Alkenes, cyclic from boranes

An alternative method of hydroboration is to use diisopinocampheylborane (12) (Scheme 4). This reaction is particularly useful for sterically hindered alkenes. Diisopinocampheylborane (12) is prepared from borane-dimethyl sulfide and (+)-pinene.[23-24] Treatment of 4-meth-ylenecyclohexanone ethylene ketal with diisopinocampheylborane (12) gives the borane 13.[25] Further treatment with 2 equivalents of an aldehyde results in the elimination of pinene and the formation of a new dialkyl boronate, e.g. treatment of 13 with acetaldehyde gives the diethyl cyclohexylmethylboronate 14J261 The dialkyl boronates thus produced can be transesterified with pinanediol to give 15[26] or with other cyclic diols. 

As is true for most reagents, there is a preference for approach of the borane from the less hindered face of the alkene. Because diborane itself is a relatively small molecule, the stereoselectivity is not high for unhindered alkenes. Table 4.4 gives some data comparing the direction of approach for three cyclic alkenes. The products in all cases result from syn addition, but the mixtures result from both the low regioselectivity and from addition to both faces of the double bond. Even 7,7-dimethylnorbornene shows only modest preference for endo addition with diborane. The selectivity is enhanced with the bulkier reagent 9-BBN. 

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. 

Figure 3.32 showed the reaction of our enantiomerically pure chiral cyclic dialkylborane with (Vi )-3-ethyl- l-methylcyclohexene. ft took place relatively slowly with the rate constant k6 The reaction of the same dialkylborane with the isomeric. S -alkene was shown in Figure 3.33. ft took place considerably faster with the rate constant ky The combination of the two reactions is shown in Figure 3.34. There the same enantiomerically pure borane is reacted simultaneously with both alkene enantiomers (i.e., the racemate). What is happening In the first moment of the reaction the R- and the 5-alkene react in the ratio k6 (small )/ 5 (big). The matched pair thus reacts faster than the mismatched pair. This means that at low conversions (< 50%) the trialkylborane produced is essentially derived from the 5-alkene only, ft has the stereostructure E. Therefore, relative to the main by-product F, compound E is produced...

Stereoselectivity in the hydroboration of asymmetric substrates is described in Section D.2.5.2.1.1. The organoborane products shown there are usually oxidized to the corresponding alcohols. In a similar manner to the symmetric substrates above, cyclic, asymmetric and functionalized alkenes, e.g., a-pinene24 and cholesterol2S, are attacked by borane and more selectively by substituted boranes from the less hindered side16-20-21 26-29. 

High selectivity is noted for relatively reactive internal alkenes (entries 3,5, and 6). Much lower selectivity is found for the more hindered trans isomers and in unstrained cyclic alkenes (entries 4,7, and 9). It is believed that this selectivity results from the more hindered alkenes reacting with a partially dealkylated, and therefore less bulky, borane. Terminal alkenes also show modest selectivity, probably because there is less steric bulk at the reaction site, and the diastereomeric transition states are therefore not very different energetically. Another reason for the diminished selectivity in terminal alkenes is that the chiral center is formed one atom further... 

While the four-center transition structure for BH3 addition is a widely used model, other reaction pathways have also been considered. In a synthesis of optically active (-)-l-butanol-l-d, Streitwieser and co-workers used the optically active borane formed from diborane and (-l- )-a-pinene (R2BH) to carry out the hydroboration-oxidation of (Z)-l-butene-l-d. To explain the observed stereochemistry of the reduction, they proposed that hydroboration involves a n complex between R2BH and the alkene (Figure 9.41). Note the close resemblance of such a complex to the cyclic structures... 

Thus, the regiochemistry of hydroboration is predicted by the same general rule that applies to all electrophilic additions to alkenes The reaction of an electrophile with a carbon-carbon double bond occurs preferentially via the transition state in which a partial positive charge develops on that carbon atom better able to accommodate it. Geometric constraints inherent in the cyclic transition state 60 require that the addition of borane to the alkene proceed so that both the boron and the hydrogen add from the same face of the double bond, a process called sy -addition. 

Oxidation of trialkylboranes with MoOgjHMPA followed by hydrolysis has been reported to give alcohols in 73—78 % yields, while oxidation of organo-boranes derived from cyclic alkenes with an excess of pyridinium chlorochromate provided ketones in yields of 81—92%, ... 

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