Lecture 18 xidation and Reduction C 4 C 3 C C C xidation Reduction March 27, 2018
Suppose you want to make this compound????? C + BrC 2 C 2 C?? CC 2 C 2 C 4-ydroxy-4-phenylbutanal It s an alcohol. Use the Grignard Reaction!! So you got a problem with this plan????? Secret is.acetals as protecting Groups
Acetals as Protecting Groups If the Grignard reagent were prepared from 3-bromopropanal, it would self-destruct! First protect the -C group as an acetal Br C C C + C C + C 2 BrC C C + 2 2 2 2 2 2 C2 2
Acetals as Protecting Groups Then do the Grignard reaction BrC 2 C 2 C 2 C C 2 1. Mg, ether 2. C 6 5 C + - [MgBr] C C 2 C 2 C C2 C 2 ydrolysis in dilute acid gives the desired product
Acetals as Protecting Groups ydrolysis (deprotection) regenerates the -C group and the hydroxyl group - [MgBr] + C2 CC 2 C 2 C C 2 Cl, 2 CC 2 C 2 C C 2 C 2 + Valuable and important trick!!
For example, the conversion shown cannot be carried out directly..why?? C 3 CC 2 C 2 C C 1. NaN 2 2. C 3 I C 3 CC 2 C 2 C C-C 3
because the carbonyl group and the carbanion are incompatible. C 3 CC 2 C 2 C C:
Strategy 1) protect C= 2) alkylate 3) restore C=
Protect C 3 CC 2 C 2 C C + C 2 C 2 benzene 2 S 4, Cat. 2 C C 2 C 3 C C 2 C 2 C C
Alkylate 2 C C 2 C C 3 C 2 C 2 C C 2 C C 2 1. NaN 2 2. C 3 I C C C 2 C 2 C C-C 3 3
Deprotect 2 C C 2 C C C 2 C 2 C CC 3 3 2 Cl C 2 C 2 + C 3 CC 2 C 2 C CC 3 Desired product
Synthesis.. benzene and 3 carbon starting materials
Synthesis B r
xidation and Reduction Aldehydes are oxidized to carboxylic acids by a variety of oxidizing agents and it is possible to do some selective reduction reactions C 4 C 3 C -4-2 0 +2 +4 xidation Reduction C C
Reduction Aldehydes can be reduced to 1 alcohols and ketones to 2 alcohols. In addition, the C= group can be reduced to a -C 2 - group Aldehydes Can be Reduced to Ketones Can be Reduced to RC RC 2 RC 3 RCR' RCR' RC 2 R'
Metal ydride Reduction The most selective reagents for the reduction of aldehydes and ketones are NaB 4 and LiAl 4 both are sources of hydride ion, : -, a very powerful nucleophile Na + -B- Sodium borohydride Li + -Al- Lithium aluminum hydride (LA) ydride ion
NaB 4 Reduction The key step in metal hydride reduction is transfer of a hydride ion to the C= group to form a tetrahedral carbonyl addition compound B R C R C R C + - R R R
Closer look at borohydride reductions B- bond is much stronger than B Bond This is the driving force for the reaction
NaB 4 Reduction Reductions with NaB 4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol RC + NaB 4 RC 2 C 3
Examples: Sodium Borohydride Aldehyde 2 N C NaB 4 methanol 2 N C 2 Ketone NaB 4 ethanol
Lithium aluminum hydride LiAl 4 More reactive than sodium borohydride Cannot use water, ethanol, methanol etc., as solvents Diethyl ether and TF are the most commonly used solvent This is a dangerous but useful reagent RC 2 CC 3 1) TF + LiAl 4 2) 3 + RC 2 CC 3
Aldehyde Examples: Lithium Aluminum ydride C 3 (C 2 ) 5 C 1. LiAl 4 diethyl ether 2. 2 C 3 (C 2 ) 5 C 2 Ketone (C 6 5 ) 2 CCC 3 1. LiAl 4 diethyl ether 2. 2 (C 6 5 ) 2 CCC 3
Selectivity neither NaB 4 or LiAl 4 will reduce isolated double bonds 1. LiAl 4 diethyl ether 2. 2
Selectivity in Reduction LiAl 4 reduces any and all carbonyl compounds to the corresponding alcohols NaB 4 only reduces aldehydes and ketone
Catalytic Reduction Catalytic reductions are generally carried out from 25 to 100 C and from 1 to 5 atm 2 Carbon-carbon double bonds can be selectively reduced using Rhodium catalysts 2 /Rh NaB 4 Me