THE REDUCTION OF ALDEHYDES AND KETONES

The reduction of (5)-2-amino-5-dibenzylamino-4-oxo-1,6-diphenylhex-2-ene was optimized for diastereoselectivity and overall conversion to (2,3,5)-5-amino-2-dibenzylamino-3-hydroxy-1,6-diphenylhexane (2a). A two-step reduction sequence is described wherein the enamine is reduced with a borane-sulfonate derivative followed by reduction of the resulting ketone with sodium borohydride. The desired 2a was obtained with 84% diastereoselectivity and an acyclic 1,4 stereoinduction ratio of 14:1. This methodology has been used to produce multikilogram quantities of the diamino alcohol core of Ritonavir and should be general to the synthesis of related diamino hydroxyethylene isosteres.

Health Effects of Alcohol and Aldehyde Oxidations:

REDUCTION OF ALDEHYDES AND KETONES

In general terms, reduction of an aldehyde leads to a .

When a person ingests alcohol, the reactions listed below occur in the liver with the aid of enzymes. The accumulation of acetaldehyde may produce nausea. Eventually, the acetaldehyde is converted to acetic acid which can be further metabolized without any problem.

Reduction of a ketone leads to a .

This page looks at the reduction of aldehydes and ketones by two similar reducing agents - lithium tetrahydridoaluminate(III) (also known as lithium aluminium hydride) and sodium tetrahydridoborate(III) (sodium borohydride).

Synthesis of Alcohols
The formation of a secondary alcohol via reduction and hydration is shown: Reactions

REDUCTION OF ALDEHYDES AND KETONES

STEP 5: Combine these half-reactions so that electrons areneither created nor destroyed. Two electrons are given off in the oxidationhalf-reaction and two electrons are picked up in the reduction half-reaction. We cantherefore obtain a balanced chemical equation by simply combining these half-reactions.

The reduction of aldehydes and ketones using metal hydrides - lithium tetrahydridoaluminate ..

Ch20: Reduction of Esters using LiAlH4 to 1o alcohols

Reactions of Alcohols
Alkoxide ions are formed from the reaction of alcohols with metal. Alcohols react with hydrogen halide, phosphorus trihalide, or thionyl chloride to form alkyl halides. Alcohols are dehydrated with acid and heat to form alkenes. Zero degree and primary alcohols are oxidized with pyridinium chlorochromate to form aldehydes. Zero degree and primary alcohols are oxidized with sodium dichromate, potassium dichromate, potassium permanganate, sodium hypochlorite, nitric acid, or chromium trioxide to form carboxylic acids. Secondary alcohols are oxidized with sodium dichromate, potassium dichromate, potassium permanganate, sodium hypochlorite, nitric acid, chromium trioxide, or pyridinium chlorochromate to ketones. Tertiary alcohols are not oxidized with sodium dichromate, potassium dichromate, potassium permanganate, sodium hypochlorite, nitric acid, chromium trioxide, or pyridinium chlorochromate. Alcohols react with carboxylic acids, in the presence of acid, to yield esters.

In general terms, reduction of an aldehyde leads to a primary alcohol.

Reduction of ketone yields 2 alcohol.

Finally, with end in sight, the final ring was installed by a clever sequence beginning with 1,4-addition of the lactam nitrogen to the unsaturated dialdehyde shown below (which was made in three steps from tartaric acid).[6] Don't forget that the small ring size in β-lactams minimises the resonance structure responsible for normal amide reactivity (i.e. through oxygen) so they are nucleophilic (and, incidentally, protonate) at nitrogen. Simultaneous cleavage of the acetonide and Boc groups with TFA also formed the second ring of the natural product by condensation of the thiol onto the nearby aldehyde in a cool one pot cascade. Finally, the known sidechain fragment was coupled on with DCC and its free acid was then protected as the 2,2,2-trichloroethyl ester by coupling with trichloroethanol, again using DCC. At this point, containing 9 chloride atoms, I imagine that the mass spec of this compound was pretty interesting. The enal was then reduced to the allyl alcohol using borane in THF, and this was then acetylated using acetic anhydride in pyridine. Further standing in pyridine for 3 days effected isomerisation of the double bond into conjugation with the nearby ester. Finally removal of all three protecting groups using zinc dust in 90% acetic acid gave the natural product which was 'identical with natural material in paper chromatographic behavior, and in antibacterial activity against Neisseria catarrhalis, Alcaligenes faecalis, Staphylococcus aureus, and Bacillus subtilis'. A great synthesis, conducted without NMR, or apparently even TLC!