Problem Set #8

ANSWERS

November 21, 1997

1. Synthesize the following from the compounds given. You may use any other reagent you like.

The desired compound is an E-alkene which contains 2 more carbon atoms than the alkyne given as starting material (phenylethyne). The synthesis must therefore contain a substitution reaction which uses a carbon nucleophile. E-alkenes can be synthesized from alkynes by dissolving metal reduction (Li or Na in liquid NH₃); thus, a direct precursor to the final product is

Comparing this structure to phenylethyne, we identify the C-C bond which must be formed (this is indicated in red in the structure above. The compound can thus be made by an S_N2 substitution, using the phenylethynyl anion as nucleophile and bromo- or iodoethane as the electrophile. Be sure to use a dipolar aprotic solvent for this, as water and alcohols (or even acetone!) will protonate the strongly basic phenylethynyl anion. A complete synthesis is:

The desired compound is a Z-alkene which contains 3 more carbon atoms than the compound given as starting material (bromomethylbenzene, or benzyl bromide). Again, a step involving nucleophilic substitution with a carbon nucleophile will be required, as we need to make a carbon-carbon bond. Z-alkynes can be synthesized from alkynes by catalytic reduction over poisoned catalysts, so a direct precursor to the final compound is (as before, the C-C bond that needs to be formed is shown in red):

A complete synthesis would be:

This one is easier. The desired compound, a 6-carbon dialdehyde, is the product of ozonolysis of cyclohexene using a reductive workup. Cyclohexene can be made from the given starting material (cyclohexanol) by dehydration. The complete synthesis is:

Careful! The desired product contains two more carbon atoms than the starting material. 1-Butanol must be converted to the tosylate or 1-bromobutane so that a 2-carbon unit can be added. As before, this can be done using sodium acetylide (HCC^-Na⁺). The resulting compound (1-hexyne) can be reduced to 1-hexene either by hydrogenation with a poisoned catalyst or with Na / NH₃:

The Hahn-Ingold-Prelog nomenclature in the following question is challenging:

17nov97; wjl