Chapter 20 The carbonyl can be an electrophile, it can be attacked. It can occur under basic or acidic conditions.

Basic Conditions: H O 1. Nu- O

2. H2O workup Nu Nu:

HOH O :

Nu

Acidic Conditions: H+ H O : 1. H+, Nu: O

Nu

H + O OH

Nu Nu:

Hydride reductions. Basic conditions, H- is the nucleophile Ketones and aldehydes react w/ LiAlH4. H O 1. LiAlH4 O

2. H2O workup - H H:

HOH O :

H Esters and acid chlorides react w/ LiAlH4. H O 1. LiAlH4 O 2. H O workup OMe 2 H - H H:

HOH O : O O :

OMe H H H - H H: There are many sources of hydride with various reactivities Hydride Aldehyde Ketone Ester Amide Carboxyllic Acid Donors acid/ acid salt halide LiAlH4 Alcohol Alcohol Alcohol Amine Alcohol Alcohol LiAlH(OtBu)3 Alcohol Alcohol Alcohol - (too slow) N.R. Aldehyde NaBH4 Alcohol Alcohol N.R. N.R. N.R. ? NaBH3CN Alcohol N.R. N.R. N.R. N.R. ? DIBAL-H Alcohol Alcohol Aldehyde * Aldehyde* Alcohol ? * Stoichiometry must be carefully controlled. H2, Pd/C reacts preferentially with carbon-carbon double bonds.

Carbon Nucleophiles: - Both of the following create reagents that act like CH3 . EtBr + 2Li →EtLi + LiBr EtBr + Mg → EtMgBr

Alkyne nucleophiles. - + CH3C≡CH + NaNH2→ CH3C≡C: Na + NH3 - + CH3C≡CH + CH3Li → CH3C≡C: Li + CH4↑

CH3C≡CH + CH3MgBr → CH3C≡CMgBr + CH4↑

Ketones and aldehydes react w/ these carbon nucleophiles. H O 1. H3C CCMgBr O

2. H2O workup - C CH3CC: C CH HOH 3 O :

Esters and acid chlorides react w/ these carbon nucleophiles. H O 1. CH3Li or CH3MgBr O

2. H2O workup CH OMe 3 CH - 3 H3C:

HOH O : O O :

OMe H CH3 CH3 H3C - H C: 3

Grignards react with carbon dioxide to for carboxylic acids.

H O 1. CH3MgBr O C O 2. H2O workup H3C O - CH3: HOH O :

H C O 3 Cuprates are another source of carbon anions but they react differently then the carbon nucleophiles we have seen before. In enones they react at the 4 position and they can react with alyls halides including vinyl and aryl halides

Preparation 2MeLi + CuI → Me2CuLi

O H3C OH 1. CH3MgBr 1,2 addition

2. H2O

O O

1. (CH3)2CuLi 1, 4 addition

2. H2O workup H3C

O

H C 3

Cuprates can substitute alkyl groups for halogens (primary) which is no big deal but they can also do it with vinyl and aryl halides!!

(CH ) CuLi H C Br 3 2 3

(CH ) CuLi H C Br 3 2 3

Alkyl anions can react with epoxides. 1. CH MgBr O 3 OH

2. H2O workup

O

H C 3

Br MgBr OH

OH Br

Chomium(VI) reagents oxidize alcohols to ketones. (p434)

OH O

+ HCrO3-

O O H O Cr OH O

Primary alcohols and aldehydes are oxidized to carboxylic acids

OH O H O H2O OH H2CrO4 OH H2CrO4 H OH

Silver(I) will oxidize aldehydes to carboxylic acids. O O Ag2O H OH NH4OH