Metal-catalyzed hydroborations

In 1985, Mannig and Noth reported the discovery that Wilkinson s catalyst ([RhlPPhjljCl]) is an effective catalyst for hydroboration of alkenes with catecholborane, a reaction that otherwise requires elevated temperatures [32], Extensive subsequent studies on metal-catalyzed hydroborations [8, 11, 33-35] revealed a range of Interesting results. Firstly, hydroboration of cyclohex-2-enols affords regioisomeric products that are complementary to those isolated from the uncatalyzed reaction with 9-BBN (Equation 2) [33, 34). Secondly, the hydroboration of 91 with 9-BBN affords anti product 93, but the Rh-catalyzed reaction leads to preferential formation of syn product 92. This feature of the metal-catalyzed process was used by Evans in the stereoselective synthesis of polyketide building blocks 92 and 93 (Equation 3) [33]. 

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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. 

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). 

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. 

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). 

An important aspect of the metal catalyzed hydroboration reaction is its ability to selectively reduce certain functionalities within a molecule. For instance, a key step in the synthesis of a tripeptide derivative containing the Phe-Arg hydroxyethy-lene dipeptide iosostere is the selective rhodium-catalyzed hydroboration of a lactone. The use of disiamylborane, 9-H-BBN, dicyclohexylborane, and (.9)-alpmeborane, however, gave only low to variable yields of the alcohol due to competitive reduction of the y-lactone to the hemiacetal (equation 8). In another example, hydroboration of the diene illustrated in equation (9) with HBcat and RhCl(PPh3)3 gave exclusive formation of the terminal alcohol derived from reaction of the less substituted alkene. Interestingly, uncatalyzed reactions failed to hydroborate this substrate selectively. ... 

In summary, the potential utility of the metal catalyzed hydroboration reaction is vast. Future work will focus on its applicability in the synthesis of biologically active compounds where conventional electrophihc additions have proven ineffective. Convenience and mild conditions required for these reactions provide the organic chemist with a valuable synthetic tool. 

In metal-catalyzed hydroborations, the addition is controlled by the catalyst and may result in different regio- and stereoselectivity compared to the uncatalyzed process. This has been observed for additions to styrenes30, allylic alcohols, and amines31,32. However, these directive effects are not yet fully understood33. 

Herein, we report on a novel process for the synthesis of organomodlfied polydimethylsiloxanes employing ionic liquids for the heterogenization and/or immobilization of the precious metal catalyst [13]. The advantage of this novel hydrosilylation process is that standard hydrosilylation catalysts can be used without the need for prior modification to prevent catalyst leaching. To the best of our knowledge, this is the first example of a hydrosilylation of olefmic compounds using ionic liquids (Scheme 1). However, a method for the transition metal-catalyzed hydroboration and hydrosilylation of alkynes in ionic liquids has recently been described [14]. 

Fu, G. C. Metal-catalyzed hydroboration reactions, in Transition Metals for Organic Synthesis (eds. Beller, M.,Bolm, C.), 2, 141-146 (Wiley-VCH, Weinheim, New York, 1998). 

The regio- and stereoselectivity of metal-catalyzed hydroboration reactions may differ from that of the uncatalyzed reaction23 25. 

Although group 5 organometallic systems have been found to be of relevance in transition-metal catalyzed hydroboration reactions, structurally authenticated group 5 boryl complexes remain relatively few in number. Smith and co-workers, for example, have probed the mechanisms for the formation of niobium and tantalum mono- and bis(boryls) from propylene complex precursors, with concomitant formation of propyl boronate esters [31,32]. Of particular interest from a structural viewpoint are the relative merits of alternative bonding descriptions for metal(V) boryl bis(hydrides) as borohydride complexes or as mono(hydride) a-borane systems [31-34]. 

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