Reductions 37

Na, Li
R  SPH 
NH   
R  H
3
O
S Na, NH3(l)
R NH R' R NH2

3  Na, NH 
R 2 N  Ts   R 2 NH

2.9. Reduction by hyride transfer-reagent:

REACTIVITY OF HYDRIDE DONAR REDUCING AGENTS

Iminium Acyl Aldehyde Ester Amide Caboxylic
ion chloride or ketone salt
Hydride Donar More Reactive  Least Reactive
LiAlH4 Amine Alcohol Alcohol Alcohol Amine Alcohol
Red Al  Alcohol Alcohol Alcohol Amine Alcohol
LiAlH (Ot-Bu4)3  Aldehyde Alcohol Alcohol Aldehyde 
NaBH4 Amine  Alcohol Alcohol  
NaBH3CN Amine     
B2H6   Alcohol  Amine Alcohol
AlH3  Alcohol Alcohol Alcohol Amine Alcohol
Disiamylborane   Alcohol  Aldehyde 
DIBAL   Alcohol Aldehyde Aldehyde Alcohol

2.9.1. Lithium aluminium hydride (LiAlH4)

Most reductions of carbonyl compounds are done with reagents that transfer a hydride from boron or
aluminium. Sodium borohydride is a mild reducing reagent that rapidly reduce aldehyde and ketones but not
esters. Lithium aluminium is strongly donor reagent and it rapidly reduce ester acids, nitriles, amides as well as
aldehyde and ketones. Neither sodium borohydride nor lithium aluminium hydride reacts with isolated carbon-
carbon double bonds.
There reagents are nucleophilic and as such they normally attack polarized multiple bond such as
C=O, C  N by transfer of hydride ion to the more positive atom.
Lithium aluminium hydride is a more powerful reducing agent than sodium borohydride and reduces most of
commonly encountered organic functional group.

AlH3 O O
O O O
H H
Al 2 3
AlH2 AlH
H H
O
OH + O
H3O

4
Al
38 Reductions

Common Functional Groups, reduced by LAH

Functional groups Reduction product

RCHO  R CH2OH
R R
C O  CH OH
R R
O
 R CH2OH + R'OH
R C OR'
O
 RCH2OH
R C OH
O
 R CH2NHR'
R C NHR'
O
 R CH2NR'2 or RCH(OH)NR'2 RCHO + R'2(NH)
R C NR'2

R C N  R CH2 NH2 or R C NH RCHO

H
R C N OH H2
H
 R C NH2

ArNO2  Ar NH NH Ar or Ar N N Ar
R CH2 Br  R CH3
O

R CH2 O S Ar  R CH3
O

O OH

R C CH2  C CH3
H R H

Aldehye, ketone, esters, carboxylic acids and lactones can all be reduced smoothly to corresponding alcohols
under mild conditions. Carboxylic amides are converted into amines or aldehydes.

OH
CHO

O N LiAlH4 O N
THF, 0ºC
O O

Ph Ph
LiAlH4
THF, heat OH
H2N COOH H2N
Reductions 39

LiAlH4
N O N
Et2O, 20ºC
Me Me

OMe OMe

Reduction of  -aryl- ,  unsaturated carbonyl compounds with lithium aluminium hydride, where the car-
bon-carbon double bond is often reduced as well as the carbonyl group.
LiAlH4
CHO
Ph Et2O, 35ºC Ph OH
LiAlH4, Et2O
CHO
Ph –10ºC Ph OH
or NaBH4, or AlH3
or DIBAL-H
Cyclic organoaluminium compound is formed.

H*
O R-OH*
Ph
Al
Ph Ph OH
1º alcohol (saturated)

Reduction of propargylic alcohols  R  C  C  CH 2 OH  with lithium aluminium hydride to give trans alk-
enes.
LiAlH4 CH2 OH
R C C CH2OH
R
OH
O O OH
(i) LiAlH 4 HO NaBH4
CO 2Et CO2Et
(ii) H3 O+ O O EtOH
OH
CO 2Et

Reduction of amide to amine by Lithium Aluminium Hydride:

O Li AlH3 NR2
Li O AlH3 O H AlH3
R CH2 NR2
R NR2 H AlH3
R H Amine
R NR2 R NR2
H H

O O AlH3 Li O

LiAlH4 H3O+
NMe2 NMe2 H
THF, 0ºC H
40 Reductions
Stereoselectivity and chemoselectivity of LiAlH4:

O H OH HO H
LiAlH4
+
Me Me Me
Me Me Me
H H H
72 : 28

H2
Al
O O
O H OH HO H
LiAlH4 H AlH3
Ph Ph + Ph
Ph
Me H Me Me Me
H H H
HO HO HO
Ratio 20 : 80

Mixture of product is obtaind, unhindered ketones react with LiAlH4, equatorial alcohols is the predominant
product. When hindered ketones reacts with LiAlH4 axial alcohol will be major product.
OH
O
LiAlH4
OH +

Ratio 90 : 10

OH
O
LiAlH4
OH +

LiAlH4 45 : 55

LiBH(sBu)3 <1 : >99

Alternative reagent can provide high selectivity. Dissolving metal reductions (Li, NH3). Provides the thermody-
namically more favourable equatorial alcohols almost exclusively from either two cyclic ketones.

O
R
HO LAH epoxidation R
R HO
HO

LiAlH4 NaBH4CN
OH O
SN2
OH
Reductions 41
2.9.2. Sodium Borohydride (NaBH4) :
[NaBH4/EtOH/25ºC]
Common Functional Groups, reduced by NaBH4

Functional groups Reduction product

RCHO  R CH2OH
R R
C O  CH OH
R R
O
 R CH2 NHR'
R C NHR'
O
 R CH2NR'2 or RCH(OH)NR'2 RCHO + R'2(NH)
R C NR'2

R C N OH H2
H
 R C NH2
R–COCl  R–CH2NH2
RCOOCOCl  RCH2OH

 RNH2
R N N N

O OH

R C CH2  C CH3
H R H

Sodium borohydride is a very selective reducing agent and reduce aldehyde and ketone to alcohols. Sodium
borohydrides is a comparatively weak reducing agent. Because boron hydrogen has more covalent character
than lithium hydrogen. It does not react or slow react in the case of ester or cyclic ester functional group.
NaBH4 is a chemoselective reagent for carbonyl compound in the presence of esters (cyclic or acyclic) and
amide functional group.
It is prepared by the reaction of sodium hydride and trimethyl borate.
250ºC
4NaH  B  OMe 3   NaBH 4  3MeONa
NaBH4 is insoluble in ether but soluble in alcohol and water. So, it is used in hydroxylic solvent like alcohol,
isopropanol etc.
Reducing properties of sodium borohydride are substantially modified in the presence of metal salt, perticularly
in the presence of cerium (III) chloride.
Sodium borohydride reduces ,  unsaturated ketone with extremely high selective, such that 1, 2,
not 1, 4 reduction occurs to gives allylic alcohols.
O OH OH

NaBH4
+
MeOH

no CeCl3 59 : 41
CeCl3.7H2O 99 : 1
42 Reductions
Sodium borohydride is a nucleophile that you have seen reducing simple aldehyde and ketone to alcohols. But
it will also do conjugate addition reaction, which of the alternatives actually takes place depends on the reac-
tivity of the C O group.

NaBH4 usually react with ,  unsaturated aldehyde to give alcohols by direct addition to the carbonyl
group.
CHO NaBH4, EtOH OH
Ph Ph
O OH

NaBH4, EtOH

Mechanism:

O O O O OH

H OEt H BH3 H OEt

H BH3

Luche reduction:

O OH
Ce3+

NaBH4, EtOH

CeCl3 : Hard Lewis acid model salt

For ester and other less reactive carbonyl compounds, conjugate addition takes place because NaBH4 does
not reduce ester or amide.
O O

NaBH4
MeO MeO
MeOH
Ph Ph
,  unsaturated ketones are reduced selectively in the presence of saturated ketones or aldehydes. ketones
can be sometimes be reduced in the presence of an aldehyde. More reactive aldehdye group is protected as
the hydrate, which is stablised by complexation with cerium ion and is generated during isolation of the prod-
uct.
O OH

NaBH4, CeCl3.7H2O
EtOH, –15ºC
CHO

CHO
Reductions 43

O OH
H
NaBH4, CeCl3.7H2O
EtOH, H2O, –15ºC
CHO CHO

NaBH4 is more chemoselective than LiAlH4. At room temperature in ethanol it readily reduce aldehyde and
ketone but it does not generally attack esters or amide
O OH
NaBH4
CO2Et CO2Et
EtOH
Stereoselectivity:

O NaBH4 H
i-BuOH
OH

H3C CH3 H3C CH3 H3C CH3

H3C H3C H3C

NaBH4
+
H OH
14% 86%
O OH H

O CH2SO2Ph OH CH2SO2Ph O CH3

H H H

NaBH4 20 : 80
NaBH4.CeCl3 95:5

OH OH
OH
R' Zn(BH4)2 R1 R1
R2 R2 + R2
ether, 0ºC
O OH OH
anti syn
(Major) (Minor)
Chemoselectivity:
Reduction of carboxylic ester in the presence of carboxylic amide is possible using sodium borohyride and
calcium chloride.
O
C NH2 NaBH4/CaCl2 NH2
Et O C HO C
O O
44 Reductions

O OH

H NaBH4
EtO EtOH EtO

O O

2.9.3. Lithium tri-t-butoxyaluminium hydride (lithium hydridotri-t-butoxyaluminate)

[LiAlH(OtBu)3]:
Common Functional Groups, reduced by [LiAlH(OtBu)3]

Functional groups Reduction product

R R
C O  C O
Cl H
O
 R CH2OH + R'OH
R C OR'

O
 R CH2NHR'
R C NHR'
R C N OH H2
H
 R C NH2
RCOOCOCl  RCH2OH

R C N  RCH2NH2

O OH

R C CH2  C CH3
H R H

[LiAlH(OtBu)3] is prepared by the action of three equivalent of tert-butyl alcohol on lithium aluminium hydride.
Lithium tri-t-butoxyaluminium hydride is a much milder reducing agent than lithium aluminium hydride. Alde-
hyde and ketones are reduced normally to alcohols, carboxylic ester and epoxides react only slowly and
halides, nitriles and nitro group are not reduced.
O O O

O O O
OHC
LiAlH(OtBu)3 HO
Amberlite resin O
MeO2C THF, –10ºC PhH
MeO2C
O
O O O

LiAlH(OtBu)3 reduce carboxylic acid, acid chloride and di-alkylamides into aldehyde.
Reductions 45

COCl CHO
t
LiAlH(O Bu)3
–78ºC
NC NC
t
LiAlH(O Bu)3 reduce tertiary amide into aldehyde.
(i) LiAlH(OEt)3
CONMe2 CHO
(ii) H3O+
NMe2
LAH (excess)

LAH R CH2 NH2

R C N
LiAlH(OEt)3 H3O+
R C N [Al(OEt)3] R CHO
H
2.9.4. Mixed lithium aluminium hydride-aluminium chloride reagent:
3LiAlH 4  AlCl3 
 3LiCl  LiAlH 3

LiAlH 4  AlCl3 
 LiCl  2AlH 2Cl (LiAlH3–ALANE)

LiAlH 4  3AlCl3 
 LiCl  4AlHCl2
The general effect of the addition of AlCl3 is to lower the reducing power of LiAlH4.
OH LiAlH4 LiAlH4-AlCl3 OH
CO2Et
Butanol (1:1) Et2O
Br Br
O OH
mixed hydride

O
mixed hydride
Ar Ar
Ar Ar
mixed hydride

O OH
Ph NMe2 LiAlH4-AlCl3(3:1) Ph NMe2
Et2O
O
46 Reductions

2.9.5. Diisobutylaluminium hydride (DIBAL-H):

[DIBAL-H or DIBAL or iBu2AlH]
Common Functional Groups, reduced by [DIBAL-H or DIBAL or iBu2AlH]

Functional groups Reduction product

R-CHO  R-CH2OH
R R
O  CH OH
R R
R
C O  R-CHO
Cl
O

C  R-CHO
R OR
O O

C C  R-CHO
R O R
O
R
C N  R-CHO
R
R
R
R
C N  R–CH2–NH–R
H
 R-CHO
R N N N
R C N  RCH2NH2
O R CH CH3

R OH

O
 R CH2OH + R'OH
R C OR'

DIBAL reduce esters and ketone into alcohols. DIBAL on reduction of nitriles gives amines and epoxides are
cleaved to alcohols. At low temperature, esters and lactones are reduced directly to aldehydes (or lactols);
nitriles and carboxylic amide gives amines which are readily converted into aldehydes by hydrolysis.
O O
DIBAL-H
O OH
PhMe, –78ºC
Reductions 47

CO2Me CHO
O DIBAL-H O
DCM, –78ºC
MeO MeO

H H
CN CHO
DIBAL-H
hexane, –70ºC

DIBAL reduce the ,  -unsaturated carbonyl compound to allylic alcohols

Boc Boc
DIBAL-H
Ph N Ph N OH
CO2Et PhMe, –78ºC
 unsaturated ester
Note: DIBAL reduce to alkyne cis alkene
R R
DIBAL-H
R C C R
H H
C4H9 C4H9
iBu AlH (i) I2, THF
2
C4H9 C C H
(ii) H3O+
AliBu2 I
Mechanism:
i
Bu
O Al AliBu2 Al iBu2
O H O
O O
DIBAL H3O+
C C
R O Et R H
R O Et R OEt R OEt
H H
stable at –78º
unreactive towards
further reaction

C4H9 C4H9 H
iBu2AlH H3O+
C4H9 C C H
H AliBu2 H H
Cis Alkene
Reduction of Nitrile:
CN CHO
(a) iBu2AlH
hexane, –78ºC
(b) H+, H2O
48 Reductions

O H O
HO

O (a) iBu2AlH O H
Et2O, –78ºC
(b) H+, H2O OH
Summary : At ordinary temperature DIBAL reduce
Ester and ketone 
 Alcohol

Nitrile 
 Amine

Epoxide 
 Alcohol

Lactone 
 Lactols

Carboxylic acid 
 Imine

Alkyne 
 cis-alkene

2.9.6. Sodium cyanoborohydride (NaBH3CN) and Sodium triacetoxyborohydride

(NaBH(OAc)3) :
Common Functional Groups, reduced by (NaBH(OAc)3) and (NaBH3CN)
Functional groups Reduction product
R-CHO  R-CH2OH
R R
O  CH OH
R R
O

C  R-CHO
R Cl
R
N
 R CH2 NH R
C
R Cl
 R-NH2
R N N N
O
 CH3–CH2–OH

Sodium cyanoborohydride is more selective reducing agent than sodium borohydride because of electron-
withdrawing effect of the cyano group. Aldehye and ketone are unaffected by sodium cyanoborohydride in
neutral solution but they are readily reduce to corresponding alcohol at pH = 3-4 by way of protonated
carbonyl group.
NaBH3CN
Aldehyde and ketone No reaction
Neutral condition

pH (3-4)
Alcohol
O NaBD3CN DO
D
D2O
Reductions 49
Iminium groups are more easily reduced than carbonyl group in acid solution. Reductive amination of aldehyde
or ketones by way of the immunium salt formed from the carbonyl compound. A primary or secondary amine,
typically at pH > 5 at this pH carbonyl group uneffected.
NaBH3CN
RCHO + HNR'2 NH2 NH2'
R R

Ph Ph

N N N
, CHCl2, Ti(OiPr)4
H H H
then NaBH3, MeOH
O N
N N
Bn Bn

Me
H
N N
CH2O (37% in water)

F F

O O
H2N Ph
O NH
NaBH(OAc)3, ClCH2CH2Cl,
O O Ph
AcOH
Eschweiler-Clark reaction:
O

H O
H
O R–NH2
N R NH R
HCOOH
H H
H
Note: Sodium triacetoxyborohydride (NaBH(OAc)3:
Reduce aldehyde selectivity in the prescence of ketones. However,  ,  hydroxy ketones are reduced with
this reagent and stereoselectively gives anti-diol product. The reagent tetramethyl ammonium
triacetoxyborohydride, Me4NBH(OAc)3 has shown excellent selectively for this transformation.
Exchange of one of the acetoxy groups for alcohol is thought to proceed stereoselective intramolecular
transfer of hydride.

OH O OH OH
Me4NBH4(OAc)3
CO2CH2CH2CH2Ph CO2CH2CH2CH2Ph
MeCN, AcOH, –40ºC
anti: syn, 95:5

Reduction of tosylhydrazone of aliphatic carbonyl group (in acidic modify):

Carbonyl compound into corresonding hydrocarbons involves reduction of the derived toluene-p-
sulfonyl (tosyl) hydrazones with sodium cyanoborohydride in acidic dimethylformamide (DMF). The reaction
is specific for aliphatic carbonyl compound, aromatic compound are normally unaffected.
50 Reductions

H H

P-TsNHNH2, TsOH
H H
O DMF, Solfolane than O
NaBH3CN, 100ºC
H H
O O

Reduction of  ,  unsaturated carbonyl compound with tosylhydrazone followed by the migration of double
bond.

AcO AcO
P-TsNHNH2-AcOH
O than NaBH3CN, 70ºC

Mechanism:

Na BH2CN
H
H H
O N N N Ts
N
+ H2NNH-Ts Ts H

N
N H

(i) NH2NHTs
(ii) NaBH3CN
DMF, heat
stereoselective for trans-alkene

Note: Zn(BH4)2 is a perticularly effective agent for the reductive amination of  ,  unsaturated
aldehyde and ketone.
CHO HC NNHTs CH3

H2NNHTs NaBH3CN
DMF, heat

*
Selective formation of primary amine uses the rhodium (III) complex  RhCp Cl2  2 as a catalyst and ammo-

nium formate  HCOONH4  , which acts as the source of the ammonia and the hydride.
Reductions 51

O NH2

HCOONH4
0.1 mol% (RhCp*Cl2)2,
MeOH, 70ºC

Cp*   Pentamethylcyclopentadienyl anion 

Note: Sodium triacetoxy borohydride can reduce aldehyde selectively in the presence of ketones.

Summary:
NaBH3CN
Aldehyde and ketone 
acidic medium
 alcohol

EtNH2, NaBH3CN
O NHEt

H
P-TsNHNH2, TsOH
O
DMF
H
O

+ H2NNH-Ts

O O

H NaBH(OAc)3
C H2C

O OH

2.9.7. Borane and its derivatives:

Table: Functional groups reduced by borane
Functional Group Reduction Product
RCOOH RCH2OH

B
RHC CHR R
R
RCHO RCH2OH
R2C = O RCH(OH)R
R C N RCH2NH2
RCONR2 RCH2NR2
RCO2COR RCH2OH
O
R CH2 OH
R
H
RCO 2 R ' RCH 2 OH  R 'OH (slow rate of reaction)
RCOCl No reaction
RNO2 No reaction