Markovnikov isomer

Irreversible acetoxyselenenylation of terminal and disubstituted olefins has been achieved on addition of PhSeBr in an acetate-buffered solution. Styrenes afford only Markovnikov adducts, while simple terminal olefins and olefins containing an allylic oxygen substituent (RCO2 or ArO group) furnish 50-80% of the anti-Markovnikov isomer. The product mixture can be isomerized to contain 90-97% of the Markovnikov product by a catalytic amount 6-41%) of BF3.Et20 in CHCI3259. 

The mechanism of selenocyclization of yS,y-unsaturated acids and their derivatives has been studied. The reactions of ( )-4-phenylbut-3-enoic acid and its silyl and alkyl esters (15 R = H, SiMe3, alkyl) with benzeneselenenyl halide PhSeX (X = Cl, Br) have been examined by VT-NMR and in situ IR spectroscopic methods. Whereas the reactions of the acid in the presence of a base were irreproducible and complicated, reactions of the silyl esters were clean and spontaneously and quantitatively afforded the corresponding chloroselenylation adduct at -70 °C as a single (Markovnikov) isomer. This adduct underwent three processes as the temperature was raised (1) reversal to the starting materials, (2) isomerization to the anti-Markovnikov product, and (3) cyclization to the selenolactone (16). All of these processes are believed to proceed via a seleniranium ion, the intermediacy of which was established by independent synthesis and spectroscopic identification. The reversible formation of chloroselenide adducts was unambiguously established by crossover experiments. The reaction of (15) with PhSeBr was found to be rapid but thermodynamically unfavourable at room temperature.29... 

The other isomer of 5.11 with one axial and one equatorial phosphine can also be seen at low temperature. Indeed at low temperature that appears to be the more stable isomer. With styrene, as shown by 5.12 the branched (Mar-kovnikov) rather than the linear (anti-Markovnikov) isomer is the major one. However, remember that the experimental conditions of an actual industrial process, and that of the NMR experiments, are different. 

The intermolecular hydrocarboxylation of phenylacetylene with a range of aliphatic carboxylic acids has been catalysed by the bimetallic Ru complex 52 (Scheme 19) [97]. The bimetallic stmcture was shown to have a significant impact on the stereoselectivity of the reaction with the anti-Markovnikov -isomer obtained in good preference to the Z-isomer. In comparison, the related monometallic catalyst 53 showed a poor stereoselectivity for the hydrocarboxylation of phenylacetylene with the Z-isomer product slightly predominant with regard to the -isomer product following catalysis. Similar reaction rates were observed with both catalysts. Analysis of the catalysis reaction by ESI-MS and NMR spectroscopy showed that both Ru centres activate a separate molecule of... 

In this section we describe the available literature on the addition reaction of thiols and selenols RZH (Z = S, Se). We do not discuss non-catalytic addition reactions carried out without transition metal catalysts as this topic has already been addressed in several publications (see [100-103,139-142] and references therein). It was shown that the non-catalytic reactions led to a different outcome the anti-Markovnikov products are formed in the addition of RZ H to alkynes. Our goal is to concentrate on the selective formation of the scarcely available Markovnikov isomer by RZH addition to the triple bond of alkynes. 

In 1992 Ogawa, Sonoda et al. carried out the first catalytic addition of aromatic thiols [143] and selenols [144] to alkynes with Pd(OAc)2. Although the Markovnikov isomer was the major product of the reactions, the yields were not very high [145]. The catalytic reaction was accompanied with non-catalytic addition, leading to the anti-Markovnikov isomers (free radical or nucleophilic reactions) as well as double bond isomerization in the case of thiols (TH F, 67 °C) and selenols (benzene, 80 °C) [143, 144]. The isomerization reaction was especially pronounced with Pd(PhCN)2Cl2 catalyst [146]. It is interesting to note that the intermediate metal complex taking part in the catalytic reaction was denoted as Pd(SPh)2L [146]. 

It was reported that the pyrazolyl-borate complex of rhodium (Tp Rh(PPh3)2, Tp =hydrotris(3,5-dimethylpyrazolyl)borate) is active not only in the hydrothiolation with ArS H, but also with AlkS H in good to high yields of Markovnikov isomer at room temperature (Scheme 3.91) [162,163]. However the reaction of 1-octyne gave a mixture of isomers in 70% yield. In addition to the double bond isomerization, a Markovnikov/anti-Markovnikov ratio of 12 1 was found in the case of 1-octyne. 

Pyridine and 2,6-lutidine are useful as acid scavengers in the chlorination of a, 8-unsaturated ketones and esters. For the ketones, the pyridine bases typically favor the Markovnikov isomer however, for esters, pyridine shows little effect on the Markovnikov (alkoxy adjacent to carbonyl)/anti-Markovnikov isomer ratios (eq 14). ... 

The palladium-catalyzed hydrothiolation of terminal alkynes has been achieved using a metallocycle catalyst that was generated through the treatment of palladium acetate with phosphinic acids (Scheme 5.53) [79], Using this catalyst system, benzenethiol was added to 1-octyne in moderate yield with high selectivity for the Markovnikov-isomer. While only a single hydrothiolation example was reported, this chemistry provides the foundation for the design of additional palladium-catalyzed reactions. 

Alkene insertion into a metal-hydrogen (2.3.2.2) bond giving the Markovnikov isomer... 

However, because of steric crowding, insertion of methyl acetylene into the Pd-H bond would be expected to give the anti-Markovnikov isomer 4.29. Coordination of CO (not shown) followed by insertion into the palladium methoxy bond would lead to the formation of 4.30, which can then reductively eliminate the product. Had this mechanism been operative, the methyl ester of crotonic acid rather than MMA would have been the main product. 

NMR spectroscopy has been very useful for the characterization of species that are very similar to the proposed catalytic intermediates. Structures 5.33 and 5.35, where L = PPhj, are two examples where the alkenes used are 1 -octene and styrene, respectively. Variable-temperature NMR shows that in solution 5.33 is in equilibrium with an isomer 5.34. With styrene, under laboratory conditions, the branched (Markovnikov) rather than the linear (anti-Markovnikov) isomer is found to be the major one. 

The catalytic cycle for the hydrocyanation of 4PN to ADN is similar to that in Figure 5.9 and is therefore not shown again. Oxidative addition of HCN to NiLj produces complex 5.56. Insertion of the double bond of 4PN in the Ni-H bond of 5.56 in an anti-Markovnikov fashion produces complex 5.66. The interaction of the bulky Lewis acid with the coordinated CN of 5.56 (not shown) ensures that 5.66 rather than the Markovnikov isomer 5.67 is selectively formed. The former... 

Indium Addition of thiols RSH (R = alkyl, Ph) to terminal acetylenes ArC=CH, catalysed by In(OTf)3, has been reported to afford anti-Markovnikov products ArCH=CHSR, typically with 4 1 to 9 1 (E)I(Z) selectivity. By contrast, heteroaromatic thiols give the Markovnikov isomers. 

Cyclic five-membered H-phosphonates were found to be much more active in the addition reaction to the multiple carbon-carbon bonds compared to acyclic phosphorus derivatives [72] Rh-catalyzed addition of the five-membered H-phosphonate to alkynes was carried out under mild conditions at room temperature and results in high yield of the ) -isomer with -configuration (Scheme 8.8). It should be pointed out that Pd- and Rh-catalyzed reactions were complementary to each other providing the access to a-(Markovnikov) and trans-) -(anti-Markovnikov) isomers, respectively (cf. Schemes 8.5 and 8.8). 

Cu-catalyzed reaction in the Cul/ethylenediamine catalytic system was studied for the phenyl-H-phosphinate addition to phenylacetylene (Scheme 8.41) [97]. Selective formation of anti-Markovnikov -isomer was found in the reaction. 

The rate of addition depends on the concentration of both the butylene and the reagent HZ. The addition requires an acidic reagent and the orientation of the addition is regioselective (Markovnikov). The relative reactivities of the isomers are related to the relative stabiUty of the intermediate carbocation and are isobutylene 1 — butene > 2 — butenes. Addition to the 1-butene is less hindered than to the 2-butenes. For hydrogen bromide addition, the preferred orientation of the addition can be altered from Markovnikov to anti-Markovnikov by the presence of peroxides involving a free-radical mechanism. 

Conjugated dienes also undergo electrophilic addition reactions readily, but mixtures of products are invariably obtained. Addition of HBr to 1,3-butadiene, for instance, yields a mixture of two products (not counting cis-trans isomers). 3-Bromo-l-butene is the typical Markovnikov product of 1,2-addition to a double bond, but l-bromo-2-butene appears unusual. The double bond in this product has moved to a position between carbons 2 and 3, and HBr has added to carbons 1 and 4, a result described as 1,4-addition. 

The hydrosi(ly)lations of alkenes and alkynes are very important catalytic processes for the synthesis of alkyl- and alkenyl-silanes, respectively, which can be further transformed into aldehydes, ketones or alcohols by estabhshed stoichiometric organic transformations, or used as nucleophiles in cross-coupling reactions. Hydrosilylation is also used for the derivatisation of Si containing polymers. The drawbacks of the most widespread hydrosilylation catalysts [the Speier s system, H PtCl/PrOH, and Karstedt s complex [Pt2(divinyl-disiloxane)3] include the formation of side-products, in addition to the desired anh-Markovnikov Si-H addition product. In the hydrosilylation of alkynes, formation of di-silanes (by competing further reaction of the product alkenyl-silane) and of geometrical isomers (a-isomer from the Markovnikov addition and Z-p and -P from the anh-Markovnikov addition. Scheme 2.6) are also possible. 

In the photoaddition of 2-pyrrolidone the 5-alkyl isomer (69) always predominates, usually in a ratio of 2 1. The formation of anti-Markovnikov 1 1 adducts, telomers, and dehydrodimers of structure (71) supports a free radical mechanism. Similarly, formamide undergoes olefin addition under... 

In most cases, it has been proposed that the cationic intermediate resulting from electrophilic attack by the mercuric ion is, in fact, a mercurinium species 109 in which the mercury cation is unsymmetrically coordinated to the two alkynyl carbon atoms. Hence, these reactions typically afford Markovnikov products. In the presence of excess Hg(OAc)2, nucleophilic attack of the mercurinium intermediate is intermolecular and occurs in an anti-fashion leading to the (ft)-isomer. When no excess of Hg(OAc)2 is present, nucleophilic attack of the mercurinium intermediate is intramolecular and occurs in a ry -fashion leading to the (Z)-isomer.1... 

The most fundamental reaction is the alkylation of benzene with ethene.38,38a-38c Arylation of inactivated alkenes with inactivated arenes proceeds with the aid of a binuclear Ir(m) catalyst, [Ir(/x-acac-0,0,C3)(acac-0,0)(acac-C3)]2, to afford anti-Markovnikov hydroarylation products (Equation (33)). The iridium-catalyzed reaction of benzene with ethene at 180 °G for 3 h gives ethylbenzene (TN = 455, TOF = 0.0421 s 1). The reaction of benzene with propene leads to the formation of /z-propylbenzene and isopropylbenzene in 61% and 39% selectivities (TN = 13, TOF = 0.0110s-1). The catalytic reaction of the dinuclear Ir complex is shown to proceed via the formation of a mononuclear bis-acac-0,0 phenyl-Ir(m) species.388 The interesting aspect is the lack of /3-hydride elimination from the aryliridium intermediates giving the olefinic products. The reaction of substituted arenes with olefins provides a mixture of regioisomers. For example, the reaction of toluene with ethene affords m- and />-isomers in 63% and 37% selectivity, respectively. 

Irradiation of 1-phenylcycloalkenes (160) with cyano-aromatics electron-accepting sensitizers in MeCN and benzene containing 1 m methanol gave trans- 6 ) and di-isomers (162) of anti-Markovnikov adducts. The (161)7(162) isomer ratio was found to depend on the ring size of 1-phenylcycloalkene but not on the sensitizer used. The mechanism of the reactions was studied by semiempirical MO calculations. 

The stereoselectivity of anti-Markovnikov adducts (161) and (162) produced through photo-induced electron-transfer reaction of (160) with MeOH in MeCN depends on the optimum structures and stabilities of the corresponding radical and carbanion intermediates (163) and (164). In PhH, steric hindrance in an exciplex, comprising an excited singlet sensitizer and (160), forced cis addition of MeOH to (160) to give trans-isomer (161) as the major addition product. 

Hosokawa, Murahashi, and coworkers demonstrated the ability of Pd" to catalyze the oxidative conjugate addition of amide and carbamate nucleophiles to electron-deficient alkenes (Eq. 42) [177]. Approximately 10 years later, Stahl and coworkers discovered that Pd-catalyzed oxidative amination of styrene proceeds with either Markovnikov or anti-Markovnikov regioselectivity. The preferred isomer is dictated by the presence or absence of a Bronsted base (e.g., triethylamine or acetate), respectively (Scheme 12) [178,179]. Both of these reaction classes employ O2 as the stoichiometric oxidant, but optimal conditions include a copper cocatalyst. More recently, Stahl and coworkers found that the oxidative amination of unactivated alkyl olefins proceeds most effectively in the absence of a copper cocatalyst (Eq. 43) [180]. In the presence of 5mol% CUCI2, significant alkene amination is observed, but the product consists of a complicated isomeric mixture arising from migration of the double bond into thermodynamically more stable internal positions. 

Markovnikov additions are called regioselective since they give mainly one of several possible structural isomers. 

When the same substituents are at each end of the double or triple bond, it is called symmetrical. Unsymmetrical means different substituents are at each end of the double or triple bond. Electrophilic addition of unsymmetrical reagents to unsymmetrical double or triple bonds follows Markovnikov s rule. According to Markovnikov s rule, addition of unsymmetrical reagents, e.g. HX, H2O or ROH, to an unsymmetrical alkene proceeds in a way that the hydrogen atom adds to the carbon that already has the most hydrogen atoms. The reaction is not stereoselective since it proceeds via a planar carbocation intermediate. However, when reaction proceeds via a cyclic carbocation intermediate, it produces regiospecific and stereospecific product (see below). A regioselective reaction is a reaction that can potentially yield two or more constitutional isomers, but actually produces only one isomer. A reaction in which one stereoisomer is formed predominantly is called a stereoselective reaction. 

The nitrosochlorination of olefins has been known for nearly a century and has materially contributed to the early development of the chemistry of ter-penes [68]. Studies of the scope of the reaction were not undertaken until relatively recently and results appear to be somewhat fragmentary. While 1-olefins such as 1-hexene, 1-heptene, and 1-octene do not react with nitrosyl chloride, the corresponding 2-isomers add the reagent in conformity with Markovnikov s rule as if NO+ and Cl- moieties were involved [69]. 

C), has proven to be too reactive and nonselective towards alkenes. In the presence of 2 % ethanol, bromine monofluoride adds to C = C bonds at controllable rates but bromo ether byproducts arc formed that make the isolation of the desired bromofluoroalkanes difficult. The addition of bromine monofluoride is less regioselective compared to the addition of iodine monofluoride positional isomers are always present in the reaction mixture together with the major Markovnikov-typc addition products. 

Addition reactions to the C = C bond arc observed in reactions of perchloryl fluoride in methanol in the presence of potassium carbonate at 15 C, when protected prostacyclins are fluorinated. Fluorine enters the molecule according to the Markovnikov rule and the formation of four isomers has been established.34... 

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