10. Addition Reactions

Which is more highly regioselective: reaction of an alkene with BH3 or with 9-BBN?

Suggest an alkene to undergo hydroboration–oxidation (1. BH₃ 2. NaOH, H₂O₂) to give exclusively the alcohols shown. Pay close attention to the relative (but not absolute) stereochemical outcome.

(c) <IMAGE>

Would you expect the following to produce an equal or unequal mixture of stereoisomers?

(c) <IMAGE>

Suggest an alkene to undergo hydroboration–oxidation (1. BH₃ 2. NaOH, H₂O₂) to give exclusively the alcohols shown. Pay close attention to the relative (but not absolute) stereochemical outcome.

(b) <IMAGE>

Suggest a reagent and a reactant that could be combined to make each of the following alcohols.

(a) <IMAGE>

Predict the products you would get when the following alkenes undergo (i) hydroboration–oxidation (1. BH₃ 2. NaOH, H₂O₂ ) or (ii) oxymercuration–reduction [1. Hg(OAc)₂ , H₂O 2. NaBH₄ ].

(a) <IMAGE>

8.71 (•••) FROM THE LITERATURE Predict the product of each of the following hydroboration–oxidation or oxymercuration–reduction reactions used in the modern synthetic organic chemistry literature (modified to use reagents we are used to seeing). [These molecules, while perhaps more complex than any you have seen previously, are, in the presence of borane or mercury(II) acetate, simply alkenes. Thus, don't get distracted by the other functional groups and abbreviations present and predict the product based on what you have learned here in Chapter 8.]

(b) A two-step hydroboration–oxidation was used to prepare a silanediol peptidomimetic as a serine protease inhibitor (Org. Lett. 2012, 14, 4422–4425).

<IMAGE>

8.71 (•••) FROM THE LITERATURE Predict the product of each of the following hydroboration–oxidation or oxymercuration–reduction reactions used in the modern synthetic organic chemistry literature (modified to use reagents we are used to seeing). [These molecules, while perhaps more complex than any you have seen previously, are, in the presence of borane or mercury(II) acetate, simply alkenes. Thus, don't get distracted by the other functional groups and abbreviations present and predict the product based on what you have learned here in Chapter 8.]

(c) A similar sequence was featured in the synthesis of muricadienin, a proposed precursor in the biosynthesis of solamin (Org. Lett. 2014, 16, 5886–5889).

<IMAGE>

a. Starting with 3-methyl-1-butyne, how can you prepare the following alcohols?

  1. 2-methyl-2-butanol

b. In each case, a second alcohol would also be obtained. What alcohol would it be?

What stereoisomers are obtained from hydroboration–oxidation of the following compounds? Assign an R

or S configuration to each asymmetric center.

a. cyclohexene

b. 1-ethylcyclohexene

Explain why 3-methylcyclohexene should not be used as the starting material in Problem 52b.

<IMAGE>

How can the following compounds be synthesized, starting with a hydrocarbon that has the same number of carbons as the desired product?

b. CH3CH2CH2CH2OH

We have studied a number of pericyclic reactions previously. Draw the mechanism of the steps shown. The section number where this material was first studied is given for your review.

(c) <IMAGE>

What reagents are needed to synthesize the following alcohols?

a. <IMAGE>

What is the major product obtained from hydroboration–oxidation of the following alkenes?

a. <IMAGE>

Disiamylborane adds only once to alkynes by virtue of its two bulky secondary isoamyl groups. Disiamylborane is prepared by the reaction of BH3·THF with an alkene.

a. Draw the structural formulas of the reagents and the products in the preparation of disiamylborane.

b. Explain why the reaction in part (a) goes only as far as the dialkylborane. Why is Sia3B not formed?

In the hydroboration of 1-methylcyclopentene shown in (Solved PROBLEM 8-3) , the reagents are achiral, and the products are chiral. The product is a racemic mixture of trans-2-­methylcyclopentanol, but only one enantiomer is shown. Show how the other enantiomer is formed.

Show how you would synthesize each compound using methylenecyclohexane as your starting material. <IMAGE>

c. <IMAGE>

When (Z)-3-methylhex-3-ene undergoes hydroboration–oxidation, two isomeric ­products are formed. Give their structures, and label each asymmetric carbon atom as (R) or (S). What is the relationship between these isomers?

When 1,2-dimethylcyclopentene undergoes hydroboration–oxidation, one diastereomer of the product predominates. Show why this addition is stereospecific, and predict the stereochemistry of the major product.

An inexperienced graduate student treated dec-5-ene with borane in THF, placed the flask in a refrigerator, and left for a party. When he returned from the party, he discovered that the refrigerator was broken and that it had gotten quite warm inside. Although all the THF had evaporated from the flask, he treated the residue with basic hydrogen peroxide. To his surprise, he recovered a fair yield of decan-1-ol. Use a mechanism to show how this reaction might have occurred. (Hint: The addition of BH3 is reversible.)

The bulky borane 9-BBN was developed to enhance the selectivity of hydroboration. In this example, 9-BBN adds to the less hindered carbon with 99.3% regioselectivity, compared with only 57% for diborane.

<IMAGE>

a. Show the two organic products generated when the trialkylborane is oxidized with H2O2/NaOH.

Draw the organic products you would expect to isolate from the following reactions (after hydrolysis).

(m) <IMAGE>

The bulky borane 9-BBN was developed to enhance the selectivity of hydroboration. In this example, 9-BBN adds to the less hindered carbon with 99.3% regioselectivity, compared with only 57% for diborane.

<IMAGE>

b. 9-BBN is synthesized by adding BH3 across a symmetric, cyclic diene. What is the structure of the diene?

Show how you would accomplish the following synthetic conversions.

b. but−1−ene→butan−2−ol

Show how you would synthesize the following alcohol from appropriate alkene.

(b) <IMAGE>

Devise a synthesis for each compound, starting with methylenecyclohexane and any other reagents you need.

(d) trans-2-methylcyclohexanol

Limonene is one of the compounds that give lemons their tangy odor. Show the structures of the products expected when limonene reacts with an excess of each of these reagents. <IMAGE>

a. borane in tetrahydrofuran, followed by basic hydrogen peroxide

What is the major product of the reaction of 2-methyl-2-butene with each of the following reagents?

k. BH3>THF, followed by H2O2, HO- , H2O