Chem 201 Van Vranken

Problem Set 3
Due Tuesday, 10/18/16
These problems are relatively challenging. If you get stuck, think backwards; use models; number atoms in
your intermediates. Above all, be persistent!

1. The natural product ptaquiloside leads tumors in animals that eat brackenfern because is alkylates
guanine bases of DNA. Suggest a plausible arrow-pushing mechanism for the reaction.

Answer:

2.a.Suggest a plausible arrow-pushing mechanism for the following reaction.1

Answer:
Chem 201 Van Vranken

b. Suggest a plausible arrow-pushing mechanism for the following reaction.2

Answer:

c. Suggest a plausible arrow-pushing mechanism for the following reaction.3

Answer:

3. Suggest a plausible arrow-pushing mechanism for the following reaction.4

(OC) 3Co Co(CO)3 ZnI2 (OC) 3Co Co(CO)3

NaCNBH 3
OBn OBn >75%
HO CH2Cl 2
OBn OTBS 23 °C, 7 h OBn OTBS

Answer: This is a simple SN1 reaction.

Chem 201 Van Vranken

(OC) 3Co Co(CO)3 (OC) 3Co Co(CO)3 (OC) 3Co Co(CO)3 (OC) 3Co Co(CO)3
OBn OBn
R + R
H H
I 2Zn :OH OBn OTBS OBn OTBS
I 2Zn O + –
– B H
metal-carbon bonds NC
H
"push out" the L.G.
and stabilize the cation

4. Suggest a plausible arrow-pushing mechanism for the following reaction. Note: silica gel
is a mild acid due to the presence of Si-OH groups. Assume that the silica gel can also serve as a source of
water.5

Answer:

5. Provide a plausible arrow-pushing mechanism for the following reaction. Predict the stereochemistry of
the products.6
Chem 201 Van Vranken

Answer: We didn’t cover formation of sulfenes using CH3SO2Cl/Et3N so I would accept an alternative
mechanism involving ROH or RO- attack on the sulfonyl chloride.

Practice Problems
The following problems demonstrate important concepts, but will not be graded.
We will cover some of them in discussion section.

6. Suggest a plausible arrow-pushing mechanism for the following reaction. Ignore the role of acetic
anhydride.7
Me O Me O
MeO 2SO KOAc
H Ac2O H

S H H AcOH H H
100 °C, 0.8 h S
S
S 73%
Answer:
Chem 201 Van Vranken

OSO 2Me R R
R R R
+
S S S S R S R
+
S
R
S:
R R SH S
S
+ :A–
episulfonium ion
Note: R
sigma-bond migration S
is not the same + R
S

7. Provide a plausible arrow-pushing mechanism for the following reaction.8

O OAc HO cat. BF 3•OEt 2 O O

AcO AcO

AcO OAc CH 2Cl 2 AcO OAc

OAc 23 °C, 24 h OAc
68%

Answer:
BF 3
.. - +
O F 3B O HOPh
..
+
O O O
.. O O O O+
AcO AcO O AcO :O AcO

AcO OAc AcO O AcO O AcO O

OAc OAc OAc OAc

- +
F 3B O You can't exclude this alternative
one-step ionization based on
O OPh
O O fundamental principals, so I AcO
AcO :O would accept it.
AcO OAc
AcO O
OAc
OAc

8. Provide a plausible arrow-pushing mechanism for the following reaction. Estimate the G° for the
reaction.9

O OMe O OMe
O O
C6H 6 Ph O SPh
Ph O OSO2Me 80 °C, 18 h
SPh OSO 2Me
99.9%

Answer:
Chem 201 Van Vranken
OMs
O O OMe O
O SPh
OMs
O O X Ph O O O OMe
Ph PhS: SPh Ph
MsO: +
-

You don't know how much S.M. was left over; product/S.M. ≥999:1.

Keq = ≥1000
Ignoring the fact that the reaction was at 80 °C, DG ≥ 4.2 kcal/mol

9. Provide a plausible arrow-pushing mechanism for the following reaction. Explain the stereoselectivity.10

Answer:

10. Rationalize the stereoselectivity in the following reaction.11

O OH
O
80%
O HO Me 2Si
Me 2Si O
CHCl3
NO 2 23 °C, 24 h
NO 2

Answer:
Chem 201 Van Vranken

+ OH
+
O: H A O H Si H
Me 2Si Me 2Si
s* H

OH OH
H H :Nu H Si OH
:Nu
H
Si + Si + + Me 2Si
H
H
p H H HO H Nu
Nu:
sSi-C is donating into the empty p orbital from the
:Nu
bottom face, so the nucleophile attacks from the
opposite face. This is the same reason why +
nucleophiles attack exo on the 2-norbornyl cation.

11. Suggest a plausible arrow-pushing mechanism for the following reaction.12

O
BF 3•Et 2O
O 98%
CH2Cl 2
N N
H 95 °C, 41 h H

Answer:
- BF 3
+ - - BF 3
O: BF 3 O BF 3 O
O+
+
N N N N
H H H H

+ + +
O
N O BF 3 N O BF 3 N BF 3
H - H - H -

12. Suggest a plausible arrow-pushing mechanism for the following reaction.13

HO
HCOOH O
N
toluene H 65%
N
111 °C, 30 min Br
Br
Asnwer:
Chem 201 Van Vranken
Ar Ar
HO HO ..
HO HO
NH + NH
+
N Ar
.. + N Ar
H
A H

Ar
Br
O HN
H + O
-A: N
H

13. Suggest a plausible arrow-pushing mechanism for the following reaction.14 Note: this transformation
occurred under conditions for mesylation with CH3SO2Cl and pyridine in CH2Cl2.
Me Me Me
pyridine
MsO 80%
CH2Cl 2 Me H
23 °C, 7 h
H Me H Me

Answer:
Me Me Me Me Me Me
Me

MsO +
+ Me H

H Me H Me H B: H CH 2 H Me
H

14. Suggest a plausible arrow-pushing mechanism for the following reaction.15

OSO2Me K 2CO3
Ac2O O
83%
AcOH O
118 °C, 10 h

Answer: Okay, I admit that this was pretty hard.

Chem 201 Van Vranken
OMs
+

+ O + AcO
+
..
cyclopropyl- 3° cyclobutyl 3° cyclopropyl- O-
carbinyl carbinyl

+
O
or -
O:

References
1
Hibino, J.-I.; Nakatsukasa, S.; Fugami, K.; Matsubara, S.; Oshima, K.; Nozaki, H. J. Am. Chem. Soc. 1985,
107, 6416.
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4
Mukai, C.; Moharram, S. M.; Kataoka, O.; Hanaoka, M. J. Chem. Soc., Perkin Trans. 1 1995, 2849.
5
Nagumo, S.; Ono, M.; Kakimoto, Y.-i.; Furukawa, T.; Hisano, T.; Mizukami, M.; Kawahara, N.; Akita, H.
J. Org. Chem. 2002, 67, 6618.
6
Wojaczynska, E.; Turowska-Tyrk, I.; Skarzewski, J. Tetrahedron 2012, 68, 7848.
7
Williams, J. R.; Sarkisian, G. M. Tetrahedron Lett. 1974, 1109.
8
Smits, E. et. al. J. Chem. Soc. Perkin 1 1996, 2873
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Hanessian, S.; Staub, A. P. A. Carbohyd. Res. 1970, 14.
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Honda, Y.; Ori, A.; Tsuchihashi, G. Bull. Chem. Soc. Jpn. 1987, 60, 1027.
11
Badali, F.; Karalis, A.; Tham, W.Y.; White, J. M. Aust. J. Chem. 1996, 49, 1293.
12
Gueller, R.; Borschberg, H. Tetrahedron Lett. 1994, 35, 865.
13
Liu, Y.; McWhorter, W. W., Jr.; Hadden, C. E. Org. Lett. 2003, 5, 333.
14
Srikrishna, A.; Vijaykumar, D. Tetrahedron Lett. 1998, 39, 5833-5834.
15
Marshall, J. A.; Greene, A. E.; J. Org. Chem. 1971, 36, 2035.