Regioselective reactions examples

Regioselective reactions belong to the most important applications of homogeneous catalysis. An example is the hydroformylation of alkenes, which is a very important industrial reaction ... 

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markovnikov rule. Internal alkynes give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to (3-acetoxy- or (3-methoxyalkenylmercury intermediates,152 which can be reduced or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate that is opened by nucleophilic attack at the more positive carbon, that is, the additions follow the Markovnikov rule. Scheme 4.8 gives some examples of alkyne hydration reactions. 

The use of a nitrogen nucleophile in the side chain (as an amide) also leads to an intramolecular 1,4-addition under the standard conditions for the palladium-catalyzed 1,4-oxidation reactions52. Nitrogen nucleophiles employed for this reaction comprise tosy-lamides, carboxamides, carbamates and ureas. The reactions are run in acetone-acetic acid with p-benzoquinone (BQ) as the oxidant. In most cases highly stereo- and regioselective reactions were obtained and some examples are given in Table 3. 

The C-H functionalization of certain hydrocarbons, catalyzed by either TpBf3Cu or Tp(CFs)2Ag, can be highly regioselective. Representative examples are the reactions with 2,3-dimethylbutane (Equation (4)) and 2,5-dimethyl-hexane (Equation (5)).49,56 In these cases, C-H insertion into the tertiary C-H site was favored over reactions at the primary and sterically crowded secondary C-H sites. 

AUyRc aluminum ate complexes. Carbanions of allylic sulfides and ethers generally react with electrophiles at both the a- and the y-position. If the carbanion is converted into an ate complex -with triethylaluminum, electrophiles react predominately at the a-position. After the reaction is completed the trialkylaluminum is destroyed with aqueous methanol. Boron ate complexes are not so generally useful for control of regioselectivity.1 Example ... 

The asymmetric dihydroxylation of dienes has been examined, originally with the use of NMO as the cooxidant for osmium [56a] and, more recently, with potassium ferricyanide as the cooxidant [56b], Tetraols are the main product of the reaction when NMO is used, but with K3Fe(CN)6, ene-diols are produced with excellent regioselectivity. The example of dihydroxylation of trans.trans-1,4-diphenyl-1,3-butadiene is included in Table 6D.3 (entry 21). One double bond of this diene is hydroxylated in 84% yield with 99% ee when the amounts of K3Fe(CN)6 and K2C03 are limited to 1.5 equiv. each. Unsymmetrical dienes are also dihydroxy-lated with excellent regioselectivity. In these dienes, preference is shown for (a) a bans over a cis olefin, (b) the terminal olefin in a,p,y,8-unsaturated esters, and (c) the more highly substituted olefin [56b],... 

It has been long established that Lewis acid-catalysed [2+2] cycloaddition of ketenes and carbonyl compounds provides access to 2-oxetanones. In the development of this reaction prior to 1996, there has been a specific focus on controlling the stereochemistry of the /3-lactone product and cycloadditions have been achieved between trimethyl-silylketene and aldehydes with up to 90% stereoselectivity, as discussed in CHEC-II(1996) <1996CHEC-II(1)721>. CHEC(1984) and CHEC-II(1996) also discuss examples of the Lewis acid-catalyzed, nonphotolytic [2+2] cycloaddition of electron-rich alkenes with aldehydes or ketones <1984CHEC(7)363, 1996GHEC-II(1)721>. While this method can have some advantages over the photolytic reaction in terms of regioselectivity, no examples of this reaction have been reported in recent years. 

A Baeyer-Villiger oxidation has the potential of being asymmetric if a regioselective reaction is conducted on a meso-substrate or if a stereodifferentiated stereogenic center is already present. The oxidation can be chemical or enzymatic.213-215 216 An example of a chemical reagent in a Baeyer-Villiger reaction is provided in the synthesis of fragment A 26 from /f-carvone (27) (Scheme 9.38) as part of a synthesis of Cryptophycin A (28).217... 

Palladium-catalyzed Stille cross-coupling of furanylstannanes to an allyl bromide was also regioselective. An example, as employed in the total synthesis of 6/3-hydroxyeuryopsin, is depicted in Equation (38) <2004CC44>. This type of reaction could also be performed by using a catalytic amount of CuCl, rather than a palladium catalyst <1999SL1942>. 

When a reaction can potentially give rise to two (or more) constitutional isomers but actually produces only one, the reaction is said to be regioselective. For example, the ambident nucleophile NCO usually gives only isocyanates R—NCO and not the isomeric cyanates, R—OCN. 

With dissymmetrical alkynes or alkenes, very clean reactions are often obtained by regiospecific processes see Regioselectivity) For example, the use of phosphorus unsaturated reagents afford the opportunity to generate various mono or diphosphanes and related species (Scheme 29). ... 

The triethylaluminum or triethylborane ate complexes (12) of the (isopropylthio)allyl carbanion react with carbonyl compounds at the a-position (equation 10). In the reactions with carbonyl compounds, very high regioselectivity (for example, butanal 95 5, 3-methylbutanal 99 1, cyclohexanone 92 8 and acetophenone 95 5) was achieved by using the aluminum ate complex. On the other hand, the a-regio-selectivity with ketones decreases if the boron ate complex is used (cyclohexanone 72 28, acetophenone 45 55). It is noteworthy that the stereoselectivity of the a-adduct from an aldehyde is low. Ihesumably the geometry of the double bond in the ate complex (12) is not homogeneous. ... 

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