Synthesize the following compound from starting material containing no more than three carbon atoms that is available from Aldrich.
When designing a synthesis that requires forming a new carbon-carbon sigma bond, split the product molecule in such a way that one part of the split would come from a nucleophilic carbon and the other part of the split would come from an electrophilic carbon atom.
The nucleophilic carbon atoms will generally come from acetylide anions, enolates, organometallic compounds, or cyanide anion.
The electrophilic carbon atoms are generally in alkyl halides or tosylates, oxiranes, or carbonyl compounds.
In this synthesis you need to split the molecule on either side of carbonyl group. The carbon of the carbonyl group would have come from the electrophilic component. One of the alpha carbons would have come from the nucleophilic component.
The electrophilic carbon atom could have come from a carboxylic acid and the nucleophilic carbon could have come from an organolithium compound. There are two different possible pathways that use this reaction.
The precursor to the ketone could also have been a secondary alcohol, which would be the conjugate acid of the alkoxide formed by the addition of an organometallic compound to an aldehyde. There are two different ways the alcohol can be constructed.
Pathway B and pathway D are related. Both use a three-carbon vinyl organometallic compound as the nucleophile. In pathway D, the organometallic compound can be either the 1-propenylmagnesium Grignard reagent or 1-propenyllithium. Only the organolithium compound would work in pathway B. Either organometallic compound can be prepared from 1-bromo-1-propene. (The corresponding chloro compound is not available from Aldrich.)
The electrophiles in pathways B and D are also related. One is a five-carbon branched aldehyde and the other is a five-carbon carboxylic acid with the same skeleton. Both can be made from isopentyl alcohol (3-methyl-1-butanol).
There are two different ways to synthesize isopentyl alcohol. One splits the alcohol between the alpha and beta carbons. The nucleophile would be an isobutyl organmetallic compound and the electrophile would be formaldehyde. The isobutyl organometallic compound can be made from an isobutyl halide.
The isobutyl halide, in turn, can be made from isobutyl alcohol (2-methyl-1-propanol). This alcohol can be prepared from a 2-propyl organometallic compound and formaldehyde.
A shorter pathway to isopentyl alcohol uses oxirane as the electrophile and a 2-propyl organometallic reagent as the nucleophile.
Try your hand at synthesizing each of the following compounds. The equations tell you how many steps were used in the literature synthesis, but other pathways may be possible.
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.GIF)
.GIF)
.GIF)
.GIF)