Chapter 13, Problem 13.1P

Interpretation Introduction

Interpretation:

The missing reagents for each step in Your Turn 13.6 are to be supplied.

Concept introduction:

In order to identify the missing reagents in the given reaction sequence, it is important to identify if the reaction involves a functional group transformation, or it is a reaction that alters the carbon skeleton. In each given reaction, the bonds which are broken and formed are to be identified. The regioselectivity and stereochemistry play an important role in the outcome of the reaction when a specific reagent is used.

Under basic conditions, the nucleophile attacks the epoxide ring at the less-substituted C atom. An alkoxide ion is formed which is on acidic workup, yeilding uncharged alcohol as the final product. When alcohol is treated with ${\text{PBr}}_{\text{3}}$, the alcoholic ($\text{OH}$) group is replaced by bromine atom via ${\text{S}}_{\text{N}}\text{2}$ reaction. As the halogens are the good leaving group, and due to the electronegativity difference, carbon of the C-Br bond is the electrophilic center for ${\text{S}}_{\text{N}}\text{2}$ reaction. The alkynes, on hydroboration-oxidation reaction, yield aldehydes or ketones. The terminal alkynes lead to form an aldehyde while an internal alkyne leads to form a ketone This conversion is achieved using a hydroboration-oxidation reaction, in which, the sterically hindered borane, like disiamylborane [${\left({\text{C}}_{\text{5}}{\text{H}}_{\text{11}}\right)}_{\text{2}}\text{BH}$] is treated with the basic solution of ${\text{H}}_{\text{2}}{\text{O}}_{\text{2}}$. The proton attached to an alpha carbon atom in the carbonyl compound is weakly acidic. A strong base is needed to abstract that proton. This leads to the formation of an enolate ion. The enolate anion serves as the nucleophile towards the electrophilic center via ${\text{S}}_{\text{N}}\text{2}$ reaction.

Answer to Problem 13.1P

The missing reagents for each step in the given reaction sequence are given below:

Explanation of Solution

The reaction sequence given in Your Turn 13.6 is:

The first reaction is the conversion of an epoxide to alcohol. Thus, it is a functional group transformation reaction in which the nucleophile, ${}^{-}{\text{OCH}}_{\text{3}}$ attacks the less substituted epoxide carbon which results in the formation of the alcohol shown. Thus, the reagents that must be used are:

$\text{1}{\text{. NaOCH}}_{\text{3}}{\text{, CH}}_{\text{3}}\text{OH}$

$\text{2}{\text{. H}}_{\text{3}}{\text{O}}^{\text{+}}$

The first reaction and the missing reagents for it are shown below:

The second reaction also involves functional group transformation. The alcoholic ($\text{OH}$) group is replaced by bromine atom via ${\text{S}}_{\text{N}}\text{2}$ reaction. This can be achieved by the use of ${\text{PBr}}_{\text{3}}$. Thus, the second reaction and the missing reagents in it are shown as:

In the third reaction, the bromine atom is replaced by an acetylene group ($\text{HC}\equiv \text{C-}$). So the required reagent for this reaction is: $\text{HC}\equiv \text{CNa}$. Thus, the third reaction and the missing reagents in it are shown as:

The fourth reaction in the given reaction sequence is a reaction involving a functional group transformation. Terminal alkynes undergo a hydroboration-oxidation reaction which leads to the formation of an aldehyde. The reagents used in the hydroboration-oxidation reaction are disiamylborane [${\left({\text{C}}_{\text{5}}{\text{H}}_{\text{11}}\right)}_{\text{2}}\text{BH}$] which is then treated with basic ${\text{H}}_{\text{2}}{\text{O}}_{\text{2}}$ solution. Thus, the fourth reaction and the missing reagents in it are shown as:

The fifth reaction involves the alteration of the carbon skeleton. The alpha hydrogen attached to an alpha carbon in aldehydes is weakly acidic. A strong base abstracts this alpha hydrogen to form an enolate ion. This enolate serves as a nucleophile and reacts with an alkyl halide via ${\text{S}}_{\text{N}}\text{2}$ reaction mechanism. As the product of this step has two additional carbon atoms, the alkyl halide that should be used is ethyl bromide. Thus, the reagents used for this transformation are:

$\text{1}\text{. NaOH}$

$\text{2}{\text{. CH}}_{\text{3}}{\text{CH}}_{\text{2}}\text{Br}$

The complete reaction sequence with appropriate reagents for each are given below:

Conclusion

In order to identify the missing reagents in the given reaction sequence, it is important to identify if the reaction involves a functional group transformation or it is a reaction that alters the carbon skeleton.