1

A REVIEW OF ORGANIC REACTIONS AND REAGENTS FOR CHEMISTRY 551

January 2002

Dr. B.A. Keay Department of Chemistry University of Calgary keay@ucalgary.ca

2 The following schemes illustrate most of the reactions you were taught in Chemistry 351/353, 354 and/or 451/453. To do well in Chemistry 551 you need to know these reactions and the reagents necessary to effect various chemical reactions. This list is only a guide. You should consult textbooks and reference books for further information on each of these reactions. Links are provided for each entry. Table of Contents Chem 351/353 and 354 Reactions
Preparation of Alkanes Reactions of Alkanes Preparation of Alkyl Halides Reactions of Alkyl Halides Preparation of Alcohols Reactions of Alcohols Preparation of Ethers Preparation of Alkenes Reactions of Alkenes Preparation of Alkynes Reactions of Alkynes Preparation of Epoxides Reactions of Epoxides Preparation of Aldehydes Preparation of Ketones Reactions of Aldehydes and Ketones Preparation of Carboxylic Acids Reactions of Carboxylic Acids Preparation of Acid Halides and Anhydrides Reactions of Acid Halides and Anhydrides Preparation of Esters Reactions of Esters Preparation of Amides Reactions of Amides Preparation of Lactones Reactions of Lactones Reactions Involving Carbanions Preparation of Amines Reactions of Amines Reactions of Benzene Reactions of Diazonium Salts Changing Directing Ability of Groups on Benzene Rings Diels-Alder Reactions Chem 451/453 Reactions Pericyclic Reactions (Cope, Claisen, Oxy-Cope, etc.) Other Sigmatropic Rearrangements Dipolar Cycloadditons Other Photochemical Reactions Rearrangements

Page
3 3 4 5 6 8 9 10 10 13 13 14 14 15 16 16 20 21 22 22 23 23 24 24 25 25 25 28 29 30 31 32 33 34 35 36 37 37

3 PREPARATION OF ALKANES 1. Hydrogenation of alkenes

H2 Pd, Pt, or Ni

2. Reduction of alkyl halides a. Hydrolysis of Grignard reagent

Mg R X X=Cl, Br, I ether R Mg X H2O R H

(b) Reduction by metal and acid

R X X=Cl, Br, I Zn HCl R H

3. Coupling of alkyl halides with organometallic compounds

R X Li CuI R Li R CuLi R R' X should be 1o

may be 1o, 2o or 3o X=Br or I

R R'

REACTIONS OF ALKANES 1. Halogenation

R H

X2

R X

Reactivity: X2: Cl2 > Br2 H: 3o > 2o > 1o > CH3 H

4 PREPARATION OF ALKYL HALIDES 1. From Alcohols

HX or PX3 R OH X=Cl, Br or I R X

2. Halogenation of certain hydrocarbons

R H

X2

R X

Reactivity: X2: Cl2 > Br2 H: 3o > 2o > 1o > CH3 H

3. Addition of hydrogen halides to alkenes.

HX C C
16 17 11

C C 12 H X

X=Cl or Br H usually attaches to least subsituted carbon atom in double bond (Markovnikov addition)

4. Addition of halogens to alkenes or alkynes.

X2 C C X=Cl or Br trans-addition across double bonds in rings C C X X C C 2 X2 X X C C X X

5. Halide exchange
R X

NaI (or NaBr) acetone

R I (or Br)

NaCl

X=Cl or Br 1o >> 2o

NaCl ppt's from acetone and drive the reaction to completion

5 REACTIONS OF ALKYL HALIDES 1. Nucleophilic Substitution

R X

+ + + +

Z:

R z

R X

HOH2 O RO-

R OH R OH

alcohol alcohol

R OR

ether (Williamson ether synthesis) R' alkyne

-C

R'

R'-M

R R'

alkane coupling

M=Li or Mg

+ +

I-

R I

alkyl iodide

-CN

R CN

nitrile

+ R'COO+ + + +
R X NH3 NH2R' NHR'R" PPh3 AlCl3

R COOR' R NH2

ester

primary amine

R NHR' secondary amine R NR'R" tetiary amine + R PPh3 phosphonium salt (for Wittig reaction) Friedel-Crafts reaction

+
O

ArH

Ar R

3o halide is best otherwise carbocation rearrangements can occur O R O R'-X R'-X R R R' O R' alkylation of ketone enolates O O R alkylation of 1,3dicarbonyl systems

R=alkyl and/or OR

6 2. Dehydrohalogenation: Elimination
C C H X base C C

3. Preparation of Grignard reagent

R-X

Mg

ether R-Mg-X

4. Reduction
R-X

H+

R-H

M+

X-

M=Mg, Na, Zn e.g. Mg followed by water, Na/EtOH, Zn/HCl,

PREPARATION OF ALCOHOLS 1. Oxymercuration-demercuration

C C
16 17

Hg(OAc)2

H2O

NaBH4 C C 11 12 HO HgOAc C C 27 28 HO H Markovnikov addition

2. Hydroboration-Oxidation
3x C C
16 17

B 2 H6 diborane

C C 11 12 H BR2

H2O 2
27

C C 28 H OH

anti-Markovnikov addition

3. Grignard synthesis
O

R-Mg-X

ether

OMgX R

H2O

OH R

ketones or aldehydes

4. Hydrolysis of alkyl halides

R-X

-OH

R-OH

X-

usually requires a silver salt so can be very expensive

7 5. Aldol condensation
O O 2x R H base R R H OH R R O H

3-hydroxyaldehyde may eliminate upon workup -usually restricted to a condensation between the same aldehyde -crossed Aldol reactions provide complex mixtures of products

6. Reduction of ketones and aldehydes

R H aldehydes R R' ketones 1) H2) acid workup R' O 1) H2) acid workup H R OH H

1o alcohols R OH H

2o alcohols

-many sources of hydride -most common are: NaBH4, LiAlH4, DIBAL-H

7. Reductions of acids and esters

R HO O 1) LiAlH4 2) acid workup H R OH H

1o alcohols R R'O esters O 1) LiAlH4 2) acid workup H R OH H

R'-OH

1o alcohols

-NaBH4 will not reduce acids and esters -reductions with LiAlH4 cannot be stopped at the aldehyde

8 8. Hydroxylation of alkenes
C C

KMnO4 or NaIO4

C C HO OH cis-addition

MCPBA C C O epoxide

H2 O H+ C C HO OH anti-addition O O O Cl

MCPBA = meta-chloroperoxybenzoic acid

9. Hydrolysis of Esters
O R OR' H3O+ or NaOH, H2O R O OH

HO

R'

10. Misc.
C C

X2, H2O X=Cl, Br or I

C C X OH anti-addition

REACTIONS OF ALCOHOLS 1. Reaction with hydrogen halides

R OH

HX

R X

reactivityof HX: HI > HBr > HCl reactivity of ROH: allyl, benzyl > 3o > 2o > 1o -poor yielding, rearrangements and eliminations can occur BETTER IS: pyridine R OH NaX R OTs X=Cl, Br or I R X

TsCl

1o alcohol is best

9 2. Reaction with phosphorus trihalides

R OH

PX3

R X

X= Br or I

3. Dehydration
C C H OH 3o > 2o > 1o acid C C rearrangements may occur

4. Reactions as acids: reaction with active metals.

R OH

R OM

M = Na, K, Mg, Al, etc. Reactivity: MeOH > 1o > 2o > 3o

5. Ester formation
O R OH

+ R'

H+ OH R'

O OR

6. Oxidation
R H H R H H OH OH PDC or Swern oxidation KMnO4 HO R H O H R' R OH KMnO4 or K2Cr2O7 R' R O

aldehyde R O R" R' R OH KMnO4

ketone no reaction

carboxylic acid

PREPARATION OF ETHERS 1. Williamson Synthesis

R X

RO-

R OR

10 PREPARATION OF ALKENES 1. Dehydrohalogenation of alkyl halides

C C X X X=Cl, Br or I Zn C C

2. Reduction of Alkynes
R C C R H2 Lindlar catalyst R H R R C C R H NH3 Na or Li R H H R

REACTIONS OF ALKENES 1. Addition of hydrogen. Catalytic hydrogenation

H2 C C Pt. Pd, or Ni C C H H syn addition

2. Addition of halogens
X2 C C X=Cl or Br C C X X anti addition

3. Addition of hydrogen halides

HX H X X=Cl or Br E.g. HBr no peroxides Markovnikov addition Br HBr with peroxides anti-Markovnikov addition Br

11 4. Addition of Water
H2O H+ H OH

Markovnikov addition

5. Halohydrin formation
C C

X2, H2O X=Cl, Br or I

C C X OH anti-addition

6. Oxymercuration-demercuration
C C
16 17

Hg(OAc)2

H2O

NaBH4 C C 11 12 HO HgOAc C C 28 HO H
27

Markovnikov addition

7. Hydroboration-Oxidation
3x C C

B 2 H6 diborane

C C H BR2

H2O 2 C C H OH anti-Markovnikov addition

8. Addition of carbenes
C C E.g. HCCl3 + NaOH :CCl2 dichlorocarbene (neutral electron defficient species-very reactive)

":CH2" formed "in situ"

12 9. Epoxidation
C C MCPBA C C O epoxide O MCPBA = meta-chloroperoxybenzoic acid Cl O O

10. Hydroxylation
C C

KMnO4 or NaIO4

C C HO OH cis-addition

11. Polymerization -not useful in synthesis 12. Allylic Halogenation

NBS H C C low conc. Br C C NBS=N-bromosuccinimide= O Br N O

13. Ozonolysis
reductive workup C C

O3

O O O ozonide

Me2S or Zn

aldehydes and ketones

H2 O 2 oxidative workup

O OH

ketones and carboxylic acids

13 PREPARATION OF ALKYNES 1. Dehydrohalogenation of alkyl dihalides

X2 X X X=Cl or Br anti addition KOH X H NaNH2

2. Reaction of metal acetylides with primary alkyl halides

NaNH2 H RX C Na+ R must be primary X = Br or I R

REACTIONS OF ALKYNES 1. Addition of hydrogen

R C C R H2 Lindlar catalyst 2 x H2 Pd, Pt or Ni R H R R C C R H NH3 Na or Li R H H R

H2 Pd, Pt or Ni

R HH

R H H

H2 Pd, Pt or Ni

2. Addition of halogens
X2 R C C R R X X2 = Cl2 or Br2 X R X2 R X X R X X

3. Addition of hydrogen halides

R C C R HX R H HX = HCl, HBr, HI X R HX R HH R X X

14 4. Addition of water
R C C R

H2O

H2SO4 HgSO4

R H

OH R

R H

O R

enol tautomerizes to ketone immediately

5. Formation of metal acetylides

NaNH2 H C Na+

PREPARATION OF EPOXIDES 1. From alkenes

epoxide C C 28 O -the more electron rich the double bond O the better the yield C C
16 17 27

MCPBA

MCPBA = meta-chloroperoxybenzoic acid Cl O H 2O 2 NaOH O O

O O

-only with conjugated enones, i.e. electron poor double bonds

2. From halohydrins
C C

X2, H2O X=Cl, Br or I

C C X OH anti-addition

NaOH C C O X and OH must be anti-periplanar for epoxide to form

REACTIONS OF EPOXIDES 1. Acid-catalyzed opening

H+ C C 11 12 O
39

Z: C C 38 O+ H

11

Z C C
12

OH

anti-opening

15

2. Base opening
Z:-

C C O

Z C C OH anti-opening

Z:- can be: RO-, RS-, R2NH, etc.

3. Reaction with Grignard reagents

R-Mg-X

H+ workup C C O

R C C OH anti-opening

PREPARATION OF ALDEHYDES 1. Oxidation of primary alcohols

R H H OH PDC or Swern oxidation R H O

aldehyde

2. Oxidation of methylbenzenes
H H H Cl2, heat or Br2, benzoyl peroxide H X X H O water

benzaldehyde

3. Reduction of acid chlorides

R Cl O LiAlH(OBu-t)3 R H O

acid chloride

aldehyde

4. Reimer-Tiemann reaction
OH CHCl3, NaOH 70 oC OH O H

-must have a phenol and aldehyde is always introduced into the ortho position to the hydroxy group

16 PREPARATION OF KETONES 1. Oxidation of secondary alcohols

R H R' OH KMnO4 or K2Cr2O7 R' R O

ketone

2. Friedel-Crafts acylation
R Cl O

Ar-H

AlCl3

R Ar O

3. Reaction of acid chlorides with organocopper compounds

R' CuX R-Li R2CuLi Cl O R R' O

4. Ethyl acetoacetate synthesis

CH3 EtO O

CH3 EtO O

1. NaOMe, MeOH 2. 10% HCl workup

O OEt

ethyl acetoacetate

REACTIONS OF ALDEHYDES AND KETONES 1. Oxidation

Aldehydes R-CHO or Ar-CHO KMnO4 or K2Cr2O7 R-CO2H or Ar-CO2H acidic workup

Methyl Ketones-haloform reaction O R or Ar O KOCl R-CO2H or Ar-CO2H acidic workup

CHCl3

17 2. Reduction to alcohols
Aldehydes NaBH4, MeOH R-CHO or Ar-CHO or LiAlH4 Ketones O R R' or Ar O R' NaBH4, MeOH or LiAlH4 R OH R' or Ar OH R' R-CH2OH or Ar-CH2OH acidic workup

3. Reduction to hydrocarbons
O Ar H or Ar O R' Zn(Hg) conc. HCl Ar H or Ar R'

Clemmensen reduction-must be an aromatic aldehyde or ketone O R R' H2NNH2 NaOH, heat R R'

Wolff-Kishner reduction

4. Reductive amination
O R R' H2NR NaCNBH3 pH 5 R NHR R'

5. Addition of cyanide
O R R'

H+
-CN

HO R

CN R'

cyanohydrin

18 6. Addition of derivatives of ammonia

O R R' HO

H2N-G

NHG R' Product N R N OH N NH2 N NHAr N R

G R'

H2N-G H2N-R H2N-OH

imine oxime

H2N-NH2

hydrazone

H2N-NHAr

phenyl hydrazone

H2N-NHCONH2

semicarbazone NHCONH2

7. Addition of alcohols
O R R'

2 R"OH

H+

R"O R

OR" R'

aldehyde or ketone

acetal or ketal

8. Addition of Grignard reagents

O R R'

H+ workup R"-Mg-X

HO R

R" R'

9. Halogenation of ketones
O R H X2 = Cl2, Br2, or I2 O

X2

H+ workup

R X

10. Addition of carbanions a) Aldol condensation

H CH3 O

CH3 H O

1% HCl or -OH

O H

19 b) Reactions related to aldol condensation

O NaOH O

Ar-CHO

Ar

c) Alkylation of Ketones
O 1) LDA, -78oC, THF 2) MeI O

O 1) KOtBu, HOtBu 2) MeI

Enamine Formation Followed by Alkylation

N H

N MeI

enamine H3O+

20 d) Wittig reaction
XX-CH2R

Ph3P

Ph3P+-CH2R phosphonium salt n-BuLi O R H H H

R'

Ph3P=CHR

R'

nonstabilized ylid

mainly Z-isomer

O R' H

H R'

R H

EtO2P=CHR stabilized ylid

mainly E-isomer

Wittig reactions can be done with unhindered ketones O H H

Ph3P=CH2

PREPARATION OF CARBOXYLIC ACIDS 1. Oxidation of primary alcohols

R H H OH KMnO4 NaOH 0 oC HO R O

carboxylic acid

2. Hydrolysis of Esters
O R OR' H3O+ or NaOH, H2O R O OH

HO

R'

3. Oxidation of alkylbenzenes
R KMnO4 NaOH heat CO2H -length and nature of R group does not matter -sidechain is cleaved to leave one carbon atom at the oxidation level of an acid

21 4. Carbonation of Grignard reagents

R-Mg-X

CO2

R-CO2-

HCl

R-CO2H

5. Hydrolysis of nitriles
R-CN

2 H2O

H+ or base

R-CO2H

NH3

REACTIONS OF CARBOXYLIC ACIDS 1. Acidity. Salt formation

R-COOH

NaOH

R-COO- Na+

H2 O

2. Conversion into functional derivatives a) Conversion into acid chlorides

O R OH SOCl2 PCl5 or PCl3 R O Cl

b) Conversion into esters

O R OH

H+ HOR' R

O OR'

H2O

c) Conversion into amides

O R OH SOCl2 R O Cl NH3 R O NH2

3. Reduction
O R OH LiAlH4 R OH

1o alcohol

4. Reaction with X2
Hell-Volhard-Zelinsky reaction O R OH red phosphorus Br2 or Cl2 O R X OH

22 PREPARATION OF ACID HALIDES AND ANHYDRIDES From Carboxylic Acids

Acid Chlorides O R OH SOCl2 R O Cl Cl O Cl O oxalyl chloride

or oxalyl chloride

Acid Anhydrides O R OH + R O OH P2O 5 R O O O R

O R Cl

+ R

O OH R

O O

O R

REACTIONS OF ACID CHLORIDES AND ANHYDRIDES Acid Chlorides

O R Cl + R O OH R O O O R

anhydride O R R ketone O R H aldehyde OH R H LiAlH4 LiAlH(OiPr)3 R O Cl HOR' R O OR' R2Cd water R O OH acid

ester H2NR2 R O NR2

alcohol

amide O 2 R OH acid

Acid Anhydrides
O R NR2

acid

H2NR2 R

O O

O R

water

amide HOR' R O

OR' ester

acid

23 PREPARATION OF ESTERS 1. From acids

O R OH

H+ HOR' R

O OR'

H2O

2. From acid chlorides or anhydrides

O R Cl O

HOR'

OR'

HCl

O R O

O R

HOR'

OR'

O R OH

anhydride

3. From esters: Transesterification

O R OR'

H+ HOR" R

O OR"

HOR'

REACTIONS OF ESTERS 1. Conversion into acids and acid derivatives a) Conversion into acids. Hydrolysis
O R OR' H+ or HOO R OH

H2 O

HOR'

b) Conversion into amides

O R OR'

NR2

H+ heat R

O NR2

HOR'

c) Conversion into esters. Transesterification

O R OR'

H+ HOR" R

O OR"

HOR'

2. Reaction with Grignard reagents

O R OR' R"

2 R"MgX

R" OH

3o alcohol

24 3. Reduction to alcohols
O R OR' LiAlH4 R OH

HOR'

1o alcohol

4. Reaction with carbanions. Claisen condensation

O 2 R OR' NaOR' heat O R R 3-keto esters O OR'

PREPARATION OF AMIDES 1. From acid chlorides

O R OH SOCl2 R O Cl HNR2 R O NR2

2. From nitriles
N R HCl H2 O heat R O NH2

REACTIONS OF AMIDES 1. Preparation of acids

O R NH2 H2SO4 H2 O heat R O OH

2. Reduction to amines
O R NR2 LiAlH4 R NR2

an amine

25 PREPARATION OF LACTONES
Baeyer-Villiger Reaction O MCPBA O O

-ring expansion and formation of lactone -oxygen atom introduced to side of ketone that is most substituted

H O HO

P2O 5

remove water -5 and 6 membered lactones are easest to form

REACTIONS OF LACTONES
O O LiAlH4 OH OH

diol O O DIBAL-H -78 oC, DCM lactol O OH

REACTIONS INVOLVING CARBANIONS 1. Halogenation of ketones

O R R' Br2 or Cl2 H+ or HOO R X R'

2. Nucleophilic addition to carbonyl compounds a) Aldol condensation

H+ or O 2 R H NaOR' heat R R OH O H H+ R R O H

26 b) Reactions related to aldol condensation

H+ or O 2 R ketone R' NaOR' heat R OH O R' R' R H+ R R R' O R'

c) Addition of Grignard and organolithium reagents

O R H R'MgX OH R R' H R

O OR'' esters

or R'Li

R'MgX or R'Li R

OH R' R'

aldehyde O R R" R'MgX or R'Li R OH R' R"

+
H OR''

ketone

d) Wittig reaction
O R H R" R" R' R R' H

R3P ylid

aldehyde

mixture of E and Z

O R R"

R"

R" R' R

R' R"

R3P ylid

ketone

mixture of E and Z

3. Nucleophilic acyl substitution a) Claisen condensation

O 2 R OR' NaOR' heat O R R 3-keto esters O OR'

27 4. Nucleophilic aliphatic substitution a) Coupling of alkyl halides with organometallic compounds

R X Li CuI R Li R CuLi R R' X should be 1o

may be 1o, 2o or 3o X=Br or I

R R'

b) Synthesis of acetylides
NaNH2 H RX C Na+ R must be primary X = Br or I R

c) Alkylation of malonic ester and acetoacetic ester

O R'O O OR'

NaOR' R"X heat R'O

O R" O R R"

O OR'

malonic ester O R O OR'

NaOR' R"X heat

O OR'

acetoacetic esters

d) Alkylation of ketones
O R 1) LDA, -78 oC, THF 2) R'X kinetic control O R 1) KOtBu, HOtBu, heat 2) R'X thermodynamic control R R' O O R R'

28 5. Addition to conjugated carbonyl compounds. Michael addition

R O R2CuLi R Micheal addition or conjugate addition enolate R O R2CuLi R enolate Robinson Annelation O O OCuLi R'X O R' R trans-stereochemistry OCuLi water R O

+
O O

NaOMe MeOH O

6. Reformansky Reaction
O R R' O

R'' Br

Zn OMe

O R'' R R' OMe OH

PREPARATION OF AMINES 1. Reduction of nitro compounds

Ar-NO2 or R-NO2 H2, Pd/C Zn, HCl Ar-NH2 or R-NH2

2. Reaction of halides with ammonia or amines

RX NH3 RNH2 1o amine RX RX R2NH 2o amine RX R3N 3o amine R4N+ Xquaternary ammonium salt

29 3. Reductive amination
O R R' H2NR NaCNBH3 pH 5 R NHR R'

4. Reduction of Nitriles
N R LiAlH4 or 2H2, Pd/C R NH2

5. Hofmann degradation of amides

O R NH2 KOBr R NH2

CO3-

chain loses one carbon atom in length O NH2 KOBr NH2

rearrangement with retention of stereochemistry

REACTIONS OF AMINES 1. Basicity. Salt Formation

R2NH 2o amine HCl ClR2N+H2 ammonium salt

2. Alkylation
RX NH3 RNH2 1o amine RX RX R2NH 2o amine RX R3N 3o amine R4N+ Xquaternary ammonium salt

3. Conversion into Amides

O R2NH O Cl R' NR2

R'

amide

30 4. Hofmann Elimination from Quaternary Ammonium Salts

NR2 RI

NR3

NaOH, heat

REACTIONS OF BENZENE
Electrophilic Aromatic Substitution of Benzene Br Cl

Br2, FeBr3 Cl2, FeCl3 SO3H SO3, H2SO4 HNO3, H2SO4 X R AlCl3 R Friedel-Crafts Alkylation rearrangements can occur with primary halides R O Cl O R AlCl3 Na, NH3(l)

Birch Reduction

NO2

Friedel-Crafts Acylation

Reactions to Remove Groups to give Benzene Br Cl Mg, ether then H2O 1) NaNO2, HCl 2) H3PO2 NH2

Mg, ether then H2O SO3H KOH, heat

31
Eelectrophilic Aromatic Substitution on Substituted Aromatic Systems Ortho/para Directors strong -NR2 -NH2 -OH -OR -NHCOMe -OCOMe -R -H Meta Directors -NR3 -NO2 -CN -SO3H -CHO -COMe -CO2H -CO2Me -CONH2 -NH3

strong

weak

weak

Activators -make benzene ring electron richer

Deactivators -make benzene ring electron poor

Halides are deactivating but ortho/para directors!! -F -Cl -Br -I

REACTIONS OF DIAZONIUM SALTS

Formation of and Reaction of Diazonium Salts NO2 Zn, HCl NH2 Cl NaNO2, HCl Br N N ClDiazo dyes H3PO2 or NaBH4 CuCl

N2 KI

HBF4 Cu, NaNO2 (aq) H2O, H2SO4 heat CuCN F

NO2

OH CN

N2 CO2H

Clwarm

Benzyne

32 CHANGING DIRECTING ABILITY OF GROUPS ON BENZENE RINGS

Changing Activators into Deactivators

KMnO4

CO2H

NH2

NaNO2, HCl

see diazonium wagonwheel

Changing Deactivators into Activators NO2

NH2

CHO H2NNH2, KOH heat O Zn, HCl

33 DIELS-ALDER REACTION

+
diene dienophile

Normal electron demand Diels-Alder reaction requires the dienophile have at least one electron withdrawing group attached and the diene should be electron rich. Reverse electron demand Diels-Alder reaction requires the diene have at least one electron withdrawing group attached and the dienophile should be electron rich.

Endo vs Exo Products O H

+
H

+
O endo product -kinetic product

exo product -thermodynamic product

Endo product forms the fastest due to secondary orbital overlap and is the kinetic product. Exo product forms if the reaction proceeds for a longer period of time (i.e. and is reversible). The exo product is thermodynamically more stable due to less steric crowding. Regiochemistry Diels-Alder reactions with unsymmetrical electron rich dienes and electron poor dienophiles give mainly cyclohexenes with the substituents in either a 1,2- or 1,4- orientation. R R

EWG

EWG

1,2-product R R

EWG

EWG 1,4-product

34 PERICYCLIC REACTIONS
These are examples of [3,3] Sigmatropic Rearrangements Cope Reaction R' R R' R

Oxy-Cope Reaction HO R' R Aza-Cope Reaction R2N R' R Claisen Reaction H R' O R 4-enal Ortho-ester Claisen Reaction OR O R' R Ortho-amide Claisen Reaction NR2 O R' R O NR2 R' R 4-enamide O OR R' R 4-enoate R2N R' R enamine H O R' R H3O+ O H R' R HO R' R O H R' R

35 OTHER SIGMATROPIC REARRANGEMENTS

You have been shown[1,3] and [1,5]-H and alkyl shifts with heat or light. These will not be shown here. [1,2] Wittig Rearrangement

n-BuLi

OH

[2,3] Wittig Rearrangement

n-BuLi

OH

[1,2] StevensRearrangement
+

base

Sommelet-Hauser Rearrangements ([2,3] Rearrangement) S

+

base

36 DIPOLAR CYCLOADDITIONS

+
A

C3

D E e.g. O a) MeO CO2Me

B 8 C A D E

C 13

B 18 C A D E

D E

MeO2C

N CO2Me

-O b)

O O

O O O

ozonide

Electrocyclic Reactions Follow the Woodward-Hoffman Rules (Chem 453) heat

[2 + 2] Cycloadditions + light

O R

+ R'

light R

O R'

Paterno-Buchi reaction not all permutations are shown

37 OTHER PHOTOCHEMICAL REACTIONS

Barton Reaction HO R NOCl NO O R light HO ON R

O nitrite ester

-conversion of a delta methyl group to an OH into an aldehyde H OH N HO

O HO

O aldehyde

O oxime

REARRANGEMENTS
Arndt-Eistert Synthesis -chain lengthened by one carbon atom O R Cl N2 H2O CHN2 Ag2O

O CH2N2 R

+
R

H2 O

O R OH

ketene Wolff Rearrangement Wagner-Meerwin Migrations -formation of carbocations followed by migration of alkyl, H, or aryl groups R1 H R2 R3 R5 Benzil-Benzilic Acid Rearrangement O Ar O Pinacol Rearrangement R3 R2 R4 R1 OH OH H+ R2 O R3 R4 R1 Ar NaOH Ar Ar OH OH O OH R2

H+ R3

R1 R5

Beckmann Rearrangement OH O N HONH2

H+

H N

oxime

lactam

38
Hofmann Rearrangement O NH2 NaOBr N C O hydrolysis
17

NH2

isocyanate Curtius Rearrangement O Cl NaN3 O N3 acyl azide Schmidt Reaction O OH heat

retention of stereochemistry hydrolysis N C O

53

isocyanate

HN3