Anti-Markovnikov reactions

There are not many examples of addition of alcohols to a triple bond proceeding through an anti-Markovnikov reaction. With RuCl(tris(pyrazolyl)borate)(pyridine)2 as catalyst, addition of allyl alcohol to phenylacetylene proceeds in 72 % overall yield in toluene under reflux, and provides a 1 1 mixture of allyl /3-styryl ether and 2-phenylpent-4-enal resulting from further Claisen rearrangement (Scheme 7) [17]. 

The change in regiochemistry is a result of a change in the mechanism of the reaction, from an ionic mechanism in the Markovnikov reaction to a radical chain mechanism in the anti-Markovnikov reaction. The radical chain mechanism for the addition of hydrogen bromide to 1-butene is outlined in the following equations ... 

In 1933, M. S. Kharasch and F. W. Mayo found that some additions of HBr (but not HC1 or HI) to alkenes gave products that were opposite to those expected from Markovnikov s rule. These anti-Markovnikov reactions were most likely when the reagents or solvents came from old supplies that had accumulated peroxides from exposure to the air. Peroxides give rise to free radicals that initiate the addition, causing it to occur by a radical mechanism. The oxygen-oxygen bond in peroxides is rather weak, so it can break to give two alkoxy radicals. 

Muzart [39] reviewed examples of such anti-Markovnikov reactions forming aldehydes. But many ofthe examples can be explained by the influence of electron-withdrawing groups, which then are Markovnikov conforming, like the formation of nitroacetaldehyde and cyanoacetaldehyde from nitroethylene and acrylonitrile, respectively (see Eq. (9.4) and Table 9.1). 

The undecene methyl ester is saponified. The acid produced is converted to 11-bromoundecanoic acid in an anti-Markovnikov reaction under the influence of peroxides or light and hydrogen bromide. The bromoacid is converted to the ammonium salt of 11-amino undecanoic acid by ammonia and the free acid is liberated on lowering the pH. The free acid is polycondensed to polyamide (Nylon 11). 

Note Do not confuse the term anti with the term anti-Markovnikov. The word anti describes the stereochemistry, while the word anti-Markovnikov describes the regiochemistry. It is possible for an anti-Markovnikov reaction to be a syn addition. In fact, we will see such an example very soon. 

It turns out there is a way to add Br or OH to the fess-substituted carbon of an alkene. These reactions are called anti-Markovnikov additions. We will learn partial mechanisms later, but most students find it helpful to make note cards of both Markovnikov and anti-Markovnikov reactions at this point. 

Oxidation. The oxidation reactions of organoboranes have been reviewed (5,7,215). Hydroboration—oxidation is an anti-Markovnikov cis-hydration of carbon—carbon multiple bonds. The standard oxidation procedure employs 30% hydrogen peroxide and 3 M sodium hydroxide. The reaction proceeds with retention of configuration (216). 

A typical example of a nonpolymeric chain-propagating radical reaction is the anti-Markovnikov addition of hydrogen sulfide to a terminal olefin. The mechanism involves alternating abstraction and addition reactions in the propagating steps ... 

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... 

Anti-Markovnikov addition (Sections 6.8, 6.11) Addition reaction for which the regioselectivity is opposite to that predicted on the basis of Markovnikov s rule. 

This reaction, now termed hydroboration, has opened up the quantitative preparation of organoboranes and these, in turn, have proved to be of outstanding synthetic utility. It was for his development of this field that H. C. Brown (Purdue) was awarded the 1979 Nobel Prize in Chemistry . Hydroboration is regiospecific, the boron showing preferential attachment to the least substituted C atom (anti-Markovnikov). This finds ready interpretation in terms of electronic factors and relative bond polarities (p. 144) steric factors also work in the same direction. The addition is stereospecific cis (syn). Recent extensions of the methodology have encompassed the significant development of generalized chiral syntheses. 

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. 

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. 

Free radical additions to mono-olefins are quite common and can frequently be employed to advantage on a synthetic scale. Formamide, for example, on exposure to sunlight or UV radiation adds to olefins in an anti-Markovnikov sense giving 1 1 adducts that are readily isolated and crystallized. Moreover, since alkyl formamides may be conveniently converted to carboxylic acids by conventional means, the reaction represents a general method of chain extension. 

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... 

The addition of (TMS)3SiH to a number of monosubstituted acetylenes has also been studied in some detail. These reactions are highly regioselective (anti-Markovnikov) and give terminal (TMSlsSi-substituted alkenes in good yields. High cis or trans stereoselectivity is also observed, depending on the nature of the substituents at the acetylenic moiety. For example, the reaction of the alkynes 23 and 24 with (TMSlsSiH, initiated either by EtsB at room temperature (method or by thermal decomposition of di-ferf-butyl peroxide at 160 °C... 

Organoboranes react with a mixture of aqueous NH3 and NaOCl to produce primary amines. It is likely that the actual reagent is chloramine NH2CI. Chloramine itself,hydroxylamine-O-sulfonic acid in diglyme, and trimethyl-silyl azide " also give the reaction. Since the boranes can be prepared by the hydroboration of alkenes (15-16), this is an indirect method for the addition of NH3 to a double bond with anti-Markovnikov orientation. Secondary amines can be prepared by the treatment of alkyl- or aryldichloroboranes or dialkylchlorobor-anes with alkyl or aryl azides. 

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