Alkene unsymmetrical, hydroboration

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

Thus, in unsymmetrical alkenes the hydroboration-oxidation sequence of reactions leads to the addition of the elements of H—OH to the original C=C in an anti-Markovnikov manner. 

Tripylborane is an interesting reagent which resembles thexylborane. One of the important uses of thexylborane lies in the synthesis of unsymmetrical thexyldialkylboranes which can then be used in the synthesis of unsymmetrical ketones. However, the reaction is only successful if the alkene used in the first hydroboration step is an internal alkene. Simple terminal alkenes such as 1-hexene react too rapidly with the initially formed thexylmonoalkylborane to allow the reaction to be stopped at that stage. Therefore, mixtures of products result (ref. 27). 

Alkylboranes can be coupled by treatment with silver nitrate and base." Since alkylboranes are easily prepared from alkenes (15-16), this is essentially a way of coupling and reducing alkenes in fact, alkenes can be hydroborated and coupled in the same flask. For symmetrical coupling (R = R ) yields range from 60 to 80% for terminal alkenes and from 35 to 50% for internal ones. Unsymmetrical coupling has also been carried out, but with lower yields. Arylboranes react similarly, yielding biaryls. The mechanism is probably of the free-radical type. 

The formation of unsymmetrical ketones can also be done starting with IpcBCl2. Sequential reduction and hydroboration are carried out with two different alkenes. The first reduction can be done with (CH3)3SiH, but the second stage requires LiAlH4. 

With unsymmetrical alkenes, hydroboration occurs so that boron becomes attached to the less-substituted end of the double bond ... 

The hydroboration of an olefin involves a cis addition of a boron-hydrogen bond to an alkene linkage, and for unsymmetric olefins occurs in a counter-Markownikoff fashion. 1-Alkenes and simple 1,2-disubstituted olefins undergo rapid conversion to the corresponding trialkylborane, whereas addition of diborane to tri- and tetrasubstituted olefins may be conveniently terminated at the respective di- and monoalkylborane stage. 1-Alkenes yield trialkylboranes in which there is a preponderant (approximately 94%) addition of the boron atom to the terminal carbon.2,3... 

Scheme 12. Allylic C-H activation via hydroboration of unsymmetrical cyclic tetrasubstituted alkenes.

Unsymmetric alkenes, which carry more alkyl substituents at the center than at the Ca center, are also hydroborated by the unhindered BH3 with considerable regioselectivity... 

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. 

CH,),QH,]2BH (1). Mol. wt. 250.20, m.p. 68°, air stable, in 70% yield by reduction of fluorodimesitylborane with LiAlHj. This borane is recommended for hydroboration of alkynes, par-e hydroboration of unsymmetrical alkynes (equation I). 1-Alkynes khydes in high yield. Since alkcnes react only slowly with this iwration of alkynes in the presence of alkenes is possible. 

Later, Brown and co-workers developed the method described above for the preparation of enantiomerically pure Ipc2BH (>99% ee) and applied the reagent in the asymmetric hydroboration of prochiral alkenes. Oxidation of the trialkylboranes provided optically active alcohols. In the case of cis-alkenes, secondary alcohols were obtained in excellent enantiomeric purity (Figure 1). The reaction is general for most types of cw-alkene, e.g. C(S-2-butene forms (R)-2-butanol in 98.4% ee, and c(s-3-hexene is converted to (R)-3-hexanol in 93% ee. However, the reagent is somewhat limited in reactions with unsymmetrical alkenes e.g. c/s-4-methyl-2-pentene yields 4-methyl-2-pentanol with 96% regioselectivity but only 76% ee (Figure 1). ... 

Hydroboration is regioselective. With unsymmetrical alkenes, the boron atom bonds to the less substituted carbon atom. For example, addition of BH3 to propene forms an alkylborane with the B bonded to the terminal carbon atom. 

The above inconveniences are circumvented by the application of substituted borane derivatives, e.g., Sia2BH and 9-BBN (see Fig. 1 for definitions), which react with high regioselectivity and sensitivity to steric factors. Thus, 1-alkenes and 1-alkynes are hydroborated at the terminal position. The internal unsymmetrically disubstituted alkenes are also selectively hydroborated. The clean transformation of 1-alkynes into vinylboranes—not possible with borane—can be achieved with these reagents (Fig. 2). 

Dialkylboranes with bulky alkyl groups do not disproportionate so readily and hydroborate alkenes of lower steric hindrance than the parent alkene to give the corresponding unsymmetrical trialkylboranes in high yield and purity. Bis(3-methyl-2-butyl)borane is one such reagent, synthesized by controlled hydroboration of... 

The method provides an efficient and convenient route to access a wide variety of unsymmetrical 1,3-dienes, because the borylation proceeds in high yields under mild conditions and is applied to the preparation of 1-alken-2-ylboron, cyclic vinylboron, and functionalized vinylboron compounds which cannot be directly obtained by the conventional methods based on hydroboration and transmetalation. Table 4.3 shows generality of the process. 

When the alkene is internal and unsymmetrical, as in 3-methyl-1-cyclohexene (22), the reaction is more complicated. In addition to the two faces (top and bottom) of the molecule, there are two different and reactive sp carbons of the alkene. Hydroboration leads to four products, 23, 24, 25, and 26. With diborane... 

Hydroboration of unsymmetrical internal alkynes leads to a mixture of regioisomers and therefore is not generally considered useful for the synthesis of ketones, but hydrogenolysis of the hydroboration product provides an alternative route to cis alkenes (equation 9.76). ° ... 

As with hydroboration of unsymmetrical alkenes, the addition of (sialjBH to a carbon-carbon triple bond of a terminal alkene is regioselective boron adds to the less substituted carbon. 

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