Reduction Notes

Common Red Agents

LiAlH4

LIBH4

NaBH4

LiAlH4

reduces everything, no selectivity

LiBH4

reduces esters, ketones, and aldehydes

not carboxy acids and amides

NaBH4

reduces aldehydes and ketones

DIBAL

can reduce esters to aldehyde

can reduce CN to imine/NH2

activating red agents

Li can be activated by carbonyl, but not Na

bc of size comparison

Borane red

selectively red carboxy acid in presence of ester to alcohol

borane rxn scheme

4 eq carboxy acid + 2 eq BH3 —> ROH (after work up)

borane red steps

-carbonyl O attacks BH3

-H- attacks OH hydrogen (produce H2)

-add 2 more eq carboxy to repeat

-BH3 attacked by carbonyl O, H- donates to carbonyl C

-carboxy acid attacks Bh2, e swings to generate aldehyde and anion

-aldehyde attacks BH2-carboxy, kicks out carboxy

-anion attacks B

-H- adds to aldehyde C to generates ester

-work up generates alcohol

DIBAL reducing ester

stops are aldehyde at -78 degrees C

DIBAL ester rxn scheme

ester + DIBAL + H3O+ X- —> MeOH and aldehyde

DIBAL reduce ester steps

-ester carbonyl O attacks DIBAL

-H- donates to carbonyl

-work up: ester O grabs H3O+ proton

-water attacks Al —> generates aldehyde and MeOH

-X- deprotonates water proton

DIABL reduces CN

to imine, can be hydrolyzed to aldehyde in work up

DIBAL CN rxn scheme

R-CN + DIBAL + H3O+ X- + water —> NH4+X- + aldehyde

DIBAL red CN steps

-CN N attacks Al

-Hi donates to C

-work up: immine N LP grabs H3)+

-water attacks Al, separates imine

-N grabs H2O proton

-water attacks imine

-PT of H2O to NH2

-OH LP swings to make carbonyl, kicks out NH3

-NH3 deprotonates carbonyl

reduction of amides

LiAlH4, pure hydride source, no activation needed

red of amides steps

-H- donates to amide carbonyl

-O LP attacks Al

-N LP swings, generates imide and LG

-H- doantes to N=C

-end w amine and AlH2O - Li+

Chemoselective rec of tertiary amides

from tertiarty amide to aldehyde

need schwartz reagent

schwartz reagent

Cp2 ZrHCL

Luche Reduction

1,2 reduction of a-b unsaturaed ketone to alcohol

reagents: NaBH4, CeCL3

attacks for diastereoselective red of cyclohexanones

axial and equitorial attack

axial attack

places hydride in axial

equitorial attack

places hydride in eq

types of steric effects (why one attack is preferred)

1,3 diaxial interactions

ecliped interaction in T.S.

1,3 diaxial interactions

occurs between incoming hydride and axial groups

why small hydrides prefer axial attack (smaller interaction)

ecliped interaction in T.S.

between carbonyl and a-CH equitorial bond

dependent on size of cyclohexanone a-substituent

MPV reduction

reverse rxn of oppenauer oxidation

ketone/alde + ispropyl acl + Al(iPrO)3 —> acetone + alc

Felkin-Ahn Model used

for reduction of acyclic ketone

Felkin Ahn steps

-place ketone in most stable confirmation

-(place H closest to R group, rotate bond)

-determine RL: EN and size

-Nu attacks carbonyl on opposite size of RL

-(same side as H)

Chelation Control

occurs with R- is an alkyl group in an a-alkoxycarbonyl

Nu will attack at least hindered side (where H is)