Chemistry 215 Name____________________ Final Examination December 17, 2011 (2.0 hr; 240 points) Signature________________________ Professor Masato Koreeda Student ID# ______________________

*If you are not in Chem 216, put an “X” here _______ Please CHECK OFF your lab section: Tue ____130 Timothy Berto Thu ____170 Michael Beck ____131 Kristin Ko ____171 Zachary Bryan ____132 Michael Beck ____172 Shana Santos ____133 Rui Huang ____173 Rui Huang ____134 David Todd ____174 Meghan Breen ____135 April Tang ____175 Benjamin Klepser ____136 Benjamin Klepser ____176 Kristin Ko Wed ____150 Danielle Zurcher ____151 Zachary Bryan ____152 Shana Santos ____153 David Todd ____154 April Tang ____155 Meghan Breen ____156 Grace Winschel ____157 Renata Everett ____158 Timothy Berto

Please read each question carefully and answer it completely and clearly. Complete Lewis structures are acceptable for answers unless you are given other specific instructions. Precision in drawing is an important skill in the communication of organic chemistry concepts. Double-check any three-dimensional representations to ensure you are implying an unequivocal direction of bonding. Do not forget to include important features such as nonbonding lone electron pairs and formal charges when appropriate. The exam has 11 pages in addition to this cover page. The last 5 pages include tables of electronegativity values for some elements, bond energies for representative bonds, pKa values of representative acids, and lists of amino acids and their pKa values, and reagents from Chem 210 and 215.

Name_______________________________ 215 F11-Final exam Page 2 I. (18 points) Glycoside 1 is a new iridoid glycoside isolated from the stems of Hedyotis hedyotidea, which have been used in traditional Chinese medicine [Helv. Chem. Acta 2011, 94, 675]. Treatment of the glycoside, 1, with the enzyme β−glycosidase provides disaccharide 2. Answer the following questions about this glycoside 1 and disaccharide 2.

II. (12 points) Using the pKa information given on page 12, match the following isoelectric point (pI) values (2.98, 6.11, and 10.76) to their corresponding amino acids by writing the correct isoelectric point value in the box beside each amino acid.

III. (16 points) Draw the full structure (including stereochemistry) for the tripeptide His-Pro-Ser (all L amino acids) in the predominant form it would exist at its isoelectric point. Use the Fischer projections.

Name_______________________________ 215 F11-Final exam Page 3

IV. (36 points) Treatment of keto-diol 3 with a catalytic amount of p-toluenesulfonic acid (p-TsOH; pKa -1.5) in benzene at reflux results in the formation of a distereomeric mixture of spiro-ketal 4 together with H2O. The transformation is believed to go through hemi-ketal 5. Provide in the box below a step-by-step mechanism for this acid-catalyzed reaction using the curved-arrow convention. You may use HA and A- to represent the Brønsted acid and its conjugate base.

V. (20 points) Draw in the box below a step-by-step, curved-arrow reaction mechanism for the following transformation [Angew. Chem. Int. Ed. 2010, 49, 5887].

Name_______________________________ 215 F11-Final exam Page 4

VI. (28 points). Treatment of a mixture of benzaldehyde (6), acetylacetone (7), and thiophenol (8) in an aqueous solvent in the presence of a catalytic amount of a base (e.g., NaOH) results in the formation of β-mercapto diketone 9 [Chinese J. Chem. 2011, 29, 1856]. The transformation involves the initial formation of an aldol condensation-like intermediate 10, followed by the Michael addition reaction of 8 to 10. As directed in the boxes below, provide a step-by-step mechanism using the curved-arrow convention for the following base-catalyzed transformations.

VII. (21 points) Draw in the box below a step-by-step, curved-arrow reaction mechanism for the following Dieckmann condensation reaction.

Name_______________________________ 215 F11-Final exam Page 5 VIII. (22 points) Complete the following reactions by providing in each of the boxes the structure of the starting compound or product. (1) [Chem. Eur. J. 2011, 17, 12037]

(2) [Tetrahedron Lett. 2011, 52, 7049]

Name_______________________________ 215 F11-Final exam Page 6 IX. (35 points) Complete the following reactions by providing in each of the boxes the structure of the starting compound, intermediate, or product.

Name_______________________________ 215 F11-Final exam Page 7 X. (32 points) Complete the following reactions by providing in each of the boxes the structure of the intermediate or product. Indicate stereochemistry for each of the products/intermediates.

Page 10 The Reagent List Shown below is a list of key reagents (not always the whole recipe) that may be useful for solving questions on the final exam. reagent classification or specialized use ____________________________________________________________________________________ From OsO4 oxidation Chem 210 KMnO4 oxidation peroxyacid epoxidation (e.g., 3- or meta-chloroperoxybenzoic acid) i. O3; ii. (CH3)2S or Zn ozonolysis i. O3; ii. H2O2 ozonolysis NaNH2 base, nucleophile NaH base KOC(CH3)3 bulky base H2/Pd hydrogenation H2/Pd, BaSO4, quinoline hydrogenation i. BH3 or 9-BBN; ii. H2O2, NaOH hydroboration PBr3 e.g., R-OH → R-Br SOCl2 e.g., R-OH → R-Cl

p-CH3C6H4SO2Cl (p-TsCl) tosylate formation CH3SO2Cl (MsCl) mesylate formation N-bromosuccinimide (NBS)

N

O

O

Br

source of electrophilic Br =========================================================================== Ch. 13 C5H5NH+•ClCrO3- (PCC) oxidant CrO3/H2SO4/H2O/acetone oxidant i. ClC(=O)-C(=O)Cl, (CH3)2SO; ii. N(CH2CH3)3 oxidant Ch. 14 NaBH4 nucleophilic hydride LiAlH4 nucleophilic hydride diisobutylaluminum hydride (DIBAL) nucleophilic hydride RMgX nucleophilic carbon RLi nucelophilic carbon 4-CH3C6H4SO3H (p-TsOH) (pKa ~ -1) organic-soluble acid Raney Ni desulfurization HSCH2CH2SH; HSCH3 thioacetal/thioketal formation BF3•O(CH2CH3)2 Lewis acid H2NNH2 hydrazone formation H2NOH oxime formation

Page 11 Ch. 15 SOCl2 R-C(=O)OH → R-C(=O)Cl Ag2O, NaOH, H2O oxidant -CH2

+N2 (diazomethane) e.g., R-C(=O)OH → R-C(=O)OCH3 Ch. 17 LiN[CH(CH3)2] (LDA) bulky base K2CO3 weak base Amino acids & proteins C6H11N=C=NC6H11 RC(=O)OH activation (DCC; dicyclohexylcarbodiimide) PhCH2OC(=O)Cl (benzyl chloroformate) N-protection ROC(=O)N3 (R = tert-butyl) N-protection [tert-butyl-O-C(=O)-]2O (Boc2O) N-protection

H3C CO O O

CCH3

H3CH3C O O CH3

CH3

(9-fluoromethyl)methoxycarbonyl chloride N-protection (Fmoc)

CH2

OCl

O

Cl3CC(=O)OH O-deprotection H2, Pd/C catalytic hydrogenolysis Sanger’s reagent N-terminus AA determination

NO2

FO2N

The 20 naturally occurring amino acids Page 12

H2N OHH CH3

O

H2N OHH

O

H2N OHH H

O

ONH2

H2N OHH

O

H2N OHH

O

SH

O NH2

H2N OHH

O

H

H2N OHH

O

H2N OHH

O

SCH3

HN

OH

O

H

H2N OHH

O

OH

H2N OHH

O

HHO

H2N OHH

O

NH

H2N OHH

O

OH

H2N OHH

O

H2N OHH

O

Alanine

Asparagine

Cysteine

Glutamine

Glycine

Isoleucine

Leucine

Methionine

Phenylalanine

Proline

Serine

Threonine

Tryptophan

Tyrosine

Valine

Acidic amino acids

Basic amino acids

Neutral amino acids

H2N OHH

O

OOH

Aspartic acid

H2N OHH

O

O OHGlutamic acid

H2N OHH

O

NHArginine

H2N OHH

O

Histidine

H2N OHH

O

Lysine

NH2

NH

NH2

HN N

pKa Values for the Ionizable Functional Groups of an α-Amino Acid Amino acid α-C(=O)OH α-NH3

+ side chain ___________________________________________________________________________________________________ Alanine 2.35 9.87 - Arginine 2.01 9.04 12.48 Asparagine 2.02 8.80 - Aspartic acid 2.10 9.82 3.86 Cysteine 2.05 10.25 8.00 Glutamic acid 2.10 9.47 4.07 Glutamine 2.17 9.13 - Glycine 2.35 9.78 - Histidine 1.77 9.18 6.10 Isoleucine 2.32 9.76 - Leucine 2.33 9.74 - Lysine 2.18 8.95 10.53 Methionine 2.28 9.21 - Phenylalanine 2.58 9.24 - Proline 2.00 10.60 - Serine 2.21 9.15 - Threonine 2.09 9.10 - Tryprophan 2.38 9.39 - Tyrosine 2.20 9.11 10.07 Valine 2.29 9.72 - ________________________________________________________________