Hydroboration steric effects

The hydroboration step, being very sensitive to steric effects, yields only secondary alkylboranes from trisubstituted double bonds, whereas the less hindered alkylborane is formed predominantly from disubstituted steroidal double bonds. The diborane attack occurs usually towards the a-side and hence results in overall a-hydration of double bonds after alkaline hydrogen peroxide oxidation. ... 

Although alkyl groups in general increase the rates of electrophilic addition, we have already mentioned (p. 974) that there is a different pattern depending on whether the intermediate is a bridged ion or an open carbocation. For brominations and other electrophilic additions in which the first step of the mechanism is rate determining, the rates for substituted alkenes correlate well with the ionization potentials of the alkenes, which means that steric effects are not important. Where the second step is rate determining [e.g., oxymercuration (15-3), hydroboration (15-17)], steric effects are important. ... 

The differences in the steric effect between catecholborane and pinacolborane, and the valence effect between a cationic or neutral rhodium complex reverse the re-gioselechvity for fluoroalkenes (Scheme 1-4) [26]. The reaction affords one of two possible isomers with excellent regioselectivity by selecting borane and the catalyst appropriately, whereas the uncatalyzed reaction of 9-BBN or SiaiBH failed to yield the hydroboration products because of the low nucleophilicity of fluoroalkenes. The regiochemical preference is consistent with the selectivity that is observed in the hydroboration of styrene. Thus, the internal products are selectively obtained when using a cationic rhodium and small catecholborane while bulky pinacolborane yields terminal products in the presence of a neutral rhodium catalyst. 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

The syntheses in Schemes 13.45 and 13.46 illustrate the use of oxazolidinone chiral auxiliaries in enantioselective synthesis. Step A in Scheme 13.45 established the configuration at the carbon that becomes C(4) in the product. This is an enolate alkylation in which the steric effect of the oxazolidinone chiral auxiliary directs the approach of the alkylating group. Step C also used the oxazolidinone structure. In this case, the enol borinate is formed and condensed with an aldehyde intermediate. This stereoselective aldol addition established the configuration at C(2) and C(3). The configuration at the final stereocenter at C(6) was established by the hydroboration in Step D. The selectivity for the desired stereoisomer was 85 15. Stereoselectivity in the same sense has been observed for a number of other 2-methylalkenes in which the remainder of the alkene constitutes a relatively bulky group.28 A TS such as 45-A can rationalize this result. 

Electronic effects can also play a part in determining which face is attacked. In the adamantane derivative 17 steric effects are about the same for each face of the double bond. Yet epoxidation, dibromocarbene attack (5-50), and hydroboration (5-12) all predominantly... 

It is clear from these representative results that regioselectivity in hydroboration is controlled by steric effects. As a result, nonsymmetric internal olefins usually yield a mixture of regioisomeric alkylboranes when they react with borane. Several hindered mono- and diakylboranes with sterically demanding alkyl groups, however, have been developed for use in selective hydroboration. Disiamylborane [bis(3-methyl-2-butyl)borane, 34], thexylborane (2,3-dimethyl-2-butylborane, 35), and 9-BBN (9-borabicyclo[3.3.1]nonane) are the most frequently used reagents. Improvements of regioselectivities in hydroboration of both... 

As we have seen, the hydroboration reaction is very sensitive to steric effects. The chiral borane approaches the alkene in such a manner as to minimize steric interactions. As shown in 0, the transition state that leads to (S)-2-butanol has fewer, steric interactions than the transition state in that leads to (/ )-2-butanol. The overall selectivity of the reaction is very high the product is almost entirely the (S)-cnantiomer. Note that, to be successful in producing a single enantiomer of the product, the borane must be enantiomerically pure. Any of the (.S, .S )-cnantiomer that is present in the borane will result in the formation of an equal amount of the other enantiomer of 2-butanol, the (/O-enantiomer in this case. 

Asymmetric olefins, which carry more alkyl substituents at the Ce center than at the Ca center, are also hydroborated by the unhindered BH3 with considerable regioselectivity (Table 3.1). After oxidative workup, one isolates the alcohol in the a position almost exclusively. According to what has already been stated, as the more bulky reagent, 9-BBN reacts with more sensitivity to steric effects than BH3 and its secondary products. It therefore makes possible olefin hydrations with almost perfect regiocontrol. 

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