Chem 206 Due: Friday, Nov.

10

Problem Set 7 Name:_____________ TF:_______________

General Instructions: Neatly, in the space allocated, provide concise answers to the following questions using clear
three-dimensional representations for all relevant structures. Address stereochemical and stereoelectronic issues
where appropriate.

Question 1. The following transformation was recently reported by Kabalka. Treatment of 1 with allylboronic acid
afforded the indicated adduct in high yield with 10:1 diastereoselection. On the other hand, the analogous reaction
of 2 was nonstereoselective. Propose a mechanism for this transformation that accounts for the stereochemical
outcome of the addition process.
OR O OH OH
25 °C
Ph
B(OH)2 45-55% Ph
diastereoselection 10:1
Me
1, R = H Me
2, R = Me
Question 2. Give your choice of a protecting group and reagent, and justify your answer with 3D drawings:

a)
O OH

Me reagent? Me
Me Me

OPG OPG

OH
O
b) MgBr reagent?
Me Me Me
+ Me
Me Me OPG
OPG
Question 2, continued

c) OPG O OPG OH

Me reagent? Me
Me Me

Me Me

OPG O OH OPG
OTMS
d) Me reagent?
Me
O + t-Bu
t-Bu
Me Me Me Me
Question 3. P. A. Evans and co-workers have recently reported a highly diastereoselective approach to the
construction of linked tetrahydropyrans. One of their cases is illustrated in Eq 1. In this transformation BiBr3 is
employed as a mild Lewis acid.

OSiMe3
1 OHC
Me 1) BiBr3
(1)
2) Et3SiH Me O O Me
OTMS OSi(i-Pr)3 H H
2 A single diastereoisomer
Me diastereoselection: 95:5 (73% yield)

Please provide a mechanism for the reaction cascade that results in the production of the illustrated product.
Your answer should include clear 3-D drawings where relevant and should provide the stereochemistry of the
major product diastereoisomer.
Question 4. Corey's CBS catalyst for ketone reduction often delivers high yields of enantioenriched secondary
alcohols. Provide a clear illustration of the transition state which predicts the absolute stereochemistry of the
product obtained in the illustrated reaction. Include an explanation of why the reduction of this practically symmetric
ketone is selective.
1 equiv.
O O HO H
B H
O

MeO NO2
0.15 equiv. CBS MeO NO2
H
Ph 75 % ee
Ph

O
N
B

Me
 Question 5. In each of the following reactions, provide the stereostructure of the major product and rationalize the
stereochemical outcome using clear 3D-drawings or Newman projections
Me

Ph H
+ BF3-OEt2
OTMS O CH2Cl2, -78 °C
Stereoselection: 16:1

Me

MeO Ph Zn(BH4)2
Et2O
O Stereoselection: 32/1

O
Me4N(AcO)3BH
OH
N

CO2Me CO2Me

O
Me
C8H17 LiEt3BH

TMS

Me Me i. PhNCO, Et3N;
O2N
ii. Raney-Ni
Stereoselection: 16:1
Question 6. Chiral auxiliaries (Xc) are routinely employed to control the absolute stereochemistry of the addition or
organometallic reagents to imines (Step A). A design requirement of these controllers is that they may be readily
cleaved after the addition step (Step B). In the two parts of this question posed below are presented two well-
established chiral controllers that employ chelate organization as an integral part of the chirality transfer process.

H R" R"
R'–M chemistry
Xc Xc
N R Step A N * R Step B H2N R
H *

Part A. Provide a mechanism for the following transformation reported by Ellman and co-workers. Include a clear
transition state representation that predicts the major product diastereomer. Clearly illustrate the absolute
stereochemistry of the product.
O H O Et
EtMgBr
S S diastereomer ratio 92:8
Me3C N Ph CH2Cl2 Me3C N Ph
H

Part B. The following stereoselective transformation has been reported by Fujisawa. Given the stereostructure of
the product, rationalize the stereochemical outcome.
Ph Ph
OMe R"-Li OMe
N HN diastereomer ratio >97:3

R H R R"
Question 7. This is a classic problem in multistep electron pushing. The following pyridine synthesis
has been reported by Tohda. Provide a plausible mechanism for this complex transformation.

O
O2N NO2
O2N Boc
NH3, MeOH N
+ other organic
N O N fragment(s)
N
Me Boc
Question 8. Chiral amino alcohol 1 efficiently mediates the addition of diethylzinc to aromatic aldehydes. While a
number of other amino alcohols are also effective in controlling the absolute course of the addition process, this
amino alcohol has been the focus of a recent computational investigation that addresses the preferred transition
state geometry for this addition process. It should be noted that, while 1 is not the actual catalyst, it is modified
under the reaction conditions to the competent catalytic agent.

O OH

6 mol-% 1 (S) Et
N H 97% ee
Ph Et2Zn, 0 °C
toluene
Ph (R)
Ph
1 OH

Provide a detailed mechanism for the overall transformation in the space below. Use three-dimensional
representations to illustrate the absolute stereochemical aspects of the indicated transformation.
Question 9. Crotyltitanium reagents have been developed for addition to C=O and C=N bonds.
OH OH
O Me TiX3
+
Ph Ph
Ph H Et2O
Me Me
major minor

R NHR NHR
N Me TiX3
+
Et Et
Et2O
Et H Me Me

minor major
Part A. Provide an explanation, including clear 3D drawings of the transition states, which account for the divergent
stereoselectivity observed in the addition reactions illustrated above.

Part B. The use of a chiral imine induces useful levels of asymmetric induction in this reaction. Provide an
explanation, including a clear 3D drawing of the transition state, which accounts for the preferred production of the
indicated diastereomer.
 HO O
Question 10. Solladie has used a chiral sulfoxide as an
O
auxiliary for the enantioselective synthesis of the lactonic O
moiety 1 of (+)-Compactin and (+)-Mevinolin.
Me O
Me
R=H: (+)-compactin
R=Me: (+)-mevinolin R

O O O i. NaH (1 eq) O O O O
ii. t-BuLi (2 eq)
S
MeO iii. O MeO pTol
2
S pTol
MenthylO DIBAL, THF
44%

O OH OH O O O OH O
Et2BOMe, NaBH4, 99%
* * S * S
MeO pTol MeO pTol
dr > 99:1 dr > 99:1

Explain which stereoselectivities are observed in the two reduction steps illustrated above. Use clear 3D
drawings for the transition states. What happens when the ZnCl2/DIBAL combination is used instead of
DIBAL for the reduction of 2?