180 C 2 -C 3 bond rotation

Transcription

1 I. ( points) Valnoctamides have been used as sedatives and inducers for hypnosis for decades. The most biologically active molecule from this class of compounds is shown. Using ewman projections, analyze two of the bonds in this molecule. view 1 - view - 1 Valnoctamide-1 ame Page 1 (a) Draw a ewman projection of the 1 - bond in valnoctamide-1 in the conformation shown; view with the 1 in front. can have double or single line, but should be mostly a straight system ethyls can be pointing any direction can be drawn D, but ignore stereochem (b) Draw a ewman projection of the - bond in valnoctamide-1 in the conformation shown; view with the in front. connectivity + stereochem +1 conformation +1 in order bond rotation (c) Draw a ewman projection of the - bond in valnoctamide-1 after a 180 bond rotation; continue to view with the in front. Must be eclipsed must be consistent with left conformer (d) Describe the relationship (if any) between the drawing (and conformation) of Valnoctamide-1provided for you in part (a) above and each of the drawings (P, Q, R, and ) shown below. heck all the descriptions that apply when comparing valnoctamide-1 (above) with each of these other drawings. (i) (ii) (iii) (iv) P Q R valnoctamide-1 with P, valnoctamide-1 with Q, valnoctamide-1 with R, valnoctamide-1 with,

2 II. (7 points) ame Page A. Telepravir is an antiviral drug that acts as a protease inhibitor. It has been a very successful treatment for hepatitis. It was approved for use in 011. ircle and label every chiral (tetrahedral) stereocenter in Telaprevir. pts per center - for "extras" Telaprevir R 18 onvert name to structure or structure to name as needed. Be sure to include all information on connectivity and stereochemistry in both your drawings and your naming. (i) Draw this compound: -1-cyclobutyl-6-propylcyclohex-1-ene -if wrong connectivity: 0 -if stereo is wrong but connectivity is right: (ii) ame this compound: Br (,E)-1-bromo-,-dimethylhexa-1,5-diene - pts/ error up to This compound should show: 1 MR signals with ratio :1:1::::1 numbers can be in any order 1

3 A. III. ( points) The transformation shown (M to F) demonstrates a highly regioselective addition of methanol. Draw the stepwise, curved arrow mechanism for this complete transformation. Be sure to use appropriate acid/base choices, and clearly show the resonance effect that explains this regioselection. Ignore stereochemistry. M ame Page (cat.) ompound F blue arrow also fine - straight to resonance choose the appropriate acid Grading stops when chemically illogical step is made (like forming an oxygen anion under acidic conditions) pts pts pts - if use - but all right after 6 total pts - must use for these points starting materials M closed shell contributor must be shown, either alone or as a resonance contributor to the + pts for this one red or blue depending on which contributor is used pts for the better one ompound F 1 The energy diagram shown could represent the transformation you have shown above in conjunction with the formation of the regioisomeric product, Q. Provide the structure of the missing regioisomer and answer questions about the energy diagram using positional labels. (i) Define the E a for the rate determining step in the formation of Q: L - M (ii) Draw Q; if the product forms as a stereoisomeric mixture, draw one showing stereochemistry clearly and write "+ enantiomer" or "+ diastereomer". Energy Q P M L A B D E F (iii) Under reversible reaction conditions the favored product is: Q (iv) Define the ΔG rxn for the formation of F? F - M reaction progress either; must show chiral center in D + enantiomer 1pt ompound Q + reaction progress + ompound F

4 A. IV. ( points) ame Page Provide the structures of all starting materials with structural formula 1 that can lead to the product shown. Be sure to draw them in the box with the matching MR data. 1 isomers, 1 -MR: 10 draw all (E) possible starting materials 1 -MR: 6 (cat.) according this is the same to -MR data 6 omplete the following reaction by providing missing product(s). If more than one compound can be formed, only provide one drawing and discuss the other products in (ii). (i) or the salt (ii) This ionic compound product forms with only its enantiomer with only one diastereomeric molecule with >1 stereoisomer with regioisomer(s) alone, with no other isomers (iii) Provide a transition state drawing that represents the single step that occurs in this reaction. (i) 1 10 The missing starting material ( 1 10 ) yields only product(s) with molecular formula Provide the missing information. (1 equivalent) (cat.) (ii) This organic product forms with only its enantiomer with only one diastereomeric molecule with >1 stereoisomer with regioisomer(s) and stereoisomers alone, with no other isomers (iii) Provide a transition state drawing that represents the ratedetermining step that occurs in this multi-step reaction. Be sure to choose your reactants carefully.

5 V. ( points) The following addition reaction yields mainly stereoisomeric products, and. Provide the structure of. ame Page 5 (a) other product (E) + 1 (b) Describe the relationship (if any) between the drawings indicated. heck all the descriptions that apply. (i) compound 1 with A, (ii) compound with B, A the B the (c) Draw the two chair conformations for ompound and indicate the K eq for your pair of chairs. As always, be sure to clearly and accurately show the axial and equatorial positions for all substituted ring atoms. You do not have to show axial and equatorial hydrogen atoms for unsubstituted ring atoms. TI I MRE TABLE circle one > 1 K eq = 1 < 1 - pts per error (bond angles, missing, etc.) pts for correct Keq (based on the drawings) if stereochem is wrong, the first chair is all wrong but the second can get points for consistency (each chair worth 5 points) if connectivity is wrong - no points 1 (d) Based on the conformational analysis you have done for compound, what do you predict about the relative amounts of each product ( and ) that forms? ircle one of the options and explain. ompound > ompound ompound < ompound ompound = ompound Briefly explain: the other stereochem would prevent all three alkyl groups from being equatorial (more stable) at the same time; this gives the conformational stability advantage.