Markovnikov addition selectivity

The basis of the high normal to isoaldehyde selectivity obtained ia the LP Oxo reaction is thought to be the anti-Markovnikov addition of olefin to HRhCOL2 to give the linear alkyl, Rh(CO)L2CH2CH2CH2CH2, the precursor of straight-chain aldehyde. Anti-Markovnikov addition is preferred ia this... 

The reason for its selectivity lies in the insertion step of the cycle. In the presence of the two bulky PPhi groups, the atiachmeni to the mcial of -CH2CH2R (anti-Markovnikov addition, leading to a straight chain product) is easier than the attachment of -CH(CHOR (Markovnikov addition, leading to a branched-chain product). 

Tucci (54), studying mainly terminal olefins, cited two reasons for the high selectivity for linear products in the phosphine-modified cobalt catalysts (a) stereoselective addition of the hydride species to the olefinic double bond, and (b) inhibition of olefin isomerization. However, the results obtained with internal olefins as substrate tended to discount the likelihood of the second reason, and it is generally accepted that selective anti-Markovnikov addition arising from steric hindrance is the principal cause for linear products from nonfunctional olefins. 

Rhodium(I) and ruthenium(II) complexes containing NHCs have been applied in hydrosilylation reactions with alkenes, alkynes, and ketones. Rhodium(I) complexes with imidazolidin-2-ylidene ligands such as [RhCl( j -cod)(NHC)], [RhCl(PPh3)2(NHC)], and [RhCl(CO)(PPh3)(NHC)] have been reported to lead to highly selective anti-Markovnikov addition of silanes to terminal olefins [Eq. 

Success was obtained with Ru3(CO)i2 as catalyst precursor [6], but the most efficient catalysts were found in the RuCl2(arene)(phosphine) series. These complexes are known to produce ruthenium vinylidene spedes upon reaction with terminal alkynes under stoichiometric conditions, and thus are able to generate potential catalysts active for anti-Markovnikov addition [7]. Similar results were obtained by using Ru(r]" -cyclooctadiene)(ri -cyclooctatriene)/PR3 as catalyst precursor [8]. (Z)-Dienylcarba-mates were also regio- and stereo-selectively prepared from conjugated enynes and secondary aliphatic amines (diethylamine, piperidine, morpholine, pyrrolidine) but, in this case, RuCl2(arene) (phosphine) complexes were not very efficient and the best catalyst precursor was Ru(methallyl)2(diphenylphosphinoethane) [9] (Scheme 10.1). 

Catalytic transformations of alkynes have recently led to tremendous developments of synthetic methods with useful applications in the synthesis of natural products and molecular materials. Among them, the selective activations of terminal alkynes and propargylic alcohols via vinylidene- and allenylidene-metal intermediates play an important role, and have opened new catalytic routes toward anti-Markovnikov additions to terminal alkynes, carbocyclizations or propargylations, in parallel to the production of new types of molecular catalysts. 

Although Markovnikov addition is generally observed, little woik on the regio- or stereo-selectivity of this reaction has been reported. Both cis- and franr-2-pentene afford mixtures of the 2- and 3-substituted amines.199 a.p-Unsaturated esters yield 3-amino esters.200 The aminomercuration of cis- and trans-2-butenes gives S 97% of the anti adducts.201... 

An attempt has been made to analyse whether the electrophilicity index is a reliable descriptor of the kinetic behaviour. Relative experimental rates of Friedel-Crafts benzylation, acetylation, and benzoylation reactions were found to correlate well with the corresponding calculated electrophilicity values. In the case of chlorination of various substituted ethylenes and nitration of toluene and chlorobenzene, the correlation was generally poor but somewhat better in the case of the experimental and the calculated activation energies for selected Markovnikov and anti-Markovnikov addition reactions. Reaction electrophilicity, local electrophilicity, and activation hardness were used together to provide a transparent picture of reaction rates and also the orientation of aromatic electrophilic substitution reactions. Ambiguity in the definition of the electrophilicity was highlighted.15... 

Addition to atkenes. Although this reagent has been studied mainly for electrophilic fluorination,1 it does add to alkenes to give cis-selective vic-fluoro alkyl sulfates with some preference for anft -Markovnikov addition. The adducts can be converted into fluoro ethoxysulfates by reaction with (C2H5)jO+BF4 .2... 

Several ruthenium complexes are able to promote the classical Markovnikov addition of O nucleophiles to alkynes via Lewis-acid-type activation of triple bonds. Starting from terminal alkynes, the anti-Markovnikov addition to form vinyl derivatives of type 1 (Scheme 1) is less common and requires selected catalysts. This regioselectivity corresponding to the addition of the nucleophile at the less substituted carbon of the C=C triple bond is expected to result from the formation of a ruthenium vinylidene intermediate featuring a highly reactive electrophilic Ca atom. 

The first example of anti-Markovnikov addition of O nucleophiles to terminal alkynes was the catalytic addition of ammonium carbamates generated in situ from secondary amines and carbon dioxide to terminal alkynes, which selectively produced vinylcarbamates (Scheme 2) [7]. 

The most efficient catalyst precursors were found in the RuCl2(arene)(phos-phine) series. These complexes are known to produce ruthenium vinylidene species upon reaction with terminal alkynes under stoichiometric conditions, and thus are able to generate potential catalysts active for anti-Markovnikov addition [8]. Dienylcarbamates could also be selectively prepared from conju-... 

Ans. The mechanism of Question 15 does not operate, since steric hindrance should favor anti-Markovnikov addition and lowering of selectivity. 

The two different ways of inserting an alkene into a metal-hydrogen bond, as shown by 5.4 and 5.5, are called anti-Markovnikov and Markovnikov addition, respectively. Insofar as hydroformylation with high selectivity to n-butyralde-hyde is concerned, it is considered to be primarily an effect of steric crowding around the metal center. The normal alkyl requires less space and therefore formed more easily than the branched one in the presence of bulky ligands. 

However, the balance between sterically demanding ligands and their ability to remain coordinated so that the product selectivity could be influenced is a fine one. This aspect is discussed in more detail in Section 5.2.4. Although not directly related to hydroformylation, it is appropriate to note here that Markovnikov additions accompanied by /3-hydride elimination is a general pathway for alkene isomerization. This is shown in Fig. 5.2 for the isomerization of both terminal and internal alkenes. 

It is obvious that such equilibria would exist for all the other catalytic intermediates. The result of all this is coupled catalytic cycles and many simultaneous catalytic reactions. This is shown schematically in Fig. 5.5. The complicated rate expressions of hydroformylation reactions are due to the occurrence of many reactions at the same time. As indicated in Fig. 5.5, selectivity towards anti-Markovnikov product increases with more phosphinated intermediates, whereas more carbonylation shifts the selectivity towards Mar-kovnikov product. This is to be expected in view of the fact that a sterically crowded environment around the metal center favors anti-Markovnikov addition (see Section 5.2.2). 

Ans. 5.8 Hydrolysis followed by dehydration, isomerization and acetylation. 5.9, 5.10 Hydrogenation. For 5.8 probably lower rate due to steric hindrance by L but no effect on selectivity. For 5.9 formation of branched isomer (Markovnikov addition). 

H, C and Si NMR studies of the products suggested that the hydrosilylation of PBD occurs selectively via an anti-Markovnikov addition, i.e., the Si-atom being attached at the terminal position of olefin bonds ( -product) (Fig. 3). 

The amount of catalyst in such cases is rather high 1000-5000 ppm and selectivity towards anti-Markovnikov addition is lower (80-90%), compared to hydrosilylation in the presence of platinum based catalyst. The synthesis of phenylethenyl substituted siloxanes is of commercial importance, driven by potential application in personal care products. Such materials should be in the form of fluids and thus in order to preserve this requirement two approaches have been exploited. One of them involved substitution of less than 100% phenylethenyl moieties, the other made use of 1-hexene as a co-reactant, leading to decreased crystallinity of the final materials. Depending on the structure of (methylhydrido)siloxanes and reaction conditions the resulting silicon fluids exhibited refraction indices ranging from 1.527 to 1.574 (Table 1). 

An interesting case in the /3-lactam series gave selective anti-Markovnikov addition, attributed to the directing effect of the lactam carbonyl group (equation 29). ... 

The catalytic system [A] based on RuCl(Cp)(tris(p-fluorophenyl)phosphine)2 (5 mol%), tris(p-fluorophenyl)phosphine (20 mol%), (BU4NPF6, 15 mol%) and N-hydroxysuccinimide sodium salt (50 mol%) led to the selective transformation of pent-4-yn-l-ols into cyclic enol ethers via intramolecular anh-Markovnikov addition of the hydroxy group to the terminal carbon of the triple bond [21],... 

The crossover product, propionaldehyde-l,3-d-3- C 12, clearly demonstrated that the isomerization occurred via intermolecular 1,3-hydrogen shift. These results are consistent with a modified metal hydride addition-elimination mechanism which involves exclusive 1,3-hydrogen shift through oxygen-directed Markovnikov addition of the metal hydride to the carbon-carbon double bond (Scheme 12.2). The directing effect of functional groups on the selectivity of transition metal catalysis is well presented [9], and an analogous process appears to be operative in the isomerization of allylamines to enamines [10]. 

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