Cumulative Exams

Organic Cumulative Exam

July 8, 2024

Topic:  Synthesis of Azabicyclo[3.1.1]heptenes Enabled by Catalyst-Controlled Annulations of Bicyclo[1.1.0]butanes with Vinyl Azides

Topic Details:

This is a recent paper on an interesting “[3+3] and [3+2]” reactions that form poly-cyclic scaffolds for medicinal chemistry drug discovery. Students are expected to read an understand the mechanistic elements that drive this reaction. This Organic Cume will be mechanism heavy. There are many transformations and rearrangements that were covered in CHEM 5202 and CHEM 5205 that students should review and recall (pertaining to the paper).

Additionally, the [3+3] and [3+2] nomenclature caught my attention. I will also test the fundamentals of cycloaddition reactions and explain why these reactions are not. Students should be able to draw molecular orbitals of 2-atom, 3-atom, and 4-atom systems (wave functions). This includes filling in electrons and finding the HOMO-LUMO interaction and determining if they are thermally allowed or forbidden TS for cycloaddition reactions. This will also include atom vs electron nomenclature.

Literature Papers: 

Attached is the paper from Zheng’s Research Group. https://pubs.acs.org/doi/epdf/10.1021/jacs.4c04485

Grading Expectations:

A: Excellent understanding of the paper & excellent demonstration of fundamental cycloadditions

B: Ok/poor understanding of the paper & excellent demonstration of fundamental concepts

C: Ok understanding of fundamental concepts

F: Poor understanding of fundamental concepts

**You need to demonstrate full understanding of fundamental concepts (which are outside the scope of this paper) in order to pass.

Organic Cumulative Exam

March 4, 2023

Topic: Asymmetric Total Synthesis of Pedrolide

Topic Details:

Students should be able to read the current literature and state-of-the-art in total synthesis. Students are expected to answer synthetic questions with their fundamental knowledge of physical organic chemistry (not necessarily memorization of facts like yields and selectivity). Students should be able to identify and draw reagents and draw reaction mechanisms (and should know key named reactions). As with many Kim Cumulative Exams, students should be able to draw reasonable mechanisms, explain reactions, and understand selectivity outcomes. Learning goals also include the ability to accurately and concisely describe things like chirality, stereochemistry, selectivity, and other items of physical organic chemistry with regards to modern organic synthesis.

Literature Papers: 

Attached is the Li Group’s asymmetric total synthesis of Pedrolide. Students should read the paper and the accompanying Supporting Information to gain further insights and details about the optimization and rigor of the challenging total synthesis. Must read this paper as the specifics of the cumulative exam questions will be on this particular total synthesis.

Students should also briefly read the Carriera’s “Enantioselective Total Synthesis of (+)-Pedrolide”. Specifics will not be discussed, only a comparison of strategy.

https://pubs.acs.org/doi/10.1021/jacs.3c14150

https://pubs.acs.org/doi/full/10.1021/jacs.3c02113

Organic Cumulative Exam

May 15, 2023

Topic: Recent Total Syntheses in JACS April 2023

Topic Details:

Students should be able to read the current literature and state-of-the-art in total synthesis. Students are expected to answer synthetic questions with their fundamental knowledge of physical organic chemistry (not necessarily memorization of facts like yields and selectivity). Students should be able to identify and draw reagents and draw reaction mechanisms (and should know key named reactions). Learning goals also include the ability to accurately and concisely describe things like chirality, stereochemistry, selectivity, and other items of physical organic chemistry with regards to modern organic synthesis.

Literature Papers: 

• Enantioselective Divergent Syntheses of Cephalotaxus Alkaloids: (−)-Cephalotaxine, (−)-Cephalotine B, and (−)-Fortuneicyclidins A and B

• Total Syntheses of Scabrolide A and Yonarolide

• Total Synthesis of (+)-Aberrarone

Organic Cumulative Exam

November 21, 2022

Topic: The Total Synthesis of Matrine Alkaloids 

Topic Details:

The faculty of the Organic Division use cumulative exams as a tool to educate and test graduate students. Often, one of the topics strategies in total synthesis. We can gauge the modern synthetic tools used in complex settings such as total synthesis. Two recent papers in JACS focus on matrine alkaloid total synthesis using two very different approaches.

I always use cumulative exams to try and test students’ knowledge on fundamentals covered in physical organic chemistry covered in Chem 5202 and Chem 5201. For first time exam takers, focus on general synthetic concepts, mechanisms, abbreviations, new terminology, and typical physical organic chemistry items.

Literature Papers: 

1. Total Synthesis of Matrine Alkaloids by Nicholas L. Magann, Erin Westley, Madison J. Sowden, Michael G. Gardiner, and Michael S. Sherburn, J. Am. Chem. Soc. 2022 144 (43), 19695–19699. DOI: 10.1021/jacs.2c09804

2. A Pyridine Dearomatization Approach to the Matrine-Type Lupin Alkaloids by Jeff K. Kerkovius, Andrea Stegner, Aneta Turlik, Pik Hoi Lam, Kendall N. Houk, and Sarah E. Reisman, J. Am. Chem. Soc. 2022 144 (35), 15938–15943. DOI: 10.1021/jacs.2c06584

Learning Goals:

• General synthetic strategies

• Draw mechanisms

• New terminologies and abbreviations in papers

• General fundamentals covered in Chem 5202 

• General fundamentals covered in Chem 5201

Organic Cumulative Exam Topic for June 6, 2022:

JACS ASAPs from May 16–20, 2022

 Readings: JACS ASAPs from May 16–20, 2022

Additional Readings: none

Graduate School Lesson: Read the literature and stay up to date with the state of the art in Organic Chemistry. Read broadly and read diligently. Learn how to other leaders in the field use fundamentals in physical organic chemistry to solve challenging problems in organic synthesis. Learn what’s trending and how to understand it and potentially incorporate it into your research as you think about your research challenges and grow as independent scientists.

Learning Goals:

• I expect the majority of this exam to be ‘do-able’ with the knowledge you’ve gained from your classes. Therefore, the exam will cover a range of topics and questions that may arise in a second-year literature seminar Q&A or in an ORP defense. This is not about specific memorization of very specific details within these selected manuscripts but broadly a chance for you to showcase the strength of your fundamentals. 

 On Exam Day: no additional notes allowed

Organic Cumulative Exam Topic for January 17, 2022:

The Chemistry of Professor Melanie S. Sanford 

(POCC Lecture Jan 27, 2022)

 Readings: Acc. Chem. Res. 2020, 53, 10, 2372–2383. https://doi.org/10.1021/acs.accounts.0c00471.

Additional Readings: citations within

The faculty of the Organic Division use cumulative exams as a tool to educate and test graduate students. Often, one of the topics includes the general body of work of a notable synthetic Organic chemist. Professor Melanie Sanford will be speaking at POCC (Philadelphia Organic Chemistry Club) this January. As such, we thought it would be fitting to cover her work over the years. Specifically, this cumulative exam will cover her fluorination chemistry.

Accounts of Chemical Research (ACR) is a journal that often provides an opportunity for groups who have made strides in a specific area of research to summarize their work and provide context. It is useful as a mini review on Professor Sanford’s work. 

This cumulative exam will focus only on her work regarding fluorination chemistry and the work found in the attached ACR. See below the learning goals to focus your study.

Learning Goals:

• Who is Professor Melanie Sanford?

• Importance of developing fluorination methodology

• Fundamental differences between electrophilic and nucleophilic fluorination reagents (and being able to differentiate them)

• Draw mechanisms

• Interpret energy diagrams

• Explain with fundamental FMO theory or stereoelectronics why specific reactions work or do not work (overcoming challenges and limitations to reactions)

 On Exam Day: no additional notes allowed

Organic Cumulative Exam Topic for July 2021:

Recent advances in Pd/NBE cooperative catalysis

Reading:

“Modular Entry to Functionalized Tetrahydrobenzo[b]azepines via the Pd/Norbornene Cooperative Catalysis Enabled by a C7-Modified Norbornene” 

by Xin Liu, Jianchun wang, and Guangbin Dong

J. Am. Chem. Soc. 2021, ASAP

https://doi.org/10.1021/jacs.1c04575 

Additional Readings: 

"Structurally Modified Norbornenes: A Key Factor to Modulate Reaction Selectivity in the Palladium/Norbornene Cooperative Catalysis "

by Renhe Li and Guangbin Dong

J. Am. Chem. Soc. 2020, 142, 17859 

(for those who want a bit more perspective) 

The exam will be a closed book exam (calculators and model kits allowed). The intention is that you can pass this exam given the information we expect an organic chemist to know. You will not be asked to memorize any specific data or result in the paper.

This exam will have concepts in spectroscopy (specifically related to the molecules shown in this manuscript). But as always, other concepts regarding, transition metal catalysis, mechanisms (both organic and organometallic), and demonstrating concepts from physical organic chemistry will also be included.

• • •

*Hello Organic Cume-taker. I will be going over this exam on Monday, July 26th at 11AM, room Beury 404. All the organic groups (broadly defined) and anybody taking this cume is welcome. Pizza at noon.  –Daniel Kim*

• • •

 updated: 7/2/2021

Organic Cumulative Exam Topic for January 2021:

Items of Chirality and a Special Case Study in Asymmetric Hydrogenation

Readings: Halpern, J. Mechanism and Stereoselectivity of Asymmetric Hydrogenation. Science 1982, 217, 401.

Additional Readings: Yoon, T. P., Jacobsen, E. N. Privileged Chiral Catalysts. Science 2003, 299, 1691.
Quasdorf, K. W., Overman, L. E. Catalytic enantioselective synthesis of quaternary carbon stereocentres. Nature 2014, 516, 181.

(Note: I'm more focused on the ideas of the Overman review versus the reactions found inside of them).

Homogeneous asymmetric hydrogenation remains one of the most common ways to deliver optically active materials to market. Attached is an important case study from Jack Halpern who studied homogeneous Rh-catalyzed asymmetric hydrogenations of enamides to amino acid analogs. You will also be asked to demonstrate your ability in using concepts from frontier molecular orbital theory & physical organic chemistry to justify and explain different stereochemical outcomes. Outside of the Halpern paper, this exam will not test you  on your knowledge of organometallic transformations/mechanisms.

Learning Goals:

• You will be tested on various concepts in asymmetric catalysis (such as dynamic kinetic resolution vs kinetic resolution)

• Be able to describe and identify various types of chirality in organic molecules

• Interpret data from Jack Halpern’s Science paper

• Propose various mechanisms that generate a stereocenter

• Propose the origin of stereoselectivity

On Exam Day: you may have access to this paper and any other resources you want (papers, books, internet, models, calculators, etc.). Given the nature of having cumulative exams online, I have decided to provide you unlimited resources. However, I believe a well-prepared student should be able to answer these questions without additional resources. Your answers must be your own, especially open-ended questions. Credit will be awarded only to relevant answers.

updated: 1/12/2021