Markovnikov hydration

Acid catalyzed hydration (Section 9 12) Water adds to the triple bond of alkynes to yield ketones by way of an unstable enol intermediate The enol arises by Markovnikov hydration of the alkyne Enol formation is followed by rapid isomerization of the enol to a ketone... 

Vn. Oxymercuration A Convenient Route to Markovnikov Hydration of Olefins... 

The acid catalyzed hydration of olefins is frequently attended by decomposition or rearrangement of the acid-sensitive substrate. A simple and mild procedure for the Markovnikov hydration of double bonds has recently been devised by Brown and co-workers 13). This reaction, which appears to be remarkably free of rearrangements, initially involves the addition of mercuric acetate to the double bond to give the 1,2-... 

Methyl-2-hexcne has a disubstituted double bond, RCH=CHR, and would probably give a mixture of two alcohols with either hydration method since Markovnikov s rule does not apply to symmetrically substituted alkenes. 3-MethyI-3-hexene, however, has a trisubstituted double bond, and would give only the desired product on non-Markovnikov hydration using the hydroboration/oxidation method. 

Alcohols can be prepared by hydration of alkenes. Because the direct hydration of alkenes with aqueous acid is generally a poor reaction in the laboratory, two indirect methods are commonly used. Hydroboration/oxiclation yields the product of syn, non-Markovnikov hydration (Section 7.5), whereas... 

Oxymercuration/demercuration provides a milder alternative for the conventional acid-catalyzed hydration of alkenes. The reaction also provides the Markovnikov regiochemistry for unsymmetrical alkenes.33 Interestingly, an enantioselective/inverse phase-transfer catalysis (IPTC) reaction for the Markovnikov hydration of double bonds by an oxymercuration-demercuration reaction with cyclodextrins as catalysts was recently reported.34 Relative to the more common phase-transfer... 

Enzyme-like Acceleration in Catalytic Anti-Markovnikov Hydration of Alkynes to... 

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. 

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 hydroboration of 3o -, 3jS-, 6o -, and 6/3-methoxyandrost-4-enes (75)-(78) has been shown to proceed predominantly trans to the MeO group, which parallels the behaviour of the corresponding alcohols. With 6-OMe derivatives (77) and (78), a small amount of Markovnikov hydration, giving 5-alcohols, has been observed. Epoxidation, osmylation, and bromination of 5/3-androst-3-enes (79) have been found to take place from the /3-face in the last reaction, diequatorial dibromide and bromohydrin accompany the axial addition products." ... 

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 10.7 A mechanism proposed for the anti-Markovnikov hydration of alkynes.

Anti-Markovnikov hydration of a vinyl chloride via oxymertcuration with mercuric trifluoroacetate in methanol was surprising [128]. However, it might be speculated that solvent modified Hg(II) species show a higher affinity for the chlorine atom than the rc-bond. The resultingchloronium ion is susceptible to attack by methanol in a manner analogous to Michael addition. Ejection of ClHgY is expected to be followed by a 1,2-hydride shift. 

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]. 

An anti-Markovnikov hydration of terminal alkynes could be a convenient way of preparing aldehydes, but so far only a few ruthenium-complexes have been identified that catalyze this unusual hydration mode ]16]. The presence of bidentate phosphine ligands ]16b], the coordination of a water molecule stabilized by hydrogen bonding ]16e] and the use of phosphinopyridine ligands ]16f] seem to be of major importance in these processes. 

Chevalher, F. and Breit, B. (2006) Self-assembled bidentate ligands for Ru-catalyzed anti-Markovnikov hydration of terminal alkynes. Angew. Chem., 118, 1629—1632 (2006) Selfassembled bidentate ligands for Ru-catalyzed anti-Markovnikov hydration of terminal alkynes. Angew. Chem., Int. Ed., 45, 1599-1602. 

Water can be added indirectly, with anti-Markovnikov orientation, by treatment of the alkene with a 1 1 mixture of PhCH2NEt3+ BH4 and Me3SiCl, followed by addition of an aqueous solution of K2C03.152 For another method of anti-Markovnikov hydration, see 5-12. With substrates of the type C=C—Z (Z is as defined on p. 741) the product is almost always HO—C—CH—Z and the mechanism is usually nucleophilic,153 though electrophilic... 

Solvomercuration,3111 484 187 or the addition of mercury(II) salts, is a convenient route to organomercurials. On the other hand, replacement of mercury with hydrogen allows Markovnikov functionalization of alkenes.488 A method called mercuration-demercuration, for instance, has been developed for the Markovnikov hydration of alkenes under mild conditions489 [Eq. (6.82)490] ... 

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. 

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