Chemoselective reactions hydroboration

Arylboranes, ArBH2 and Ar2BH, have been studied as an alternative to alkylboranes in order to avoid potential problems related to retrohydroboration reactions. Moreover, fiuther stabilization may be readily achieved by 2,6-disubstitution on the phenyl ring. Smith and Pel ter reported the synthesis and properties of mesitylborane (9) and tripylborane (10). Mesitylborane (9), which is obtained from Mes2BH (11) and BH3 THF, shows not only better stability in solution compared to thexylborane (2), but also exhibits very high regio- and chemoselectivity in hydroboration reactions. Polymer-supported versions of these arylboranes have been developed. ... 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

In terms of scope and chemoselectivity, hydrozirconation takes its place between hydroboration and hydroaiumination. However, the synthetic applications of organozirconocene complexes have been considerably expanded over these last few decades, and it can be expected that they will become more and more attractive in the future. Beside the direct substitution sequences, indirect reaction pathways involving transmetalation or activation by ligand abstraction have been successfully applied in a number of cross-coupling and C-C bond-forming reactions. 

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. 

The normal synthetic pathway for hydroboration is reaction with an ambiphilic nucleophile of which the simplest example is hydroperoxide ion. This elicits a 1,2-migration of an alkyl group from boron to oxygen with concurrent loss of hydroxide ion. The step occurs with essentially complete retention of configuration. In similar vein, ambiphilic species with the structure NH2X may be used in amination, so that the overall reaction is an addition of ammonia to the alkene with the regio- and chemoselectivity driven by the hydroboration step. A majority of reactions of organoboranes can be rationalized in terms of these ionic mechanistic pathways, or closely related protocols (Scheme 2). 

The hydroboration-coupling approach for the construction of carbon skeletons affords several advantages [139]. The high stereoselectivity of the hydroboration reaction provides a stereodefined alkyl center on boron. For instance, in the reaction shown in Scheme 2-49, the hydroboration occurs chemoselectively at the less hindered C(19)-C(20) double bond. In addition, the alkylboron group thus constructed can be readily cross-coupled with alkenyl or aryl halides under mild conditions. 

Remarkably, cross-couplings of alkyl boranes with alkyl bromides or even chlorides are possible using the catalyst [Pd2(dba)3] and the ligand tricyclohexylphos-phine, PCys (Cy = CeHn). For example, the alkyl chloride 203 was coupled to the alkyl borane 204 (prepared by chemoselective hydroboration with 9-BBN see Section 5.1) to give the product 205 (1.206). The [Pd2(dba)3]/PCy3 catalyst system overcomes the normally slow oxidative addition of the alkyl halide to the palladium and promotes cross-coupling to alkyl boranes in preference to p-hydride elimination. Such B-alkyl Suzuki reactions are likely to be used as key carbon-carbon bond-forming reactions in future synthetic sequences. 

The hydroboration of olefins is a classic reaction in organic synthesis. - Dialkylbo-ranes add rapidly to alkenes in the absence of catalyst. However, dialkoxyboranes, such as catecholborane and pinacolborane, add more slowly to olefins and alkynes. Thus, transition metal complexes could catalyze the addition of dialkoxyboranes to olefins and alkynes without interference from the background reaction. The potential to alter chemoselectivity, regioselectivity, enantioselectivity, and diastereoselectivity has led a munber of groups to develop metal-catalyzed versions of hydroboration. " Enantioselective hydroboration would alleviate the need to use boranes containing stoichiometric amounts of chiral substituents to generate optically active alkylboranes. 

The first examples of catalytic hydroborations were reported in the 1980s. Sneddon published a series of papers on the additions of the B-H bonds in boron clusters to alk5mes catalyzed by transition metal complexes. " An example of these processes is shown in Equation 16.42. These reactions provided precursors to new boron cages and to boron-carbide materials. In 1985, Noth published the hydroboration of olefins with catecholborane catalyzed by Wilkinson s catalyst. One example of this process (Equation 16.43) shows the difference in chemoselectivity between the catalyzed and uncatalyzed processes. This report by Noth led to the development of catalytic hydroboration as a method for organic synthesis. Studies on both early and late transition metal catalysts have been conducted, and these studies included experiments to probe for differences in selectivities between catalyzed and uncatalyzed processes. 

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