Hydroboration of 1-alkenes

Hydroboration was discovered by Professor Herbert C. Brown (1912-2004). This reaction is so useful in synthesis that Brown s work earned him a Nobel Prize in 1979. We will describe here only one practical example of hydroboration, a two-step alcohol synthesis from alkenes. 

Hydroboration involves addition of a hydrogen-boron bond to an aikene. From 

it resembles a normal electrophilic addition to an aikene, following Markovnikov s Rule, even though the addition is concerted (that is, all bond-breaking and bond-making occur in one step). 

Because it has three B—H bonds, one molecule of borane, BH3, can react with three molecules of an aikene. For example, propene gives tri-n-propylborane. 

The trialkylboranes made in this way are usually not isolated but are treated with some other reagent to obtain the desired final product For example, trialkylboranes can be oxidized by hydrogen peroxide and base to give alcohols. 

We have seen two methods for hydrating an alkene with to kovnikov orientatioa What if we need to convert an alkene to the anti-Markovnikov alcohol For example, the following transformation cannot be accomplished using the hydration procedures covered thus far. 

Such an anti-Markovnikov hydration was impossible until R C. Brown, of Purdue University, discovered that diborane (B2H6) adds to alkenes with anti-Markovnikov orientation to form alkylboranes, which can be oxidized to give anti-Markovnikov alcohols. This discovery led to the development of a large field of borane chemistry, for which Brown received the Nobel Prize in chemistry in 1979. 

Diborane (B2H6) is a dimer composed of two molecules of borane (BH3). The bonding in diborane is unconventional, using three-centered (banana-shaped) bonds with protons in the middle of them. Diborane is in equilibrium with a small amount of borane (BH3), a strong Lewis acid with only six valence electrons. 

Diborane is an inconvenient reagent. It is a toxic, flammable, and explosive gas. It is more easily used as a complex with tetrahydrofuran (THF), a cyclic ether. This complex reacts like diborane, yet the solution is easily measured and transferred. 

The BH3 THF reagent is the form of borane commonly used in organic reactions. BH3 adds to the double bond of an alkene to give an alkylborane. Basic hydrogen peroxide oxidizes the alkylborane to an alcohol. In effect, hydroboration-oxidation converts alkenes to alcohols by adding water across the double bond, with anti-Markovnikov orientation. 

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BH3 SMe2, CH2CI2, 0°, 1 h, then BF3, 5 min. Simple benzylidene acetals are cleaved efficiently without hydroboration of alkenes that may be present, and acetonides are converted to the hydroxy isopropyl ethers. 

Other convenient routes to carboranes, selected from the growing number of recently reported syntheses, are as follows. Monocarbon carboranes can be prepared in good yield by the transition-metal catalysed hydroboration of alkenes followed by thermal rearrangement of the intermediate product, c.gP" ... 

Organoboranes react with a mixture of aqueous NH3 and NaOCl to produce primary amines. It is likely that the actual reagent is chloramine NH2CI. Chloramine itself,hydroxylamine-O-sulfonic acid in diglyme, and trimethyl-silyl azide " also give the reaction. Since the boranes can be prepared by the hydroboration of alkenes (15-16), this is an indirect method for the addition of NH3 to a double bond with anti-Markovnikov orientation. Secondary amines can be prepared by the treatment of alkyl- or aryldichloroboranes or dialkylchlorobor-anes with alkyl or aryl azides. 

Hydroboration of alkenes or alkynes followed by cross-coupling with organic electrophiles provides a straightforward method for the carbon-carbon bond formation (Scheme 1-19). The hydroboration of thioalkynes with catecholborane in the presence of a nickel or palladium catalyst yields P-(aLkylthio)-l-alkenylboronates (72a)... 

Hydroboration of alkenes with chiral hydroboration reagents such as di-isopinocamphenylborane succeeds in various syntheses of chiral organoboron com-... 

The reactions can be made enantioselective by using enantiomerically pure IpcBH2 for hydroboration of alkenes and then transforming the products to enantiomerically pure derivatives of 9-BBN by reaction with 1,5-cyclooctadiene.22... 

The formation of vinylboranes and vinylboronate esters during some metal-promoted hydroboration of alkenes has led to the suggestion of an alternative mechanistic pathway. Insertion of the alkene into the metal-boron bond occurs in preference to insertion into the metal-hydride bond.44,51,52 In a competing side-reaction to reductive elimination, f3-H elimination from the resulting borylalkyl intermediate furnishes the vinylborane byproduct.52 There remains however a substantial body of evidence, both experimental53 and theoretical,54 that supports the idea that transfer of hydride to the coordinated alkene precedes transfer of the boryl fragment. 

Hartwig65 reported that dimethyltitanocene is an efficient catalyst for the hydroboration of alkenes and examined the mechanism of titanocene dicarbonyl-catalyzed the hydroboration of alkynes (Scheme 5).66... 

Scheme 4.S8. Zirconium- and rhodium-catalyzed hydroborations of alkenes and alkynes with pinacolborane.

In total, over the past six years, the chelating P,N-ligands have shown considerable promise in a variety of enantioselective processes, including transfer-hydrogenation and hydrosilylation of ketones, hydroboration of alkenes, conjugate addition to enones and Lewis-acid catalysed Diels-Alder reactions, in addition to those described above.128,341 It is anticipated that this list will continue to grow, and... 

B-alkylcatecholboranes, prepared by rhodium(I)-catalyzed hydroboration of alkenes, are suitable radical precursors for conjugate addition to activated olefins. This procedure is particularly useful for the control of the regio- and... 

Hydroboration of alkenes generates organoboranes, which react with sodium azide in the presence of an aqueous acid to give primary amines (equation 58). Thus 1-nonene... 

Hydroboration of alkenes in non-ethereal solvent has been reported using diborane generated in situ from a quaternary ammonium borohydride and bromoethane (see Section 11.5). Almost quantitative yields of the alcohols are reported [e.g. 1 ]. As an alternative to the haloalkane, trimethylsilyl chloride has also been used in conjunction with the ammonium borohydride [2]. Reduction of the alkene to the alkane also occurs as a side reaction (<20%) and diphenylethyne is converted into 1,2-diphenylethanol (70%), via the intermediate /ra 5-stilbene. 

Phase-transfer generated diborane has been used for the hydroboration of alkenes and their conversion into alcohols [1,2] and the procedure has also been employed for the cleavage of formamido compounds to yield the amines [3]. Cyclododecan-1,3- and 1,4-diones have been obtained in a 3 1 ratio and overall yield of 59% via... 

We note that there are NMR-based kinetic studies on zirconocene-catalyzed pro-pene polymerization [32], Rh-catalyzed asymmetric hydrogenation of olefins [33], titanocene-catalyzed hydroboration of alkenes and alkynes [34], Pd-catalyzed olefin polymerizations [35], ethylene and CO copolymerization [36] and phosphine dissociation from a Ru-carbene metathesis catalyst [37], just to mention a few. 

While the introduction of aryl groups has been well documented, the use of alkylboronic acids to decorate the pyridazine core is hitherto not well explored. Wermuth and co-workers nicely showed that hydroboration of alkenes with 9-BBN followed by Suzuki coupling with 3-iodopyridazines 180 and 182 yielded the corresponding 3-alkylpyr-idazines 181 and 183 in good yield (Schemes 43 and 44) <2002SL1123>. 

Guided by Marks s report of the samarium-catalyzed hydroboration of alkenes, Molander has developed a samarium-catalyzed protocol for the cyclization/hydroboration of unfunctionalized 1,6-dienes. In an optimized procedure, reaction of 1,5-hexadiene and l,3-dimethyl-l,3-diaza-2-boracyclopentane catalyzed by Gp 2Sm(THF) in toluene at room temperature for 18 h followed by oxidation gave hydroxymethylcyclopentane in 86% yield (Equation (70) R = H, n — ). The transformation was stereoselective, and Sm-catalyzed cyclization/hydroboration of 2-phenyl-1,5-hexadiene followed by oxidation formed /ra/ i--l-hydroxymethyl-2-phenylcyclopentane in 64% yield (Equation (70) R = Ph, n = ). The samarium-catalyzed reactions was also applicable to the synthesis of hydroxymethylcyclohexanes (Equation (70), n=X) but tolerated neither polar functionality nor substitution on the alkenyl carbon atoms. 

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