Final Exam /415 ( CHEM 6352 Fall 2011

%) _______________________________Name Dec. 15th, 2011 8:00-12:00

You may NOT use any references or aids to complete the following with the exception of a chemical model set and the scrap paper that I provide at the end of the test. Note that showing proper stereochemistry and the rational for that stereochemistry will be graded. ALWAYS show a rationale for new stereochemistry (including substituted olefins) if a reaction would be selective. Also note that chiral structures with designated stereochemistry (i.e. hashes and wedges) are assumed to be enantiopure unless a racemic mixture is explicitly stated. You may use existing structures in the problems for your rational if appropriate. <<BONUS items are optional but worth additional points.>> (25 bonus points) Note that the following compounds can be used for any problem on the test. All other reagents you use may incorporate in the reaction product only 4 carbons or less in a given reaction.

BnBr SiCl

O

O

HO OH OH

C6H13

O

CHEM 6352 Library

NB

O

H Ph Ph

Bu

NB

O

HPhPh

Bu

Cl

O

O

OH Bu4NF

NHO

NHO

O

O

Ph

OH

NH

B

O

O

i-PrO2C

i-PrO2C

B

O

O

CO2i-Pr

CO2i-Pr

Et3N

Bu2BOTf

9-BBN

(EtO)2P(O)CHCO2Et

BrOH

O

HMPU

O

I

O

OAcAcO

OAc

I

O

BH

O

Ti

H2C

ClAl

Me

Me

Cp

Cp

TMS

TMS

Grubb's Catalyst

O O OHHEtHMeO

OO

H

O

TMSLi

1. Predict the major products and any new stereochemistry found therein. A. (10 points)

 

<<BONUS (5 points): What Baldwin’s rules classification(s) would used for bond formation here?>>

B. (10 points)

C. (10 points)

<<BONUS (10 points): provide a mechanism for this transformation.>>

KOt-Bu, HOt-BuO

OO

O

H

1) CBr4, PPh3, Zn

2) nBuLi (2 equiv)3) aqueous workup

O

H

P

N2

O OOEtOEt

D. (10 points)

E. (10 points)

F. (10 points)

OCN

KOt-Bu

OCN

KOt-Bu

O

O

h!

2. Provide reagents for these transformations. A. (5 points)

B. (5 points)

C. (5 points)

Ph

O

NMe2

O

Ph NMe2

O

Ph

O

NMe2

O

Ph NMe2

Ph

O

NMe2

O

Ph

O

NMe2

D. (10 points)

E. (10 points)

3. Pick your favorite name reaction! Provide the name of the reaction and an example of the overall transformation. Also, state why you think it is useful. (15 points)

PhPh

Br

OMe

O

OH OMe

O

O

4. Describe a synthesis of the compounds on the left from the starting materials on the right. Use reagents from the CHEM 6352 library or that add 4 carbons or less. A. (15 points)

B. (5 points)

O

HO

OOH

C. (5 points)

5. Draw a mechanism for the following reaction. (10 points)

O

OH

Ph OMe

O NH2NH2

65 °C HN NH

OPh

6. A. Predict the major product for the following reaction and provide a detailed explanation of the chemoselectivity, regioselectivity, and diastereoselectivity involved. (20 points)

B. Propose a strategy and reagents to make this reaction enantioselective and provide product B as one enantiomer. (10 points)

OMe

OOMe

TMSO

1) Me2AlCl (1.1 equiv)

CH2Cl2, -40 °C2) LiBH4

3) H3O+

A B

C. Using the enantiopure B made above, propose reagents to provide the final product shown below as one enantiomer. Give a reason for stereoselectivity. (10 points)

7. John Soderquist spoke to use about the allyl borane shown below. We also mentioned it in lecture. Show the transition state for this reagent reacting with the indicated aldehyde. Then, show the expected product for the reaction. (15 points)

 

OH

O

Me

B

BTMS

H

O

PhH2O workup

8. The following reactions would NOT give the indicated product. State WHY NOT. Predict the actual outcome of the reaction. A. (10 points)

B. (5 points)

C. (10 points)

O O

One Enantiomer! One Enantiomer!

Ph

LDA; BnBr

BrNaOMe

OMe

O

O

Brheat

O

O

Br

(±)H

D. (5 points)

E. (15 points)

NO

O O(Bu)2BOTf

Et3N

H

OOH

NO

O O OHOH

O O

O

mCPBA

9. Propose two different enantioselective syntheses for the following two molecules using substantially different strategies. A. (30 points)

Approach #1: Approach #2:

O

H

OMe

OBn

S

S

One Enantiomer!

O

H S

S

B. (30 points)

Approach #1: Approach #2:

O

H

OMe

OBn

S

S

One Enantiomer!

O

H S

S

10.Below is the entire synthetic sequence for Danishefsky’s approach to (+)-Estrone. A. Provide structures for synthetic intermediates of the sequence in the boxes provided. (25 points)

N

O OO1) Et3N

2) L-phenyl alanine, HClO43) NaBH4

1) H2, Pd/C

2) HO(CH2)2OH, H+

1) Li, NH3 (l)

2) NaOH then H+

OH

H

O

O

O

1) CrO3, H2SO4

2) pTsOH, AcOH

H

H

HHO

O

1) AcBr, Ac2O

2) K2CO3, MeOH

(+)-Estrone

B. Provide a mechanism for the Birch reduction/base/acid to form the enone shown below. You may abbreviate any unchanging portions of the compound as “R” groups. (10 points)

1) Li, NH3 (l)

2) NaOH then H+

OH

H

O

O

O

11. Propose an ENANTIOSELECTIVE synthesis for each of the following molecules. (25 points each) A.

H

H

One Enantiomer!

B.

OO

H

HOne Enantiomer!

C.

One Enantiomer!

OO

<<12. BONUS (10 points): Give an example of a new discovery that has appeared in the chemical literature during this semester. For full points you should include the name of the author and journal in which it appeared.>>