Anti-Markovnikov addition metal catalysts

Hydroboration, the addition of B-H bonds to carbon-carbon multiple bonds, is an attractive route to organoboranes, which can be converted into a variety of functional groups such as alcohols upon alkaline hydrogen peroxide treatment to give the corresponding anti-Markovnikov products. Metal catalysts allow for these hydroborations to be carried out under milder reaction conditions, improved or even altered reaction selectivity and more importantly, enantioselectively. 

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. 

In hydrocarboxylations, as in the 0x0 process, selectivity of linear versus branched products is an important issue, because (in general) mixtures of isomeric carboxylic acids are obtained, owing not only the occurrence of both Markovni-kov and anti-Markovnikov addition of the alkene to the metal hydride, but also to metal-catalyzed alkene isomerization (eq. (2)). In the case of higher olefins, Co2(CO)g as catalyst leads to a number of different carboxylic acid isomers due to the isomerization activity of the catalyst. 

The addition of HCN to C=C double bonds can be effected in low yields to produce Markovnikov addition products. However, through the use of transition metal catalysts, the selective anti-Markovnikov addition of HCN to alkenes can take place. The most prominent example of the use of aqueous media for transition metal-catalyzed alkene hydrocyanation chemistry is the three-step synthesis of adi-ponitrile from butadiene and HCN (Eqs. 5-7). First discovered by Drinkard at DuPont [14], this nickel-catalyzed chemistry can use a wide variety of phosphorus ligands [15] and is practiced commercially in nonaqueous media by both DuPont and Butachimie, A DuPont/Rhone-Poulenc joint venture. Since the initial reports of Drinkard, first Kuntz [16] and, more recently, Huser and Perron [17, 18] from Rhone-Poulenc have explored the use of water-soluble ligands for this process to facilitate catalyst recovery and recycle from these high-boiling organic products. 

The addition of HCN to C=C double bonds can be effected in low yields to produce Markovnikov addition products. However, through the use of transition metal catalysts, the selective anti-Markovnikov addition of HCN to alkenes can take place. The most prominent example of the use of aqueous media for transition metal-catalyzed alkene hydrocyanation chemistry is the three-step synthesis of adiponitrile... 

Gunnoe has also reported examples of catalytic aromatic alkylation using a ruthenium complex and olefins. With propylene and other terminal olefins, a 1.6 1 preference for anti-Markovnikov addition was seen. The proposed mechanism involved olefin insertion into the metal-aryl bond followed by a metathesis reaction with benzene to give the alkylated aromatic and a new metal-phenyl bond (Equation (26)). DFT calculations supported the proposed non-oxidative addition mechanism. The work was extended to include catalytic alkylation of the a-position of thiophene and furan. With pyrrole, insertion of the coordinated acetonitrile into the a-C-H bond was observed. Gunnoe has also summarized recent developments in aromatic C-H transformations in synthesis using metal catalysts. ... 

A series of arylations of olefins by C-H bond cleavage without direction by an ortho functional group has also been reported, and these reactions can be divided into two sets. In one case, the C-H bond of an arene adds across an olefin to form an alkylarene product. This reaction has been called hydroarylation. In a second case, oxidative coupling of an arene with an olefin has been reported. This reaction forms an aryl-substituted olefin as product, and has been called an oxidative arylation of olefins. The first reaction forms the same t)q)es of products that are formed from Friedel-Crafts reactions, but with selectivity controlled by the irietal catalyst. For example, the metal-catalyzed process can form products enriched in the isomer resulting from anti-Markovnikov addition, or it could form the products from Markovnikov addition with control of absolute stereochemistry. Examples of hydroarylation and oxidative arylation of olefins are shown in Equations 18.63 - and 18.64. ... 

The transition metal catalyzed addition of amides to alkynes provides a useful approach to the preparation of enamides. In this context, Gooden and coworkers have developed efficient ruthenium catalysts, which allow the anti-Markovnikov addition of amide to terminal alkynes (Scheme 4.46) [187]. 

Another approach toward C-O bond formation using alkynes that has been pursued involves the intermediacy of transition metal vinylidenes that can arise from the corresponding y2-alkyne complexes (Scheme 13). Due to the electrophilicity of the cr-carbon directly bound to the metal center, a nucleophilic addition can readily occur to form a vinyl metal species. Subsequent protonation of the resulting metal-carbon cr-bond yields the product with anti-Markovnikov selectivity and regenerates the catalyst. 

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... 

The addition of HCN to olefins catalyzed by complexes of transition metals has been studied since about 1950. The first hydrocyanation by a homogeneous catalyst was reported by Arthur with cobalt carbonyl as catalyst. These reactions gave the branched nitrile as the predominant product. Nickel complexes of phosphites are more active catalysts for hydrocyanation, and these catalysts give the anti-Markovnikov product with terminal alkenes. The first nickel-catalyzed hydrocyanations were disclosed by Drinkard and by Brown and Rick. The development of this nickel-catalyzed chemistry into the commercially important addition to butadiene (Equation 16.3) was conducted at DuPont. Taylor and Swift referred to hydrocyanation of butadiene, and Drinkard exploited this chemistry for the synthesis of adiponitrile. The mechanism of ftiis process was pursued in depth by Tolman. As a result of this work, butadiene hydrocyanation was commercialized in 1971. The development of hydrocyanation is one of tfie early success stories in homogeneous catalysis. Significant improvements in catalysts have been made since that time, and many reviews have now been written on this subject. ... 

Catalysts for tfie additions of amines to vinylarenes have also been developed. These catalytic reactions include some of the first hydroaminations of unstrained olefins catalyzed by late transition metals, as well as examples catalyzed by lanthanide complexes. These additions occur with Markovrukov selectivity with one set of catalysts and with anti-Markovnikov selectivity with several others. These additions occur by several different mechanisms that are presented in Section 16.5.3.2. 

In this section we describe the available literature on the addition reaction of thiols and selenols RZH (Z = S, Se). We do not discuss non-catalytic addition reactions carried out without transition metal catalysts as this topic has already been addressed in several publications (see [100-103,139-142] and references therein). It was shown that the non-catalytic reactions led to a different outcome the anti-Markovnikov products are formed in the addition of RZ H to alkynes. Our goal is to concentrate on the selective formation of the scarcely available Markovnikov isomer by RZH addition to the triple bond of alkynes. 

In 1992 Ogawa, Sonoda et al. carried out the first catalytic addition of aromatic thiols [143] and selenols [144] to alkynes with Pd(OAc)2. Although the Markovnikov isomer was the major product of the reactions, the yields were not very high [145]. The catalytic reaction was accompanied with non-catalytic addition, leading to the anti-Markovnikov isomers (free radical or nucleophilic reactions) as well as double bond isomerization in the case of thiols (TH F, 67 °C) and selenols (benzene, 80 °C) [143, 144]. The isomerization reaction was especially pronounced with Pd(PhCN)2Cl2 catalyst [146]. It is interesting to note that the intermediate metal complex taking part in the catalytic reaction was denoted as Pd(SPh)2L [146]. 

In addition to ruthenium-catalyzed reactions, a range of other transition metal catalysts have shown activity toward the addition reaction. A series of air-stable gold compounds promoted the addition of carboxylic acids to alkynes (Scheme 2.93) [138]. A variety of gold and silver compounds were screened as catalysts for the reaction, and the most effective pair under the mildest conditions was (Ph3P)AuCl and AgPF. Under the reactions conditions, the reaction was highly selective for the formation of the Markovnikov addition product, and minimal or none of the anti-Markovnikov products were observed. 

While the majority of metal catalysts generated the Markovnikov addition product, a few catalyst systems were able to generate the anti-Markovnikov vinyl esters with Z-stereochemistry [136]. In related work, rhodium catalysts were also able to promote the addition reaction to regioselectively generate the anti-Markovnikov vinyl esters with Z-stereochemistry (Scheme 2.96) [141]. A wide range of carboxylic acids and a number of alkylalkynes were used in this chemistry. Curiously, phenylacetylene was unable to be converted into the vinyl ester following this approach. Additionally internal alkynes were also unresponsive under the reaction conditions. 

Metal-catalyzed oxidative addition of nitrogen nucleophiles such as amines and amides to olefins represents a straightforward atom economical approach for the preparation of enamines and enamides, respectively. These aminatimi processes may proceed with Markovnikov or anti-Markovnikov regioselectivity and in the latter case such products can be obtained as either or Z isomers (Scheme 1). Therefore, the ability of the catalyst to control that regiochemistry and stereoselectivity constitutes a chaUenging issue for synthetic chemists. 

Even in the absence of catalyst, thiols add to alkynes under neutral conditions to afford a f -Markovnikov-type vinyhc sulfides with excellent regioselectivity usually as a stereoisomeric mixture. Indeed, the reaction of benzenethiol with 1-octyne in the absence of transition metal catalyst provides a t/-Markovnikov adduct 4a regioselectively with the E Z ratio of ca. 1 1. This hydrothiolation takes place, most probably via the radical process induced by trace amounts of oxygen existed in the reaction system. The radical addition of thiols to alkynes sometimes seems to proceed even in the presence of transition metal catalysts. Accordingly, when the a f -Markovnikov adducts are obtained with approximately equal amounts of E- and Z-isomers, the following possibility is present the anti-Markovnikov adducts are formed by the radical process, regardless of the presence of transition metal catalysts. 

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