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week5_questions - Chemistry S-20 Week 5 Carbohydrates 1....

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Unformatted text preview: Chemistry S-20 Week 5 Carbohydrates 1. When glucose is treated with methanol and acid, the methyl glucoside is formed. Provide a complete curved-arrow mechanism for this transformation: OH HO OH HO HO CH3OH, H+ O O HO OH OH OMe OH 2. The correct stereochemistry of only one stereocenter is indicated on the above structure. The actual stereochemistry of methyl glucoside is such that, when it is in a chair form, all of the substituents fall in the equatorial positions, except for the –OMe, which is found in the axial position. Given this information, draw a clear, correct representation of methyl glucoside in a chair conformation, with all substituents properly indicated. In addition, explain why the –OMe group preferably adopts an axial conformation; a diagram will be essential. 3. When glucose is in its open-chain form, its stereochemistry can best be represented using a Fischer projection. On the skeleton Fischer projection shown at right, fill in the H and OH groups of the glucose "backbone" with the correct stereochemistry as determined from your structure shown above. H O CH2OH 152 Chemistry S-20 Week 5 Carbohydrates: Mechanisms 1. Provide a complete curved-arrow mechanism for all steps in the following transformation. OH HO HO O HO OH– catalyst O H O OH HO OH OH glucose 153 OH Chemistry S-20 Week 5 More Carbohydrates Mechanisms 1. Sorbitol is a sugar alcohol that is used as a sweetener in many low-calorie foods. It can be prepared from glucose. Provide a complete curved-arrow mechanism for the following reaction. You may ignore stereochemistry for the purpose of this mechanism. CH2OH HO OH NaBH4 O HO OH NaOH , H2O OH HO OH OH OH glucose sorbitol 154 OH Chemistry S-20 Week 5 The Anomeric Effect 1. Draw the most stable chair conformations of the following molecules. Explain your choices in terms of either sterics or molecular orbital interactions. Which would you expect to have a shorter C-Cl bond? Cl Cl S 2. Explain why the molecule H3C—S—S—CH3, when viewed along the S—S bond, prefers to adopt the gauche conformation. (A Newman projection will be helpful). Describe the orbital interaction(s) involved. 155 Chemistry S-20 Week 5 More Anomeric Effect 1. Each of the following observations can be explained by a frontier molecular orbital (FMO) argument. Provide such an explanation for each observation. Be sure to label the relevant donor-acceptor interactions and provide a clear diagram showing the interacting orbitals. (An energy-level diagram is not expected.) a) The following ester prefers conformation A rather than conformation B. (Hint: Consider all the lone pairs in the molecule. A "steric" argument is not acceptable.) O O H3C O CH3 preferred to H3C O CH3 A B b) The two conformers of the nitrite ester shown below have slightly different bond lengths (as indicated). (Note that both conformations are entirely planar. How are the bond lengths different between A and B?) O 1.17 Å O N 1.19 Å O 1.43 Å A R R 1.39 Å N O B 156 Chemistry S-20 Week 5 Synthesis and Properties of Amino Acids Here are three of the naturally-occuring amino acids: O H2N O OH H2N O H2N OH OH OH NH2 serine OH lysine O glutamic acid 1. Draw the structures of these three amino acids as they would appear at pH = 7. Classify each one as "neutral," "basic," or "acidic." 2. Match these amino acids with the following isoelectric points: Explain your reasoning. 3.2 5.8 3. Propose a synthesis of serine (as a racemic mixture) using the Strecker synthesis. 157 10.1 Chemistry S-20 Week 5 Peptide Synthesis 1. Provide reagents for protecting and deprotecting an amino acid as shown: O H2N O H2N OH R R OH R O H N t OH R H2N OMe O H2N O BuO O O H2N OH R OH R 2. Using these protecting groups, synthesize the following dipeptide using traditional solution-phase chemistry. You may start with amino acids that are already protected in any way you choose. O H2N Me OH N H O glycylalanine 158 Chemistry S-20 Week 5 Complete Peptide Synthesis 1. Provide a multistep synthesis for the desired product. You may use any inorganic reagents, plus any organic reagents with 8 carbons or less, the protected amino acid shown below, and the organic reagent DCC. The best answer will require six or fewer steps. (Hint: Think carefully about protecting-group strategy; it is possible to hydrolyze a t -butyl ester using dry acid without disturbing other esters.) For the purpose of this question you may ignore the stereochemistry of the product. Starting material: the following partially-protected amino acid, plus any compounds with 8 carbons or less. O O OH H2N O O HO O H N H2N O aspartame (NutraSweet®) 159 OCH3 Chemistry S-20 Week 5 Solid-Phase Peptide Synthesis 1. Now show how you could use solid-phase peptide synthesis to synthesize the same dipeptide, below. Again, you may start with amino acids which are protected in any way you choose. O H2N Me OH N H O glycylalanine 160 Chemistry S-20 Week 5 More Complete Peptide Synthesis 1. Provide a complete synthesis of the dipeptide, lysylglycine, shown below. You may start with unprotected amino acids only. All of the carbon atoms from these amino acids must end up in the product. You may use any organic or inorganic reagents; you may use a Merrifield resin (but it is not required). The best answer will require seven or fewer steps. O H2N OH N H O NH2 lysylglycine (as a racemic mixture) 161 Chemistry S-20 Week 5 Putting It Together: Synthesis 1. Provide a multistep synthesis for the desired product (an unnatural amino acid) from the indicated starting material. You may use any inorganic or organic reagents. The best answer will require eight or fewer steps. Starting material: O H EtO O O O O NH3 Desired product (an unnatural amino acid) 162 Chemistry S-20 Week 5 Acidity of Carbonyl Compounds 1. All of the following compounds have acdic C—H bonds. The pKa of each compound is indicated: Compound O pKa Conjugate Base O 11 R OR H H O O 13 RO OR H H O 20 R CH2R O RO N 25 CH2R C 31 CH2R With each of the above compounds: • identify the most acidic proton of each compound • draw each conjugate base • use resonance structures to show stabilization of the conjugate base • rationalize the acidity order shown • predict and explain the order of nucleophilicity of the conjugate bases 2. Provide reasonable curved-arrow mechanisms for keto-enol tautomerization in acid and in base: O OH H3O+ O OH OH– 3. The following molecules are both ketones, and are structurally similar. However, they display strikingly different basicity. Explain this observation. O O pKa = 20 pKa = 40 163 Chemistry S-20 Week 5 Alpha Bromination Mechanisms 1. Provide a curved-arrow mechanism for each of the following transformations. O Br2 O O O Br trace H+ O O Br2, NaOH 164 Br Br Chemistry S-20 Week 5 Basic Aldol Mechanisms 1. Predict the product, and provide a curved-arrow mechanism for each of the following transformations. O NaOEt O H H O O H + NaOMe H 165 Chemistry S-20 Week 5 Basic Claisen Mechanisms 1. Predict the product, and provide a curved-arrow mechanism for each of the following transformations. O 1) NaOEt 2) H+ wkup OEt O OMe MeO H O 1) NaOMe 2) H+ wkup 166 Chemistry S-20 Week 5 More Aldol and Claisen Mechanisms 1. Provide curved-arrow mechanisms for the following transformations: O O O NaOH H OH O H O H3O+ H 167 O H Chemistry S-20 Week 5 Still More Aldol and Claisen Mechanisms 1. Provide curved-arrow mechanisms for the following transformations: O O NaOH OH O O O– OMe NaOMe 168 O OMe Chemistry S-20 Week 5 Synthesis using Aldol and Claisen Reactions 1. Propose synthetic pathways for the following multistep transformations. An aldol or claisen reaction will form a crucial step in each synthesis. O O O (any acyclic starting material) O OH OH O O O coumarin (first synthetic perfume) 169 Chemistry S-20 Week 5 More Synthesis 1. Provide a multistep synthesis for the desired products from each indicated starting material. You may use any inorganic reagents. Starting material: O O Desired product Starting material: O O Desired product 170 Chemistry S-20 Week 5 Controlling Enolate Formation 1. Each of the following enolates can be formed from a specific carbonyl compound. Write the structure of the carbonyl precursor which could be used, and give specific conditions to form the enolate. O– O– O– O H OCH3 O H 171 O– OCH3 Chemistry S-20 Week 5 Using Lithium Enolates 1. Provide a synthetic pathway and show the curved-arrow mechanisms for the following transformation. O O HO 2. Explain why only one of the three possible products below is observed: 1. LDA (1.1 eq.) 2. MeI Me no H O O H yes Me O no Me O 172 Chemistry S-20 Week 5 Simple Enolate Reactions 1. Each of the following transformations can be carried out in one or two steps. Fill in the reagents required for each step. Be specific! If a second step is not needed, please put an "X" through the second box. O O 1. 2. O O 1. 2. O O CH3 CH3 1. Br 2. O O 1. OCH3 OCH3 Br CH3 2. N C H O 1. C N OH 2. 173 Chemistry S-20 Week 5 Decarboxylation: Mechanisms 1. Provide a curved-arrow mechanism for the following transformation. O O + OCH3 Br Br NaOCH3 (excess) 174 1. NaOH 2. H3O+, O Chemistry S-20 Week 5 Decarboxylation: Synthesis 1. Using starting materials containing no more than 3 carbons, synthesize the following target using a route that involves decarboxylation as the final step. O 2. Show how the two starting materials shown below could be used to make the indicated product. What is the importance of the extra ester group in this synthtic route? O Ph O O + MeO OMe O Ph 175 O OH Chemistry S-20 Week 5 Conjugate Additions: Mechanisms 1. Provide a complete curved-arrow mechanism for all steps in the following multi-step transformation. O O 1. Me2CuLi H 2. H2O, OH- O 176 Chemistry S-20 Week 5 Robinson Annulation: Mechanism 1. The Robinson annulation can be used to produce a six-membered ring. Show the product formed when the following two molecules are reacted with a base: O O O NaOEt + OEt EtOH Provide a curved-arrow mechanism for the transformation you indicated above: O O O NaOEt + OEt EtOH 177 Chemistry S-20 Week 5 Robinson Annulation: Retrosynthesis 1. Give the structures of the organic compounds required to prepare each of the following cyclic ketones using the Robinson Annulation for the key bond forming steps. EtO2C a) + O CO2Me b) + O CO2Me O O c) OEt Ph + Ph 178 Chemistry S-20 Week 5 Conjugate Additions: Reactions 1. Work through the steps of the following reactions, showing all the intermediates, and the final products. (The molecular formula of the final product is given for you to check.) O O O OMe + 1. NaOMe 3. H3O+ , 2. NaOH C10H14O O CuLi Ph 2 179 Br C16H20O Chemistry S-20 Week 5 Conjugate Addition: Mechanisms 1. Provide a curved-arrow mechanism for each of the following transformations. O O H3C Ph NO2 NaOCH3 Ph NO2 O O O + Cl MeO O NaOCH3 OMe Cl Cl 180 Chemistry S-20 Week 5 Conjugate Addition: More Mechanisms 1. Provide a complete curved-arrow mechanism for the following transformation. O N H2N NH2 H+ 181 NH Chemistry S-20 Week 5 Mechanisms Practice 2 1. Consider the following multi-step transformation: O O H3CO CuLi + H3CO CH3 Anionic Intermediate X 2 H3O+ OH– CH3 H a) In the box below, draw the structure of the "Anionic Intermediate X." b) Provide a complete curved-arrow mechanism for the transformation of "Anionic Intermediate X" into the observed final product under the given conditions (aqueous acid, followed by aqueous base). 182 Chemistry S-20 Week 5 Putting It Together: Recognizing Acyclic "Aldols" 1. Identify the starting materials which could produce each of the "skeleton" products below, give the name of the reaction, and provide the reagents necessary to carry out both steps of the transformation. O OH O O O O OEt O O O OEt R R O O O OEt R R' O O 183 R O OEt O R' O Chemistry S-20 Week 5 Putting It Together: Recognizing Cyclic "Aldols" 1. Identify the starting materials which could produce each of the "skeleton" products below, give the name of the reaction, and provide the reagents necessary to carry out both steps of the transformation. (The strange curved loops below are meant to represent a ring of any size; most common are 5- and 6-membered rings.) O O OH OH O O O O O OEt O O O OEt O R O O R OEt 184 Chemistry S-20 Week 5 Synthesis . Provide a synthesis for the desired product. You may use any inorganic or acyclic (NO RINGS) organic reagents, but you must also use the indicated starting material. The best answer will require seven or fewer steps. Starting material: O MeO O OMe O MeO2C CO2Me (+/–) Desired product 185 Chemistry S-20 Week 5 Synthesis . Provide a synthesis for the desired product. You may use any inorganic or acyclic (NO RINGS) organic reagents, but you must also use the indicated starting material. The best answer will require five or fewer steps. You may neglect stereochemistry. Starting material: O O O O Desired product _______ / 15 186 Chemistry S-20 Week 5 Synthesis . Provide a synthesis for the desired product. You may use any inorganic or acyclic (NO RINGS) organic reagents, but you must also use the indicated starting material. The best answer will require seven or fewer steps. You may neglect stereochemistry. Starting material: O CO2Me Desired product _______ / 18 187 ...
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