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Organic Synthesis A problem–solving guide for Organic Chemistry I/II ? Goal: propose a synthesis of a target molecule H OH N using given starting materials and any other N reagents you need. starting target materials molecule These key strategies should guide your approach:1 Mapping • Systematically label all the atoms in the ? 1 starting materials, then identify those atoms in H OH N 6 N the target molecule 2 4 5 7 6 1 3 5 7 2 3 4 • Use landmarks (heteroatoms, functional groups) to help you Identifying bonds formed/broken ? and atoms added/removed H OH 1 N 6 N Having labeled atoms, it becomes easier to see: 2 4 5 7 6 1 3 5 7 2 3 4 bonds formed: C7–N2 σ, C6–O σ atoms added • where bonds have been formed/broken bonds broken: C6–C7 π atoms removed • where atoms (including protons) have been added/removed ? Regiochemical and stereochemical analysis H OH 1 N 6 N 2 4 5 7 6 • Look for regiochemical patterns that can 1 3 5 7 2 3 4 provide ideas for synthetic strategies target molecule is 1,2–difunctionalized at C6–C7 • Look for changes in configuration at C7–N2 bond formed at less substituted C of propylene stereocenters (not always applicable) reaction: base–catalyzed epoxide opening 1 OH OH 1 Synthon-based retrosynthetic analysis N + N 6 2 4 6 2 4 Construct hypothetical starting materials for 5 7 3 5 7 3 • synthons forming required bonds 1 This process is called constructing synthons, O δ- • + + HN 6 6 δ 2 4 and it is the basis of retrosynthetic analysis 5 7 5 7 3 possible reagents • Synthons are a tool for choosing reagents 1Based in part on strategies observed in successful students’ responses to synthetic Flynn Research Group 2017 – FlynnResearchGroup.com problems on exams; see: Bodé, N. E.; Flynn, A. B. J. Chem. Educ. 2016, 593–604. Created by Nicholas Bodé Organic Synthesis A problem–solving guide for Organic Chemistry I/II Constructing synthons to identify intermediate reagents Select a bond that was formed (as you identified in prior steps) OH 1 N “hockey stick” represents a 6 5 7 2 3 4 retrosynthetic disconnection Draw the products of the reverse mechanism for its formation Electrons in the disconnected bond go to one of the bonding atoms, creating a negatively charged synthon (donor) and a positively charged synthon (acceptor) 1 OH OH 1 N + N 6 2 4 6 2 4 5 7 3 5 7 3 acceptor (a) donor (d) Choose two reagents that have the same reactivity as your synthons OH 1 1 O + δ- + N δ+ HN 6 2 4 6 2 4 5 7 3 5 7 3 acceptor (a) donor (d) electrophile nucleophile synthons possible reagents Repeat this process, switching the donor and acceptor synthons OH 1 OH 1 OH OBn - + + N + δ N δ N 6 6 6 2 4 5 7 2 4 5 7 2 3 4 5 7 3 1 3 donor (d) acceptor (a) nucleophile electrophile synthons possible reagents Evaluate which reagents are more appropriate for forming the bond you need 1 OH OBn O + - - + + + HNδ δ N δ 6 δ 2 4 6 2 4 5 7 3 5 7 1 3 electrophile nucleophile nucleophile electrophile strong nucleophile and electrophile weak nucleophile and electrophile nucleophile is given starting material nucleophile and electrophile not readily electrophile easily accessed from given accessible from given starting materials starting material (1 step) Flynn Research Group 2017 – FlynnResearchGroup.com | Created by Nicholas Bodé .

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Modern Organic Synthesis an Introduction
Modern Organic Synthesis an Introduction G. S. Zweifel M. H. Nantz W.H. Freeman and Company Chapter 1 Synthetic Design • What is an ideal or viable synthesis, and how does one approach a synthetic project? • The overriding concern in a synthesis is the yield, including the inherent concepts of simplicity (fewest steps) and selectivity (chemoselectivity, regioselectivity, diastereoselectivity, and enantioselectivity). • This chapter outlines strategies for the synthesis of target molecules based on retrosynthetic analysis. 1 1.1 Retrosynthetic Analysis Basic Concept The symbol signifies a reverse synthetic step and is called atransform. The main transforms are disconnections, or cleavage of C-C bonds, and functional group interconversions (FGI) Retrosynthetic analysis involves the disassembly of a TM into available starting materials by sequential disconnections and functional group interconversions(FGI). Synthons are fragments resulting from disconnection of carbon-carbon bonds of the TM. The actual substrates used for the forward synthesis are the synthetic equivalents (SE). Synthetic design involves two distinct steps (1) Retrosynthetic analysis (2) Subsequent translation of the analysis into a “forward direction” synthesis. Chemical bonds can be cleaved heterolytically, homolytically, or through concerted transform. 2 Donor and Acceptor Synthons Acceptor synthon Æ carbocation (electrophilic) Donor synthon Æ carbanion (nucleophilic) Table 1.1 Common Acceptor Synthon Synthetic equivalents Common Acceptor Synthon Synthetic equivalents 3 Table 1.2 Common Donor Synthons Common Donor Synthon Synthetic equivalents Retrosynthetic Analysis A Synthesis A 4 Retrosynthetic Analysis B Synthesis B Alternating Polarity Disconnections The presence of a heteroatom in a molecule imparts a pattern of electrophilicity and nucleophilicity to the atom of the molecule. The concept of alternating polarities or latent polarities (imaginary chargies) often enables one to identify the best positions to make a disconnection within a complex molecule.
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Protokoll Handledarmöte 2020-02-14
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Amide Activation: an Emerging Tool for Chemoselective Synthesis
Featuring work from the research group of Professor As featured in: Nuno Maulide, University of Vienna, Vienna, Austria Amide activation: an emerging tool for chemoselective synthesis Let them stand out of the crowd – Amide activation enables the chemoselective modification of a large variety of molecules while leaving many other functional groups untouched, making it attractive for the synthesis of sophisticated targets. This issue features a review on this emerging field and its application in total synthesis. See Nuno Maulide et al., Chem. Soc. Rev., 2018, 47, 7899. rsc.li/chem-soc-rev Registered charity number: 207890 Chem Soc Rev View Article Online REVIEW ARTICLE View Journal | View Issue Amide activation: an emerging tool for chemoselective synthesis Cite this: Chem. Soc. Rev., 2018, 47,7899 Daniel Kaiser, Adriano Bauer, Miran Lemmerer and Nuno Maulide * It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives. This results in a considerably reduced reactivity towards nucleophiles. Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts. Received 27th April 2018 However, a significant body of research on the selective activation of amides to achieve powerful DOI: 10.1039/c8cs00335a transformations under mild conditions has emerged over the past decades. This review article aims at placing electrophilic amide activation in both a historical context and in that of natural product rsc.li/chem-soc-rev synthesis, highlighting the synthetic applications and the potential of this approach. Creative Commons Attribution 3.0 Unported Licence.
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Bsc Chemistry
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2614-2625 Research Article Synthon Disconnection Strategy for Th
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Acetylene in Organic Synthesis: Recent Progress and New Uses
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Methods of Reactivity Umpolung
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Weinreb Amide Based Building Blocks for Convenient Access to Various Synthetic Targets
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