33 ch203 fall 2014 lecture 33 yz.pdf

8/10/2019 33 CH203 Fall 2014 Lecture 33 YZ.pdf

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Reactions to Learn

Announcement

Suggested questionsfrom Brown:

Chapter 6: 6.17; 6.21; 6.28; 6.31; 6.35; 6.37; 6.40; 6.42;

6.45; 6.46; 6.48Chapter 7: 7.8; 7.10; 7.11; 7.14; 7.20; 7.21; 7.25

Lecture onMonday, No Lectureon Wednesday

No discussionnext week, normal office houron

Tuesday 4:30-5:30


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Reactions to Learn

Alkyne reactions last time:

Hydroboration-Protonolysis to syn-alkene

Reducing using Na or Li to trans-Alkene

Reducing with Lindlar Catalyst tosyn-alkene

1. Addition of X2- halogenation

2. Addition of HX - hydrohalogenation

3. Hydroboration - oxidation (hydration)

4. Acid - catalyzed hydration

5. Catalytic reduction to alkane

Alkyne reactions today:

Reactions Learned today

Markovnikov!s rule

Non-Markovnikov!s rule

Markovnikov!s rule


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Reduction to Alkane

Treatment of an alkyne with H2in the presence ofa transition metal catalyst, most commonly Pd,

Pt, orNi, converts the alkyne to an alkane. The

reduction occurs in to stages: (1) addition of 1

mole of H2to form an alkeneand (2) addition ofthe second mole H2to the alkene to form the

alkane.


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Reduction to Alkane

Step 2:Repeat step 1one more time. The metal adsorbs hydrogenand the system of the intermediatealkene.One carbon adds a

hydrogen and is released from the metal surface. The second carbon

then adds a hydrogen and is released from the metal surface to form

alkane product.


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Reduction to syn-Alkene: Lindlar Cat.

In most cases, it is not possible to stop thereaction at the alkene stage.However, with the

Lindlar catalyst, the reduction stops at syn-

stereoselectiveaddition of one mole of H2 to

afford cis-alkeneproduct.

It is thought that the role of lead (Pb) is to reduce

the amount of H2absorbed, while quinoline

helps avoid the formation of unwanted byproducts,

but its hard to be more specific than that.

syn-addition


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Syn-stereoselective hydroboration gives atrialkenylborane.

Treatment of a trialkenylborane with acetic acid

results in stereoselective replacement of Bby H. The

net effect of hydroboration followed by protonolysis is

reduction of the alkyne to a cis-alkene. Thus this aalternativemethod for Lindar reduction to provide a

cis-alkene.

Hydroboration - ProtonolysisReduction to syn-Alkene:

Hydroboration-Protonolysis

syn-addition


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Reduction of an alkyne with Naor Liin liquid

ammoniaconverts an alkyne totans-alkenewith

antistereoselectivity.

Dissolving Metal ReductionReduction to trans-Alkene:

Dissolving Metal Reduction

anti-addition


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e uc on o rans- ene:


Step 1: A one-electron reduction. Addition of oneelectron to the triple bond gives a radical anion, a

species containing negative charge and unpaired electron.

e-

Na+Na e-+

The net effect ofstep 1 and 2 is to add one hydrogen

atomto the triple bond.

Step 2: Add a proton. The alkenyl radical anion (a very

strong base) abstracts a proton from solvent ammonia

(a very weak acid) and yields aradical.


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e uc on o rans- ene:


Step 3: A second one-electron reductiongives analkenyl anion.

This step establishes the configurationof the alkene

A trans alkenyl anion is more stablethan its cis isomer.

Step 4: Add a proton. A second acid-base reaction

gives the trans alkene.

e-

The net effect ofstep 3 and 4 is to add the second

hydrogen atomto the triple bond.


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Question

Provide the reaction reagents in the boxbased on the structure of the products.

Problem

Na or Li,NH3(liquid)

Lindlar Catalyst


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Organic SynthesisOrganic Synthesis


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A successful synthesis must

provide the desired product in maximum yield.

have the maximum control of stereochemistryand

regiochemistry.

do minimum damage to the environment (it must be a

green synthesis).

Organic SynthesisOrganic Synthesis

Synthesis is generally the most important objective

of organic chemists, applicable to the preparation of

compounds for use as pharmaceuticals, plastics,

agrochemicals, and textile fibers.


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Organic Synthesis

We analyze a target molecule in the following ways: The carbon skeleton: Count the carbonsin the target

molecule versus the available starting material so that you

know what fragment must be added or subtracted. how

can we put it together?

Our only method to date for forming a new C-C bond is the alkylation

of alkyne anions with 1 haloalkanes.

The functional groups: what are they, how can they be

used to facilitate formation of the carbon-skeletonof the

target molecule, and how can they be changed to give thefunctional groups of the target molecule? Regio-

specificity and sterospecificity need to be considered.

Work backward: Our strategy will be to work backwards

from the target molecule.


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Example - Palytoxin Retrosynthesis

next page

The toxicity of palytoxin is due to its

binding to sodium pump of body


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Example - Palytoxin Retrosynthesis


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Organic Synthesis

Target molecule: 2-heptanone

OH

OH


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Organic Synthesis

Starting materials are acetylene and 1-bromopentane.


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Provide the reaction reagents or the missing starting

material in the box based on the structure of the

products.

Question QuestionQuestion

1)NaNH2(or otherstrong base)2)

INa or Li,

NH3(liquid)

reduction of alkyneto trans alkene

alkylation of terminalalkyne to internal alkyne

33 ch203 fall 2014 lecture 33 yz.pdf

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