Anti-Markovnikov reactions hydration

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). 

As was already mentioned, the standard procedure for acid catalyzed alkene hydration exhibits a rather low selectivity. On the other hand, the use of a hydroxymercuration-reduction sequence leads to the exclusive formation of Markovnikov s alcohols. A nearly exclusive anti-Markovnikov s hydration is achieved via a hydroboration-oxidation reaction (see Section 2.4). The result in both these cases is the net addition of H2O, but the basic differences in the reaction mechanisms unambiguously determine a reversed regioselectivity pattern. 

Recently, Dong et al. reported a multicatalytic cascade reaction combining Pd, acid, and Ru catalysis [11]. By coupling palladium-catalyzed oxidation, acid-catalyzed hydrolysis, and ruthenium-catalyzed reduction, the elusive anti-Markovnikov olefin hydration was formally achieved, affording primary alcohols from waters and aryl-substituted terminal alkenes (Scheme 9.8). 

In 1998, Wakatsuki et al. reported the first anti-Markonikov hydration of 1-alkynes to aldehydes by an Ru(II)/phosphine catalyst. Heating 1-alkynes in the presence of a catalytic amount of [RuCljlCgHs) (phosphine)] phosphine = PPh2(QF5) or P(3-C6H4S03Na)3 in 2-propanol at 60-100°C leads to predominantly anti-Markovnikov addition of water and yields aldehydes with only a small amount of methyl ketones (Eq. 6.47) [95]. They proposed the attack of water on an intermediate ruthenium vinylidene complex. The C-C bond cleavage or decarbonylation is expected to occur as a side reaction together with the main reaction leading to aldehyde formation. Indeed, olefins with one carbon atom less were always detected in the reaction mixtures (Scheme 6-21). 

We are applying the principles of enzyme mechanism to organometallic catalysis of the reactions of nonpolar and polar molecules for our early work using heterocyclic phosphines, please see ref. 1.(1) Here we report that whereas uncatalyzed alkyne hydration by water has a half-life measured in thousands of years, we have created improved catalysts which reduce the half-life to minutes, even at neutral pH. These data correspond to enzyme-like rate accelerations of >3.4 x 109, which is 12.8 times faster than our previously reported catalyst and 1170 times faster than the best catalyst known in the literature without a heterocyclic phosphine. In some cases, practical hydration can now be conducted at room temperature. Moreover, our improved catalysts favor anti-Markovnikov hydration over traditional Markovnikov hydration in ratios of over 1000 to 1, with aldehyde yields above 99% in many cases. In addition, we find that very active hydration catalysts can be created in situ by adding heterocyclic phosphines to otherwise inactive catalysts. The scope, limitations, and development of these reactions will be described in detail. 

In an effort to apply the cooperative principles of metalloenzyme reactivity, involving a combination of metal-ligand and hydrogen bonding, we have reported a ruthenium catalyst incorporating imidazolyl phosphine ligands that efficiently and selectively hydrates terminal alkynes (5). We subsequently found that application of pyridyl phosphines to the reaction resulted in a >10-fold rate enhancement and complete anti-Markovnikov selectivity, even in the... 

The hydration of alkynes represents a prime example in which simple coordinative activation by transition metal complexation greatly facilitates an otherwise very slow chemical process (Equation (107)). This reaction has been a long-studied problem, but only recently have alternatives to the classical use of catalysts such as Hg(n) salts been sought. These new catalyst systems typically display much enhanced reactivity, and some can mediate an anti-Markovnikov hydration through a novel mechanism (Table 1). 

A most significant advance in the alkyne hydration area during the past decade has been the development of Ru(n) catalyst systems that have enabled the anti-Markovnikov hydration of terminal alkynes (entries 6 and 7). These reactions involve the addition of water to the a-carbon of a ruthenium vinylidene complex, followed by reductive elimination of the resulting hydridoruthenium acyl intermediate (path C).392-395 While the use of GpRuGl(dppm) in aqueous dioxane (entry 6)393-396 and an indenylruthenium catalyst in an aqueous medium including surfactants has proved to be effective (entry 7),397 an Ru(n)/P,N-ligand system (entry 8) has recently been reported that displays enzyme-like rate acceleration (>2.4 x 1011) (dppm = bis(diphenylphosphino)methane).398... 

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]. 

A highly regioselective, efficient, and clean anti-Markovnikov hydration of terminal acetylenes has been realized through the use of catalytic amounts of Ru complexes.561 Typically, [CpRu(dppm)Cl] catalyzes the reaction at 100°C to give aldehydes in high yields (81-94%). Triflic acid or trifluoromethanesulfonimide effectively catalyzes the hydration of alkynes without a metal catalyst to afford Markovnikov products (ketones).562... 

Some other catalytic events prompted by rhodium or ruthenium porphyrins are the following 1. Activation and catalytic aldol condensation of ketones with Rh(OEP)C104 under neutral and mild conditions [372], 2. Anti-Markovnikov hydration of olefins with NaBH4 and 02 in THF, a catalytic modification of hydroboration-oxidation of olefins, as exemplified by the one-pot conversion of 1-methylcyclohexene to ( )-2-methylcycIohexanol with 100% regioselectivity and up to 90% stereoselectivity [373]. 3. Photocatalytic liquid-phase dehydrogenation of cyclohexanol in the presence of RhCl(TPP) [374]. 4. Catalysis of the water gas shift reaction in water at 100 °C and 1 atm CO by [RuCO(TPPS4)H20]4 [375]. 5. Oxygen reduction catalyzed by carbon supported iridium chelates [376]. - Certainly these notes can only be hints of what can be expected from new noble metal porphyrin catalysts in the near future. 

Another strategy for the synthesis of 5-deoxyhexoses involves the anti-Markovnikov hydration of a 5,6-alkene derivative, as first developed by Wolfrom.97,100 Since that report, the same approach has been followed by several authors, and conditions for the key step have been improved. For example, starting from tosylate 43, treatment with sodium iodide resulted in the alkene 44. Addition of iodine trifluoracetate (produced in situ by the reaction of silver trifluoroacetate and iodine) to 44, followed by hydrogenation over... 

The anti-Markovnikov hydration of a,p-unsaturated esters to provide a-hydroxy esters 341 (R1 C02R) succeeded in 50-83% yield when the intermediate hydroperoxide was reduced by sodium thiosulfate (entry 10) [375]. An exception also pointing to the involvement of radicals was ethyl cinnamate, where the reaction occurred with completely opposite regioselectivity. 

The reaction of the 9-hydroxy-ergoline derivative (74), prepared by reduction with diborane and anti-Markovnikov hydration of lysergic acid, with phosphorus oxychloride-pyridine results49 in expansion of ring C by displacement of the equa-49 L. Bernardi, C. Elli, and A. Temperilli, J.C.S. Chem. Comm., 1976, 570. 

This hydration of an alkene by hydroboration-oxidation is another example of a reaction that does not follow the original statement of Markovnikov s rule (the product is anti-Markovnikov), but still follows our understanding of the reasoning behind Markovnikov s rule. The electrophilic boron atom adds to the less substituted end of the double bond, placing the positive charge (and the hydrogen atom) at the more substituted end. 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

A Ni-catalyzed cyclization cross-coupling reaction of iodoalkenes with alkyl zinc halides has been employed for the synthesis of various tetrahydrofuran derivatives <2007AGE-ASAP>. The TiCU-catalyzed anti-Markovnikov hydration of alkynes has been applied to the synthesis of various benzo[3]furans <2007JOC6149>. 

Hydration of terminal alkynes can proceed with anti-Markovnikov addition. When 1-octyne was heated with water, isopropanol and a ruthenium catalyst, for example, the product was octanal. A similar reaction was reported in aqueous acetone using a ruthenium catalyst. The presence of certain functionality can... 

Anti-Markovnikov hydration is achieved by means of hydroboration with BH3. Hydrogen adds to the more alkylated carbon, and BH2 to the less alkylated, from the less hindered side in a reaction that proceeds via a four-centred transition state. 

The examples given below illustrate the synthetic utility of the hydro-boration reaction for anti-Markovnikov hydration of the double bonds in compounds 55-58, with formation of alcohols 59-62, and with predominant net delivery of the elements of water to the less-hindered alkene face, where relevant. Alcohols 61 and 62 are threo and erythro, respectively. Cis hydration of the double bonds of cyclic alkenes is described in the papers of Brown et al. and Alldred et al. and the text of Pelter et al. (see Further Reading). 

Hydroboration-oxidation occurs by syn addition. The reagents are borane or an alkyl or dialkyl derivative, followed by oxidation, usually with HjOj and "OH. The oxidation occurs with retention of configuration of the alkyl group. The regioselectivity favors addition of the boron at the less-substituted carbon of the double bond. As a result, the reaction sequence provides a stereospecific syn, anti-Markovnikov hydration of alkenes. 

Preparation. - By Addition to Alkenes. Triethylborane and phenyl-borinic acid have been found to catalyse hydroalumination of alkenes, and reaction of the intermediate alane with atmospheric oxygen efficiently furnished alcohols resulting from anti-Markovnikov hydration.1 Procedures for the preparation of methylborane and dimethylborane and their use in the synthesis of... 

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