ANSWER KEY PAGE 1 of 12 - University of...
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ANSWER KEY PAGE 1 of 12 UNIVERSITY OF MANITOBA DEPARTMENT OF CHEMISTRY CHEM 3390 STRUCTURAL TRANSFORMATIONS IN ORGANIC CHEMISTRY FINAL EXAMINATION - PAPER # 433 Dr. Phil Hultin Friday December 12, 2008 – 9:00 am. NAME:____ANSWER KEY _______________STUDENT NUMBER:_______________________ Section 1: Concepts and terminology Section 2: Stereochemistry and conformation Section 3: Reaction products and reagents Section 4: Mechanisms and experimental explanations Section 5: Applications of spectroscopy TOTAL (100 Marks): Put all answers in the space provided for each question. You may use the backs of the sheets if necessary, but none of the answers requires a long written answer. Clearly drawn chemical structures will greatly assist the marking process and will reduce the likelihood that your answer will be misinterpreted. You may use molecular models during the exam. Note that a spectroscopic data sheet is not provided.
Transcript of ANSWER KEY PAGE 1 of 12 - University of...
ANSWER KEY PAGE 1 of 12
UNIVERSITY OF MANITOBA DEPARTMENT OF CHEMISTRY
CHEM 3390 STRUCTURAL TRANSFORMATIONS IN ORGANIC CHEMISTRY FINAL EXAMINATION - PAPER # 433
Dr. Phil Hultin Friday December 12, 2008 – 9:00 am.
NAME:____ANSWER KEY_______________STUDENT NUMBER:_______________________
Section 1: Concepts and terminology
Section 2: Stereochemistry and conformation
Section 3: Reaction products and reagents
Section 4: Mechanisms and experimental explanations
Section 5: Applications of spectroscopy
TOTAL (100 Marks):
Put all answers in the space provided for each question. You may use the backs of the sheets if necessary, but none of the answers requires a long written answer.
Clearly drawn chemical structures will greatly assist the marking process and will reduce the likelihood that your answer will be misinterpreted.
You may use molecular models during the exam.
Note that a spectroscopic data sheet is not provided.
ANSWER KEY PAGE 2 of 12
1. (20 Marks Total) Concepts and terminology. For each of the following, provide a specific example. When a chemical reaction or structure is required, do not use generic “R” or “X” groups! For reactions, show starting material, reagents and products explicitly.
a. A compound that contains diastereotopic methyl groups.
NH2
O
OH
L-Valine
Obviously there are many correct answers - this is thef irst one I thought of .
b. A reaction that involves anchimeric assistance.
c. A Wagner-Meerwein rearrangement reaction.
d. A compound that can be used as a free-radical initiator.
e. A stereospecific reaction.
f. A meso compound.
N
N CN
NC
AIBN
O O
t-Bu
t-Bu
O O
Bz
Bz
di-tButyl peroxide Benzoyl peroxide
e would be acceptable - they are the examples mentioned in the text. Others could belong as they actually are usef ul as radical initiators.
Any of these thresuggested too as
ANSWER KEY PAGE 3 of 12
g. A hydrogenolysis reaction.
h. A molecule that exhibits transannular strain.
i. A reaction coordinate diagram for a reaction that is exoergic overall, and has two steps of which the first step is rate-determining.
j. A reaction whose stereochemical outcome is primarily controlled by chelation between the reagent and the substrate.
OH
O
Zn(BH4)2
THF
OH
OH
Reduction of ketones containing a Lewis-basic group on the -position.
ANSWER KEY PAGE 4 of 12
2. (20 Marks Total) STEREOCHEMISTRY AND CONFORMATION
a. (8 Marks) The conformational preferences of cis-3-aminocyclohexane carboxylic acid in water depend on the pH. When the pH of the solution is ≤ 2, the molecule slightly prefers a chair conformation in which both substituents are equatorial. When the solution is between pH 6 - 9, the molecule significantly prefers a chair in which both substituents are axial. Briefly explain this behaviour using structures as needed to illustrate your explanation.
COOH
NH2
b. (8 Marks) In each of the following structures, clearly identify all pairs of stereoheterotopic atoms or groups. Label each pair as being either enantiotopic or diastereotopic.
i. ii.
iii. iv.
OH
OH
H
H
H
H
diastereotopic pairs
O
OH
H H
enantiotopic
H
H3CCH3
H
H
H
diastereotopic methyl pair
diastereotopic H pair
diastereotopic H pair
ANSWER KEY PAGE 5 of 12
c. (4 Marks) Designate each of the following objects as being either chiral or achiral.
CHIRAL Click the picture to go to a Wikipedia article
about the trefoil knot at http://en.wikipedia.org/wiki/Trefoil_knot.
H2C CH2
CH2H2C
H2CCH2
CH2H2C
Si
H3C CH3
Note: bold = in front of plane; regular = in
plane; grey = behind plane
CHIRAL See Jones, P.G. et al. Acta Cryst. 1997, C53,
612-615.
ACHIRAL Click on the image to see a Wikipedia article
about the figure-8 knot at http://en.wikipedia.org/wiki/Figure-
eight_knot_(mathematics).
ACHIRAL Unless there is writing on the tennis ball, it is
symmetrical.
ANSWER KEY PAGE 6 of 12
3. (20 Marks Total) Provide the missing product(s), reactant(s) or reagent(s)/solvent(s)/conditions to complete the following reactions correctly. Each question is an application of chemistry from this course, although it may also include common reactions covered in introductory organic chemistry.
a.
O
HO
H
mCPBA(1 equiv.)
-20 oCCH2Cl2
Snider, B.B.; Hawryluk, N.A. Org. Let t. 2000, 2, 635.
O
HO
H
O
(2)
b.
CO2H
1. I2, KI,NaHCO3H2O
2. DBU, CH2Cl2
Thibonnet, J.; Abarbri, M.; Parrain, J-L.; Duchene, A. T etrahedron Let t.,1996, 37, 7507. ^
Note: DBU is a non-nucleophil ic amine base.
OO
(2)
c.
OO
H
O
O
I
42%Begley, M. J.; Pattenden, G.; Smithies, A. J.; Walter, D. S.Tetrahedron Lett . 1994, 35, 2417.
Bu3SnHAIBNToluene, reflux
(3)
d.
OH
O O Ph
O3, CH2Cl2
thenMe2S OH
OH
O O Ph
Nakata, T.; Fukui, M.; Oishi, T. T etrahedron Lett. 1983, 24, 2657.
O
OH
O O Ph
Zn(BH4)2THF
(3)
e.
N
O
O O
Bn
1) K-SelectrideTHF
O
OBn 2) H2, Pd/C
EtOH
Brooks, C.A.; Comins, D.L. T etrahedron Let t. 2000, 41, 3551.
NH
OH
O
OH
H
(2)
ANSWER KEY PAGE 7 of 12
f.
BH3 S(CH2CH2OCH3)2.THF
thenH2O2, aq. NaOH
Zaidlewicz, M.; Kanth, J.V.B.; Brown, H.C. J. Org. Chem. 2000, 65, 6697.
HO H
(2)
g.
O
HO
PO
O
ClClPh
DMSO
Et3N, CH2Cl2
Liu, H.J.; Nyangulu, J.M. Tetrahedron Lett., 1988, 29, 3167-3170.
O
O
(2)
h.
O
CO2MeTsOCH2Cl2
TBSDIBAL
-78 oC
Pommier, A.; Pons, J-M.; Kocienski, P.J. J. Org. Chem. 1995, 60, 7334.
Note: Ts = p-Toluenesulfony l; T BS = t-Butyldimethy lsi ly l
O
TsO
TBSO
H
(2)
i.
O O
Denmark, S.E.; Marcin, L.R. J. Org. Chem. 1995, 60, 3221.
LiAlH4, THF, reflux
(2)
ANSWER KEY PAGE 8 of 12
4. (20 Marks Total) MECHANISMS AND EXPLANATIONS
a. (5 Marks) We discussed the oxidation of primary and secondary alcohols using pyridinium chlorochromate, but we did not talk about what happens when tertiary alcohols are treated with PCC. In 1977, Dauben reported that tertiary allylic alcohols underwent an interesting oxidative rearrangement. Suggest a
mechanism to explain this process.
ANSWER KEY PAGE 9 of 12
b. (7 Marks) The following reaction proceeded cleanly and spontaneously when the aminoalcohol shown was stirred at room temperature in water/THF. Assume that the solution was slightly acidic – perhaps around pH 5 or so. Provide a stepwise mechanism to explain the result.
NH
OH
Ph
O
O
H
H
H2O/THF
N
O
Ph
OH
H
OH
72%Yoshifuji, M.; Tagawa, J.; Inamoto, N. T etrahedron Let t. 1979, 26, 2415.
O
O
H
H
pH 5 OH
O
H
H
NH
OH
Ph
NH
O
Ph
O
HO H
H
H
NH
O
Ph
O
HO H
H
H
NH
O
Ph
OH
HO H
HNH
O
Ph
OH
HOH
HN
O
Ph
OH
HOH
H
H
N
O
Ph
OH2
HOH
H
N
O
Ph
HOH
H N
O
Ph
H
OH
OH H
N
O
Ph
OH2
H
OH
N
O
Ph
OH
H
OH
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c. (8 Marks) Cyclopropyl rings are highly strained, as you know. This makes them quite reactive. Provide a mechanism to explain the following reaction.
Me
O
SiMe3
Me
Me
S
N NBu3SnH
AIBN (cat.)
Me
Me
Me
SiMe3
79%
Motherwell, W.B. T etrahedron, 1992, 48, 8031.
N NCN
NC
2 CN + N2 (g)
NC + H Snn-Bu
n-Bun-Bu NC H + Sn
n-Bu
n-Bun-Bu
Snn-Bu
n-Bun-Bu + Me
O
SiMe3
Me
Me
S
N N
Me
O
SiMe3
Me
Me
S
N N
Snn-Bu
n-Bun-Bu
Me
SiMe3
Me
Me
O
S
N N
Snn-Bu
n-Bun-Bu
+Me
CH2
SiMe3
Me
Me
Me
Me
Me
SiMe3
HSn
n-Bu
n-Bun-Bu
Me
Me
Me
SiMe3
H
+ Snn-Bu
n-Bun-Bu
ANSWER KEY PAGE 11 of 12
5. (20 MARKS) Compound A is a highly polar white crystalline powder melting at 167-170 ºC. Mass spectrometry indicates a molecular formula of C6H14O6. Its 1H and 13C NMR spectra (acquired in D2O solution) are shown on this page, below. An aqueous solution of A
has an optical rotation D = +24.0°.
A sample of compound A was subjected to the following reactions which led to a new substance, compound B. (N.B. ZnCl2 is a Lewis acid in the first step.)
Compound B was a clear oil, not very soluble in water. Its 1H and 13C NMR spectra (acquired in CDCl3 solution) are shown on the next page. A pure sample of B has an optical
rotation D = +13.5°.
a. What are the structures of compounds A and B? Put your answers in the boxes on the next page.
b. For each structure, assign the 1H and 13C NMR signals to the corresponding atoms in your structures. You do not have to analyze couplings.
The IR spectrum of Compound A showed a broad absorbance between 3400-3200. The rest of the spectrum was uninformative.
Ha/b Ha/b
Hc Hd
C2,3
C1
Compound A 13C spectrum (D2O solution)
Compound A 1H spectrum (D2O solution) Note: these are the only 1H signals!
ANSWER KEY PAGE 12 of 12
Compound A Compound B
PPM 4.2 4.0 3.8 3.6 3.4
X 1.000
PPM 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0
Compound B 1H spectrum (CDCl3) CH3 CH3 Sample contains a small amount of acetone
Hd/e Ha/bHc
OH
PPM 180 160 140 120 100 80 60 40 20 0
Compound B 13C spectrum (CDCl3)
O
C
C
O
C
O
C
H3C
CH3
Ha Hb
Hc
HdHe
12 3
4
56
H
C4
C5/6 C1 C2/3
Cpd A has 0 degrees of unsaturation. IR indicates OH group(s). Three unique carbons but 6 in total says symmetry. Note 13C shifts are consistent with C-O groups. Only 4 unique hydrogens but 14 in total. All 1H shifts fall between 3.6-3.9 ppm, also consistent with CH-O. Note that since spectrum is in D2O, no signals from OH protons will be observed. Cpd A is also CHIRAL (despite symmetry) since it has a non-zero optical rotation. The reactions suggest that diol structure must be present – periodate cleavage would give an aldehyde or ketone, and borohydride reduction would give an alcohol. The first reaction, Lewis acid plus acetone, is not obvious but should become clearer from Cpd B. Cpd B has 6 unique carbons – note probable methyls plus signal at ~110 ppm. The 1H spectrum shows 12 hydrogens – one obvious OH and two obvious CH3 groups plus 5 1-proton multiplet signals all of which are in the CH-O region.
