CHEMISTRY 534 PROBLEM SET 1 -KEY FALL 2013 DUE FRI. SEPT. 13, 2013 I. These assigned problems are for drill only. They will not be graded.

a. Do Carey and Sundberg, Part B; Ch. 12: 1d, i, l, q; 2b, e, k; 4, 8d, f; 9c, f, i, l; 12b, c.

5th Ed.: 1d, i, l, q; 2b, e, k; 4, 7d, f; 8c, d, g, j; 13a ,b. b. Do Carey and Sundberg, Part B: Ch. 13; 1, 2 (both editions)

II. List the major uses and limitations of the following reagents

a. Fremy’s salt (aka Potassium Nitrosodisulfonate)

Uses: 1. Oxidizes phenols to 1,2 and 1,4-quinones (ratio depends on substitution on the arene).

Applies to naphthols, anilines, quinolinols,

2. Oxidizes benzylic alcohols to the corresponding aldehyde/ketone in the presence of allylic

and saturated alcohols

Limitations: 1. Limited shelf life.

b. dichlorodicyanoquinone (aka DDQ)

Uses:

1. Powerful reagent for aromatization reactions (dehydrogenation of carbocyles and

heterocycles).

2. Dehydrogenation of ketones to form α,β-unsaturated carbonyl compounds. 3. Rapid oxidation of benzylic alkyl groups.

4. Oxidizes phenols to the corresponding oxygen heterocyclic in the presence of alkenes or

arenes.

Limitations:

1. Decomposes and forms HCN in the presence of water. 2. Reacts with amines

c. ruthenium tetroxide (RuO4)

Uses:

1. Converts primary alcohols to carboxylic acids and secondary alcohols into ketones, usually

in excellent yields.

2. Cleaves double bonds to yield ketones/carboxylic acids. 3. Cleaves arenes to yield carboxylic acids.

4. Dihydroxylates olefins giving cis diols (see limitation 3).

Limitations:

1. Reactions are typically done in CCl4 as many organic solvents are in compatible.

2. Decomposes at moderate temperatures. 3. Careful monitoring of reaction conditions required.

d. tert-butylhydroperoxide (tBuOOH)

Uses:

1. Used as a stoichiometric oxidant with various, more expensive, more toxic, oxidants such as

SeO2,OsO4, VO(acac)2 and MoO2(acac)2.

2. Epoxidizes double bonds with a vanadium or molybdenum catalyst. 3. Oxidizes allylic and benzylic alcohols with the aid of a catalytic amount of diphenyl

diselenide

4. Oxidizes alkyl phosphines to the corresponding phosphine oxide.

5. Oxidizes sulfides stopping at the sulfoxide. The sulfone if used in excess with a vanadium or

molybdenum catalyst. Limitations:

1. Must be used in the presence of water.

e. N-methylmorpholine-N-oxide (aka NMO aka NMMO)

Uses:

1. Used as a mild co-oxidant (e.g. with OsO4 or ruthenates to avoid the use of a stoichiometric

amount of the reagent). 2. Oxidizes activated halogens to yield the corresponding aldehyde.

f. dimethyldibromohydantoin (aka DBH)

Uses:

1. Replaces NBS on industrial scale reactions for electrophilic bromination of alkenes. 2. Bromination at the benzylic position of arenes.

3. Deprotects dithioacetals and dithianes

g. (diacetoxyiodo)benzene (PhI(OAc)2)

Uses:

1. Oxidative cleaves 1,2-diols to aldehydes. 2. Stoichiometric oxidant used for transition-metal catalyzed oxidations such as epoxidations

using Ru, primary C-H oxidations using Pd, aziridinations using Rh.

3. Oxidation of C-H bonds α- to ketones.

4. Deprotects dithioacetals to yield the corresponding ketone.

5. Oxidizes phenols with nucleophilic attack by solvent yielding the cyclohexadienone. Limitations:

1. Iodobenzene forms as a stoichiometric byproduct.

h. Oxone (aka Potassium peroxymonosulfate)

Uses:

1. Forms epoxides with electron rich alkenes via dioxiranes formed from ketones.

2. Selectively oxidizes sulfides to sulfones even in highly functionalized molecules. 3. Oxidizes amines to nitro compounds.

4. Oxidizes ketones to esters (Baeyer-Villiger).

Limitations:

1. Not tolerant to most functional groups.

2. Difficult to achieve chemoselectivity.

III. Suggest reagents for carrying out the following selective transformations without making recourse

to protective groups. Suggest possible side reactions.

a.

b.

c.

d.

e.

IV. Provide the major product expected from these transformations. Show stereochemistry. a.

b.

c.

d.

Predictive model: Chair-like transition state - Make sure stereochemistry is correct (stereogenic carbon and double bond configuration).

- Maximize the number of groups at equatorial position.

- When redrawn the product from the chair-like model, make sure the configuration of the epoxy

ring is maintained.

e.

f.

V. Devise synthetic routes to accomplish the following transformations enantioselectively. Show

intermediates.

a.

b.

c.

d.

e.

VI. Read Chapter 19 in Nicoloau and Sorensen on the Sharpless/Masamune synthesis of the l-hexoses

and familiarize yourselves with the stereochemical controlling strategies. Following their example devise a de novo, enantioselective total synthesis of the rare eight carbon sugar d-threo-l-talo-octose

given any achiral starting material of no more than four carbon atoms and any chiral reagents, etc.

Show all intermediates and conditions for each step.