disulfide dumbbell and a crown ether macrocycle to yield a mixture of [2]- and [3]rotaxanes quantitatively [194], (b) Olefin metathesis at high concentration on a benzylic amide macrocycle greatly favors the catenated species [196]. (c) Self-correcting imine bonds allow for nearly quantitative selection of a [2]rotaxane from an appropriate dynamic combinatorial library [76], (d) A weak nucleophile (E) equilibrates the components of a donor-acceptor [2]catenane in a dynamic Sn2 reaction [205]...

There are many methods of control to eliminate or mitigate identified hazards. The selected controls for a hazard should be recorded on the FMEA template. Examples of hazard controls include change in design specification, implementing alarms/wamings/error messages, and instituting a manual process. The most cost-elfective hazard coutrol should be selected and described in the FMEiA template. 

In contrast, when the experiment is conducted with preexposure of the substrates to aluminum additive (8), the corresponding tertiary carbinol (10) resulting from preferential addition to the ketone component is produced in excess (compare entries 8 and 10, 11 and 14 in Table 6). Comparison of entries 16 and 17 demonstrates the most dramatic example of total control of this type of site selective process, since in the... 

Another example of remote control of cis/trans selectivity was provided by Kallmerten. He studied Wittig rearrangements of the tertiary oxazolinyl ethers (40 equation 14) (Table 3). ° By changing (off the pericyclic transition state) a meAyl group into MOMO the previous 72 28 (Z)-selectivity was completely inverted into >100 1 ( )-selectivity. Remarkably, the MOMO effect depends heavily on which of... 

The question of cross-coupling of different phenols was alluded to above. An interesting example" of selectivity is shown in Scheme 9 the major product, shown, forms a relatively stable radical anion under the reaction conditions. To what extent this thermodynamic factor controls product ratios is not clear. 

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