Organic Cumulative Exam April 26, 2018

Transcription

1 rganic Cumulative Exam April, 0 Answer only three of the five questions. o more than three question answers will be graded and any work not to be considered must be clearly marked as such. Clearly indicate which questions are to be graded on the front of your answer booklet.. ( points) The following reaction was observed to result in formation of a biaryl. Hori et al. Angew. Chem., Int. Ed., 0,,. I m-cpba (. eq) (. eq) I Ac 0 C, h Ac C, h The reaction works for a range of aryl iodides (although poorly for iodobenzene). Several naphthols can also be used. (a) Draw the intermediate formed from the initial reaction between the iodoarene and mcpba/ac. (b) The key C-C bond formation might occur from a radical, ionic, or concerted mechanism. Draw each of these key processes. (c) Propose an experiment to test whether your radical process operates. Be sure to describe the predicted outcome if the process is radical-mediated, as well as how a null result would rule out a radical mechanism. (d) Propose an experiment to test whether your ionic process operates. Be sure to describe the predicted outcome if the process is radical-mediated, as well as how a null result would rule out an ionic mechanism. (e) Propose an experiment to test whether your concerted process operates. Be sure to describe the predicted outcome if the process is radical-mediated, as well as how a null result would rule out a concerted mechanism. page of

2 . Sarlah and coworkers recently reported a useful enantioselective i-catalyzed dearomative trans-,-carboamination of benzene derivatives. The transformation relies on desymmetrization of photocycloadducts (e.g., ) formed from MTAD (). visible light CH Cl, C J. Am. Chem. Soc. 0, 0, 0. i-pr RMgBr i(acac) (. mol%) Ph P ( mol%) 0 C to rt Fe R H R = vinyl, aryl %, 0% ee (a) (b) Provide mechanisms for the formation of cycloadduct from benzene and MTAD () and its further conversion to carboaminated product in the presence of a Grignard reagent, i(acac), and the illustrated chiral ligand. ( points) The above chemistry was instrumental to a concise synthesis of (+)-pancrastatin (), key aspects of which are summarized below. ( points) Sarlah et al. J. Am. Chem. Soc. 0, 9,. H (+)-pancratistatin () H m-cpba Ts, H CH Cl (F C) CH % H H steps? H steps? H H i. Give reagents and reaction conditions for the synthesis of from benzene, and the later conversions of to and to. ii. Explain the stereo- and regio-chemical outcome of treatment of diene with m- chloroperoxybenzoic acid in the presence of aqueous tosylic acid. (c) Give two other examples of reactions that result in the dearomatization of benzene derivatives. Why are such reactions comparatively rare? ( points) page of

3 . ( points) The following questions have to do with polyaromatic hydrocarbons (PAHs). A relevant publication is: Environ. Sci. Technol. 0,,. 9 0 naphthalene acenaphthene acenaphthylene anthracene 0 9 phenanthrene 9 0 benzo[a]phenanthrene (chrysene) 0 9 dibenzo[a,i]perylene 0 9 pyrene (a) What are the favored products of Diels-Alder reactions between the above PAHs and butadiene? Consider single additions only. (b) Explain the regioselectivity for your answers in question a. (c) (d) PAHs react with radicals (hydroxy and peroxy) in the upper atmosphere. These functionalized PAHs have greater ecosystem and organism penetration and thus possess more harmful toxicological profile than the parent PAHs. Explain what factors are responsible for the regioselectivity of radical additions to these PAHs in the upper atmosphere. Devise non-destructive experimental test(s) that you could perform on PAHs to predict the regioselectivity of additions. For an example, let s suppose you isolate a nanomolar sample of a novel and highly toxic PAH, and there is not enough to run a reaction but enough to run non-destructive characterizations. What test(s) would you run to predict the reactivity of this new PAH? page of

4 . Recently, the Smolke group at Stanford demonstrated the de novo production of noscapine, a potential anticancer compound, in Saccharomyces cerevisiae, via the construction of a biosynthetic pathway comprising more than 0 enzymes from plants, bacteria, mammals, and yeast itself. Below is a simplified version of the pathway. Proc. at. Acad. Sci. 0, doi:0.0/pnas.9 H H -HPAA dopamine H CS H H H H (S)-orcoclaurine H H Ac -hydroxy---acetyl-methylcanadine CYPX CXE H H H oscapine arcotolinehemiacetal (a) Show the mechanism for the transformation of -HPAA and dopamine to (S)-norcoclaurine. ( points) (b) Dopamine is derived from L-tyrosine by the enzymes tyrosine hydroxylase and L- DPA decarboxylase. Show the conversion from L-tyrosine to dopamine. ( points) (c) The transformation of -hydroxy---acetyl--methylcanadine to narcotolinehemiacetal is catalyzed by a hydroxylase (CYPX) and a carboxylesterase (CXE). Show the mechanism for this transformation. ( points) (d) Propose the mode of formation of the methylenedioxy bridge and describe the types of enzymes involved. ( points) (e) Describe two classes of enzymes that may be involved in the transformation of narcotolinehemiacetal to noscapine. ( points) page of

5 . Recently, Weiss and co-workers disclosed a route to -azido-l-phenylalanine () via an Ullman-like Cu(I)-catalyzed azidation. J. rg Chem. 0, DI: 0.0/acs.joc.b000 (a) Weiss construction of the phenyl-azide in is praised for its safety. Can you name two other reactions or reagents to install of the phenyl-azide? What are their drawbacks? ( points) (b) Can you think of an application of the unnatural amino acid? ( points) (c) Weiss and co-workers recognized potential explosion hazards associated with their synthesis of. After each reaction step, they tested the product and side products (filtrates, washes) for their explosive potential and they assigned the highest explosion risk to compound. Hypothetical - How could you assess the reaction thermodynamics? Come up with an experiment. What other precautions can be included in the synthesis to avoid exposure to? ( points) (d) Previously, no consensus existed for the physical properties of compounds and, e.g., optical rotations for have been variously reported as: 0, 0., 9.,., and +0, making the assignment of the absolute configuration difficult. ame three spectroscopic techniques or approaches, aside from Mosher s analysis, to assign the absolute configuration of an amine. ( points) (e) The Authors used Mosher s analysis to define the absolute configuration of the amino acid by making the Mosher amide. Explain briefly the theory behind Mosher s amide analysis to determine the absolute configuration. ( points) question is continued on the page... page of

6 ...question continued from page (f) H and 9 F chemical shifts are given below for Mosher s (S)-amide (blue) and (R)- amide (red). Assign the configuration of the amino acid used here as either D or L and explain you rationale. ( points) (g) As a second method, the authors prepared menthyl esters with D- and L-menthol. Explain advantages and disadvantages of this method to separate and assign the absolute configuration of amino acids. ( points) page of

7 . ( points) Boger and coworker published the synthesis and some interesting transformations of heterocyclic molecule. rg. Lett. 0, doi: 0.0/acs.orglett.b00 + Ph H H CH C, RT, 0 min 9% Ph Et Et Ph (a) Is compound aromatic? List the three structural properties that all aromatic molecules share. Give three experimental, physical, or spectroscopic tests that could be used to support whether or not is aromatic. (b) Compound reacts with rapidly at RT to give. Give a mechanism for this transformation that accounts for the fate of all nitrogen atoms. How could isotope labeling experiments be used to support your mechanism? (c) Some mechanistically-related reactions of led to the production of,, and. Give reagents for these one-step transformations. (d) Propose a synthesis of from simple starting materials (you need not use the same strategy as the authors). Feel free to offer more than one potential strategy. (e) The isolation of was complicated by several physical properties. Why might isolation/handling of be difficult? page of