Hydroboration dialkylboranes

Mono- and diaLkylboranes obtained by controlled hydroboration of hindered olefins and by other methods can serve as valuable hydroborating agents for more reactive olefins. Heterosubstituted boranes are also available and used for this purpose. These borane derivatives show differences in reactivity and selectivity. 

A number of less hindered monoalkylboranes is available by indirect methods, eg, by treatment of a thexylborane—amine complex with an olefin (69), the reduction of monohalogenoboranes or esters of boronic acids with metal hydrides (70—72), the redistribution of dialkylboranes with borane (64) or the displacement of an alkene from a dialkylborane by the addition of a tertiary amine (73). To avoid redistribution, monoalkylboranes are best used /V situ or freshly prepared. However, they can be stored as monoalkylborohydrides or complexes with tertiary amines. The free monoalkylboranes can be hberated from these derivatives when required (69,74—76). Methylborane, a remarkably unhindered monoalkylborane, exhibits extraordinary hydroboration characteristics. It hydroborates hindered and even unhindered olefins to give sequentially alkylmethyl- and dialkylmethylboranes (77—80). 

Primary dialkylboranes react readily with most alkenes at ambient temperatures and dihydroborate terminal acetylenes. However, these unhindered dialkylboranes exist in equiUbtium with mono- and ttialkylboranes and cannot be prepared in a state of high purity by the reaction of two equivalents of an alkene with borane (35—38). Nevertheless, such mixtures can be used for hydroboration if the products are acceptable for further transformations or can be separated (90). When pure primary dialkylboranes are required they are best prepared by the reduction of dialkylhalogenoboranes with metal hydrides (91—93). To avoid redistribution they must be used immediately or be stabilized as amine complexes or converted into dialkylborohydtides. 

Borabicyclo [3.3.1] nonane [280-64-8], 9-BBN (13) is the most versatile hydroborating agent among dialkylboranes. It is commercially available or can be conveniendy prepared by the hydroboration of 1,5-cyclooctadiene with borane, followed by thermal isomerization of the mixture of isomeric bicychc boranes initially formed (57,109). 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

Another example of great synthetic interest, involves the hydroboration reaction of alkenes [62], In general, the addition of borane to alkenes proceeds stepwise, the final product being the trialkylborane. However, hindered alkenes react slowly, especially when the dialkylborane precipitates from the medium. It was found that trialkyl bor-anes could be obtained rapidly under sonication, even with highly hindered substrates (Eq. 3.5). Applications of this useful modification were published, among which were the reduction-hydroxylation of vinyl groups by 9-BBN [63,64]. 

Since the olefin is hydroborated to the dialkylborane stage (RgBH), a large amount of hydrogen is evolved on hydrolysis. Consequently, the addition of water should be carried out slowly (dropwise) and adequate ventilation is recommended. 

Hydroboration-oxidation of alkynes preparation of aldehydes and ketones Hydroboration-oxidation of terminal alkynes gives syn addition of water across the triple bond. The reaction is regioselective and follows anti-Markovnikov addition. Terminal alkynes are converted to aldehydes, and all other alkynes are converted to ketones. A sterically hindered dialkylborane must be used to prevent the addition of two borane molecules. A vinyl borane is produced with anU-Markovnikov orientation, which is oxidized by basic hydrogen peroxide to an enol. This enol tautomerizes readily to the more stable keto form. 

Exercise 11-10 What products would you expect from hydroboration of the following alkenes with a dialkylborane, R2BH, followed by isomerization at 160° ... 

In the hydroboration/oxidation reaction of 2-cyclohexen-l-ol derivatives the regio- as well as the stereoselectivities can be steered in either of two directions by use of different reagents and reaction conditions. Dialkylboranes, e.g., 9-BBN, give mainly tn rs-l,2-diols, whereas with 1,3,2-benzodioxaborole ( catecholborane") in the presence of the rhodium hydrogenation catalyst Rh(PPh3)jCl the trans-1,3-diols become predominant. The cis- 1,2-diols are usually only formed in trace amounts, but the cis-l,3-diols are always produced as byproducts in 10 — 20% yield (D.A. Evans, 1988). 

The hydroboration of a trisubstituted olefin, exemplified by the reaction of 2-methyl-2-butene with diborane, is conveniently stopped at the dialkylborane stage to produce disiamyl-borane. As a result of its rather large steric requirements this... 

Simultaneously with Tilley, we studied the hydroboration of diphenyl (vinyl)phosphine with dialkylboranes (Scheme 29). 54,55 The reactions can be conducted in toluene as well as THF, and required a slightly elevated temperature for 9-H-BBN (60 °C) compared to Cy2BH (room temperature). PBs 40e and 40f were obtained in near quantitative yields as extremely hygroscopic white solids. The P-B adducts [(vinyl)Ph2P-BHR2] are likely intermediates in these hydroboration reactions. The 31P and rlB NMR data substantiate monomeric open structures for both 40e and 40f in solution. 

With increasing steric hindrance around the double bond, the second and third hydroboration steps become increasingly sluggish and so, for example, hydroboration of cyclohexene with H3B.THF may be stopped at the dialkylborane stage, and hydroboration of 1,2-dimethyIcyclopentene with H3B.THF does not proceed beyond the monoalkylborane. 

Borane transforms a wide range of alkenes into trialkylboranes under mild conditions but the trifunctional nature of borane and its trialkylborane products imposes some limitations on its use. Many of the synthetically useful reactions of the trialkylboranes (see Chapters B.2 and B.3) use all three alkyl substituents, but some reactions only utilize either two or even one of the alkyl substituents. This sets a maximum yield (based on the alkene starting material) for these latter transformations of 66% and 33% respectively which is clearly undesirable especially if the alkene involved is the product of a multi-step synthetic sequence. To overcome this problem, and others such as the production of intractable polymers on addition of borane to dienes and alkynes, monoalkylborane and dialkylborane hydroborating reagents were introduced. Some commonly used reagents are depicted in Figure B 1.2 and two are described in more detail below. 

Addition of H3B.THF to 1,5-cyclooctadiene gives a mixture of 9-borabicyclo[4.2.1]nonane and 9-borabicyclo[3.3.1]nonane. On heating, the [4.2.1] system isomerizes to the thermodynamically more stable [3.3.1] compound which is known as 9-BBN (Equation B1.12). As 9-BBN is crystalline, relatively stable to air and heat, and is available from commercial sources, this dialkylborane is a popular hydroborating agent. 

Bisdiborane, B-C-B, compounds are usually prepared by double hydroboration of terminal alkynes with dialkylboranes.93 95 They are... 

Transfers of hydride from boron or lithium to carbon usually occur in the context of addition of the complete M—H moiety to polar or non-polar unsaturation. Additions of boranes to alkenes have been extensively reviewed (Brown et al., 1983a), but the experimental characterization of the hydroboration transition state remains problematic. Dialkylboranes, including 9-borabicyclo[3.3.1]nonane (Wang and Brown, 1980), borinane (Brown et al., 1984), and disiamylborane (Chandrasekharan and Brown, 1985) have now been shown to be dimeric in hydrocarbon and ethereal solvents. With unreactive alkenes, their additions are first order in alkene and half order in the dimer. With reactive terminal alkenes, the reactions are first order only in dimer, with intermediate behaviour between these extremes. A reaction scheme (10) involving reaction of monomeric borane with the alkene satisfies the data, with the observed order depending on the ratio k i/k2. 

The hydroboration of unsymmetrical alkenes thus gives monoalkylboranes (addition of H—BH2), dialkylboranes (addition of H—BHR), or trialkylboranes (addition of H—BR2), which are typical anti-Markovnikov products. Therefore, the reaction sequence hydrobora-tion/oxidation/hydrolysis brings about the anti-Markovnikov addition of H20 to unsymmetrically substituted alkenes. 

The conclusion drawn from Section 3.4.1 for the hydroborations to be discussed here is this an addition reaction of an enantiomerically pure chiral reagent to a C=X double bond with enantiotopic faces can take place via two transition states that are diastereotopic and thus generally different from one another in energy. In agreement with this statement, there are diastereoselective additions of enantiomerically pure mono- or dialkylboranes to C=C double bonds that possess enantiotopic faces. Consequently, when one subsequently oxidizes all C— B bonds to C—OH bonds, one has realized an enantioselective hydration of the respective alkene. 

During the addition of a racemic chiral dialkylborane to a racemic chiral alkene a maximum of four diastereomeric racemic trialkylboranes can be produced. Figure 3.31 illustrates this using the example of the hydroboration of 3-ethyl-l-methylcyclohexene with the cyclic borane from Figure 3.30. This hydroboration, however, has not been carried out experimentally. This should not prevent us from considering what would happen if it were performed. 

Thought Experiment IV on the Hydroboration of Chiral Olefins with Chiral Dialkylboranes Kinetic Resolution... 

If the hydroboration reaction is to be used to convert 1-alkynes into aldehydes, some way to stop the addition at the vinylborane stage is needed. The problem is that there is not enough steric hindrance at the end carbon of the vinylborane. The solution is to build extra steric hindrance into the other alkyl groups attached to the boron of the vinylborane. A borane, R2BH, with two bulky R groups already attached to the boron is used as the hydroboration reagent. One such reagent is prepared by the reaction of two equivalents of 2-methyl-2-butene (also known by the common name of isoamylene) with borane to produce a dialkylborane called di si amyl borane (a shortened version of diisoamylborane) ... 

Fig. 3.15. Synthesis of monoalkyl- and dialkylboranes through incomplete hydroboration of multiply substituted C=C double bonds.

Alkenylboronic acids and esters have been prepared by thermal or catalyzed hydroboration of 1-alkynes with catecholborane (HBcat), pinacolborane (HBpin), or dihaloboranes 41-43, followed by hydrolysis to boronic acids or alcoholysis to boronic esters. A convenient alternative to improve chemo- and regioselectivity is the hydroboration of alkynes with dialkylboranes. For selective removal of dummy groups, the oxidation of two cyclohexyl groups was conduced by treatment of l-alkenyl(dicyclohexyl)borane intermediates with Me3N-0 (Equation (7)).116 The... 

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