CHEM 30A/30B(Yves Rubin)

• Alkane Formation: Corey-Posner reaction. (THIS IS NOT COVERED IN F&B!)

H

R–X

D

1) Li

2) CuIR2CuLi R–R'

Br

Overview of most Reactions Emphasized in 30A / 30B

CH2Br

dialkyl cuprate

R'–X

only primary alkyl,secondary cyclic,or phenyl halide

any alkyl orcycloalkyl halidewith X = Cl, Br, I

C X

• Deprotonation/Protonation:

H

R'R

R–H B– or B:

RA-H

(or A-D; A-T)

CNu

any base strongerthan R–

H

R'R

any acid strongerthan R–H where H+,

D+, or T+ is transferred

1) NaNH2

2) D2O

Typical Example:

R–H (or R-D; R-T)

1) Li

2) CuI

Typical Example:

n-Bu2CuLi

• Nucleophilic Substitution: SN2

Nu– or Nu:

H3C Br

any non-tertiaryalkyl halide;

X = good leaving group

any good nucleophile;best in polar,

aprotic solvent

inversion of configurationat asymetric carbon

H3C CN

Typical Example:

K+CN–

DMF

C X

R"

R'R

CNu

R"

R'R

H3CBr

MeOH

+

CH3

H3COCH3

CH3

C Nu

R"

R'R

CH3

OH

CH3

SCH3

CH3

OTs

CH3

• Alkyl Sulfonate Formation: Formation of a good leaving group from R-OH

R"

Br

H

R–OH R–OSO2R'

good leaving grouppoor leaving group

R"

R'

• Nucleophilic Substitution: SN1

CH3S–Na+

DMSO

R'

• Elimination Reaction: E2

Nu:

best with tertiaryalkyl halides;

X = good leaving group

any weak nucleophile that istoo weak for SN2 reaction;

best in polar, protic solvent

racemization at asymetric carbon;planar carbocation as common intermediate

H

RR

R'–SO2Cl,

Et3N or pyridine

R' = CH3 (=>Ms; mesylate), CF3 (=>Tf; triflate), (=>Ts; tosylate)

Typical Example:

R"

R'

Typical Example:

TsCl

pyridine

antiperiplanararrangement

of H and Br in T.S.is required

RMeO–Na+

MeOH

Typical Example:

Br

t-BuO–K+

THF

CH3

small, strong base

most substituted alkene=> Zaitsev product

least substitutedalkene

CH3t-BuO–K+

THF

CH2MeO–Na+

MeOH

bulky, strong base

• Elimination Reaction: E1

Typical Example:

OH

X

RR'

CH2R"R R'

CH2R"

R R'

R"

CH3

CH3

Br

R

H+, heat

• Radical Reaction: Bromination of alkanes and cycloalkanes

Typical Example:

R–HBr2, hν

R–Br

Br2, hν

H3C

H3C

tertiary hydrogen isabstracted the fastest

• Hydrogenation: Alkenes and alkynes

H3C

H3C

carbocation rearrangeswhen more stable one can be formed

best with tertiary systemX = good leaving group

such as H2O, Br–

heat

R’ R”

H

syn additionH2, catalyst

D2 or T2 canbe used insteadcatalysts:

Pd-C, Pt, Raney-Ni

most substituted alkeneZaitsev product

RR'

R"H

Typical Example:

H2, Pd-C

H H

R R'

R R'

RR'

H3C EtH3C Et

H3CEt

R R'R

Br

Br

R'

Br

Br Br

1) Li, EtNH2

2) aq. NH4Cl

trans-alkenecis-alkene

H2, Ni2B

(or Lindlar'scatalyst)

• Controlled Reduction of Alkynes:

1) Li, EtNH2

2) aq. NH4Cl

H2, Ni2B

• Synthesis of Alkynes:

Typical Example:

R–X

R

R'

R"

Typical Example:

R'-C≡C– Li+NaNH2

mineral oil110-160 ˚C

(must have R' = H)

RR'

R"

(SN2)

Br

Br

H

must be primaryalkyl halide

H-C≡C– Li+

Br

THF

Br

NaNH2

mineral oil110-160 ˚C

• Addition of Br2 to alkenes:

H

HH H

Typical Example:

Br2

anti addition througha bromonium cation

Br2

R'

R"

R''' R"R'

R'''OR

Br

H

OCH3

Br

R

R'

R"R

R'

R"Br

H

Br

• Addition of Br2 to alkenes in presence of H2O or ROH:

Typical Example:

• Addition of HBr to alkenes in presence of a peroxide:

Typical Example:

R

R'

R"

Br2, ROH

anti addition througha bromonium cation;ROH adds to most

substituted site

Br2

CH3OH

HBr, RO-OR

R

R'

R"

R = H or alkyl

Typical Example:

H

Br• adds to least substituted site to give most stable radical

=> anti-Markovnikov product Br

H+ adds to least substituted site to give most stable carbocation

=> Markovnikov product

• Addition of HBr to alkenes:

HBr

HBr

Br

HBr

R

R'

R"

R'RR"

HO OH

H

OH

OH

R

R'

R"

• Oxidative cleavage of alkenes with KMnO4:

Typical Example:

R

O

R'

O

R"

OHH

If an H is a substituent on the C=C bond, it

will be oxidized => OH group

O HOOC

+

+

Typical Example:

• Addition of OsO4 to alkenes: syn-dihydroxylation

syn addition

the double bond is cleaved andits carbons oxidized to the highest

oxidation level

1) OsO4

2) NaHSO3

KMnO4, OH–, heat

KMnO4, OH–

heat

1) OsO4

2) NaHSO3

• Oxidative cleavage of alkenes with ozone (O3):

Typical Example:

R

R'

R"1) O3

2) Me2S

the double bond is cleaved andits carbons remain at the +2

oxidation state

R

O

R'

O

R"

HH

+

O OHC+1) O3

2) Me2S

R

R'

R"

CH3

OH

R

R'

R"

R

R'

R"HO

H

• Addition of H2O to alkenes: alcohols from alkenes

1) Hg(OAc)2, H2O

2) NaBH4

Hg++ adds to least substituted site to give most stable carbocation

=> Markovnikov product

Typical Example:

1) Hg(OAc)2, H2O

2) NaBH4

Typical Example:

R'RR"

H OH

H

R

R'

R"R

R'

R"

OH

CH3

OH

• Oxymercuration of alkenes: alcohols from alkenes

• Hydroboration of alkenes and oxidation: alcohols from alkenes

H2SO4, 25 ˚C

CH3

H

water adds at most substituted site, => Markovnikov product.

Note: Intermediate carbocationcan rearrange

Typical Example: OH

Boron adds to least substitutedsite in a syn addition

=> anti-Markovnikov product

1) BH3, THF

2) H2O2, OH–

H2SO4, 25 ˚C

1) BH3, THF

2) H2O2, OH–

• Alkyl halides from alkohols and HX:

Typical Example:

R

R'

OH Br

• Alkyl halides from alkenes using SOCl2 or PBr 3:

OH

Br

R

R'

Cl

R

R'

OH

PBr3

1) Me2C=CH2, H+

2) i-PrMgBr

3) H+, H2O

SOCl2PBr3

• tert-Butyl ethers from alcohols: protection of alcohols

X = Cl, Br, I

OH Br

, H+

H+, H2O

For primary chlorides,ZnCl2/HCl has to be used

R

R'

X

R

R'

OHHX

HBr

R"

R

R'

OH

R

R'

O

O

Typical Example:

OH

HO

variant of SN2 where alcohol is activated through the formation

of an ester of inorganic acid

variant of SN2 or SN1 wherealcohol is activated to form a

better leaving group by formationof an oxonium cation

Typical Example:

(protection)

(deprotection)

R'

R

R"R

R'R"

anti addition throughan oxonium cation;

ROH adds to the most substituted site

O

H

RO–

O

H+

CH3OH

R"R'

R'''OR

OH

H

OCH3

OH

• Acid-catalyzed reaction of epoxides with H2O or ROH:

• Base-catalyzed reaction of epoxides with H2O or ROH:

R"R'

R'''

O

H

syn addition

RCO3H

Typical Example:

R"R'

R'''OH

OR

H

OH

OCH3

ROH, H+

R = H or alkyl

Typical Example:

R"R'

R'''

O

H

Typical Example:

• Epoxidation of alkenes with peracids: oxiranes

O

anti addition whereROH adds to the least

substituted site(steric hindrance)

ONaOCH3

CH3OH

RCO3H

1) RMgX

2) H3O+

Typical Example:

• Addition of Grignard reagents to epoxides: alcohol formation

Typical Example:

R"R'

R'''OH

R

H

OH

n-Bu

RMgX

anti addition whereR– adds to the least

substituted site(steric hindrance)

n-BuMgBr

R"R'

R'''

O

H

Typical Example:

• Addition of Grignard reagents to carbonyls: alcohol formation

O

• Addition of Grignard reagents to esters: alcohol formation

R'

R"

O

R'

R"

OHR

OEt

OH

R' OR"

O R

R

OHR'

COOEt

Et

Et

OH

1) RMgX

2) H3O+

1) EtMgI

2) H3O+

1) EtMgBr

2) H3O+

R" - H or alkyl(aldehyde or ketone)

R– adds twice

Jones rgt.

(H2CrO4)

Jones rgt. (H2CrO4) or KMnO4, OH–, heat

R' = H if ester is startingmaterial where R' = OR"

Typical Example:

• Reduction of carbonyls with NaBH4: alcohol formation

Typical Example:

R

R'

O

R

R'

OHH

O HOH2COH

CH2OH

R–COOH

CHO

MeOOC

1) LiAlH4

2) H3O+

H

PCC

CH2Cl2

• Reduction of carbonyls and esters with LiAlH4: alcohol formation

PCC

Typical Example:

R

R'

O

R

R'

OHH

O1) NaBH4

2) H3O+MeOOC

OH

• Oxidation of 1˚ alcohols: aldehyde or carboxylic acid formation

MeOOC

R–CH2OH

H

R–CHO

1) NaBH4

2) H3O+

Esters and carboxylicacids are not reduced

1) LiAlH4

2) H3O+

R' - H or alkyl(aldehyde or ketone)

R' - H, alkyl, OH, or OR"(aldehyde, ketone, carboxylic acid or ester)

• Oxidation of 2˚ alcohols: ketone formation

Typical Example:

OHCrO3, H2SO4

acetone(Jones rgt.)

O

R

R'

OH

R

R'

OCrO3, H2SO4

acetone(Jones rgt.)