Hydroboration chemoselective

Many other examples ia the Hterature illustrate the possibiUties of chemoselective hydroborations (124,186—189). For example, selectivity between double and triple bonds has been shown (124). 

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. 

In Baldwin s formal total synthesis of haliclamines A and B, a Suzuki coupling of 3-bromopyridine was the central operation [52], Chemoselective hydroboration of diene 66 employing 9-BBN occurred at the less hindered terminal olefin. Suzuki coupling of the resulting alkylborane with 3-bromopyridine then furnished alkylpyridine 67 as a common intermediate for the synthesis of haliclamines A and B. 

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 high chemoselectivity of BHCl2 SMe2 was demonstrated in the selective reduction of azide group in the presence of an ester, halide, nitrile, and nitro group (Equation (257)).1073 The reduction of azides with BHCl2-SMe2 was faster than the hydroboration of alkenes. 

A practical synthesis of 1,3-OX AZEPINES VIA PHOTOISOMERIZATION OF HETERO AROMATIC V-OXIDES is illustrated for 3,1-BENZOXAZEPINE. A hydroboration procedure for the synthesis of PERHYDRO-9b-BORAPHENALENE AND PERHYDRO-9b-PHEN-ALENOL illustrates beautifully the power of this methodology in the construction of polycyclic substances. The conversion of LIMONENE TO p-MENTH-8-EN-YL METHYL ETHER demonstrates a regio-and chemoselective method for the PHOTOPROTONATION OF CYCLOALKENES. An efficient method for the conversion of a ketone to an olefin involves REDUCTIVE CLEAVAGE OF VINYL PHOSPHATES. A mild method for the conversion of a ketone into the corresponding trimethylsiloxy enol ether using trimethylsilyl acetate is shownforthe synthesis of (Z)-3-TRIMETHYLSILOXY-2-PENTENE. 

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. ... 

The availability of the Schwartz s reagent Cp2Zr(H)Cl (see Schwartz s Reagent) and its versatile behavior explain its extensive use in orgaiuc chemistry. The scope of hydrozirconation (see Hydrozirconation) with respect to both substrate structure and chemoselectivity lies somewhere between those of hydroboration (see Hydroboration) and hydroalumination. 

Cross-coupling between 1-alkenyl- and arylboron compounds with organic electrophiles have found wide application (see Sect. 1.5.1.1) in organic synthesis [125, 132, 269-271]. The value of this methodology is further realized with the use of alkylboranes, such as B-alkyl-9-borabicyclo[3.3.1]nonanes (B-R-9-BBN), which can be conveniently prepared Ijy hydroboration of olefins [272]. The hydroboration proceeds with high stereoselectivity and chemoselectivity. The choice of phosphines in a catalytic system sometimes affects the chemo- and regioselectivity of the hydroboration. Hydroboration of l-(ethylthio)-l-propyne with catecholborane can be satisfactorily carried out with PdClj (dppf) but the regioselectivity is best for the dppe and dppp complexes of Ni [273]. Notably, PPhj complexes perform poorly. 

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. 

Chemoselectivity. The rates of hydroboration of alkenes with dialkylboranes vary over a wide range. Thus, it is possible to selectively react one double bond in dienes, as shown in Table 5.2." Relative rates of hydroboration with dialkylboranes are as follows ... 

Thus, chemoselective hydroborations of the triple bond in various enynes have been achieved. A similar chemoselectivity is predicted for hydroborations with the slightly less hindered dicyclohexylborane. - ... 

A reversal of the chemoselectivity is observed when enynes are hydroborated using 9-BBN. 3... 

For the synthesis of trialkylboranes. hydroboration is carried out with a borane solution in THF or with the borane-methyl sulfide complex (BMS) in THF, diethyl ether, or dichloromethane. Diborane reacts rapidly and quantitatively with alkenes to produce a solution of trialkylborane [16] (eq (13)). The addition of dialkylboranes. such as 9-borabicyclo[3.3.1]nonane (9-BBN. 3). disiamylborane (1), or dicyclohexylb-orane (2), to alkenes or alkynes gives mixed alkylboron compounds. The high regio-. stereo-, or chemoselectivity in the additions of these borane reagents unsaturated C—C bonds have been extensively used in organic syntheses. 

A simple example is the oxidation of an alkene to a carboxylic acid 93 in Evans synthesis of cytovaricin. The alkene had been put in by allylation and the optically active unsaturated alcohol 90 was first protected 91 and then subjected to hydroboration and oxidation. Protection before the second alcohol appeared prevented impossible chemoselectivity problems.14... 

Alkenylzinc reagents. Hydroboration of pinacolatoborylalkynes with dicyclohexyl-borane affords 1,1-diboryl-l-alkenes. The dicyclohexylboryl group is selectively exchanged on treatment with Me2Zn, and the resulting species show differentiated chemoselectivity such that homologation/functionalization proceed in a desired manner. ... 

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