Chapter 26, Problem 26.44P

Devise a synthesis of each substituted cyclopropane. Use acetylene $\left(\text{HC}\equiv \text{CH}\right)$ as a starting material in part (a) and (b), and cyclohexanone as a starting material in part (c) and (d). You may use any other organic compounds and any needed reagents.

a. b. c. d.

+enantiomer +enantiomer

Interpretation Introduction

(a)

Interpretation: A synthesis of given substituted cyclopropane from acetylene $\left(\text{HC}\equiv \text{CH}\right)$, any organic compounds, and reagents, is to be stated.

Concept introduction: The nonhalogenated cyclopropanes are synthesized by the treatment of an alkene with ${\text{CH}}_{\text{2}}{\text{I}}_{\text{2}}$, in the presence of zinc-copper couple $\left[\text{Zn}\left(\text{Cu}\right)\right]$. This process is known as Simmons-Smith reaction.

Answer to Problem 26.44P

A synthesis of given substituted cyclopropane from acetylene $\left(\text{HC}\equiv \text{CH}\right)$, any organic compounds, and reagents is,

Explanation of Solution

The synthesis of given compound involves four steps.

The first step involves reaction of acetylene with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, then with $\left[2\right]$ isobutylbromide. When acetylene reacts with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, it yields an acetylide anion. This acetylide anion reacts with $\left[2\right]$ isobutylbromide to yield $\text{3-methylbut-1-yne}$. The second involves reaction of $\text{3-methylbut-1-yne}$ with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, then with $\left[2\right]$ bromopropane. When $\text{3-methylbut-1-yne}$ reacts with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, it yields an $\text{3-methylbut-1-yn-1-ide}$ anion. This anion reacts with $\left[2\right]$ bromopropane to yield $\text{2-methylhept-3-yne}$. The third step is treatment of $\text{2-methylhept-3-yne}$ with Lindlar catalyst to yield cis alkene. In fourth step, this cis alkene undergoes Simmons-Smith reaction to yield the enantiomeric mixture of desired compounds. These steps are shown below.

Figure 1

Conclusion

A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents, is shown in Figure 1.

Interpretation Introduction

(b)

Interpretation: A synthesis of given substituted cyclopropane from acetylene $\left(\text{HC}\equiv \text{CH}\right)$, any organic compounds, and reagents, is to be stated.

Concept introduction: The nonhalogenated cyclopropanes are synthesized by the treatment of an alkene with ${\text{CH}}_{\text{2}}{\text{I}}_{\text{2}}$, in the presence of zinc-copper couple $\left[\text{Zn}\left(\text{Cu}\right)\right]$. This process is known as Simmons-Smith reaction.

Answer to Problem 26.44P

A synthesis of given substituted cyclopropane from acetylene $\left(\text{HC}\equiv \text{CH}\right)$, any organic compounds, and reagents is,

Explanation of Solution

The synthesis of given compound involves four steps.

The first step involves reaction of acetylene with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, then with $\left[2\right]$$\text{3-}\left(\text{bromomethyl}\right)\text{pentane}$. When acetylene reacts with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, it yields an acetylide anion. This acetylide anion reacts with $\left[2\right]$$\text{3-}\left(\text{bromomethyl}\right)\text{pentane}$. The second step involves reaction of resulting compound with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, then with $\left[2\right]$ isobutylbromide. First it reacts with $\left[\text{1}\right]{\text{NaNH}}_{\text{2}}$, to yield an $\text{3-methylbut-1-yn-1-ide}$ anion. This anion reacts with $\left[2\right]$ isobutylbromide. The third step involves the reduction of alkyne to trans alkyne by treating alkyne with sodium in the presence of liquid ammonia. In fourth step, this trans alkene undergoes Simmons-Smith reaction to yield the enantiomeric mixture of desired compounds. These steps are shown below.

Figure 2

Conclusion

A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents, is shown in Figure 2.

Interpretation Introduction

(c)

Interpretation: A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents, is to be stated.

Concept introduction: The nonhalogenated cyclopropanes are synthesized by the treatment of an alkene with ${\text{CH}}_{\text{2}}{\text{I}}_{\text{2}}$, in the presence of zinc-copper couple $\left[\text{Zn}\left(\text{Cu}\right)\right]$. This process is known as Simmons-Smith reaction.

Answer to Problem 26.44P

A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents is,

Explanation of Solution

The synthesis of given compound involves two steps.

In the first step of reaction, cyclohexanone undergoes Wittig reaction with Ylide, ${\text{CH}}_{\text{2}}={\text{PPH}}_{\text{3}}$, which results in the formation of alkene. In the final step, alkene reacts with ${\text{CH}}_{\text{2}}{\text{I}}_{\text{2}}$, in the presence of zinc-copper couple $\left[\text{Zn}\left(\text{Cu}\right)\right]$ to form the desired product.

These steps are shown below.

Figure 3

Conclusion

A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents, is shown in Figure 3.

Interpretation Introduction

(d)

Interpretation: A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents, is to be stated.

Concept introduction: The treatment of $\text{KOC}{\left({\text{CH}}_{\text{3}}\right)}_{\text{3}}$ with ${\text{CHX}}_{\text{3}}$ yields a dihalocarbene. The dihalocarbene is an electrophile that readily reacts with $\text{C}=\text{C}$ of an alkene to form a cyclopropane ring. This step leads to the formation of two new $\text{C}-\text{C}$ bonds.

Answer to Problem 26.44P

A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents is,

Explanation of Solution

The synthesis of given compound involves six steps.

The first step is alpha bromination of cyclohexanone in the presence of acetic acid. The second part is reaction of $\text{α}$-brominated product with $\text{LiBr,}{\text{Li}}_{\text{2}}{\text{CO}}_{\text{3}}$ to form $\text{α,β}$-unsaturated carbonyl compound. The third step is treatment of $\text{α,β}$-unsaturated carbonyl compound with ${\left({\text{CH}}_{\text{3}}\right)}_{\text{2}}\text{CuLi}$ to yield $3$-methylcyclohexanone. The fourth step is conversion of the $\text{C}=\text{O}$ bond of carbonyl compound to the $\text{C}=\text{C}$ bond, by Wittig reaction, using ${\text{Ph}}_{\text{3}}\text{P}={\text{CH}}_{\text{2}}$ ylide. The fifth steps is treatment of Wittig product with dichlorocarbene that is formed by the reaction of $\text{KOC}{\left({\text{CH}}_{\text{3}}\right)}_{\text{3}}$ with ${\text{CHCl}}_{\text{3}}$, to form dihalogenated cyclopropane ring. The sixth step is conversion of dihalo cyclopropane to dimethyl cycloprane by ${\left({\text{CH}}_{\text{3}}\right)}_{\text{2}}\text{CuLi}$ to yield the desired compound.

These steps are shown below.

Figure 4

Conclusion

A synthesis of given substituted cyclopropane from cyclohexanone, any organic compounds, and reagents, is shown in Figure 4.