Chapter 9 9.1 Which of the following objects are chiral? (a) A screwdriver (b) A screw (c) A bean stalk (d) A shoe (e) A hammer Solution: chiral objects: screw, bean stalk, shoe. 9.2 Identify the chirality centers in the following molecules. Build molecular models if you need help.

(a) (b) (c)

NH

CH2CH2CH3

Coniine(poison hemlock)

H

H CH3

HO

H

menthol(flavoring agent)

H

N

H

CH3

H3CO

Dextromethorphan(cough suppressant)

Solution:

(a),

NH

CH2CH2CH3

chirality center

(b),

H

H CH3

HO

H

chirality center(R)

chirality center(R) chirality center(S)

(c),

H

N

H

CH3

H3CO

chirality center(S)

chirality center(S)

R

9.3 Alanine, an amino acid found in proteins, is chiral. Draw the two enantiomers of alanine using the standard conversion of solid, wedged, and dashed lines.

CH3CHCO2HNH2

Alanine Solution:

H

NH2H3C

HO2C

H

H2NCH3

CO2H

S R

9.4 Identify the chirality centers in the following molecules. (a)

HOCH2

CC

HO H

OHH

HC

O

S (b)

C

H2C

F

H

Cl

O

F2C

H

R

9.5 A 1.50g sample of coiine, the toxic extract of poison hemlock,was dissolved in 10.0mL of ethanol and placed in a sample cell with a 5.00 cm pathlength. The observed rotation at the sodium D line was +1.21°. Calculate [α] D for coiine. Solution: Sample concentration: 1.50g/10.0mL=0.150g/mL [α] D=+1.21°/(0.150 g/mL *5.00*0.1dm)=16.1°

9.6 Assign priorities to the following sets of substituents: (a) ­H, ­Br, ­CH2CH3, ­CH2CH2OH Solution: ­Br > ­CH2CH2OH > ­CH2CH3 > ­H (b) ­CO2H, ­CO2CH3, ­CH2OH, ­OH Solution: ­OH > ­CO2CH3 > ­CO2H > ­CH2OH

(c) ­CN, ­CH2NH2, ­CH2NHCH3, ­NH2 Solution: ­NH2 > ­CN > ­CH2NHCH3 > ­CH2NH2 (d) ­Br, ­CH2Br, ­Cl, ­CH2Cl Solution: ­Br> ­Cl > ­CH2Br > ­CH2Cl 9.7 Orient each of the following drawings so that the lowest-priority group is toward the rear, and the assign R or S configuration:

1

342

3

421

4

213

Solution:

1

342

3

421

4

213

3

2

14

1

42

1

342 3

R SS

9.8 Assign R or S configuration to the chirality center in each of the following molecules:

C

CH3

COOHHBr

C

OH

H3C COOHH

NH2

CN

CH3H

(a) (b) (c)

Solution:

C

CH3

COOHHBr

C

OH

H3C COOHH

NH2

CN

CH3H

(a) (b) (c)

41 2

3

4

1

23

1

4

2

3

S S R 9.9 Draw a tetrahedral representation of (S)-2-pentanol (2-hydroxypentane). Solution:

H

HO

9.10 Assign R or S configuration to the chirality center in the following molecular model of the amino acid methionine(red=O, blue=N, yellow=S)

Solution: First you can change the molecular model into the corresponding line-bond structure following, and then assign R or S after identifying the priority of the atoms attaching to the chirality center:

H3CS

CH2

H2C

C O

O

H

H2N H

32

1

S

9.11 Assign R or S configuration to the chirality center in the following molecules. Which are

enantiomers, and which are diastereomers?

C

C

CH3

Br

OHH

H CH3

C

C

OH

CH3

HH3C

H BrC

C

OH

CH3

CH3H

Br HC

C

H

H

OHH3C

Br CH3

(a) (b) (c) (d) Solution: First you can identify the priority of the group attached to the chirality center as following Br 〉—OH 〉—CH3 〉H And then you can assign R or S easily:

C

C

CH3

Br

OHH

H CH3

C

C

OH

CH3

HH3C

H BrC

C

OH

CH3

CH3H

Br HC

C

H

H

OHH3C

Br CH3

R

R

S

R S S

SR

(a) (b) (c) (d)

Obviously (a) and (d), (b) and (c) are enantiomers for their mirror relationships, however, (a) and (d) are diastereomeric with (b) and (c). 9.12 Chloramphenicol, a powerful antibiotic isolated in 1949 form the Streptomyces venezuelae bacterium, is active against a broad spectrum of bacterial infections and is particularly valuable against typhoid fever. Assign R,S configurations to the chirality centers in chloramphenicol

O2N

H2C

OH

HN

H

H C CHCl

Cl

O

OH

Solution:

O2N

H2C

OH

HN

H

H C CHCl

Cl

O

OHR

1

23

R1

3

9.13 Assign R, S configuration to each chirality center in the following molecular model of the

amino acid isoleucine (red = O, blue = N): Solution S

S 9.14 Which of the following structures represent meso compounds?

(a)

H

HOH

OH

(b)

H

HOH

OH

(c)

H

CH3 (d) C

CH3C H

CH3Br

H

Br

Solution: (a) (d) 9.15 Which of the following have a meso form? (a) 2,3-Dibromobutane (b) 2,3-Dibromopentane (c) 2,4-Dibromopentane Solution: (a) (c) 9.16

Does the following structure represent a meso compound? If so, indicate the symmetry plane(red=O). Solution: It is a meso compound. The symmetry plane is shown as following :

OH

9.17 How many chirality centers does morphine have? How many stereoisomers of morphine are possible in principle?

HO OH H

OH

H

NCH3

*

*

*

*

*

morphine

There are five chirality centers in morphine .It has 25 stereoisomers in principle. 9.18 What stereoisomers would result from reaction of ( )-lactic acid with (S)-1-phenyl-ethylamine,and what is the relationship between them? Solution: The products of the reaction of ( )-lactic acid with (S)-1-phenyl-ethylamine is a R,S salt and a S,S salt. They are diastereomers. 9.19 What kinds of isomers are the following pairs? (a) (S)-5-Chloro-2-hexene and chlorocyclohexane (b) (2R,3R)-Dibromopentane and (2S,3R)-dibromopentane Solution: (a)

H Cl Cl

They are constitutional isomers. (b)

Br

Br

H

H

H

Br

Br

H

RR R

s

They are diastereomers. 9.20 Addition of Br2 to an unsymmetrical alkene such as cis-2-hexene leads to racemic 2,3-dibromohexane, even though reaction of Br- ion with the unsymmetrical bromonium intermediate is not equally likely at both ends. Make drawings of the intermediate and the products, and explain the observed stereochemical result. Solution:

cis-2-hexene

There are two intermediates leads to two products respectively.

H

Br

H

Br

BrH

H

Br

H

Br

H

BrH

Br

H

BrH Br

H

Br

H

S

Smajor

H

S

S

major

R

R

R

R

The result is that there are racemic mixture of (2S,3S) and (2R,3R) 2,3-dibromoheane. 9.21 Predict the stereochemistry outcome of the reaction of Br2 with trans-2-hexene, and explain your reasoning. Solution:

There are two intermediates lead to two products respectively.

BrH

Br

H

H

Br

Br

BrH

H

H

HH

Br

Br

Br

H

R

Br H

Br

HR

RS

majorS

Smajor

SR

H

The outcome is that racemic mixture of (2S,3R) and (2R,3S). The reason is that: the first step can occur equally well from either face of the double bond, to give a 50:50 mixture of enantiomeric bromonium ions. Because the bromonium ions do not have symmetry planes, reaction on the left and right is not equally likely, so an unequal mix of (2S,3R) or (2R,3S) and (2R,3S) or (2S,3R) will be formed from each. The minor product from one bromonium ion, however, will be the major product from the other, so overall a 50:50(racemic)mixture of (2S,3R) and (2R,3S) dibromides will result. 9.22: What products are formed from reaction of HBr with racemic (+)-4-methyl-hexene? What can you say about the relative amounts of the products? Is the product mixture optically active?

Solution: Racemic mixture (1R,3S),(1S,3S) and (1S,3R),(1R,3R) Ratio 50:50 Optically inactive

9.23: What products are formed from reaction of HBr with 4-methyl-cyclopentene? What can you say about the relative amounts of the products? Solution: Racemic mixture (1R,3R),(1S,3R) and (1S,3R),(1S,3S) Ratio not 50:50 9.24: Identify the indicated hydrogens in the following molecules as pro-R or pro-S. Solution:

(a)

H

HO

H

HHO

CHO

pro-Rpro-S

(b)

H

H3C

H

HH3N

CO2

pro-Spro-R

9.25 Identify the indicated faces in the following molecules as re or si:

(a) Solution:

CH3C

CH2OH

O

re face

si face

(b) Solution:

CC

CH2OHH3C

H

H

re face

si face

9.26 Lactic acid buildup in tired muscles results from reduction of pyruvate. If the reaction occurs from the re face, what is the stereochemistry of the product？

O

CH3C CO2

OH

CHH3C CO2

Solution: It’s

OH

H3C HCO2

and is S-Lactate. 9.27 Which of the following structures are identical?

(a) It’s R configuration.

(b) It’s R configuration.

(c)

It’s S configuration.

(d)

It’s R configuration. Solution: (a)(b)(d) are identical. 9.28: Assign R or S configuration to the chirality centers in the following molecules(red=O, blue=N):

(a) Serine (b)

Adrenaline

Solution: (a)

CN

H

HOHH

O

OHH

H (S)

Serine (b)

N

H OH

HHO

HO

(R)

Adrenaline

9.29: Witch, if any, of the following structures represent meso compounds?(red=O. blue=N, yellow-green=Cl.)

(a) (b)

(c)

Solution: (a)

HO OH

H H(S)

(R)

There are two chirality centers which are of different direction, and there is a symmetrical plane, so it is a meso-compound.

(b)

H HH2N H2N

(S)(R) Just the same as problem (a), there are two chirality centers which are

of different direction, and there is a symmetrical plane, so it is a meso compound.

(c)

H

H

Cl

Cl

(R) (R)

As there are two chirality centers with the same direction, it is not a meso compound. 9.30: Assign R or S configuration to each chirality center in paeudophedrine, an over-the-counter decongestant found in cold remedies(red=O, blue=N).

Solution:

N

HO H

H

H

(S) (R)

9.31 Polarimeters for measuring optical rotation are so sensitive that they can measure rotations to 0.0010, an important fact when only small amounts of sample are available. Ecdysone, for example, is an insect hormone that controls molting in the silkworm moth. When 7.00 mg ecdysone was dissolved in 1.00 ml chloroform and the solution was placed in a cell with a 2.00 cm pathlength, an observed rotation of +0.0870 was found. Calculate [α]D for ecdysone. Solution: C=7.00mg/1.00ml=0.007g/ml

[α]D=α/(l*C)= +0.0870/(2.00cm*0.007g/ml)=+62.140 9.32 Which of the following compounds are chiral? Draw them, and label the chirality centers. (a) 2,4-Dimethylheptane (b) 5-Ethyl-3,3-dimethylheptane (c) cis-1,4-Dichlorocyclohexane (d) 4,5-Dimethyl-2,6-octadiyne

Solution: (a) 2,4-Dimethylheptane and (d) 4,5-Dimethyl-2,6-octadiyne are chiral. Followings are their structures.

(a)

∗

CH3

CH3

(d)

∗

∗

HH CH3

CH3

9.33 Draw chiral molecules that meet the following descriptions: (a) A chloroalkane, C5H11Cl (b) An alcohol, C6H14O (c) An alkene, C6H12 (d) An alkane, C8H18

Solution: (a)

H3C CHH2C

H2C CH3

Cl

(b)

HC

H2C

H2C

H2C CH3H3C

OH (c)

H2C CH

HC

H2C CH3

CH3 (d)

CH3

9.34 Eight alcohols have the formula C5H12O. Draw them. Which are chiral?

Solution: Not chiral:

OH

OHOH

OHOH

Chiral:

OH

* OH

OH

**

9.35 Draw the nine chiral molecules that have the formula C6H13Br Solution:

*Br

Br

*

Br Br

Br

** * *

BrBr

BrCH2Br

*** *

9.36 Draw compounds that fit the following descriptions:

(a) A chiral alcohol with four carbons. (b) A chiral carboxylic acid with the formula C5H10O2 (c) A compound with two chirality centers (d) A chiral aldehyde with the formula C3H5BrO

Solution: (a) H3CH2CCOH

CH3H

(b)

CCOOH

H3CH2C HCH3

(c)

H OHCOOH

HO HCOOH

(d)

CCHO

H3C HBr

9.37 Draw examples of the following: (a) A basketball (b) A fork (c) A wine glass (d) A golf club (e) A monkey wrench (f) A snowflake Solution: (e) A monkey wrench is chiral. 9.38 Penicillin V is an important broad-spectrum antibiotic that contains three chirality centers. Identify them:

Solution:

O C

O

N

H

N

H H

O

SCH3

CH3

HCO2H

* *

*

Penicillin V

9.39 Draw examples of the following: (a) A meso compound with the formula C8H18

Solution:

C

C

CH3H

H CH3

CH2CH3

CH2CH3

(b) A meso compound with the formula C9H20

Solution:

CCH2

H

H3CH2CH3C

C

H

CH2CH3CH3

(c) A compound with two chirality centers, one R and the other S

Solution:

C

C

H Br

HH3C

CH3

OH

9.40 What is the relationship between the specific rotations of (2R,3R)-dichloropentane and (2S,3S)-dichloropentane? Between (2R,3S)-dichloropentane and (2R,3R)-dichloropentane? Solution: (2R,3R)-dichloropentane and (2S,3S)-dichloropentane are enantiomers.

(2R,3S)-dichloropentane and (2R,3R)-dichloropentane are diastereomers.

(R) (R)

Cl

Cl

(R) (S)

Cl

Cl

(S) (S)

Cl

Cl

(2R,3S)-dichloropentane(2R,3R)-dichloropentane (2S,3S)-dichloropentane

9.41 What is the stereochemical configuration of the enantiomer of (2S,4R)-dibromooctane? Solution: (2R,4S)-dibromooctane is the stereochemical configuration of the enantiomer of (2S,4R)-dibromooctane.

(2S,4R)-dibromooctane(2R,4S)-dibromooctane

Br

(S)(R)

BrBr

(R)(S)

Br

9.42 What are the stereochemical configurations of the two diastereomers of (2S,4R)-dibromooctane? Solution: (2S,4S)-dibromooctane and (2R,4R)-dibromooctane are the stereochemical configurations of the two diastereomers of (2S,4R)-dibromooctane.

(2S,4R)-dibromooctane

Br

(S)(R)

Br

Br

(S)(S)

Br

(2S,4S)-dibromooctane (2R,4R)-dibromooctane

Br

(R)(R)

Br

9.43 Orient each of the following drawings so that the lowest-priority group is toward the rear , and then assign R or S configuration:

(a).

G4

G3G1G2 (b).

G3

G1G4G2 (c).

G4

G2G3G1

Solution

(a). G3

G2G1

G4

R (b). G1

G3G2

G4

R (c). G2

G1G3

G4

R 9.44 Assign Cahn-Ingold-Prelog priorities to the following sets of substituents:

(a). CH

CH2 CH(CH3)2 C(CH3)3 CH2CH3

(b).

C CH CH

CH2 C(CH3)3

(c). CO2CH3 COCH3 CH2OCH3 CH2CH3

(d). C N CH2Br CH2CH2Br Br Solution:

(a). CH

CH2 CH(CH3)2C(CH3)3 CH2CH3> > >

(b).

C CH CH

CH2C(CH3)3>> >

(c). CO2CH3 COCH3 CH2OCH3 CH2CH3> > >

(d). C NCH2Br CH2CH2BrBr > > >

9.45 Assign R or S configuration to the chirality centers in the following molecules

(a).

H OH

(b).

Cl H

(c). HOH2C CO2H

H OCH3

Solution:

(a).

H OH

S (b).

Cl H

S

(c). HOH2C CO2H

H OCH3

S 9.46 Assign R or S configuration to each chirality center in the following molecules:

(a)

OH

H

H

Cl

S

S

(b)

CH3H

HCH2

H3C

S S

(c)

HO OH

H3C CH3

R S

9.47 Assign R or S configuration to each chirality center in the following biological molecules:

(a)

N N

S

HH

H

O

H H

CH2CH2CH2CH2CO2

Biotin

R

S

S

(b)

O

H

H

HO H

CO2H

HO H

Prostaglandin E1

S

R

R

S

9.48 Draw tetrahedral representations of the following molecules: (a) (S)-2-Butanol, CH3CH2CH(OH)CH3

C

OH

H3C CH2CH3H

(b) (R)-3-Chloro-1-pentene

C

Cl

CH

CH2CH3H

H2C

9.49 Draw tetrahedral representations of the two enantiomers of the amine acid cysteine,

HSCH2CH(NH2)COOH, and identify each as R or S. Solution:

C

H

HSH2CCOOH

NH2

C

H

CH2SHH2N

HOOC

S R 9.50 Which of the following pairs of structures represent the same enantiomers, and which represent

different enantiomers? (a) (b)

CN

Br

H3CH CH3

CN

HBr

Br

COOH

HNC CN

Br

HHOOC

(c) (d)

OH

CH3

HH3CH2C

CH2CH3

OH

HH3C H

COOH

H3CH2N

COOH

CH3

HH2N

Solution: (a) is different and (b), (c), (d) are the same. 9.51 Assign R or S configuration to each chirality center in the following molecules: (a) (b)

Br

H3C

H

H

CH3

Br

H

OH

NH2H

H

H

COOH

Solution: (a) (b)

Br

H3C

H

H

CH3

Br

S

S

H

OH

NH2H

H

H

COOHS

R

9.52 Draw tetrahedral representations of the following molecules.

(a) The 2S,3R enantiomer of 2,3-dibromopentane (b) The meso form of 3,5-dichloroheptane.

(a) H Br

HBr

(b)

H HCl Cl 9.53 Draw the meso form of eachof the following molecules, and indicate the plane of

symmetry in each.

(a)H HHOOH

The plane of symmetry

(b)

The plane of symmetry

(c)

OH

The plane of symmetry 9.54 Assign R or S configurations to the chirality centers in ascorbic acid (vitamin c)

9.55: Assign R or S sterochemistry to the chirality centers in the following Newman projections:

Cl

H3C H

H

CH3HH

CH3

H

OHH3C

H3C

S R

(a) (b)

9.56: Xylose is a common sugar found in many types of wood, including maple and cherry. Because it is much less prone to cause tooth decay than sucrose, xylose has been used in candy and chewing gum. Assign R or S configuration to the chirality center in xylose.

HO H

OHC

HO H

HHO

CH2OHR S R

9.57: Ribose, an essential part of ribonucleic acid (RNA), has the following structure:

H H

HO

HO H

OHH

CHO

HHO

(a) How many chirality centers does ribose have? Identify them

Solution: Three chirality centers.

∗

H H

HO∗

HO H

OHH

∗CHO

HHO

(b) How many stereoisomers of ribose are there? Solution: There are eight stereoisomers of ribose. (c) Draw the structure of the enantiomer of ribose.

Solution:

H H

HO

H OH

HHO

CHO

OHH

S S S

(d) Draw the structure of a diastereomer of ribose. Solution:

H H

HO

HO H

HHO

CHO

OHH

R S S

H H

HO

HO H

OHH

CHO

OHH

R SR

H H

HO

HO H

HHO

CHO

HHO

R RS

H H

HO

H OH

HHO

CHO

HHO

S RS

H H

HO

H OH

OHH

CHO

HHO

S RR

H H

HO

H OH

OHH

CHO

OHH

S SR

9.58 On catalytic hydrogenation over a platinum catalyst, ribose (Problem 9.57) is converted into ribitol. Is ribitol optically active or inactive? Explain.

HOCHO

H

H

OHH H

HOHO

CH2OH

H

H

OHH H

HO HHOHHO

Ribose Ribitol

HOC

H

H

OHH H

HO HHORibitol

H

H OH

Solution: The product ribitol is optically inactive , because it is Meso compound.

R S

S

9.59 Hydroxylation of cis-2-butene with OsO4 yields butane-2,3-diol. What steeochemistry do you expect for the product?

C CCH3

H

H3C

H

OsO4Pyridine

C C

H3C CH3H H

O OOs

O O

NaHSO3H2O

C C

H3C CH3H H

HO OHSR

9.60: Hydroxylation of cis-2-butene with OsO4 yields butane-2,3-diol. What steeochemistry do you expect for the product? Solution:

C CH

CH3

H3C

H

OsO4Pyridine

C C

H3C HH CH3

O OOs

O O

NaHSO3H2O

C C

H3C HH CH3

HO OHRR

9.61 Alkenes undergo reaction with peroxycarboxylic acids (RCO3H) to give threemembered-ring cyclic ethers called epoxices. For example, 4-octene reacts with a peroxyacid to yield 4,5-epoxyoctane:

CH3CH2CH2CH CHCH2CH2CH3 CH3CH2CH2CH CHCH2CH2CH3

ORCO3H

4-Octene 4,5-Epoxyoctane

Assuming that this epoxidation reaction occurs with syn stereochemistry, draw the structure obtained from epoxidation of cis-4-octene. Is the product chiral? How many chirality centers does it have? How would you describe it stereochemically? Solution:

RCO3H

O

cis-2,3-Dipropyl-oxiranecis-Oct-4-ene

S R

9.62 Answer Problem 9.61, assuming that the epoxidation reaction is carried out on trans-4-octene. Solution:

trans-Oct-4-ene

RCO3H

O

trans-2,3-Dipropyl-oxirane

R R

9.63 Identify the indicated hydrogens in the following molecules as pro-R or pro-S:

(a)

H H

HHO

COOHHOOC

(b)

H

H H3NH H

H

H3CS CO2

(c)

H H

HH3N

CO2HS

Solution:

a)

H

HO

H

H

HO2C

CO2H

pro-Rpro-S

b)

CO2H3CS

H

H H3N

H

H H

pro-S por-R

pro-R pro-S

c)

H

H3N

H

H

HS

CO2

pro-S pro-R

9.64 Identify the indicated faces in the following molecules as re or si:

(a) H3C

CCO2

O

(b) C

CH

CH3

HO2C

Solution:

(a)

H3CC

CO2

O

re

si

(b)

CC

HCH3

HO2C

si

re 9.65. Write the products of following reaction and indicate the stereochemistry obtained in each instance:

(a)Br2,H2ODMSO

?

(b) Br2CH2Cl2 ?

(c) OsO4NaHSO3

?

Solution:

(a)Br2,H2ODMSO

(b) Br2CH2Cl2

(c) OsO4NaHSO3

Br

H

H

OH

Br

H

H

Br

OH

OH

H

H

9.66. Draw all possible stereoisomers of cyclobutane-1,2-dicarboxylic acid, and indicate the interrelationships. Which, if any, are optically active? Do the sane for cyclobutane-1,3-dicarboxylic acid. Solution: the stereoisomers of cyclobutane-1,2-dicarboxylic acid:

HOOC HH

COOH

COOHH HOOC COOHH

H

COOH

H

1 2 3 1 and 2 are optically active.

the stereoisomers of cyclobutane-1,3-dicarboxylic acid:

H

COOH

HOOC

COOH

H

H

COOH

H

H

H

COOH

COOH

They are all optically inactive.

9.67 Compound A, C7H12, was found to be optically active. On catalytic reduction over a palladium catalyst, 2 equivalents of hydrogen were absorbed, yielding compound B, C7H16. On ozonolysis of A, two fragments were obtained. One fragment was identified as acetic acid. The other fragment, compound C, was an optically active carboxylic acid, C5H10O2.Write the reactions, and draw structures for A, B, C. Solution:

A. CH3C CCHC2H5

CH3

B. C3H7CHC2H5

CH3

C. C2H5CHCO2H

CH3

CH3C CCHC2H5

CH3

C3H7CHC2H5

CH32H2

Pd

C2H5CHCO2H

CH3

CH3C CCHC2H5

CH3

+ CH3CO2HO3

9.68 Compound A, C11H16O, was found to be an optically active alcohol. Despite its apparent unsaturation, no hydrogen was absorbed on catalytic reduction over a palladium catalyst. On treatment of A with dilute sulfuric acid, dehydration occurred and an optically inactive alkene B, C11H14, was produced as the major product. Alkene B, on ozonolysis, gave two products. One product was identified as propanal, C2H5CHO. Compound C, the other product, was shown to be a ketone, C8H8O. How many degrees of unsaturation does A have? Write the reactions, and identify A, B, and C. Solution: The degree of unsaturation of A is 4.

A.

C2H5CHCHCH3

OH

Ph

B. C2H5CH CCH3

Ph

C. CH3C

O

Ph

C2H5CHCHCH3

OH

Ph

C2H5CH CCH3

Ph

H2SO4

C2H5CH CCH3

Ph

CH3C

O

PhO3

+ C2H5CH

O

9.69 One of the steps in fat biosynthesis is the hydration of crotonate to yield 3-hydroxybutyrate. The reaction occurs by addition of —OH to the si face at C3, followed by protonation at C2, also from the si face. Draw the product of the reaction, showing the stereochemistry of each step.

H3CCO2

CHCH2CO2

OH3

2H3C

Solution:

H3CCO2

3

2H3C

CO2

OH

H

H H3CCO2

OH

H

H

H

9.70 The dehydration of citrate to yield cis-aconitate, a step in the citric acid cycle, involves the pro-R “arm” of citrate rather than the pro-S arm. Which of the following two products is formed?

CO2O2C

CO2HO

CO2O2C

CO2

CO2O2C

CO2or

Solution: This product is formed: CO2O2C

CO2

9.71 Hydration of cis-aconitate yields (2R, 3S)-isocitrate. Show the stereochemistry of the product, and tell whether the addition of the OH group takes place on the re or si face of cis-aconitate.

COO

COO

OOC

COO

COO

OOCH2O

cis-Aconitate

Isocitrate

OH

Solution: the stereochemistry of the product as follow

OH

O

-O

O

O-

O

-O

H

H

And the OH group takes place on the re face of the cis-aconitate 9.72 The so-called tetrahedranes are an interesting class compounds, the first example of which was synthesized in 1979. Make a model of a substituted tetrahedrane with four different substituents. Is it chiral? Explain.

W

X

YZ

Solution: It is chiral.because

W

X

YZ Y WZ

X

I II

II is mirror-image of I, and they are enantiomers. Therefore I is chiral.

9.73 llenes are compounds with adjacent carbon-carbon double bonds. Many allenes are chiral, even though

they don’t contain chirality centers. Mycomycin, for example, a naturally occurring antibiotic isolated from the bacterium Nocardia acidophilus, is chiral and has [α]D = -130º. Explain why mycomycin is chiral. Making a molecular model should be helpful.

HC C C C CH

C CH

CH

CH

CH

CH

CH2CO2H

Mycomycin (an allene)

Solution:

According to the molecular model, we can see the atoms are arranged symmetrically besides the carboxylic group. Except C1, there isn’t any symmetric element in the molecule, so the molecule is chiral.

9.74

Long before chiral allenes were known , the resolution of 4-methylcyclohexylideneacetic acid into two enantiomers had been carried out. Why is it chiral? What geometric similarity does it have to allenes?

C

H3C

H CO2H

H methylcyclohexylideneacetic acid Solution:

The geometry of the acid is similar to the allene, the atoms are arranged symmetrically besides the carboxylic group. Except C1, there isn’t any symmetric element in the molecule, so it is also chiral.

9.75

Suppose that racemic lactic acid reacts with methnol, CH3OH, to yield the ester, methyl lactate. What stereochemistry would you expect the products to have? What is the relationship of one product to another? Solution:

CCOOH

H

HO

H3C

CCH3

H

HO

HOOC

OHH3C

CCOOCH3

H

HO

H3C

CCH3

H

HO

H3COOC

S

R

S

R

50% 50%

50% 50%

9.76 Suppose that (S)-lactic reacts with (R)-2-butanol to form an ester. What stereochemistry

would you expect the products to have?

Solution:

CCOOH

H

HO

H3C

CC

H

HO

H3C

S

C

H

H3CH2CCH3

OH

R

O

O C

CH3

H

CH2CH3

S R

9.77 Suppose that racemic lactic acid reacts with (S)-2-butanol to form an ester (Problem 9.76). What stereochemistry does the product(s) have? What is the relationship of one product to another? Assuming that esters can be converted back into carboxylic acids, how might you use this reaction to resolve (±)-lactic acid? Solution： (1) The products are:

HHO CH3

OOCH3

H3C H

S

R

and

HHO CH3

OOCH3

H3C H

S

S

(2) They are diastereomers. (3) The diastereomers have different boiling point, so they can be separated by distillation. So we can let the racemic lactic acid reacts with (S)-2-butanol to form these two esters, then separate them by distillation, at last we can convert them back to (±)-lactic acid. 9.78 (S)-1-Chloro-2-methylbutane undergoes light-induced reaction with Cl2 by a radical mechanism to yield a mixture of products. Among the products are 1,4-dichloro-2-methylbutane and 1,2-dichloro-2-mehylbutane. (a)Write the reaction, showing the correct stereochemistry of the reactant. (b)One of the two products is optically active, but the other is optically inactive. Which is which? (c)What can you conclude about the stereochemistry of radical chlorination reactions? Solution: (a)

ClH2CCH3

H3C H

+ Cl2 hv Cl CH3 +

Cl CH2Cl

H3C Cl

H3C H

Cl CH3

Cl CH3

+

(b) 1,2-dichloro-2-mehylbutane is optically inactive, because it is racemic. (c) Conclusion: when forming 1,2-dichloro-2-mehylbutane,half inversion occurs. 9.79 Draw the structure of a meso compound that has five carbons and three chirality centers. Solution: Sorry, I don’t know. I am wondering how can a meso compound which has odd chirality centers.

（my solution:

CH3

H OHH OH

CH3

H OH

CH3

HO HH OH

CH3

HO H

S

RS

R

S

R

Both of them are meso-cpds, because of the symmetrical plane

(C3-H-OH).)

9.80 How many stereoisomers of 2,4-dibromo-3-chloropentane are there? Draw them, and indicate which are optically active. Solution:

CH3

Cl

Br Br

H3CH H

H

Cl

Br Br

H3CH CH3

CH3

Cl

Br Br

HCH3 H

(2R,4S)-Dibromo-3-chloro-pentane

(2S,4S)-Dibromo-3-chloro-pentane(2R,4R)-Dibromo-3-chloro-pentane

The first two of them are optically active. 9.81 Draw both cis- and trans-1,3-dimethylcyclohexane in their most stable chair conformations. (a) How many stereoisomers are there of cis-1,4-dimethylcyclohexane, and how many of

trans-1,4-dimethylcyclohexane? (b) Are any of the structures chiral? (c) Whar are the stereochemical relationships among the various stereoisomers of

1,4-dimethylcyclohexane? Solution:

CH3

CH3

CH3H3C

CH3

CH3

trans cis-1,4-dimethylcyclohexane trans-1,4-dimethylcyclohexane (a) There is only one cis-1,4-dimethylcyclohexane and two

trans-1,4-dimethylcyclohexanes. (b) Because of the existence of the symmetrical axes in cis or trans-1,4-dimethylcyclohexane,

neither of them have the structures chiral. (c) They are diastereomers, in more detailed description, they are configurations and

Cis-trans diastereomers. 9.82 Draw both cis- and trans-1,3-dimethylcyclohexane in their most stable chair conformations. (a) How many stereoisomers are there of cis-1,3-dimethylcyclohexane, and how many of

trans-1,3-dimethylcyclohexane? (b) Are any of the structures chiral? (c) Whar are the stereochemical relationships among the various stereoisomers of

1,3-dimethylcyclohexane? Solution:

CH3H3C

cis-1,3-dimethylcyclohexane

H3C

CH3 CH3

CH3

(1S,3S)-1,3-dimethylcyclohexane (1R,3R)-1,3-dimethylcyclohexane (a) There are one cis-1,3-dimethylcyclohexane and two trans-1,3-dimethylcyclohexanes. (b) They are all chiral. (c) They are diastereomers, in more detailed description, they are configurations and

Cis-trans diastereomers. 9.83 How can you explain the observation that cis-1,2-dimethylcyclohexane is optically inactive even it has two chirality centers? My Solutions :

H

CH3H

CH3

H

H3C

CH3

H

H

CH3CH3

H

H

H3C

CH3

H

A B

ring flip ring flipring flip

H

H3C

CH3

H

B

H

CH3H

CH3

A

racemic pairs

The resolution of them is impossible, for the ring flip is very fast.

9.84 An alkyl halide reacts with a nucleophile to give a substitution product by a mechanism that involves inversion of stereochemistry at carbon:

C XNu

CNu+ X

Formulate the reaction of (S)-2-bromobutane with HS- ion yield butane 2-thiol , CH3CH2CH(SH)CH3 .What is the stereochemistry of the product?

My Solution:

HBr HS

HHS

S R

9.85 Grignard reagents, RMgX, react with aldehaydes to yield alcohols. For example, the reaction of methylmagnesium bromide with propanal yields 2-butanol:

H3CH2C C H

O

H3CH2C C CH3

OH

H

1.CH3MgBr

2.H3O+

(a) Is the product chiral? Is it optically active? (b) How many stereoisomers of butanol are formed, what are their stereochemical relationships, and what are their relative amounts? Solution: (a) The product id chiral and it’s optically active.

(b) A pair of enatiomers.

C2H5 H

OH

CH3

OH

CH3

C2H5H

(R)- 2-butanol (S)- 2-butanol The ratio is 1 : 1 9.86 Imagine that another Grignard reaction similar to that in Problem 9.85 is carried out between methylmagnesium bromide and (R)-2-phenylpropanal to yield 3-phenyl-2-butanol:

CC

H

O

H CH3

H3CHC C

HCH3

OH

1.CH3MgBr

2.H3O+

(a) Is the product chiral? Is it optically active? (b) How manystereoisomers of 3-phenyl-2-butanol are formed, what are their stereochemical relationships ,and what are their relative amounts? Solution: (a) chiral product, optically active (b)

H

CH3

CH3Ph

HOH

H

CH3

CH3Ph

OHH

（2S,3R）-3-Phenyl-2-butanol (2R,3R)-3-Phenyl-2-butanol The ratio: 1 : 1 Meso-compound chiral product