1. for This Question, Split Into Two Teams and RACE to the Finish. Last Team Done Is A

1. For this question, split into two teams and RACE to the finish. Last team done is a rotten egg.

Professor Ben Zeen has been working hard his laboratory on a new analgesic drug called No Pain. The synthetic scheme for No Pain is shown below. I have taken the liberty of removing the structures and replacing them with the letters K-V. It is your job to:

(a) complete the following synthetic sequence by providing the structures for products K-V. Be sure to draw them with the correct regiochemistry and stereochemistry and to indicate stereochemical configuration where appropriate (R/S and E/Z).

(b) indicate the general reaction category for each reaction (e.g. EAS, electrophilic addition, oxidation, SN2, E1, etc.)

2. Stay in your teams and race to the finish of this one. You are to synthesize the following target compounds shown below starting from benzene and any carbon-based reagent of 4 carbons or less. HINT: "Victor" may hold the key to victory here.

2. Provide the structure of the expected product (functional group is indicated in parenthesis) as well as the mechanism for each product's formation:

***DCC = dicyclohexylcarbodiimide -- see page 907 of Jones for more info on this reagent

Based upon what you learned in class last Tuesday regarding reactions involving enolates, try the following reactions:

2. Present-day peptide synthesis can be accomplished in a reaction flask by a careful protection/activation synthetic strategy. One common protecting group used is di-tert-butyl dicarbonate (tBOC) and the activator is dicyclohexylcarbodiimide (DCC). Let’s say that our company (Peptides ‘R Us – experts in nucleophilic acyl substitution) has been contracted to synthesize a tripeptide (three amino acid polypeptide) for use in a biochemistry on the metabolism of the alanine (ALA)/glycine (GLY) bond in vivo. The general strategy is as follows:

Now, notice from the scheme shown above that the amino terminus needs to be protected. Our protecting group tBOC will need to be added on (via NAcS) and removed (via CF3COOH, trifluoroacetic acid). Our carboxy terminus activator is DCC. The general outline of reactions is shown on the next page. With this outline in hand, provide answers for the following directives:

(a) Show the complete mechanism for the formation of the tBOC protected glycine (step #1)

(b) Show the complete mechanism for the activation of the glycine with DCC for peptide coupling (steps #2 and #3)

(d) Show (via a reaction mechanism) how you can use trifluoroacetic acid to deprotect the amino terminus to yield the final dipeptide (gly-ala) --- HINT: remember that a tertiary carbocation is especially stable.

(e) Why is tBOC an especially good candidate for use as a protecting group?

(f) What makes DCC such a powerful activator?