Hydroboration, alkene stereochemistry

It is important to recognize that this reaction gives products corresponding to anti-Markovnikov addition of water to the carbon-carbon double bond. This behavior evidently results because carbonium ions are not intermediates - rearrangement does not occur in hydroboration. The stereochemistry of this reaction involves syn addition, that is, addition to the double bond is on the same face of the alkene. 

The regioselectivity and syn stereochemistry of hydroboration-oxidation coupled with a knowledge of the chemical properties of alkenes and boranes contribute to our under standing of the reaction mechanism... 

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. 

Hydration of an alkene—the addition of water—is carried out by either of two procedures, depending on the product desired. Oxymercuration involves electrophilic addition of Hg2+ to an alkene, followed by trapping of the cation intermediate with water and subsequent treatment with NaBH4. Hydroboration involves addition of borane (BH3) followed by oxidation of the intermediate organoborane with alkaline H202- The two hydration methods are complementary oxymercuration gives the product of Markovnikov addition, whereas hydroboration/oxidation gives the product with non-Markovnikov syn stereochemistry. 

The following alkene undergoes hydroboration/oxidntion to yield a single product rather than a mixture. Explain the result, and draw the product showing its stereochemistry. 

C3-hydroxy benzylation, through alkylation of the intermediate 2,3-0-dibutylstannylene of mannose acetal 24, gives 25 (Scheme 5). Hydroboration of the exocyclic 5-alkene derived from this material provides 26, in which the C5 stereochemistry is inverted. Benzylation and acetate methanolysis leads to the suitable glycosyl acceptor 27. 

The hydroboration of 6a- and 6/(-hydroxyandrost-4-cnc-17-onc (57) and (58) has been shown to take place predominantly on the face of the alkene opposite to the allylic OH group (Scheme 14).58 The same stereochemistry has been observed for 5a-hydroxy-2-enes (59),59 5a-hydroxy-2-enes (60), and la-hydroxy-2-enes.60... 

The anti-cancer compound coriolin 23 has three fused five-membered rings and two epoxides. Notice that the 3/5 and both 5/5 ring fusions are cis. There have been many syntheses of coriolin, most using stereochemistry from folded precursors.7 We shall feature a couple of examples. Matsomoto s synthesis involves the hydroboration of alkene 24. The addition of borane is cis 25 and the boron is replaced by OH with retention of configuration to give 26. The hydroboration occurred on the outside of the molecule, on the same face as the ring junction hydrogens.8... 

Asymmetric hydroboration followed by oxidation is used to give optically active alcohols. For example, addition of (+)-IpcBH2 to 1-phenylcyclopentene followed by oxidation gives S,2R)-trans-2-phenylcyclopentanol in 100% e.e. (Equation B2.9). The structure of the product alcohol reveals that the homochiral hydroborating reagent encounters fewer unfavourable steric interactions with alkene substituents if it approaches the lower face of the alkene as drawn in Equation B2.9. This preference determines the absolute stereochemistry of the product. (The regiochemistry and relative stereochemistry of the product are determined by fundamental hydroboration characteristics.)... 

Protonolysis of alkenylboranes by carboxylic acids occurs readily. The stereochemistry of the alkenyl group is retained during the reaction and so hydroboration/protolytic cleavage of alkynes leads to cis alkenes. Deuterated... 

Hydroboration of alkenes.2 Wilkinson s catalyst is effective for catalysis of hydroboration with catecholborane (CB), which can differ from the regioselectivity and stereochemistry of uncatalyzed hydroboration with 9-BBN. In the case of... 

The currently available methods for the synthesis of the title compounds are confined to the preparation of homo-1,1-dihalo-1-alkenes 180 while only a few reports are available for mixed 1,1-dihalo-1-alkenes of defined stereochemistry 18u. As the hy-droboration reaction proceeds in a stereospecific manner, the hydroboration-oxi-dation-bromination-debromoboration sequence of 1-chloro-l-alkynes produces selectively (Z)-l-bromo-l -chloro-l-alkenes (Eq. 116),82>. The oxidation with anhydrous trimethylamine oxide of the alkenylborane prior to the addition of bromine is necessary to avoid the competing transfer of one of 1,2-dimethylpropyl group from boron to the adjacent carbon atom. Similar reaction sequence provides 1,1-dibromo-l-alkenes (Eq. 117)182). 

Predict the stereochemistry observed in the hydroboration, halogenation, and dihy- Problems 8-46, 47,49, and 66 droxylation reactions of alkenes. 

We know that this is not the whole story because of the stereochemistry. Hydroboration is a syn addition across the alkene. As the addition of the empty p orbital to the less substituted end of the alkene gets under way, a hydrogen atom from the boron adds, with its pair of electrons, to the carbon atom, which is becoming positively charged. The two steps shown above are concerted, but formation of the C-B bond goes ahead of formation of the C-H bond so that boron and carbon are partially charged in the four-centred transition state. 

The same alcohol could be made by the Baeyer-Villiger rearrangement but the stereochemistry would have to be set up before the Baeyer-Villiger step. Hydroboration has the advantage that stereochemistry is created in the hydroboration step. We have discussed the details of this step. In drawing the mechanism it is usually best to draw it as a simple concerted four-centre mechanism providing you remember that the regioselectivity is controlled by the initial interaction between the nucleophilic end of the alkene and the empty p orbital on boron. 

The stereochemical outcome would also be different as the hydroboration adds syn to the alkene, whereas oxymercuration gives the anti product though in this case the stereochemistry is lost in the reduction step. 

However, the utility of this Zweifel synthesis was limited in the past by the limited availability of dialkylboranes, because direct hydroboration leads cleanly to the formation of dialkylboranes only in the case of relatively hindered alkenes such as 2-methyl-2-butene and cyclohexene. More generally, the hydroboration fails to stop at the R2BH stages. Recent developments have provided a general preparation of a variety of dialkylboranes via the hydridation of dialkylhalo-boranes. Thus, dialkylvinylboranes prepared via the hydridation of dialkylhalo-boranes in the presence of an alkyne, react with iodine under basic conditions to produce disubstituted alkenes (Eq. 58) and trisubstituted alkenes (Eq. 59) of established stereochemistry. These results indicate a mechanism analogous to that... 

Why does alkene hydroboration take place with non-Markovnikov rc o-chemiatry, yielding the less highly substituted alcohol Hydroboration differs from many other alkene oddition reactions in that it occurs in a single step without a carlK>cation intemnediate. We can view the reaction as taking place through a four-center, cyclic transition state, as shown in Figure 7.6 Cp. 244 j. Since both 0-H and C-B bonds form at the same time and from the same face of the alkene, syn stereochemistry is observed. 

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