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    Retrosynthetic Analysis PDF

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    Nole
    The document provides guidance for a chemistry assignment on multi-step organic synthesis, including reading materials, practice problems, and solutions. It discusses retrosynthesis, the process of working backwards from a target molecule to design a synthesis route. An example retrosynthesis shows converting an aldehyde to an alcohol precursor in two steps of hydroboration and oxidation. Practice problems require students to design retrosynthetic routes for additional substrate conversions.

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    © All Rights Reserved
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    Retrosynthetic Analysis PDF

    Uploaded by

    Nole
    608 views6 pages
    The document provides guidance for a chemistry assignment on multi-step organic synthesis, including reading materials, practice problems, and solutions. It discusses retrosynthesis, the process of working backwards from a target molecule to design a synthesis route. An example retrosynthesis shows converting an aldehyde to an alcohol precursor in two steps of hydroboration and oxidation. Practice problems require students to design retrosynthetic routes for additional substrate conversions.

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    The document provides guidance for a chemistry assignment on multi-step organic synthesis, including reading materials, practice problems, and solutions. It discusses retrosynthesis, the process of working backwards from a target molecule to design a synthesis route. An example retrosynthesis shows converting an aldehyde to an alcohol precursor in two steps of hydroboration and oxidation. Practice problems require students to design retrosynthetic routes for additional substrate conversions.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    608 views6 pages

    Retrosynthetic Analysis PDF

    Uploaded by

    Nole
    The document provides guidance for a chemistry assignment on multi-step organic synthesis, including reading materials, practice problems, and solutions. It discusses retrosynthesis, the process of working backwards from a target molecule to design a synthesis route. An example retrosynthesis shows converting an aldehyde to an alcohol precursor in two steps of hydroboration and oxidation. Practice problems require students to design retrosynthetic routes for additional substrate conversions.

    Copyright:

    © All Rights Reserved
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    Download as pdf or txt
    of 6

    CFQ & PP: Multi-step Organic Synthesis

    Reading
    Brown and Foote: Sections 10.10
    Appendix 7: Reagents and Their Uses
    Appendix 8: Summary of Methods for the Synthesis of Functional
    Groups
    Lecture Supplement
    Multistep Organic Synthesis (page 9 of this Thinkbook)
    Optional Web Site Reading
    The 1990 Nobel Prize in Chemistry (http://www.nobel.se/chemistry/laureates/1990/
    index.html)
    Review
    Topics to review from Chem 30A, as needed: SN2/SN1, elimination, radical
    halogenation, addition to carbon-carbon bonds
    Suggested Text Exercises
    Brown and Foote: Chapter 8: 46, 50
    Chapter 9: 41, 43, 46
    Chapter 10: 6, 19 - 31 Chapter 11: 32 - 39
    Miscellaneous Projects
    Create reaction flash cards (Brown and Foote Appendix 8 very useful for this!)
    Concept Focus Questions
    1. Define "retrosynthesis."
    2. Describe the retrosynthesis process used to design a multi-step organic synthesis.
    Use the example shown below.

    Convert

    into
    O

    Concept Focus Questions Solutions


    1. Retrosynthesis is the process of thinking backwards in synthesis design. We consider
    how a given target molecule is made from some precursor molecule, instead of
    starting with the given starting material.
    2. We start by examining the aldehyde target structure.
    Can it be made in a single step from the given starting material? No.

    74

    CFQ & PP: Multi-step Organic Synthesis

    Therefore we must decide what sequence of reactions is appropriate. There is no


    chance in the basic carbon skeleton (number or sequence of carbons), so we need
    only be concerned with functional group changes. What functional group(s) are in
    the product, and how are they prepared?

    Benzene ring: A benzene ring is present in the target and the starting material, so
    we don't have to be concerned about adding it.

    Aldehyde: We know several ways to make an aldehyde.


    Alkene ozonolysis: Alkene ozonolysis involves changing the carbon skeleton.
    Since the carbon skeleton is unchanged in this synthesis problem, ozonolysis
    would require adding this extra carbon at some point. The route employs extra
    steps and is therefore less efficient.
    Alkyne hydroboration: Alkyne hydroboration cannot be used here, because the
    alkyne that would lead to this aldehyde would have to have a pentavalent carbon.
    Primary alcohol oxidation: The only viable choice left.

    The more reactions you know, the more flexibility you have, and thus synthesis
    problems are easier. This is an excellent time to bring your flash cards up to date,
    and start using them every night!
    We have identified a primary alcohol as a reasonable precursor to the aldehyde
    target. This is written as:

    oxidation
    OH

    The fat retrosynthesis arrow means "the aldehyde can be made from the alcohol by
    oxidation." While it is not necessary to write the reaction above the retrosynthesis
    arrow, it helps you to remember what you planned to do.
    transformation
    oxidation

    retrosynthesis arrow

    Now we repeat the process, with the primary alcohol as the new target molecule.

    CFQ & PP: Multi-step Organic Synthesis

    75

    Can the target molecule be made from the given starting material (the alkene) in a
    single step? Yes, by hydroboration:
    hydroboration
    OH

    Thus, the complete two-step retrosynthetic scheme is:

    hydroboration

    oxidation

    OH

    O
    target molecule

    given starting material

    The process is not yet complete. The last step is to write out the synthesis in the
    forward direction. This is when specific reagents for each step are chosen. It is also
    a good time to critically review each step to make sure it will proceed exactly as
    expected. Forward direction:

    1. BH3

    PCC

    2. H2O2
    NaOH

    OH

    We must use PCC for the alcohol oxidation to stop at the aldehyde and avoid overoxidation to the carboxylic acid.
    Practice Problems
    Show how the following transformations may be carried out. Include your retrosynthetic
    reasoning.

    1.

    into
    C

    Br

    2.

    CH3

    OH
    into

    OH

    3.

    76

    into

    CO2H

    CFQ & PP: Multi-step Organic Synthesis

    OH

    4.

    into
    OCH3

    5.

    into

    6.

    into

    Practice Problems Solutions


    There may be more than one solution to each synthesis problem. If you have questions
    about the viability of your synthesis, consult a TA or Dr. Hardinger.
    1. Retrosynthesis:
    -

    N S N2

    E2

    HBr

    CN

    Br H2O2

    Br

    Forward direction:
    NaOCH3

    HBr

    CH3OH

    H2O2

    NaCN
    Br DMSO

    Br

    2. Retrosynthesis:
    CH3

    hydroboration

    elimination

    OH

    OH

    Forward direction:
    OH

    H2SO4

    1. BH3
    2. H2O2, NaOH

    CFQ & PP: Multi-step Organic Synthesis

    CH3
    OH

    77

    3. Retrosynthesis:
    oxidation

    hydroboration

    CO2H

    CH2OH

    Forward direction:
    1. BH3

    CH2OH

    2. H2O2, NaOH

    CrO3

    CO2H

    aq. H2SO4

    4. Retrosynthesis:
    hydroboration

    Williamson
    OCH3
    dehydration

    OH
    OH

    Forward direction:
    OH H2SO4

    1. BH3

    1. NaH

    2. H2O2
    NaOH

    2. CH3I
    OCH3

    OH

    5. Retrosynthesis:
    Br

    Br
    Br2

    E2 twice

    E2

    Br
    radical
    bromination

    78

    CFQ & PP: Multi-step Organic Synthesis

    Forward direction:
    Br
    Br2, h

    Br
    Br2

    NaOCH3

    Br
    (CH3)3CO-

    In the last step, use of a sterically hindered base such as (CH3)3CO- helps ensure that
    the less substituted alkene is formed.
    6. Retrosynthesis:
    CH3
    C
    alkyne reduction

    alkyne anion SN2

    Br
    radical halogenation

    Forward direction:
    CH3
    C

    Br
    Br2, h

    CH3C

    H2
    Lindar catalyst

    CFQ & PP: Multi-step Organic Synthesis

    79

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