Hydrations anti-Markovnikov

S Addition of water (hydration) anti-Markovnikov addition... 

Hydration. Anti-Markovnikov hydration of 1-alkynes to afford aldedydes is accomplished by treatment with the title complex and a 2-diphenylphosphino-6-arylpyridine. 

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). 

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). 

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. 

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. 

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... 

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 10.7 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... 

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. 

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... 

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