1

Chapter 11
Alcohols, Ethers and Phenols
Alcoholsstructure, nomenclature and properties as before Phenolbenzene with OH attached
OH

EtherROR, where R = alkyl group

O

Simple ethers are named using the alkyl group attachements. Butyl pentyl ether above. ethyl methyl ether
O

tert-butyl ethyl ether

diethyl ether
O

In more complex molecules, ethers are named as alkyloxy. Examples methoxy, ethoxy

OH

6-tert-butoxy-5-ethoxy-2-methoxy-4- methyl-3-octen-1-ol

Cyclic ethers3-sidedoxirane, 4-sidedoxetane, 5-sidedTHF, 6-sided1,4-dioxane

O O O

Physical properties of ether No hydrogen bonding possible so ethers have low boiling points similar to hydrocarbons However because of Oxygen ethers are good solvents can dissolve organics and ionics. Some common examplesMethanolwood alcohol, originally prepared by distillation of wood toxic, small quantities can cause blindness, large quantitiesdeath Ethanoldrinking alcohol, made through fermentation of sugars sugars can come from many sources mostly grain, hence, grain alcohol Fermentation can only generate maximum 12-15%v/v of ethanol due to high solubility of water. To get higher percentages water must be distilled away. Hence Jack Daniels DistillariesProof = 2 xs the %. 100 proof = 50%. Even with distillation highest percentage possible is 95%. The last 5% of water can not be eliminated because it forms an azeotrope that boils at lower temperature than the ethanol itself. This is pure grain alcohol190 proof = 95%. To remove the last 5% water impurity, benzene is added and a new azeotrope forms that boils even lower than the water/ethanol azeotrope. 200 proof = 100 % is called absolute alcohol. It is denatured by adding a toxic substance such as methanol or benzene. This is called denatured alcohol. Ethylene glycolantifreeze Diethyl etherflammable used as anesthetic

Cl F3C C H O CF2H HFClC

F C F O CF2H

CH3OH CH3CH2OH Methanol Ethanol

OH

OH

Ethylene glycol

Isofluorane

Enfluorane

Synthesis of alcohols from alkenes

1) Acid-catalyzed hydration of alkenesChapter 8, not useful synthetically. Rearrangements make this a very non useful reaction. Markovnikov addition.
OH

H3O

2) Oxymercuration-DemercurationMarkovnikov addition. Usually less than one hour in 90-100% yields.

1) H 2O/Hg(acetate)2 THF 2) NaBH 4/OH
-

OH

Hg(OAc)2 H2O

Hg+OAc + OAcH2O
OH2

Like the halohydrin intermediate

+

Hg OAc

HgOAc

The mechanism for the removal of the HgOAc is not understood.

3) Hydroboration-OxidationAnti-Markovnikov addition 1) BH3:THF 3 2) H2O2/OH

H B H H B

OH

Boron adds to less substituted side. Hydrolyze

R= Transition state. B(OR)3 Repeat twice

syn addition

Transition state collapses.

H BH2 B O

Repeat twice

O B

H H O O

Reaction of Alcohols
The OH of the alcohol is basic and can act as a nucleophile. It is a very bad leaving group. Protonation of the alcohol makes the OH a good leaving group. Water has a pKa of 15.7. Most alcohols have higher pKa than water(the exception being methanol). This is due to the steric hindrance created by the alkyl groups. The large the alkyl group = higher the pKa which = less acidic. Acidity Water > ROH > Alkyne > H2 > NH3 > RH Basicity R- > NH2 - > H- > Alkynide- > RO - > OHCONVERTING OH TO GOOD LEAVING GROUP Mesylates, Tosylates and Triflates make very good leaving groups. Ms-Cl, Ts-Cl, Tf-Cl in the presence of base converts alcohols to those very good leaving groups. These mesylates, tosylates and triflates can undergo SN2 reactions very easily. In the process of converting OH to these good leaving groups the stereochemistry of the carbon remains unchanged(retention of configuration). However once the SN2 reaction occurs, then inversion of configuration occurs. Triflates are such good leaving groups that even vinylic cations can form.
O Ms O Cl O Ts S O R

Base(N aH ...)/MsCl
OH

Base(NaH ...)/TsCl

Ms = R = CH3
OT f

Base(N aH...)/TfCl

Ts =

CH 3

Tf = R = CF 3

OH Cl

B
S O R

OL

OL

L = Ms, Ts or Tf

To prepare Ms, Ts or Tf add PCl5 to the corresponding alcohol.

O

Ms = R = CH3 Ts =
CH3

PCl5
HO S O R Cl

O S O R

Tf = R = CF3

CONVERTING ALCOHOLS TO ALKYL HALIDES Acids such as HCl and HBr can be used to convert alcohols to alkyl halides. These reactions lead to carbocations and rearrangements(Primary and methyl still use SN2 mechanism to form the alkyl halides). HCl and HBr will usually produce alkylhalides instead of elimination(dehydration) products because Cl and Br are good nucleophiles. Recall if you want dehydration you add sulfuric acid or phosphoric acid. HCl and HBr work fine for allylic, benzylic and tertiary alcohols. However primary and secondary are too unreactive to work with HCl. So lewis acids are usually added to increase the reactivity. Phosphorous tribromide and thionyl chloride are modern alternatives that work extremely well. With primary and secondary alcohols phosphorous tribromide and thionyl chloride proceed with no carbocations and no rearrangements.

OH

Br

PBr 3

PBr2 O H

HOPBr2 This can react twice more with alcohol to brominate the alcohol

Br

O Cl S Cl Cl

OH

O H S O

Cl
Cl

O Cl S O

Cl-

trialkyl amines(such as triethylamine(TEA)) are used to scavenge the HCl that is formed in this reaction.

Synthesis of Ethers
BY DEHYDRATION OF ALCOHOLS Primary alcohols in the presence of acids create ethers with the elimination of water. Secondary and tertiary do not work well. Alkenes form instead(dehydration). Also mixed ethers do not form using this method.
2
OH

H2SO4
O
o

Reactions works ok with 1 since they are hard to dehydrate.

OH

H2SO4

H2SO4

OH

2 and 3 alcohols are easily dehydrated

OH

H2SO4

+
OH

Does not form.

WILLIAMSON SYNTHESIS The alcohol is deprotonated with a base such as sodium hydride. Then it reacts in an SN2 fasion with an alkyl halide. This results in the formation of an ether. Problem 11.20retention vs. inversion. One reaction only occurs at the oxygen. Therefore, retention of configuration of the original carbon is observed. The other reaction involves an SN2 attack and inversion of configuration.
1) NaOCH3 2) CH3I
OH O

OH

1) NaOEt 2) CH3CH2OTs

1)
OH

OK

2)

OMs O

The alcohol can be 1 , 2 , or 3 . The base should be an alkoxide base such as sodium ethoxide. The leaving group can be halogen or sulfonate. This is SN2 reaction. Therefore, 1 or 2 carbon attached to leaving group only.
o o

10

PROTECTING GROUPS Ethers can be used to protect alcohols. The alcohol is converted into an ether that is unreactive. Then reactions can be carried out on the compound without affecting the alcohol. Later the ether is removed to reveal the unchanged alcohol. The protecting group should be fairly nonreactive and should be easily removable. Tert-butyl ether is an OK protecting group. It is removed by dilute acid. One of the more modern preferred protecting groups is tert-butyldimethylsily ether(TBDMS) which is a large bulky group that is nonreactive to most reagents. It is easily removed in the presence of fluoride ion(TBAFtetrabutylammonium fluoride).
OH O TBDMS

TBDMS-Cl im idazole/DMF (pyridine can also be used)

OP

OR

T BDMS-Cl =
Si Cl

Bulky group. Can withstand pH from 4-12.

P = protecting group

OTBDMS

OH

TBAF/THF

TBAF =

N
-

OR (B u) 4NF
F Silicon-fluorine is one of the strongest covalent bonds. Fluorine seeks out the silicon and bonds to it.

11

REACTIONS OF ETHERS Ethers in general have low reactivity and usually act as solvents which can dissolve both covalents and ionics. The oxygen of the ether is basic and nucleophilic so some reactions are possible. Ethers react with strong acids to form alkyl halides.
Br O

HBr

AND
Br

EPOXIDES Epoxides are a special class of ethers. Epoxides are three-membered cyclic ethers. Alkenes will in the presence of peroxy acids(such as MMPP) will convert into epoxide. In the formation of the epoxide the stereochemistry of the double bond is retained(lik e in the Diels-Alder reaction). Epoxides are extremely reactive. Dilute acids can open up the epoxide to form a diol. Epoxides can also undergo nucleophilic attack. Just like in the halohydrin reaction from chapter 8,

the nucleophile attacks the more substituted carbon of the epoxide if the reaction is acid-catalyzed(formation of carbocation-like intermediate). If the reaction is base-catalyzed the nucleophile attacks the least substituted carbon(SN2 reaction). The attack of the nucleophile on the epoxide leads to an anti-product. If you use an alkoxide base(methoxide) the reaction produces a reactive intermediate. This reaction keeps repeating creating a polymer chain. This is called anionic polymerization. Methanol can be added to quench(stop) the reaction.

12

M M PP
O O

OOH

M M PP =

OH O

OH

H+
HO

+
HO

This is similar to the addition of acids to non-cyclic ethers. This is an anti-hydroxylation of an alkene. Unlike KMnO4 and OsdiO4 which give syn dihydroxylations. This reaction is analagous to the bromination reactions of Ch. 8. Acid-catalyzed reactions can be carried out with other nucleophile. This will also lead to anti-addition. The incoming nucleophile adds to the more substituted carbon, as in the halohydrin reaction. The intermediate is unsymmetric and resembles a carbocation.
Cl O

HCl

HO

Bases(nucleophiles) can also be used to open cyclic ethers(they can not open non-cyclic ethers). The base-catalyzed reaction is a SN2 reaction. This also leads to anti-addition. The incoming nucleophile attacks at the least substituted carbon.
OH O

NaCl

Cl

Stronger nucleophiles are needed. I used Cl just to make the point.

13

CROWN ETHERS Polar aprotic solvents greatly enhance and speed up SN2 reactions. However, there are disadvantages to polar aprotic solvents. They usually have high boiling points making them tough to remove at the end of the reaction. They need to be purified to be used in reactions(distilled). This is costly and time-consuming. Also at high temperatures, polar aprotic solvents can decompose. Nonpolar aprotics would be excellent solvents. Nonpolar aprotics would still greatly enhance SN2 reactions but without all the problems of polar aprotics. Benzene, toluene, hexanes, dichloromethane are examples of nonpolar aprotics. They are all low boiling point and fairly easily purified. The problem is the nonpolar aprotics do not dissolve ionic reagents because of their nonpolar nature. SN2 reactions usually require ionic reagents(sodium iodide, potassium bromide). A recent development called phase-transfer catalysts(PTC) help solve this problem. PTC are both hydrophilic and lipophilic. They can go into the aqueous layer grab the anion and then bring it into the organic layer where the reaction will take place. They will then bring the leaving group back to the aqueous layer and pick up another anion to start the process over again. Tetrabutylammonium fluoride is an example of a PTC. SN2 reactions work extremely well with PTC. Other reactions are possible. Oxidation with potassium permanganate can be carried out with PTC. A test for alkenes is to take a potassium permanganate solution with TBAF. An unknown is added to the permanganate(purple) solution. If the unknown contains double or triple bond then the purple solution will turn brown.

14

Crown ethers are also good PTC. Crown ethers can completely solvate the cation of the ionic substance creating a naked anion which then undergoes an SN2 reaction. The crown ether acts as the host and the cation that is trapped is called the guest. Crown ethers are named x-crown-y. X stands for the total number of atoms. Y is the number of oxygens. 18-crown-6 is especially good at solvating potassium.

O O

36-crown-12

O O O

15

REACTIONS FROM CHAPTERS 8, 11 and 12

HCl

Cl

HBr/CCl4

Br Br

HBr/H2O2

Br

Br2/H2O

OH

Br

Br2

Br

H3O+

OH

1) HgAcetate, THF, H2O 2) NaBH4, NaOH

OH OH

1) BH3:THF 2) H2O2, OH-

1) Hg(O2CCF3), CH3CH2CH2OH 2) NaBH4, NaOH

OCH2CH2CH3

16

Diazomethane

CH2I2/Zn(Cu)/diethyl ether

MMPP
O

1) MMPP 2) H
+

OH

OH

KMnO4, OH , H2O, cold

OH OH

1) OsO4, pyridine 2) NaHSO3, H2O

OH OH Br

Br2, H2O

1) MMPP 2) HBr

OH

OH

Br

Br

1) MMPP 2) NaBr

OH

17

1) KMnO4, OH-, H2O heat

5 6 4 3 2 1 5 3 4

O
1 2

b a c

2) H3O

+
c

O a

OH

OH O

1) KMnO4, OH-, H2O heat 2) H3O+

7 8 6 5 4 3 2 1 5 6 4 3

1 2

OH

a O

+
C

1) KMnO4, OH-, H2O heat

1

O
6 7 5 4 2 3 1

2) H3O+
b a

6 7 5

4 3

+
b

O a OH

1) KMnO4, OH-, H2O

1

heat
c b a

O
+
6 7 5 4 2 3 1

6 7 5

4 3

2) H3O

+
O b c

18

1) O3, CH2Cl2, -78oC 2) Zn, AcOH

5 6 4 3 2 1 6

5 4

1 2

b a c

+
c

O a

b O

1) O3, CH2Cl2, -78oC 2) Zn, AcOH

7 8 6 5 4 3 2 1 5 6 4 3 1 2

+
O a

H O

1) O3, CH2Cl2, -78oC

1

2) Zn, AcOH
7

6 5

2 3 1

6 7 5

4 3

b a

+
b

O a H

1) O3, CH2Cl2, -78oC

c b a

O
6 7 5 4 2 3 1

6 7 5

4 3

2) Zn, AcOH

+
O b c

19

Br

1 mole HBr
Br Br

2 moles HBr
Br

1 mole Br2
Br Br Br

2 moles Br2
Br

HgSO4, H2SO4, H2O

Br

1) O3 2) Zn, AcOH or 1) KMnO4, OH5 6 4 3 2 1 6 5 4 3 2

O
1

OH

2) H

+
H

O a OH O

1) O3 2) Zn, AcOH or 1) KMnO4, OH

4 5 3 2 1

5 4 3 2 1

a b

2) H

OH O a

+
b

OH

1) O3 2) Zn, AcOH or 1) KMnO4, OH2 3 1 3 2

O
1

a b

c d

2) H+
d

+
c b

OH O a OH

20

OH

NaH, TsCl

OTs

OH

OTf

NaH, TfCl

OH

OMs

NaH, MsCl

OH

OTBDMS

TBDMS-Cl, pyridine
OH

1) TBDMS-Cl, imidazole 2) TBAF/THF

OH

OH

HBr

Br

OH Br

PBr3

OH

OH

Br

Br

PBr3

OH OH

Br

SOCl2

Cl

21

OH

H2SO4
5 6 4 3 2 1

5 6 4

3 2

3 2 4

5 6

2 1 3

4 5

H2SO4
5

4 3

2 1

O
1

2 3

4 5

OH

OH

H2SO4

NO REACTION ONLY PRIMARY WORKS NO REACTION ONLY PRIMARY WORKS

H2SO4

OH

1) NaOMe 2) pentyl bromide

OH
5

4 3

2 1

1) NaOEt 2) hexyl iodide

OH

OH

1) NaH Br 2)

22

OH

H2CrO4
O OH

OH

KMnO4, OH-, H2O, Heat

OH O

OH

PCC
H OH O

Jones
OH O

H2CrO4 OR
OH

KMnO4, OH-, H2O, Heat H2CrO4 OR KMnO4, OH-, H2O, Heat NO REACTION TERTIARY ALCOHOLS DO NOT OXIDIZE

1) NaBH4 or H2/Pd or Na/MeOH or LAH 2) H3O

+

OH

1) NaBH4 or H2/Pd or Na/MeOH or LAH 2) H3O+

H

OH

OH

OH O

1) LAH 2) H3O+
OH

OCH3

1) LAH 2) H3O+

23

OH

1)
H O

MgBr

2) 1) 2)

H O+ 3
OH MgBr

H3O+
O

1)
OH

MgBr
+ HO 3

2)

OH

1)
OR

MgBr

2)

H3O+

1)
O

MgBr

2)

H3O+
OH

Grignard's attack less-substituted carbon

OH

1)
H O

2) 1) 2)

H 3O +
OH

H 3O +
O

1)
OH

2)

H3O +
O

1)
OR

2)

H 3O +

1)
O

2)

H 3O +
OH

Alkynide's attack less-substituted carbon

24

4 5 3

2 1

Br f g e d c b a

1) 2 Li/ether 2) CuI 3) heptyl bromide

f g e

d c

b a

Br

1) 2 Li/ether 2) CuI 3) phenylbromide

b c a

Br b

1) 2 Li/ether 2) CuI 3) Br
1 2 3 4 5 6 7

4 3 5

6 7

HOW DO YOU MAKE THIS?

a b c

a
Br

1) 2 Li/ether 2) CuI 3) Br

25

HOW DO YOU MAKE THIS?

a b c

b
Br

1) 2 Li/ether 2) CuI 3)
Br

Br

1) 2 Li/ether 2) CuI 3)
Br

d
Br

1) 2 Li/ether 2) CuI 3) Br

26

Bromination

Br

BrBr
Br Br Br

BrBr Br

Conversion to a good leaving group

OH Cl

B
S O R

OL

OL

L = Ms, Ts or Tf

27

Converstion of alcohol to halide

OH

Br

PBr3

PBr2 O H

HOPBr2 This can react twice more with alcohol to brominate the alcohol

BrO Cl S Cl Cl

OH

O H S O

ClCl O

O Cl S

Cl-

trialkyl amines(such as triethylamine(TEA)) are used to scavenge the HCl that is formed in this reaction.

28

Oxymercuration

1) HgAcetate/THF/H2O 2) NaOH/NaBH4
OH O O

HgAcetate = Hg(OCCH3)2 MECHANISM

OCCH3 = Ac

other steps

Hg(OAc)2

HgOAc + OAc
HgOAc

H O

H O

H O H

!+
HgOAc HgOAc

!+

29

Hydroboration
1) BH3:THF 2) H2O2/OH
-

OH H

MECHANISM + enatiomer

H H B H H B H H H B H

O B

unstable intermediate

R B R O OH

3 R
OR

R B R OR

repeat 2x's

RO B RO OR RO

OR B OH OH H OR

RO H

B O

OH

O R = ROH

30

Reduction of ketone/aldehyde
O OH

1) NaBH4
R(H) 2) H 3O + H3 B H H O OH2 R(H)

R(H)

Oxidation of alcohol
[Cr]
R(H) R(H)

OH O H O Cr O H O H R(H) H O

H 2O
H R(H)

O O HO HO Cr O H O H H O HO Cr

H 2O

R(H)

O HO H2 O Cr

31

OH

BH3
O OH

H+
BH2 O-

OHR 2B O OH O BR2

32

Chapter 11 Homework

Name:

1. For the reactions on the next two pages, indicate if they are Markovnikov or anti-Markovnikov, syn or anti addition. Also indicate which reactions are regioselective and which are stereospecific.

HCl

Cl

HBr/CCl4

Br Br

HBr/H2O2

Br

Br2/H2O

OH

Br

Br2

Br

H3O+

OH

1) HgAcetate, THF, H2O 2) NaBH4, NaOH

OH OH

1) BH3:THF 2) H2O2, OH-

1) Hg(O2CCF3), CH3CH2CH2OH 2) NaBH4, NaOH

OCH2CH2CH3

33

Diazomethane

CH2I2/Zn(Cu)/diethyl ether

MMPP
O

1) MMPP 2) H
+

OH

OH

KMnO4, OH , H2O, cold

OH OH

1) OsO4, pyridine 2) NaHSO3, H2O

OH OH Br

Br2, H2O

1) MMPP 2) HBr

OH

OH

Br

Br

1) MMPP 2) NaBr

OH

34

2. Fill in the products for the following reactions.

Excess HCl PBr5 SOCl2

1) NaH/Tf-Cl 2) NaSH MMPP

OH

1) MMPP 2) Excess HCl 1) TBDMS-Cl 2) BH3:THF 3) H2O2/OH4) NaH/CH3I 5) TBAF 6) NaH/TsCl 7) NaOMe/MeOH 1) MMPP 2) TBDMS-Cl 3) NaSH 4) PBr5 5) TBAF

35

3. Fill in the reagents needed to accomplish these changes.

Br

Br

OH

Br

Br

Br

Br

O O OH

OCH3 Br

OH

Br OH H3CO

36

KEY For the reactions on the next two pages, indicate if they are Markovnikov or anti-Markovnikov, syn or anti addition. Also indicate which reactions are regioselective and which are stereospecific.

HCl

Markovnikov and Regioselective

Markovnikov and Regioselective HBr/CCl4

Cl

Br Br

HBr/H2O2

Anti-Markovnikov and Regioselective

Br

Mark., Regio, Anti Addition, Stereo. Br2/H2O

OH

Br

Br2

Anti-Addiction, Stereo.

Br

H3O+

Markovnikov and Regioselective

1) HgAcetate, THF, H2O 2) NaBH4, NaOH

Markovnikov and Regioselective

OH

OH

OH

1) BH3:THF 2) H2O2, OH-

Anti-Mark., Regio, SYN Addition, Stereo.

Markovnikov and Regioselective 1) Hg(O2CCF3), CH3CH2CH2OH 2) NaBH4, NaOH

OCH2CH2CH3

37

Diazomethane

Syn addition, stereospecific

Syn addition, stereospecific CH2I2/Zn(Cu)/diethyl ether

MMPP

Syn addition, stereospecific

1) MMPP 2) H+

OH

Anti-addition, stereospecific

OH

KMnO4, OH , H2O, cold

Syn addition, stereospecific

OH

1) OsO4, pyridine 2) NaHSO3, H2O

Syn addition, stereospecific

OH

OH OH

Br2, H2O

Mark., Regio, Anti, Stereo.

Br

1) MMPP 2) HBr

Anti-Mark., Regio, Anti, Stereo.

OH

OH

Mark., Regio, Anti, Stereo. 1) MMPP 2) NaBr

Br

Br

OH

38

2. Fill in the products for the following reactions.

Cl

Br

Cl

Excess HCl PBr5 SOCl2

Cl

1) NaH/Tf-Cl 2) NaSH MMPP

SH

OH

1) MMPP 2) Excess HCl 1) TBDMS-Cl 2) BH3:THF 3) H2O2/OH4) NaH/CH3I 5) TBAF 6) NaH/TsCl 7) NaOMe/MeOH
Cl

1) MMPP 2) TBDMS-Cl 3) NaSH 4) PBr5 5) TBAF

OH

Cl

OH

Br

OCH3 OH SH

39

3. Fill in the reagents needed to accomplish these changes.

Br

Br

HBr

OH

1) NaH, TfCl 2) NaBr

Br

Br

1)

OK

1) NaOCH3 2) Ethyl iodide

Br

2) MMPP
Br

O O OH

1) TBDMS-Cl 2) NaBr 3) NaH, CH3I 4) TBAF

OCH3

1) TBDMS-Cl 2) HBr 3) NaH, CH3I 4) TBAF

Br

OH

Br OH H3CO

40

Homework

Name:

1. Fill in the products of these reactions.

1) MMPP 2) H+

1) MMPP 2) HBr

1) MMPP 2) NaSH 1) Hg(O2CCF3), Propanol 2) NaBH4, NaOH

PBr3

HBr TBDMS-Cl/NaH

OH

SOCl2

41

2. For the following, fill in the reagents.

OH

OH

OH OH

OH

OCH3

OH

HO

42

3. Show the mechanisms for the following.

HBr/H2O2

Br

OH

Br

PBr3

43

OH

Cl

SOCl2

OH

1) HgAcetate/THF/H2O 2) NaOH/NaBH4

44

1) BH3:THF 2) NaOH/H2O2
OH

45

Homework KEY
1. Fill in the products of these reactions.
OH OH OH Br

1) MMPP 2) H+

1) MMPP 2) HBr
SH

1) MMPP 2) NaSH 1) Hg(O2CCF3), Propanol 2) NaBH4, NaOH

OH

OCH2CH2CH3

Br

Br

PBr3

HBr TBDMS-Cl/NaH
OTBDMS

SOCl2

Cl

46

2. For the following, fill in the reagents.

OH

1) BH3:THF 2) H2O2, OH-

OH

1) NaH 2) Cl

OH

KMnO4, H2O, cold

OH

OH

1) TBDMS-Cl 2) BH3:THF 3) H2O2, OH4) NaH 5) CH3I 6) TBAF 7) TfCl 8) NaH 9) MMPP 10)H+

OH

OCH3

HO

47

5. Show the mechanisms for the following.

HBr/H2O2

Br

Heat or h

2 RO
H Br

ROH + Br

Br

Br
Br

Br

Br

OH

Br

PBr3

H O

PBr2

Br-

48

Cl OH

O S Cl Cl

O H O S Cl

Cl-

1) HgAcetate/THF/H2O 2) NaOH/NaBH4 HgOAc other steps

O H OH

HgOAc

H O

H O

+
HgOAc

HgOAc

49

1) BH3:THF
H H B H H H

2) NaOH/H2O2
OH

OBR2 H O O H O RO B OR

BR2 O OH

O BOR2

OH