#3 of this PSet. ?Can you explain the 1,2 and 1,4 on this?
Chemistry E-2b Problem Set #7
Due: Thursday, 04/04/2016, 6:00 pm
Instructions: Answer the following questions on separate sheets of paper and turn them in to your TF's mailbox (2nd
floor of the Science Center) by the date and time indicated. These sheets should be stapled together and each should
be headed with your name, the names of any classmates with whom you worked, and your TF's name.
1. Each of the following compounds can be obtained from a Robinson annulation. Provide the acyclic precursors.
(In other words, do the Robinson retrosynthetic analysis for each.)
a)
O
b)
O
c)
Ph
O
OMe
MeO
Ph
O
CH 3
O
C
N
O
OMe
2. Provide complete curved-arrow mechanisms for all steps of the following sequences of reactions.
O
a)
O
1. LDA
OH
2. O
O
3. H + workup
O
b)
(That reagent in step 2 is not a typo! Some
basic HOMO/LUMO analysis will help you
determine how it behaves.)
O
1. Ph 2CuLi
2. H 3O+
H
Ph
O
O
c)
1.
O
OMe
O
NaOMe, MeOH
OMe
2.
O
H+
O
workup
O
O
d)
1.
O
O
OMe
O
MeO
(Keep in mind that organometallic
reagents, including dialkyl lithium
cuprates, are incompatible with protic
functional groups, so there are no H+
sources in the first step.)
OMe
O
EtO
EtO
O
OEt
O
2. H + workup
, NaOEt, EtOH
O
EtO
O
Duplication of this problem set for any purpose other than official Harvard Extension School business is prohibited.
3. Reaction of the enolate of N,N-dimethylacetamide (A) with (E)-6-methylhept-2-en-4-one (B) results in different
products depending on whether the reaction is conducted at -78 ?C or 65 ?C.
O
1. LDA
CH 3
H 3C
N
CH 3
2.
O
1,2-addition product
, -78 ?C
3. H + workup
O
H 3C
1. LDA
CH 3
N
CH 3
2.
O
1,4-addition product
, +65 ?C
3. H + workup
a) At -78 ?C, the reaction favors a 1,2 (direct) addition to the carbonyl, as indicated above. Draw the product
formed.
b) At +65 ?C, the reaction favors a 1,4 (conjugate) addition to the a,b-unsaturated system, as indicated above.
Draw the product formed.
c) Provide a complete curved-arrow mechanism for the formation of the 1,4-addition product.
d) For these products to be obtained, what must be true about the pathways leading to each of the addition
products? (Think "reaction coordinate diagrams.") Your answer should be thorough and in accordance with
what you learned about these additions in lecture and review.
4. Provide complete multi-step syntheses of the following transformations. You may use any organic or inorganic
compounds that you require, unless noted otherwise.
a)
MeO 2C
O
… In FIVE or fewer steps.
O
CO2Me
b)
O
HO
O
OH
EtO
OEt
O
… In FIVE or fewer steps.
O
Duplication of this problem set for any purpose other than official Harvard Extension School business is prohibited.
O
c)
… In FIVE or fewer steps.
NHEt
d) You have seen spiro compounds (compounds that have two rings that share a common vertex) in E-2a in the
context of unusual sources of chirality, and now you have the tools to synthesize them:
O
O
O
EtO
OH
OEt
…and ALL carbons in the product
must come from the given
starting material.
e) Quiactin is an anxiolytic drug that was used briefly in the 1950's and 1960's:
O
O
O
H 2N
H
…and ALL carbons in the product
must come from the given
starting material.
Quiactin
f) Gingerol, the primary flavor/fragrance compound in ginger, can by synthesized from vanillin, the primary
flavor/fragrance compound in vanilla:
O
O
OH
MeO
MeO
HO
HO
Gingerol
+
H
Vanillin
any acyclic compounds that add
6 carbons or fewer
+ any protecting groups you wish
Duplication of this problem set for any purpose other than official Harvard Extension School business is prohibited.