Markovnikov products

The presence of free radicals can invert this rule, to form anti-Markovnikov products. Free-radical addition in this fashion produces a radical on the central carbon, C-2, which is more stable than the allyl radical. This carbon can then experience further addition. For example, acid-catalyzed addition of... 

Conversion of alkenes to alcohols by hydroboration is a synthetically-valuable reaction as it leads to the anti-Markovnikov product. 

Dimethylborane+propene C2 and 2-propyldimethyl borane depict the regioisomeric transition state and addition product. Calculate the energies of these species relative to those of the alternative transition state and product. Given these energy differences, and the experimental observation that this addition is almost completely selective for the anti-Markovnikov product, does it appear that this reaction is under kinetic or thermodynamic control Explain. 

Is the location of positive charge in the more stable cation also where the lowest-unoccupied molecular orbital (LUMO) is most concentrated Rationalize what you observe. Does attack by a nucleophile (bromide) lead to the Markovnikov or anti Markovnikov product ... 

Electrophilic addition of hydrogen bromide to alkenes follows Markovnikov s rule, leading to the product with halogen on the more-substituted position. However, trace amounts of hydroperoxides (among other impurities ) may initiate a reaction that gives rise to the anti-Markovnikov product, with bromine in the less-substituted position. 

In addition to the oxymercuration method, which yields the Markovnikov product, a complementary method that yields the non-Markovnikov product is also useful. Discovered in 1959 by H. C. Brown and cailed hydroboration, the reaction involves addition of a B-H bond of borane, BH3, to an alkene to yield an organoborane intermediate, RBH2. Oxidation of the organoborane by reaction with basic hydrogen peroxide, H2O2, then gives an alcohol. For example ... 

Like alkenes (Sections 7.4 and 7.5), alkynes can be hydrated by either of two methods. Direct addition of water catalyzed by mercury(II) ion yields the Markovnikov product, and indirect addition of water by a hydroboration/ oxidation sequence yields the non-Markovnikov product. 

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. 

A DEPT-90 spectrum would show two absorptions for the non-Markovnikov product (RCH=CHBr) but no absorptions for the Markovnikov product (RBvC=CH2). 

The reversibility of halohydrin dehalogenase-catalyzed reactions has been used for the regioselective epoxide-opening with nonnatural nucleophiles (an example is given in Scheme 10.34) [133]. The stereoselectivity of the enzyme results in the resolution of the racemic substrate. At the same time, the regioselectivity imposed by the active site geometry yields the anti-Markovnikov product. [128]... 

Se-phenyl areneselenosulfonates (24) undergo facile free-radical addition to alkenes to produce / -phenylseleno sulfones (25) in excellent yield86,87 (see Scheme 7). The addition occurs regiospecifically and affords anti-Markovnikov products contrary to the analogous boron trifluoride catalyzed reaction which produces exclusively Markovnikov and highly stereospecific products86 (equation 37). Reaction 36 has been shown to have the radical... 

A catalytic system comprising TiCNMe ), LiNCSilVIej) and IMes has been developed for the intermolecular hydroamination of terminal aliphatic alkynes (1-hexyne, 1-octyne, etc.) with anilines [toluene, 100°C, 10 mol% TiCNMe ) ]. Markovnikov products were dominant. Substituted anilines reacted similarly. High conversions (85-95%) were observed with specific anilines. The optimum Ti/IMes/ LiN(SiMe3)2 ratio was 1 2 1. However, the nature of the active species and especially the role of LiN(SiMe3)2 are unclear [74]. 

Anfj-Markovnikov products are only observed. The postulated mechanism for these reactions is analogous to the previously discussed for the copper-catalysed hydroamination (Scheme 2.15) with the coordinated thiolate (rather than the amide) acting as nucleophile [82, 85]. 

As previously mentioned [155], PhNHj does not react with styrene under the above conditions. However, Beller et al. discovered that the hydroaminahon of styrene could be achieved in excellent yield by using either a w-BuLi-K2C03 mixture or, better, t-BuOK as catalysts [159]. Using LBuOK (10%) in THE at 120°C (pressure tube), styrene is hydroaminated with aniline (5 equiv.) to give the anh-Markovnikov product in 96% yield (Eq. 4.34), R = = R = R = H, TOE = 0.5 h ]. The scope of... 

Palladium(O) or readily reduced paUadium(II) complexes were the most efficient catalysts, giving higher yields than analogous Pt catalysts. The Markovnikov product was formed with high regioselectivity. In dialkynes, both C=C bonds could be hy-drophosphorylated, while the C=C double bond in a cyclohexenyl alkyne subshtuent did not react. With trimethylsilylacetylene, unusual anti-Markovnikov selectivity was observed. 

The anti-Markovnikov product was formed with >95% regioselectivity at 35°C. The examples in Scheme 5-21, Eq. (1) show that cyano and hydroxyl functional groups are tolerated by the catalyst, and diphenylphosphine oxide can be added to both C=C bonds in a di-alkyne. The reaction also worked for internal alkynes (Scheme 5-21, Eq. 2). Unusual Markovnikov selectivity was observed, however, for 1-ethynyl-cyclohexene (Scheme 5-21, Eq. 3) [17]. 

The regioselectivity of these reactions was reversed (the Markovnikov product was now favored) simply by the addition of a catalytic amount of phosphinic acid (Scheme 5-23, Eq. (1) compare Scheme 5-21) [18]. 

Trimethylsilylacetylene is an exception, giving the anti-Markovnikov product. Internal alkynes also underwent the reaction, as observed without phosphinic acid (Scheme 5-23, Eq. 2). 

Pt-catalyzed hydration of various aliphatic and aromatic alkynes under phase transfer conditions in (CH2C1)2/H20 in the presence of Aliquat 336 led to either a Markovnikov product, mixtures of two ketones, or ketones with the carbonyl group positioned away from the bulky side.72 In the absence of the phase transfer reagent, Aliquat 336, hardly any reaction took place. Recently, a hydrophobic, low-loading and alkylated polystyrene-supported sulfonic acid (LL-ALPS-SO3H) has also been developed for the hydration of terminal alkynes in pure water, leading to ketones as the product.73 Under microwave irradiation, the hydration of terminal arylalkynes was reported to proceed in superheated water (200°C) without any catalysts.74... 

Since HC1 and HBr absorb light at wavelengths shorter than 290 nm, 254-nm light or photosensitizers (acetone, acetaldehyde, tetraethyl lead, etc.) are commonly employed/11 Anti-Markovnikov products result(113> ... 

More stable radical anti-Markovnikov product... 

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... 

Homogeneous iridium(m) catalysts mediate arene C-H activations to form anti-Markovnikov products as in the hydroarylation of propene (Equation (631).64... 

The uncatalyzed hydroboration-oxidation of an alkene usually affords the //-Markovnikov product while the catalyzed version can be induced to produce either Markovnikov or /z/z-Markovnikov products. The regioselectivity obtained with a catalyst has been shown to depend on the ligands attached to the metal and also on the steric and electronic properties of the reacting alkene.69 In the case of monosubstituted alkenes (except for vinylarenes), the anti-Markovnikov alcohol is obtained as the major product in either the presence or absence of a metal catalyst. However, the difference is that the metal-catalyzed reaction with catecholborane proceeds to completion within minutes at room temperature, while extended heating at 90 °C is required for the uncatalyzed transformation.60 It should be noted that there is a reversal of regioselectivity from Markovnikov B-H addition in unfunctionalized terminal olefins to the anti-Markovnikov manner in monosubstituted perfluoroalkenes, both in the achiral and chiral versions.70,71... 

Ground-state alkenes generally undergo electrophilic addition with alcohols in the presence of a Bronsted acid catalyst, yielding the Markovnikov product ... 

Thymine also undergoes a photoaddition reaction with water to form the anti-Markovnikov product ... 

The iridium(III)-complex, [Ir(p-acac-0,0,C )(acac-0,0)(acac-C )]2, mediates the activation of unactivated aromatic C—H bond with unactivated alkenes to form anti-Markovnikov products [57]. The reaction of benzene 131 with propene 132 (0.78 MPa of propylene, 1.96 MPa of N2) leads to the formation of n-propylbenzene 133 in 61% selectivities (turnover number (TON) = 13 turnover frequency (TOE) = 0.0110 s ) (Equation 10.34). The reaction of benzene with ethane at 180 °C for 3h gave ethylbenzene (TON = 455 TOE = 0.0421s ). The anti-Markovnikov selectivity was also proven for the reaction with 1-hexane and isobutene, giving 1-phenyUiexane (69% selectivity) and isobutylbenzene (82% selectivity), respectively. 

The reaction of / with bromine in carbon tetrachloride confirms the prediction that / is an alkene. The reaction with HBr means that G is the Markovnikov addition product, and the reaction in the presence of peroxides makes //the anti-Markovnikov product. 

Oxo reaction or hydroformylation reaction involves addition of a hydrogen atom and a formyl group (-CHO) to C=C double bond of an olefin making both anti—Markovnikov and Markovnikov products ... 

It is possible to obtain anti-Markovnikov products when HBr is added to alkenes in the presence of free radical initiators, e.g. hydrogen peroxide (HOOH) or alkyl peroxide (ROOR). The free radical initiators change the mechanism of addition from an electrophilic addition to a free radical addition. This change of mechanism gives rise to the anh-Markovnikov regiochemistry. For example, 2-methyl propene reacts with HBr in the presence of peroxide (ROOR) to form 1-bromo-2-methyl propane, which is an anh-Markovnikov product. Radical additions do not proceed with HCl or HI. 

The peroxide effect is also observed with the addition of HBr to alkynes. Peroxides (ROOR) generate anh-Markovnikov products, e.g. 1-butyne reacts with HBr in the presence of peroxide to form 1-bromobutene. 

In the case of terminal alkynes, the propargyl position promoted the normal Markovnikov product. 

The impressive activity achieved by Teles catalyst was improved some years later by the use of CO as an additive [92]. In this study, Hayashi and Tanaka reported a TOF of 15600h 1, at least two orders of magnitude higher than [as-PtCl2(tppts)2], for the hydration of alkynes, providing an alternative synthetic route to the Wacker oxidation. Although several solvents were tested, the best results were obtained with aqueous methanol, and sulfuric acid or HTfO as acidic promoters. Unlike Utimoto s observation, in this case terminal propargylic alcohols partially (17-20%) delivered anti-Markovnikov product, in addition to the Markovnikov species. Some years before, Wakatsuki et al. had already reported the anti-Markovnikov hydration of terminal alkynes catalyzed by ruthenium(II) [93]. 

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