Alcohols anti-Markovnikov

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... 

Hydroboration is widely employed to obtain an anti-Markovnikov alcohol from an olefin. Addition of diborane to the double bond produces an organoborane intermediate. Three equivalents of the olefin are needed to consume the BH3 and a trialkylborane is produced. Reaction with basic H202 converts the carbon-boron bond to a carbon oxygen bond. This process is effective and widely used. 

Catalytic hydroboration of perfluoroalkenes 68 with catecholborane provides either terminal 69 or internal alcohols 70 regioselectively <19990L1399>. The regioselectivity is controlled by a judicious choice of catalyst. The anti-Markovnikov alcohol can be obtained with very high selectivity by using cationic rhodium catalysts such as Rh(COD)(DPPB)+BF4, while neutral Rh catalysts such as Wilkinson s catalyst provide the Markovnikov product (COD = cyclooctadiene Equation 3) <19990L1399>. 

We have seen two methods for hydrating an alkene with Markovnikov orientation. What if we need to convert an alkene to the anti-Markovnikov alcohol For example, the following transformation cannot be accomplished using the hydration procedures covered thus far. 

Such an anti-Markovnikov hydration was impossible until H. C. Brown, of Purdue University, discovered that diborane (B2H6) adds to alkenes with anti-Markovnikov orientation to form alkylboranes, which can be oxidized to give anti-Markovnikov alcohols. This discovery led to the development of a large field of borane chemistry, for which Brown received the Nobel Prize in Chemistry in 1979. 

Trialkylboranes react exactly as we have discussed, and they oxidize to give anti-Markovnikov alcohols. Trialkylboranes are quite bulky, further reinforcing the preference for boron to add to the less hindered carbon atom of the double bond. Boranes are often... 

Water can be added indirectly, with anti-Markovnikov orientation, by treatment of the alkene with a 1 1 mixture of PhCHaNEts BH4 and MesSiCl, followed by addition of an aqueous solution of K2C03. Reaction of alkenes with Ti(BH4)3, and then aqueous K2CO3 also leads to the anti-Markovnikov alcohol. Reaction of... 

Hydroboration-oxidation is a useful method when the desired product is the anti-Markovnikov alcohol. The borane-containing reactant is normally dibo-rane (B2Hg) or the borane tetrahydrofuran complex (BH, THF). No matter what hydroboration agent is used, it s usually simplified to BH3 in the mechanism. BH3 is a useful reactant because it s a good Lewis acid. 

The hydroboration reaction with alkenes to produce alkylboranes (sec. 5.2) proceeds by a four-center transition state rather than a cationic intermediate. The regiochemistry of the final alkylborane product is controlled by the nonbonded steric interactions of the groups attached to boron (in this case sec-isoamyl from the disiamylborane) and the groups on the alkene. Oxidation with basic hydrogen peroxide converts the borane to the anti-Markovnikov alcohol (2). The difference in regiochemistry between 1 and 2 arose because the mechanism for generating each relied on difference factors. 

Preparation.—Alcohols can be obtained from terminal alkenes by hydro-alumination with lithium aluminium hydride in the presence of a titanium complex, followed by oxidative cleavage of the adduct (Scheme 1). The sequence provides anti-Markovnikov alcohol. 

In ether solvents, borane adds to alkenes via a four-centered transition state to give an alkylborane. Borane adds by a cis addition that places the boron on the less substituted carbon as the major product. Alkylboranes react with NaOH/HgOg to give an anti-Markovnikov alcohol. 

The use of the NaBH4/l2 reagent system in THF for the hydroboration of alkenes has been examined using representative olefins (29,31). The corresponding anti-Markovnikov alcohols (13-15) have been isolated after H202/Na0H or H202/NaOAc oxidation. 

Preparation.—Hydration of an alkene to the anti-Markovnikov alcohol can be accomplished with a titanium tetrachloride-sodium borohydride reagent [equation (1)] a boron complex of low-valent titanium may be involved. 

In Summary Hydroboration-oxidation constitutes another method for hydrating alkenes. The initial addition is syn and regioselective, the boron shifting to the less hindered carbon. Oxidation of alkyl boranes with basic hydrogen peroxide gives anti-Markovnikov alcohols with retention of configuration of the alkyl group. 

At the same oxidation level, alcohols can be prepared by substitution reactions and addition reactions. Alkali hydroxides will convert appropriate alkyl chlorides, bromides, iodides, and sulfonates to alcohols. Oxymercuration of alkenes gives Markovnikov alcohols, and hydrobora-tion followed by oxidation gives anti-Markovnikov alcohols. Hindered boranes such as 9-BBN are used when selectivity toward one double bond or higher regioselectivity is needed (Eq. 6.41) [66]. 

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

In 1993, ten challenges faced the catalysis research community. One of these was the anti-Markovnikov addition of water or ammonia to olefins to directly synthesize primary alcohols or amines [323]. Despite some progress, the direct addition of N-H bonds across unsaturated C-C bonds, an apparently simple reaction, stiU remains a challenging fundamental and economic task for the coming century. 

The stereochemical outcome is replacement of the C—B bond by a C—O bond with retention of configuration. In combination with stereospecific syn hydroboration, this allows the structure and stereochemistry of the alcohols to be predicted with confidence. The preference for hydroboration at the least-substituted carbon of a double bond results in the alcohol being formed with regiochemistry that is complementary to that observed by direct hydration or oxymercuration, that is, anti-Markovnikov. 

Although extremely rare, a recent report documents the intramolecular S -type displacements of (TPP)Rh-alkyl complexes (TPP = tetraphenylporphyrin) by alcohols and phenols to form THFs (Scheme 19). The intermediate rhodium alkyl complexes are themselves prepared by anti-Markovnikov hydrorhodation, and although the (TPP)Rh-H... 

Hydrate to alcohol hydroborate/oxidize (THF/B2H5,H202/0H-) (syn, anti-Markovnikov)... 

The first anti-Markovnikov hydration of terminal acetylenes, catalyzed by mthenium(ll)-phosphine complexes, has been described in 1998 [27]. As shown on Scheme 9.8, the major products were aldehydes, accompanied by some ketone and alcohol. In addition to TPPTS, the fluorinated phosphine, PPh2(C6Fs) also formed catalytically active Ru-complexes in reaction with [ RUC12(C6H6) 2]. 

It is noteworthy that the indenyl complex RuCl(ri -C9H7)(PPh3)2l4 provides an efficient catalyst precursor for the anti-Markovnikov hydration of terminal alkynes in aqueous media, especially in micellar solutions with either anionic (sodium dode-cylsulfate (SDS)) or cationic (hexadecyltrimethylammonium bromide (CTAB)) surfactants [38]. This system can be applied to the hydration of propargylic alcohols to selectively produce P-hydroxyaldehydes, whereas RuCl(Cp)(PMe3)2 gives a,P-unsat-urated aldehydes (the Meyer Schuster rearrangement products)(Scheme 10.8) [39]. 

Scheme 10.11 Formation of unsaturated ketones via anti-Markovnikov addition of allylic alcohols to terminal alkynes.

The anti-Markovnikov addition of carbamates to terminal alkynes was introduced as the first example of catalytically active metal vinylidene in 1986. The development of this concept to other O-nucleophiles followed immediately and carboxylic adds, water and allylic alcohols were used to produce the corresponding addition produds. The... 

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. 

Hydroboration-oxidation of alkenes preparation of alcohols Addition of water to alkenes by hydroboration-oxidation gives alcohols via anti-Markovnikov addition. This addition is opposite to the acid-catalysed addition of water. Hydrohoration is regioselective and syn stereospecific. In the addition reaction, borane bonds to the less substituted carbon, and hydrogen to the more substituted carbon of the double bond. For example, propene reacts with borane and THF complex, followed by oxidation with basic hydrogen peroxide (H2O2), to yield propanol. 

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]. 

The use of silica-supported Zn(BH4)2 is a useful procedure for the hydration of unactivated alkenes and alkynes.559 The main products are usually formed as a result of anti-Markovnikov addition. In contrast to acid-catalyzed hydration (see Section 6.1.2), this procedure allows the transformation of alkynes to alcohols. 

Acid-catalyzed addition of water and alcohols to 4/f-chromenes gives the expected products as predicted by Markovnikov s rule (56JCS4785) an anti-Markovnikov addition of methanol followed by the reintroduction of a double bond in the alternative position gives an overall effect of substitution of hydrogen by methoxy and this is effected by treating methyl 2if-chromene-3-carboxylate (166) with triphenylmethyl perchlorate and addition of methanol to the resulting benzopyrylium salt (167) (72CR(C)(274)650). 

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