Q32E - Organic Chemistry (Mcmurry)

Question

Fluoxetine, a heavily prescribed antidepressant marketed under the

name Prozac, can be prepared by a route that begins with the reaction between a phenol and an alkyl chloride.

1. The rate of the reaction depends on both phenol and alkyl halide. Is this an SN1 or an SN2 reaction? Show the mechanism.
2. The physiologically active enantiomer of fluoxetine has (S) stereochemistry. Based on your answer in part (a), draw the structure of the alkyl chloride, you would need, showing the correct stereochemistry.

Step-by-Step Solution

Answer

1. The reaction proceeds by the SN2 mechanism

Mechanism followed as:

b. 

Alkyl chloride to form the stereo R

SN2 reaction

These are the unimolecular reaction in which no carbocation intermediate is formed a single-step process occurs in the removal of leaving group and attacking of the nucleophile occur simultaneously and the rate of the reaction depends upon the substrate as well as a nucleophile.

So, as the given, the rate of the reaction depends upon the phenol as well as alkyl halide that is on the substrate as well as nucleophile so follow the SN2 mechanism.

Mechanism

Mechanism followed as:

1. Reaction of formation of enol form carbonyl
2. Converting alkene to OH on reacting with osmium tetraoxide
3. The addition of NHMe occur
4. The base is reacted for the removal of halide
5. Formation of the desired product

$a. TiC{l}_4, b. Os{O}_4, c. NaB{H}_4, d. E{t}_{3}N,MsCl, e. MeN{H}_2, f. KOH,DMSO,HCI$

Alkyl halide require for R stereo

When carbonyl form is converted to the enolic form that should be in the R stereo to form the R-fluoxetine rest of the reagents and the process is same 

Stereochemistry