Download Designing Organic Compounds from Precursors: Retrosynthesis in Multi-step Synthesis and more Study notes Organic Chemistry in PDF only on Docsity! 74 CFQ & PP: Multi-step Organic Synthesis CFQ & PP: Multi-step Organic Synthesis Reading Brown and Foote: Sections 10.10 Appendix 7: Reagents and Their Uses Appendix 8: Summary of Methods for the Synthesis of Functional Groups Lecture Supplement Multistep Organic Synthesis (page 9 of this Thinkbook) Optional Web Site Reading The 1990 Nobel Prize in Chemistry (http://www.nobel.se/chemistry/laureates/1990/ index.html) Review Topics to review from Chem 30A, as needed: SN2/SN1, elimination, radical halogenation, addition to carbon-carbon π bonds Suggested Text Exercises Brown and Foote: Chapter 8: 46, 50 Chapter 9: 41, 43, 46 Chapter 10: 6, 19 - 31 Chapter 11: 32 - 39 Miscellaneous Projects Create reaction flash cards (Brown and Foote Appendix 8 very useful for this!) Concept Focus Questions 1. Define "retrosynthesis." 2. Describe the retrosynthesis process used to design a multi-step organic synthesis. Use the example shown below. Convert into O H Concept Focus Questions Solutions 1. Retrosynthesis is the process of thinking backwards in synthesis design. We consider how a given target molecule is made from some precursor molecule, instead of starting with the given starting material. 2. We start by examining the aldehyde target structure. Can it be made in a single step from the given starting material? No. CFQ & PP: Multi-step Organic Synthesis 75 Therefore we must decide what sequence of reactions is appropriate. There is no chance in the basic carbon skeleton (number or sequence of carbons), so we need only be concerned with functional group changes. What functional group(s) are in the product, and how are they prepared? • Benzene ring: A benzene ring is present in the target and the starting material, so we don't have to be concerned about adding it. • Aldehyde: We know several ways to make an aldehyde. Alkene ozonolysis: Alkene ozonolysis involves changing the carbon skeleton. Since the carbon skeleton is unchanged in this synthesis problem, ozonolysis would require adding this extra carbon at some point. The route employs extra steps and is therefore less efficient. Alkyne hydroboration: Alkyne hydroboration cannot be used here, because the alkyne that would lead to this aldehyde would have to have a pentavalent carbon. Primary alcohol oxidation: The only viable choice left. The more reactions you know, the more flexibility you have, and thus synthesis problems are easier. This is an excellent time to bring your flash cards up to date, and start using them every night! We have identified a primary alcohol as a reasonable precursor to the aldehyde target. This is written as: O H OH oxidation The fat retrosynthesis arrow means "the aldehyde can be made from the alcohol by oxidation." While it is not necessary to write the reaction above the retrosynthesis arrow, it helps you to remember what you planned to do. oxidation retrosynthesis arrow transformation Now we repeat the process, with the primary alcohol as the new target molecule. 78 CFQ & PP: Multi-step Organic Synthesis 3. Retrosynthesis: CO2H CH2OH oxidation hydroboration Forward direction: CH2OH 1. BH3 2. H2O2, NaOH CrO3 CO2H aq. H2SO4 4. Retrosynthesis: OCH3 OH OH Williamson hydroboration dehydration Forward direction: OH OH OCH3 1. NaH 2. CH3I H2SO4 1. BH3 2. H2O2 NaOH 5. Retrosynthesis: Br Br Br E2 twice E2Br2 radical bromination CFQ & PP: Multi-step Organic Synthesis 79 Forward direction: Br Br Br Br2, h NaOCH3 Br2 (CH3)3CO - In the last step, use of a sterically hindered base such as (CH3)3CO - helps ensure that the less substituted alkene is formed. 6. Retrosynthesis: alkyne reduction C C CH3 alkyne anion SN2 Br radical halogenation Forward direction: Br2, h Br CH3C C C C CH3 H2 Lindar catalyst
