Recommended
More Related Content
Similar to Master thesis defence - Magnus 20-10-2015
Similar to Master thesis defence - Magnus 20-10-2015 (20)
Master thesis defence - Magnus 20-10-2015
- 1. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU EXPLORATION AND INVESTIGATIONS OF ENANTIOSELECTIVE AMINOCATALYTIC CYCLOADDITIONS
- 2. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU OUTLINE Introduction Norcamphor scaffolds Preliminary work on higher order cycloadditions Inclusion tubular cavitaries 2
- 3. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU CHIRALITY “I call any geometrical figure, or group of points, chiral, and say that it has chirality, if its image in a plane mirror, ideally realized, cannot be brought to coincide with itself” Lord Kelvin 3
- 4. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU EFFECTS OF CHIRALITY Limonene (R)-Limonene (S)-Limonene Citrus Terpentine Carvone (R)-Carvone (S)-Carvone Caraway Spearmint 4
- 5. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU EFFECTS OF CHIRALITY Thalidomide Drug for reducing morning sickness Developed in the 1950’s on marked in 1960’s (R) reduced morning sickness (S)had a teratogenic effect 5
- 6. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR SCAFFOLDS Norcamphor scaffold overview Norcamphor in natural and bioactive compounds Screening Scope Mechanistic considerations Transformations Conclusion 6
- 7. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - BIOACTIVITY 7
- 8. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - BIOACTIVITY 8
- 9. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR SCAFFOLDS 9
- 10. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – PREVIOUS EXAMPLES 10
- 11. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCREENING a Entry Solvent Time (h) Conversion (%)b Yield (%)b 1 CDCl3 60 30 19 2 H2O 19 0 0 3 Toluene 19 4 7 4 Toluene 70 11 10 5 THF 19 25 5 6 THF 70 39 10 a Reactions were performed with 2a (0.2 mmol), 3a (0.1 mmol), catalyst (0.02 mmol), additive (0.02 mmol) in solvent (0.1 mL). b Yield and conversion were determined by 1 H-NMR spectroscopy of the crude reaction mixture with 1,3,5- tris(trifluoromethyl)benzene as the internal standard. 11
- 12. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCREENING 12
- 13. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCREENING Entrya Additive Time (h) Conversion (%)b Yield (%)b ee (%) 1 EtCOOH 19 91 52 90 2 AcOH 18 85 48 89 3 PhCOOH 18 100 51 90 4 PhCOONa 18 68 20 91 5 p-NO2(C6H4)COOH 18 90 34 87 6 Salicylic acid 18 90 44 91 7 TFA 18 62 14 90 8 Bu4N+ - BF4 18 23 13 n.d. a Reactions were performed with 2a (0.2 mmol), 3a (0.1 mmol), 1d (0.02 mmol), additive (0.02 mmol) in solvent (0.1 mL). b Yield and conversion were determined by 1 H-NMR spectroscopy of the crude reaction mixture with 1,3,5-tris(trifluoromethyl)benzene as the internal standard. 13
- 14. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 14
- 15. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 15
- 16. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 16
- 17. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 17
- 18. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 18
- 19. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 19
- 20. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 20
- 21. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 21
- 22. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR - SCOPE 22
- 23. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU ABSOLUTE CONFIGURATION 23
- 24. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – MECHANISTICS Our proposed mechanism 24
- 25. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – MECHANISTICS Mechanism proposed by Chen et al.[1] [1] X. Feng, Z. Zhou, R. Zhou, Q.-Q. Zhou, L. Dong, Y.-C. Chen, J. Am. Chem. Soc. 2012, 134, 19942. Our proposed mechanism 25
- 26. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – MECHANISTICS 26 [1] X. Feng, Z. Zhou, R. Zhou, Q.-Q. Zhou, L. Dong, Y.-C. Chen, J. Am. Chem. Soc. 2012, 134, 19942.
- 27. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – MECHANISTICS 27 [1] X. Feng, Z. Zhou, R. Zhou, Q.-Q. Zhou, L. Dong, Y.-C. Chen, J. Am. Chem. Soc. 2012, 134, 19942.
- 28. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – MECHANISTICS 28
- 29. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – TRANSFORMATIONS 29
- 30. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – TRANSFORMATIONS 30
- 31. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – TRANSFORMATIONS 31
- 32. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – TRANSFORMATIONS 32
- 33. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – TRANSFORMATIONS 33
- 34. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – TRANSFORMATIONS 34
- 35. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU NORCAMPHOR – CONCLUSION We have developed a method with high Versatile Efficiency Potential for future development 35
- 36. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU HIGHER-ORDER CYCLOADDITION 36
- 37. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU HIGHER-ORDER CYCLOADDITION 37
- 38. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU HIGHER-ORDER CYCLOADDITION 38
- 39. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU HIGHER-ORDER CYCLOADDITION [4+2] and [6+4] cycloaddition products 39
- 40. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU HIGHER-ORDER CYCLOADDITION [8+2] cycloaddition Future work 40
- 41. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU HIGHER-ORDER – CONCLUSION In the process of developing a method for producing multibridged polycyclic compounds First time these are made enantioselectively Exploration of mechanisms 41
- 42. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU TUBULAR INCLUSION CAVITIES 42
- 43. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU TUBULAR INCLUSION CAVITIES 43
- 44. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU TUBULAR INCLUSION CAVITIES Hexagonal Orthorhombic 44
- 45. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU TUBULAR INCLUSION CAVITIES Hexagonal Orthorhombic 45
- 46. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU TUBULAR INCLUSION CAVITIES 46
- 47. 20. OKTOBER 2015 MASTER THESIS DEFENCEMAGNUS EMIL JENSENAARHUS UNIVERSITETAU ACKNOWLEDGEMENTS Karl Anker Jørgensen Rasmus Mose, Gert Preegel Lydia Klier and Christian Sibbersen Jacob Overgaard and the crystallographers Group 109 and Lise Ravn Petersen UNF and AAK Mads Mørk Jensen, friends and my family for all the support You! 47
Editor's Notes
- Welcome to my defence, titled exploration and investigations of enantioselective aminocatalytic cycloadditions.
- The talking points Firstly I will give a brief introduction to the world of chirality and after that it should be more clear why our line of work is important Then I will talk about the main project I have been involved in during my master thesis, which has also recently been published in angewanted chemie From here we continue to the future prospect this project brought in the form of higher order cyclo additions and lastly I would like to show a small pet project I did during my master thesis.
- Chirallity is seen everywhere in the world, from your own body to the humble snail who can only mate with a patner of similar chirality. As Lord Kelvin presented it so elegantly any put it ” read Kelvin quote” The mirror images that arise from this are called enantiomers. Which is why the word enantiomeric excess will be used a lot throughout this presentation. What is the impact of chiral molecules ? (change slide)
- The impact can be seen in a multitude of ways, from the curious example of the snail to the sense of smell we humans are so fond of. Two classic examples often described is the case of r and s limonene which have the smells of either citrus or terpentine, which is in and of itself magical, such a minute change gives rise to a change in how we percieve the smell of the molecule. What actually happens is that the body has a fixed chirallity and when a molecule interacts with a receptor, in this case the nasal receptor the two enantiomers have different ways to interact since they cannot fit the same way. While the changes in smell can seem facinating and are great for the fragrance industry it can have a much more dark and sinister side (change slide).
- The case of Thalidomide is brought up a lot within our field, it is a case that shall never be forgotten and we live to ensure this does not happen again. In the 1950s the company called Chemie Grúnenthal it went rapidly from development to marked, it was sold as an over the counter drug in 1957 in 1961 it was taken off the marked again, since it was discovered that while it did reduce morning sickness it also reduced growth of the extermities of the fetus. Following this incident it was deemed that all companies must manufacture both of the enantiomers of their compounds and show the effects of both. Because of this development the field of asymmetric catalysis got a big boost and from this giant of a field the field of organocatalysis sprouted. (change slide)
- The main project I was part of was that of forming norcamphor scaffolds via aminocatalysis, this is just to give a brief overview of the order I will present the project for you. A brief overview of the project and what the scaffolds look like. Followed by an introduction to where we see this scaffold, then we will go into the screening and scope followed by the mechanistic considerations lastly I will present the transformations performed for the project and we will wrap it all up in a nice bow in the end.
- During the writing of our publication we did a search for structures that contained the desired norcamphor scaffold. It was found in over 100.000 compounds of which 15.000 have shown bioactivity. During the writting of my thesis I did another structure search and found additional compounds. Some of which were even closer than the ones previously found. There are many compounds with this moiety but I will only talk briefly about three.
- The first similar bioactive compound that springs to mind is ofcourse Camphor, since it is commonly used in a lot of household items. The second one is US 5731337 A compound 3, this is the name given in the patent, they could have made a simpler name and they might later, it was choosen because of the similarities it shares with out products of the nitrostyrene scope. The last one was choosen as it is part of a ligand system developed and tested in cis platin, the world famous chemotherapy pharmaceutical.
- These two scopes were of nitrostyrenes and Chalcones. These two were choosen for scope due to their avaliability and ease of synthesis, which gave us the posibility as will be shown to make a diverse scope and show how both EWG and EDG interfere with the reaction.
- The norcamphor scaffold has been synthesised before, though by way or cyclopentenone organocatalytically there are only three publications and they only show singular examples. The first of these was presented by Cordova, applying the same conditions as they had for their cyclohexenone. It is important to note that although they do make the norcamphor scaffold they do it in very poor enantiomeric excess. The second example was presented by Xu et al. They showed the posibility to perform the reaction in excellent yield and decent enantiomeric excess. A peculiar note is that they were only able to perform the reaction using the 3-methyl cyclopentenone. A lot of inspiration for our conditions came from this publication. The third and latest example was presented by Chen et al. Where they achieved good yield and good enantiomeric excess. They furthermore proposed a mechinism which will be discussed later. Following the results presented by these grops it was clear that the possibility to form norcamphor scaffolds from cyclopentenone was possible and should be explored. Therefore a screening was undertaken.
- Initially benzylamine was choosen as a catalysts, due to it being a simple primary amine and it was easy to work with. We employed cyclopentenone and nitrostyrene as the base reagents since they had shown reactivity and we had a full catalogue if we succeeded. We first screened solvent effects from a quick glance it may look like deutorated chloroform is the optimal solvent. Though while significantly slower, toluene has a better conversion to yield ratio. Which should mean that if we optimise the additive and catalyst we can get a much better reaction. Following this solvent screening a brief additive screening was undertaken using benzylamine as catalysts. Though, we needed a chiral catalyst to achieve enantioselectivity. Therefore we made a catalyst screening.
- Shown here is a short overview of all the catalyst tested. It is interesting to see the difference between the primary and secondary amines. It is possible for the TMS-Protected pyrrolidine catalyst to induce enantioselectivity although poorly. We also see that simple primary amines can activate the reaction in higher yields. Combining this knowledge should lead us to conclude that a primary with potential for steric shielding such as catalyst 1d would allow for a better reaction.
- Although we did a quick additive screening using benzylamine we concluded that a second screening was needed to ensure we had indeed choosen the right additive. Some trends that are worth noting is that an acid ensures the reaction goes faster and achieves higher yield. As we seen when employing benzoate there is still recorded yield. It is important to remember the conversion going up does not in this case mean a higher yield. This often occures due to polymerisation of the nitrostyrene. The same is seen when employing a very strong acid such as TFA. Lastly we attempted some lewis acids, though they performed very poorly and was therefore scrapped. We found the optimal conditions to be propionic acid catalyst 1d in toluene. With the optimal conditions in hand we started our efforts to form a scope firstly based on nitrostyrene.
- The system tolerates electron withdrawing groups in the form of halides both it para and ortho position
- Further we see that going from a ortho to a para position reduces both yield and enantiomeric excess
- We are able to have heterocycles though at significantly reduced yield
- The second scope, and for personal reason my favorite scope, consistes of a myriade of different products based mainly on chalcone. We wanted to show all the diversity possible for the aromatic substituents and I think we succed in showing a very diverse scope. (change slide)
- Firstly we showed the ”plain” reaction with no substituents which showed good yield and good enantiomeric excess further adding electron donating groups increased ee but lowered yield. From here we experimented with electron withdrawing groups in the form of nitro groups (change slide)
- Sadly we could not complete the trend and show how nitro in the ortho position reacts, this is because while synthesising the chalcone it polymerised resulting in a black tar. It is interesting to note the reduction in yield of the para nitro compared to the meta nitro. Though there is an increase in enatiomeric excess. Furthermore para on the keto side shows high yield and slightly lower ee but at elevated temperature. It is interesting to see that by adding a bromine in the para position of the other ring while having the nitro group increases the yield and ee significantly. Following the investigation of electron withdrawing effects we changed our focus to electron donating (slide change)
- As was also the trend from nitrostyrenes when going from ortho to para with methoxy the yield falls significantly, furthermore for the reaction to even proceed the temperature has to be increased to 100 degress, it is further possible to have electron donating groups in both ortho and meta position which gives similar results to the para methoxy result.
- Lastly we tried some different heterocycles and napthyl to show how these changes to the aromaticity changes the reaction and we showed that the reaction is not limited to alkyl systems but aliphatic ketones are also able to participate in the reaction. Entry 6n is particually interesting, since it has the possibility to form another cross-dienamine species, this could account for the low yield.
- As mentioned in the teased at the start of this project we were able to apply our conditions to all the most common classes of dienophiles. The result of 8b is from the same starting material as employed by Xu et al. As can be seen we achieve a higher enantiomeric excess though a poorer yield. But in contrast with Xu it was only possible for them to employ 3-methyl cyclopentenone. With a large scope established a mechanism for the reaction is needed.
- As mentioned earlier all the products derived from Chalcone were isolated as solids the product of 6l was isolated as brown crystals (both after column and after recrystalisation) While the reaction cooled the product crashed out into the reaction mixture, though as very thin fine needles. After purification the crystals were redissolved in hot toluene and placed in a heating block at 80 degrees overnight. During this time large needles formed and these were big enough for single crystal X-ray messurments.
- We propose that the mechanism is a Diels Alder reaction, most importantly we conclude that it is a concerted Diels-Alder, the topic of whether or not these reactions are concerted or stepwise has been debated a lot. We say it is concerted due to the dual activation of the primary amine which ensures the reagents are held in position untill the reaction is performed. A big argument for step-wise comes from Chen et al. In the same publication where they also presented their example of cyclopentenone synthesis. (slide change)
- As can be seen by the proposed mechanism of Chen, they envision a Michael-Michael addition. By first having the cross-dienamine attacking from the alpha postion onto the electron poor double bond. Moving the electrons up onto the bond stabilised by the EWG. From here it can attack on the iminium-ion and after subsequent hydrolysis form the bicyclic ring. They base this on experiments they have conducted (slide change)
- In these experiments they attempted to show the reaction underwent a stepwise mechanism and not a concerted. It is interesting to note that while employing their ”standard” compounds they observe a faint dr but only formation of the bicyclic system. But when they employ the unsubstituted cyclohexenone they observed, after 114hours formation of the claimed Michael adduct (slide change)
- And only traces of the bicyclic product. Because of this, they claim that the reaction is step-wise via and michael-michael and not a concerted Diels-Alder reaction, however! (slide change)
- This could product could also be formed if the reaction underwent a ring opening which would also account for the lack of main product. This ring opening ring closing could also be responsible for the observed dr. We observed a dr of 19:1 in the cases where we had an extended conjugation. Though based on this information and the information from Houk et al. Applied on trienamine systems with other substituents we are adament that our system undergoes a concerted Diels-Alder reaction, atleast untill better evidence is shown.
- Following the large scope, we wanted to shown even more possibilities to diversify. This was achived by performing transformations. The first of these was a Baeyer-Villiger (slide change)
- The reasoning behind the Baeyer-Villiger, was to show that we could exand our bicyclic ring system which worked well except for getting a 9:1 regioisomeric ratio. Furthermore, during the writting of my thesis I found a further reason why our transformation is interesting (slide change)
- In a publication from Murakami et al in 2010 they showed their synthesis of Valtrate and 5,6 dihydrovaltrate. The synthesis they present go through two intermediates which are simliar to both our product and to our transformation. It is facinating to note that we with our compound can arrive close to an intermediate in a natural synthesis. (slide change)
- The follow-up transformation to our Baeyer-Villiger is the ring opening of the newly formed extended ring. This worked amazingly, in a very clean reaction requiering only a very fast column. This product is of great interest as a building block in organic synthesis and therefore it is great to present an easy way to achieve it while at the same time controlling all stereocenters.
- The last successfull transformation performed was that of a reductive amination of the ketone moeity, this was in an attempt to create a secondary amine moeity which would possily allow for even further reactions of the compound. Furthermore, performing this transformation allowed us to introduce a new stereocenter to further determine this stereocenter we either needed a multitude of NMR spectroscopy or (slide change)
- A crystal structure, it was possible to obtain crystals suitable for single crystal X-ray diffraction by adding HCl in ether dropwise, by doing this the product percipitated out the product was the recrystalised from hot methanol.
- In conclusion! Of this project We have developed a versitile
- During the investigation of the Norcamphor scaffolds scope we discovered that applying tropone under our conditions led to a new product, that of a 6+4 cycloadditon. This inspired us to intiate an investigation into this new scaffold. From the NMR we were sure that we had formed the [6+4] cycloaddition product, though given we had a crystaline product we choose to confirm the structure by X-ray crystallography. We found similar large polycyclic systems in different natural compounds (change slide)
- Following the intial results we looked for potential natural products which contained a similar skeleton, three natural products were found and one which was based upon these natural compounds. Picato which is produced by LeoPharma to combat keratosis, an early stage of skin cancer. As can be seen these are not readily avaliable from our product but over a few steps such as a Baeyer-Villiger followed by a ring opening the core of Goyazensolide and Eremantholide C can be achieved.
- As can be seen it is possible to apply several different starting materials, all resulting in okay yields and varying ee’s
- During the initial part of this project where I worked partly on both projects I synthesised the cyclopentenone 2h we did this in an attempt to see if this could increase the yield of the reaction by being able to coordinate with the catalyst, via the hydroxy group furthermore we suspected this group would leave on reaction completion. While performing the raction we discovered that two products were being formed one of which was the predicte product, but furthermore we also saw formation of another product which turned out to be a [4+2] cycloaddition product this gave significantly higher ee though poorer yield.
- When we tried to expand the scope further using another heptafulvene we found that it reacted in another pattern, it reacts in an [8+2] cycloaddition manner via a linear dienamine, which is not what we would expect. We futher suspect that the formation of this 8+2 product is an intermediate in the [4+2] cycloadditions shown on the previous slides, that it undergoes an 8+2 and then rearranges into the 4+2 product. A future idea of the project, is one that I was going to do before we started finishing the first project, it is a way to achieve a product close to the ingenol scaffold shown earlier.
- In conclusion! Of this project We have developed a versitile
- During the investigation of the norcamphor scope, I discovered while recording the crystal structure of 6l that the crystal had a very perculiar space group for an organic molecule. I spent some time trying to ”force it” into an orthorhombic spacegroup but after integrating the data a unit cell of p65 was found. Furthermore it showed something more facinating, it packed in a way that gave tubular inclusion cavities. Because of this a lot of the Chalcones crystal structures were recorded. The same patter also appears when applying DCM as the solvent
- After it was discovered that product 6l formed these tubular inclusion cavities several other of the products derived from Chalcone were measured. These were all recrystalised from DCM by slow evaporation. The three presented structures all showed a P212121 unit cell, which is very common in organic molecules. Though this is a orthorhombic unit cell and not a hexagonal as the product that showed inclusion cavaties. These three molecules all showed ”normal” packing systems. Product 6p was made in an attempt to expand the cavities, though it did not work. Initially the thought was that the cavities formed due to pi-pi stacking, it would seem that it is more complicated than that.
- The figure on the right, I am sorry for the resolution, shows the unit cell of 6l as the sharp observer can see two of the sides are identical and one is very, VEEEERY thin 50x50x10 Furthermore the angle of 120 deg is visable, all of this is idencators of a hexagonal unit cell. If we were to expand further so we could see all the molecules, we should also be able to see a 6. 5 screw axis. Though it is hard to visualise with such a large molecule. When measuring the other products, I quickly discovered they packed in a more standard way.
- As can be seen from the figure on the right, the napthyl napthyl product packs in an orthorhombic unitcell as can be seen from the three sides being different in size and all angles being 90. When the molecule is in this unit cell they did not pack in a way that formed the cavaties. Therefore, all following crystals were only checked with a quick preexperiment to see whether they had a hexagonal or orthorhombic unitcell sadly non of the following crystals showed this pattern.
- In summation, this seems very interesting and could potentially be more than just a fluke. Though time does not permit me to investigate it further. If more time had been avaliable for it, I would have liked to recrystalise some of the other compounds from toluene to perform a control. Furthermore I would have liked to make the napthyl-napthyl with bromo and nitro substituents.