Draw the structure of each compound: (a)

Assign an IUPAC name for each of the following compounds: HO (a) OH (b) OH (c) Br OH (d)

Draw the structure of each compound: (a) cis-1,2-Cyclohexanediol (b) Isobutanol (c) 2,4,6- Trinitrophenol (d) (R)-2,2-Dimethyl-3-heptanol (e) Ethylene glycol (f) (S)-2-Methyl-1-butanol

Draw and name all constitutionally isomeric alcohols with molecular formula C4H10O.

Rank each set of alcohols below in order of increasing acidity. Cl Cl OH Cl Cl Cl Cl Cl OH Cl Cl (a) OH (b) OH OH OH OH OH OH (c) NO2

Draw resonance structures for each of the following anions: O (a) @ O (b) @ O (c) @

Predict the major product of the reaction between 1-butanol and: (a) PBr3 (b) SOCl2, py (c) HCl, ZnCl2 (d) Conc. H2SO4, heat (e) PCC, CH2Cl2 (f) Na2Cr2O7, H2SO4, H2O (g) Li (h) NaH (i) TMSCl, Et3N (j) TsCl, pyridine (k) Na (l) Potassium tert-butoxide

Acid-catalyzed hydration of 3,3-dimethyl-1-butene produces 2,3-dimethyl-2-butanol. Show a mechanism for this reaction.

Starting with 1-butanol, show the reagents you would use to prepare each of the following compounds: O (a) H O (b) OH OH (c) OH (d) O (e)

Using a Grignard reaction, show how you could prepare each of the following alcohols: OH (a) OH (b) OH (c) OH (d)

Each of the following alcohols can be prepared via reduction of a ketone or aldehyde. In each case, identify the aldehyde or ketone that would be required. OH (a) OH (b) OH (c) OH (d)

What reagents would you use to perform each of the following transformations? O H O (a) O H OH (b)

Propose a mechanism for the following reaction: Br OH O NaH

Acid-catalyzed hydration of 1-methylcyclohexene yields two alcohols. The major product does not undergo oxidation, while the minor product will undergo oxidation. Explain.

Consider the following sequence of reactions and identify the structures of compounds A, B, and C: O 1) 2) H2O Compound C conc. H2SO4 Heat Compound A Compound B (C6H11Br) Mg

Consider the following sequence of reactions and identify the reagents ah: O H O H OH a OH e OH O c Br OH g b d h f

Using 2-propanol as your only source of carbon, show how you would prepare 2-methyl-2-pentanol.

Predict the product and draw a mechanism for each of the following reactions: O 1) LAH 2) H2O (a) ? O 1) LAH 2) H2O (b) ? O (c) ? NaBH4 MeOH

Draw a mechanism for each of the following reactions: OH Cl py SOCl2 (a) OH Br PBr3 (b) O O OH + CH3OH 1) Excess LAH 2) H2O (c)

Identify the reagents you would use to accomplish each of the following transformations: OH O (a) OH O H (b) OH O (c) OH O OH (d) O OH H (e) O OH (f)

Predict the products for each of the following: 1) O3 2) DMS 3) Excess LAH 4) H2O (a) ? (b) ? 1) O3 2) DMS 3) Excess LAH 4) H2O 1) O3 2) DMS 3) Excess LAH (c) 4) H2O ? H O 1) EtMgBr 2) H2O 3) Na2Cr2O7, H2SO4, H2O 4) EtMgBr (d) 5) H2O ? O H 1) LAH 2) H2O 3) TsCl, pyridine (e) ? 1) H3O+ 2) Na2Cr2O7, H2SO4, H2O 3) PhMgBr 4) H2O (f)

ns: O OH 1) MeMgBr 2) H2O (a) HO OH 1) Excess MeMgBr 2) H2O (b) O O

Identify the reagents that would be necessary to accomplish each of the transformations shown here: H O OH Br

Propose an efficient synthesis for each of the following transformations: H O O (a) H O (b) H O O (c) H O (d) Cl H O (e) Cl O (f) O (g) OH (h) (i) OH (j) OH (k) H O OH (l) O (m) O (n) O HO (o) O (p) O OH (q) H Br O (r) OH (s)

Propose a structure for a compound with molecular formula C10H14O that exhibits the following 1 H NMR spectrum: Chemical shift (ppm) 8 7 6543 2 1 2 1 9 2 Proton NMR

Propose a structure for a compound with molecular formula C3H8O that exhibits the following 1 H NMR and 13C NMR spectra: 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 Proton NMR Carbon 13 NMR 3 1 2 70 60 50 40 30 20 10 0 Chemical shift (ppm) Chemical shift (ppm)

Propose two possible structures for a compound with molecular formula C5H12O that exhibits the following 13C NMR and IR spectra: Chemical shift (ppm) Carbon 13 NMR 100 90 80 70 60 50 40 30 20 10 0 73.8 29.1 9.5 Wavenumber (cm1) 4000 3500 3000 2500 2000 1500 1000 % Transmittance 0 20 40 60 80 100

Propose a structure for a compound with molecular formula C8H10O that exhibits the following 1 H NMR spectrum: Chemical shift (ppm) 2 5 2 1 Proton NMR 8 7 6 5 4 3 2 1

Propose a mechanism for the following transformation: HO OH O O O O 1) Excess LAH 2) H2O

Propose a mechanism for the following transformation: O O O O HO OH 1) Excess MeMgBr 2) H2O

Show the reagents you would use to achieve the following transformation:

Propose a mechanism for the following transformation: O O O CH3OH 1) Excess LAH 2) H2O

A carbocation is resonance stabilized when it is adjacent to an oxygen atom: Resonance stabilized O O! ! Such a carbocation is even more stable than a tertiary carbocation. Using this information, propose a mechanism for the following transformation exhibited by a diol. This reaction is called a pinacol rearrangement: HO OH O conc. H2SO4 Heat

Determine whether the pinacol rearrangement, shown in the previous problem, is a reduction, an oxidation, or neither.

(S)-Gizzerosine is an amino acid that is believed to be responsible for a serious disease called black vomit in chickens. However, the same compound is a potential drug for the treatment of osteoporosis and acid buildup in the stomach. Provide a two-step synthesis for achieving the following transformation, which was employed during a recent synthesis of (S)-gizzerosine (Tetrahedron Lett. 2007, 48, 84798481): N 2 steps N HO Boc = O O OCH3 O OCH3 O H Boc H Boc H O

4 Briarellin E (compound 3) is produced by coral in the Caribbean and Mediterranean seas and belongs to a larger family of marine natural products that are currently being investigated as potential anticancer agents. During a recent synthesis of 3, compound 1 was treated with TBAF to give compound 2 (J. Org. Chem. 2009, 74, 54585470). Draw the structure of compound 2. O H H O O HO Si Si O H H O O HO H OH 1 3 2 TBAF

5 Lepadiformine is a cytotoxic agent (toxic to cells) isolated from a marine tunicate. During a recent synthesis of lepadiformine, the investigators observed the formation of an interesting byproduct (3) while treating diol 1 with a reagent similar in function to PBr3 (J. Org. Chem. 2012, 77, 33903400): OH R HO PBr3 O R 3 dibromide 1 2 + (a) Draw a structure for the desired product (2). (b) Propose a plausible mechanism for formation of byproduct 3 using PBr3 as the reagent. Make sure that your mechanism provides a justification for the stereochemical outcome.

The compound duryne was one of several structurally related compounds isolated from a marine sponge (J. Nat. Prod. 2011, 74, 12621267). Propose an efficient synthesis of duryne starting with any compounds containing eleven or fewer carbon atoms. OH (CH2)9 (CH2)9 OH Duryne

Estragole is an insect repellant that has been isolated from the leaves of the Clausena anisata tree (J. Nat. Prod. 1987, 50, 990991). Propose a synthesis of estragole starting from 4-methylphenol. O Estragole

s isolated from the steam-distilled volatile oil of fresh and air-dried marijuana buds (J. Nat. Prod. 1996, 59, 4951). Propose a separate synthesis for each of these two compounds using only disubstituted alkenes containing four carbon atoms as starting materials. O O

Lithium borohydride (LiBH4) is a useful reducing agent, as it is more selective than LAH but less selective than NaBH4. Unlike the latter, LiBH4 will reduce esters. However, it will not reduce amides (LAH reduces amides, as we will see in Chapter 21). This selectivity is frequently employed by synthetic organic chemists. For example, during a synthesis of (-)-croalbinecine, a natural product with cytotoxic properties, compound 1 was converted to compound 3, as shown below (J. Org. Chem. 2000, 65, 92499251). Draw the structures of 2 and 3. N O HO CO2Et 1) Excess NaH, excess PhCH2Br, DMF 2) H2O 1) Excess LiBH4 Ph 1 2 2) H2, Pd/BaSO4, quinoline, CH3OH 3 OCH3

In a study of the chemical components of salted and pickled prunes, hexyl butanoate was identified as one of 181 detected compounds (J. Agric. Food Chem. 1986, 34, 140144). Propose a synthesis of this compound using acetylene as your only source of carbon atoms. O O Hexyl butanoate

The compound 5,9,12,16-tetramethyleicosane was synthesized as part of a study of the male sex pheromone of a Brazilian bug that feeds on the leaves and fruit of tomato plants (J. Chem. Ecol. 2012, 38, 814 824). The synthesis of this alkane was reported using compounds AC. O Br O A B C O 5,9,12,16-Tetramethyleicosane A key step in the synthesis is shown below, in which a mixture of E and Z isomers is obtained: OH HBr Br (a) Draw a plausible mechanism for this process. (b) Propose an efficient synthesis of 5,9,12,16-tetramethyleicosane using A, B, and C as your only sources of carbon.

Brevetoxin B (compound 2) is produced by Ptychodiscus brevis Davis, a marine organism responsible for red tides. Brevetoxin B is a potent neurotoxin, as a result of its ability to bind to sodium channels and force them to remain open. Its biological action, together with its complex architecture, has made it an attractive synthetic target. During K. C. Nicolaous synthesis of brevetoxin B, the K ring was assembled via the construction of compound 1. The syn disposition of the hydroxyl group and the silicon-based protecting group in 1 was established via the successful conversion of a small amount of 1 into 5, as shown below (J. Am. Chem. Soc. 1989, 111, 66826690). Note that the conversion of 3 to 4 involves the selective tosylation of the primary hydroxyl group: O O O O O O O O O O O HO H H H H H H Me H H H O H O Me H H Me Me H H H Me H Me Me 2 (Brevetoxin B) K J I E F G H CBA D 1 5 3 TBAF O O H HO 4 TsCl pyridine O O O H H NaOMe K O Si R R R (a) Draw the structures of 3 and 4. (b) Draw a mechanism for the conversion of 4 to 5 upon treatment with NaOMe. (c) Explain why the successful conversion of 1 to 5 verifies the syn relationship between the hydroxyl group and the silyl protecting group in 1.