Metal-catalyzed hydroboration

Scheme 25 Transition metal catalyzed hydroboration of 1,3-dienes...

The field of transition metal-catalyzed hydroboration has developed enormously over the last 20 years and is now one of the most powerful techniques for the transformation of C=C and C=C bonds.1-3 While hydroboration is possible in the absence of a metal catalyst, some of the more common borane reagents attached to heteroatom groups (e.g., catecholborane or HBcat, (1)) react only very slowly at room temperature (Scheme 1) addition of a metal catalyst M] accelerates the reaction. In addition, the ability to manipulate [M] through the judicious choice of ligands (both achiral and chiral) allows the regio-, chemo-, and enantioselectivity to be directed. 

Wilkinson s catalyst has also been utilized for the hydroboration of other alkenes. Sulfone derivatives of allyl alcohol can be hydroborated with HBcat and subsequently oxidized to give the secondary rather than primary alcohol. This reactivity proves to be independent of substituents on the sulfur atom.36 Similarly, thioalkenes undergo anti-Markovnikoff addition to afford a-thioboronate esters.37 The benefits of metal-catalyzed reactions come to the fore in the hydroboration of bromoalkenes (higher yields, shorter reaction times), although the benefits were less clear for the corresponding chloroalkenes (Table 3).38,39 Dienes can be hydroborated using both rhodium and palladium catalysts [Pd(PPh3)4] reacts readily with 1,3-dienes, but cyclic dienes are more active towards [Rh4(CO)i2].40... 

Burgess, K. Ohlmeyer, M. J. Stereocontrol in Catalysed and Uncatalysed Hydroborations. In Homogeneous Transition Metal Catalyzed Reactions Moser, W. R. Slocum, D. W., Eds. Advances in Chemistry Series 230 American Chemical Society Washington DC, 1992 pp 163-177. 

This chapter has been organized into three sections. The first section deals with transition metal-catalyzed hydroboration in organic synthesis and this is divided into three subsections - mechanism, chemoselectivity, and stereoselectivity. The second section deals with the application of transition metal-catalyzed hydroalumination reactions in organic synthesis, and this is also divided into three subsections - mechanism, chemoselectivity, and stereoselectivity. The third section examines the application of both hydroborations and hydroaluminations in total synthesis. 

This landmark discovery paved the way for the development of transition metal-catalyzed hydroboration. The conversion of an alkene into an organoborane intermediate has made this a valuable synthetic technique, particularly since the development of enantioselective variants.9,10 They serve as synthons for numerous functional groups11 and are often subjected to a consecutive carbon-oxygen, carbon-carbon, boron-carbon, boron-chlorine, or carbon-nitrogen24 bond-forming reaction (Scheme 3). 

Shortly after the key mechanistic papers on rhodium-catalyzed hydroboration, Marks reported a hydroboration reaction catalyzed by lanthanide complexes that proceeds by a completely different mechanism.63 Simple lanthanide salts such as Sml3 were also shown to catalyze the hydroboration of a range of olefins.64 The mechanism for this reaction was found to be complex and unknown. As in other reactions catalyzed by lanthanides, it is proposed that the entire catalytic cycle takes place without any changes in oxidation state on the central metal. 

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... 

Among the hydrometallations reported to date, hydroboration and hydrosilylation have been the most widely investigated while hydroalumination has received less attention. The resulting organoalanes from hydroalumination are often more reactive than the organoboranes or organosilanes. While the first metal-catalyzed hydroalumination... 

Among recent examples that highlight the synthetic utility of transition metal-catalyzed hydroborations are its direction toward a formal syntheses of the non-steroidal anti-inflammatory agents Ibuprofen 131 and Naproxen 13214 15 139 as well as the anti-depressant Sertraline 133 (Figure 14).140 In the majority of cases, rhodium-catalyzed hydroboration is utilized and the rhodium(i) source generally is Wilkinson s catalyst RhCl(PPh3)3. 

While transition metal-catalyzed hydroboration is a well-established reaction, the same cannot be said for the transition metal-catalyzed hydroalumination. The synthetic utility of this reaction is only just beginning to emerge. Lautens has led the way in the use of hydroaluminations as the key step in the total synthesis of complex natural products. The synthesis of the anti-depressant sertraline130 involved the formation of the tetrahydronaphthalene core, and this is best achieved using the nickel-catalyzed hydroalumination of oxabicyclic alkenes (Table 16). 

In conclusion it is evident from the foregoing examples that transition metal-catalyzed hydroborations and hydroaluminations occupy an important role in organic synthesis. While rhodium-catalyzed hydroboration has been extensively developed, the hydroalumination is just starting to emerge as a useful reaction in organic synthesis. 

As mentioned in the introduction, early transition metal complexes are also able to catalyze hydroboration reactions. Reported examples include mainly metallocene complexes of lanthanide, titanium and niobium metals [8, 15, 29]. Unlike the Wilkinson catalysts, these early transition metal catalysts have been reported to give exclusively anti-Markonikov products. The unique feature in giving exclusively anti-Markonikov products has been attributed to the different reaction mechanism associated with these catalysts. The hydroboration reactions catalyzed by these early transition metal complexes are believed to proceed with a o-bond metathesis mechanism (Figure 2). In contrast to the associative and dissociative mechanisms discussed for the Wilkinson catalysts in which HBR2 is oxidatively added to the metal center, the reaction mechanism associated with the early transition metal complexes involves a a-bond metathesis step between the coordinated olefin ligand and the incoming borane (Figure 2). The preference for a o-bond metathesis instead of an oxidative addition can be traced to the difficulty of further oxidation at the metal center because early transition metals have fewer d electrons. 

In this chapter, theoretical studies on various transition metal catalyzed boration reactions have been summarized. The hydroboration of olefins catalyzed by the Wilkinson catalyst was studied most. The oxidative addition of borane to the Rh metal center is commonly believed to be the first step followed by the coordination of olefin. The extensive calculations on the experimentally proposed associative and dissociative reaction pathways do not yield a definitive conclusion on which pathway is preferred. Clearly, the reaction mechanism is a complicated one. It is believed that the properties of the substrate and the nature of ligands in the catalyst together with temperature and solvent affect the reaction pathways significantly. Early transition metal catalyzed hydroboration is believed to involve a G-bond metathesis process because of the difficulty in having an oxidative addition reaction due to less available metal d electrons. 

Boronic esters have been used in a wide range of transformations. These useful reagents have been transformed into numerous functional groups and are essential reagents for several C-C bond-forming reactions. Transition metal-catalyzed hydroboration of olefins often leads to mixtures of branched and linear products. Several groups have reported asymmetric reductions of vinyl boronic esters [50-52] with chiral rhodium P,P complexes however, the first iridium-catalyzed reduction was reported by Paptchikhine et al (Scheme 10) [53]. 

It is a striking feature of metal-catalyzed hydroboration that alkoxyboranes are more effective than borane or its alkyl derivatives. Analysis of the electronic features of the two classical reagents, catecholborane and 9-BBN, reveal only modest differences in the B-H region (Fig. 2.3). This by itself does not explain the narrow convergence of... 

Transition-metal-catalyzed hydroboration, a reduction using B H bonds, of styrene derivatives has been demonstrated to occur in supercritical carbon dioxide using tunable Rh(I) complexes as catalysts. In the case of vinyl anisole (eq. 2.5), significantly higher regioselectivities were reported for the reaction in this medium than in THF or perfluoro(methylcyclohexane) (Carter et ah, 2000). 

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