Assignment OF

RETROSYNTHESIS

Topic: Stereoselectivity In Retrosynthesis of Organic Compounds

Submitted By: M. Naeem
Submitted To: Ma’am Ambreen Ghani
Class: Bs Chemistry
Semester : 8th
Roll no. BSF1603449

Date: 28-05-2020

University of Education Lahore, Vehari Campus

Definition

 Retrosynthetic analysis (retrosynthesis) is a technique for planning a

synthesis, especially of complex organic molecules, whereby the complex
target molecule (TM) is reduced into a sequence of progressively simpler
structures along a pathway which ultimately leads to the identification of a
simple or commercially available starting material (SM) from which a
chemical synthesis can then be developed.
 Retrosynthetic analysis is based on known reactions (e.g the Wittig reaction,
oxidation, reduction etc).
 The synthetic plan generated from the retrosynthetic analysis will be the
roadmap to guide the synthesis of the target molecule
Synthetic Planning

 Synthesis is a construction process that involves converting simple or

commercially available molecules into complex molecules using specific
reagents associated with known reactions in the retrosynthetic scheme.
 Synthesis can be grouped into two broad categories:
(i) Linear synthesis
(ii) Convergent synthesis
Linear Synthesis

 In linear synthesis, the target molecule is synthesized through a series of

linear transformations.
 Since the overall yield of the synthesis is based on the single longest route to
the target molecule, by being long, a linear synthesis suffers a lower overall
yield.
 The linear synthesis is fraught with failure for its lack of flexibility leading to
potential large losses in the material already invested in the synthesis at the
time of failure
Convergent Synthesis

 In convergent synthesis, key fragments of the target molecule are synthesized

separately or independently and then brought together at a later stage in the
synthesis to make the target molecule.
 A convergent synthesis is shorter and more efficient than a linear synthesis
leading to a higher overall yield. It is flexible and easier to execute due to the
independent synthesis of the fragments of the target molecule
One Functional Group

 One Functional Group Analysis Synthesis (path a)

Disconnection close to the functional group
(path a) leads to substrates (SE) that are readily
available. Moreover, reconnecting these
reagents leads directly to the desired TM in high
yield using well-known methodologies.
Disconnection via path b also leads to readily
Analysis
accessible substrates. However, their
reconnection to furnish the TM requires more
steps and involves two critical reaction
attributes: quantitative formation of the
enolate ion and control of its monoalkylation by
ethyl bromide.
Alkene Synthesis

 Alkenes can be made by the dehydration of alcohols 2, usually under acidic

conditions.
 This route is particularly good for cyclic alkenes 3
 The same alkene is formed from 2 regardless of which side eliminates but 4
gives a 76% yield of an 80:20 mixture of 5and 6
 When Zimmermann and Keck wished to study the photochemistry of a series
of alkenes of the general structure 7
 They used the Grignard method and dehydrated 8 with POCI3 in pyridine
 Eliminations on alkyl halides done by the E2 mechanism with a strong
hindered base to avoid SN2 reactions.
 This approach is good for terminal alkenes 10 as the elimination is successful
on primary halides
 Triphenyl phosphine, reacts with an alkyl halide in an SN2 reaction to give a phos-
phonium salt 18. Treatment with base, gives the phosphoniumylid 19.

 The carbanion end of the ylid adds to the aldehyde 22 and the 'betaine' then cyclises 23 to
the four-membered ring which frag- ments to give the products 24. So the Z-alkene 20 is
formed from the cis oxaphosphetane 24