Synthesis Problems Review for Final

Evaluate the starting material and the product for each. Count carbons.
functional groups. Contemplate how to transform the first into the second.

Evaluate

a.
OH

Same number of carbons. Alcohol is turning into alkene. First thought might be
dehydrate! This problem looks straight-up, doesnt it? Except if you try to dehydrate
that alcohol, youll make the Zaitsev product, not the Hoffman. You need to force the
Hofmann product and you can only do that with an E2 elimination on an alkyl halide. So
convert that alcohol to a halide (use HBr) and then form the Hofmann product using
KOtBu in tBuOH.
OH

Br

b.

O
H

Nine carbons to start. Eight carbons to end. Lost a carbon the only type of reaction
you know is the oxidative cleavage. Whats the catch? You cannot form aldehydes
though when you oxidatively cleave alkynes (you always get carboxylic acids). So what
do you do to the triple bond? Convert it to a double bond (use Na, NH3 or H2 with
Pd/CaCO3/Pb) and THEN use 1. O3 2. Zn, H3O+ to form an aldehyde (with one less C).
O

c.
O

9 Carbons to start. 12 carbons (and an oxygen) to end. Starting with an alkene. Ending
with an ether. Ethers (asymmetrical primary ethers) come from alcohols in the
Williamson ether synthesis. The alcohol must be forming on the less substituted end of
the alkene hydroboration. So 1. BH3 2. NaOH, H2O2 and then 1. NaH 2. CH3CH2CH2Br.
OH

d.

Br

5 carbons to start. 5 carbons to end. Alkene in starting material. Bromide in product.

Catch? Its on the less substituted end (and you dont know how to make the nonMarkovnikov bromide from an alkene). But you DO know how to make a bromide from
alcohols and you do know how to make the non-Markovnikov alcohol. So 1. BH3 2.
NaOH, H2O2 and then use PBr3.
OH

Br

e.

8 carbons to start with. 9 carbons in the product. Adding 1 C. Find that specific
carbon (see the methyl group?) and locate where it is relative to the alkene. Which end
is it attached to? More substituted end. How do we add alkyl groups? (Cant use
acetylide anion no triple bond. Cant use Williamson not making an ether. What else
do you have in your arsenal of reactions? The Cuprate but first you need a halide to
couple it to Start this synthesis by adding HBr to the alkene, and then add (CH3)CuLi.
Br

f.

6 carbons to start with. 8 carbons to end with. Match up the carbons. Notice that
there are two methyls on the right side of the starting material and two methyls on the
left side of the product. Guess what? Those are the same. Flip that starting material
over. Now note that you need to add the two carbons to the end of the double bond.
Couple of options now You could add Br2 to the alkene and then 2 equiv. of KOtBU and
form a terminal alkyne, then add 1. NaNH2, NH3 2. CH3CH2Br and finally H2, Pd/C:

Or you could hydroborate the alkene to form a primary alcohol, then use PBr3 to form a
primary bromide and couple that bromide with diethyl copper lithium, (CH3CH2)2CuLi.
Br

g.
O

5 carbon terminal alkyne starting material. 5+1 carbon ether product. Obviously adding
one carbon. And forming an ether (think Williamson ether synthesis for that part).
Ethers come from alcohols. Alcohols do not come from alkynes but they do come from
alkenes. Alkenes come from alkynes. Use Na, NH3 to form the alkene (or hydrogenate
with Lindlars catalyst, Pd/CaCO3/Pb) then hydroborate with 1. BH3 2. NaOH, H2O2 and
do the Williamson Ether synthesis 1. NaH 2. CH3I.
O

OH

h.
OH
Cl

7 carbons with a tertiary alcohol. 7 carbons with a secondary chloride, one carbon over
from where the alcohol was positioned. How do we get to that carbon?? What can we
do to the alcohol and incorporate some sort of reactivity on that carbon next door?
Dehydrate to form an alkene. It will want to form Zaitsev. Now that other carbon is
accessible and reactive and you have a less substituted end. Hydroboration will allow
you to form an alcohol on that secondary carbon and thionyl chloride and pyridine will
form the chloride you want.

OH
OH

Cl

i.

HO

8 carbons to start with a primary alcohol. 11 carbons to end, no alcohol. Adding three
carbons (isopropyl type piece only reaction that allows you to do that is the coupling

reaction via a cuprate). You will need a halide in place first. Use PBr3 first then add
((CH3)2CH)2CuLi.

HO

Br

j.

OH

OH

Obviously forming a diol where the alkene is located. The diol is anti so you will need to
use that nucleophilic epoxide opening reaction, with NaOH. First, make an epoxide with
mCPBA, then add the NaOH. Anti diol!
O

OH

OH