Where I've Been.

Sorry about the lack of posts lately! Ive been really busy with this fall semester getting mediocre grades in my "grade boosting" semester.. I guess you lose focus when you don't have any chemistry classes. Well as of right now I'm signing up for REU projects all across the nation and some even jump a small pool of water to places where people talk funny! But hopefully, then I can get back into reading papers and crankin out some posts.

Until then you can listen to my music! www.myspace.com/kiddiekhem
Hope you like it!

Pranks!

Pranks are fun and can be a fun way to add some spice to your lab but how can you implement them without getting caught and hurting the science.

Whether you're acting like you didnt bring the compound to the spectra lab, when your in a group or something more complicated like what ive got for you today, its always interesting to see what happens.

This prank was executed by simply setting it on a lab member's desk, I followed up by asking "how weird was the Tungsten reaction?" He answered with "yes it was somewhat hard to follow the mechanism though." (hes not an organo-metallic guy)


Well now ive got a lab partner that thinks hes a pro at terminal alkane coupling... Id say it worked out well. Voice any lab pranks youve done in the comments!!!!

Enantioselective Total Synthesis of the Potent Anti-inflammatory (+)-Myrrhanol A
Victoriano Domingo, Lucia Silva, Horacio R. Dieguez, Jesus F. Arteagas, Jose F. Quilez del Moral, and Alejandro F. Barreo
Link to the Paper

So this latest taste of Science is freshly out of Spain. The main reaction here which caught my eye was the Ti catalyzed radical cyclization, forming a few new bonds and creating 3 stereocenters. Some other good science: a nice Negishi Carbometalation, a Suzuki using 9-BBN, and a nice epoxidation followed by reduction.

Well they started early with the Ti cyclization. It has a radical mechanism where the Titanium catalyzes a heterolitic bond breakage between the oxygen in the epoxide and the more highly substituted carbon in which its attached to. They formed this epoxide using DMAP. This carbon then attacks the neighboring sp2 carbon to form a chair, generating the sterocenter. This then pushes one electron from the pi bond over to then react with the other alkene in the same chair which then eliminates giving the lone electron back to the Titanium. Quite the proposed mechanism, but I love the end product of this reaction. It reminds me of the excitement I once had from studying the Diels Alder and the two bonds and stereocenters it formed. Here's the paper they referenced on this step PDF.

The next reaction in their synthesis was their chiral epoxidation. It looks as though the Chirality was obtained via the steric bulk of the adjacent methyl and other parts of the ring structure. After this they simply used LiAlH4 to reduce the epoxide on the less substuted carbon, affording the alcohol on the tertiary carbon.

Here is a reaction I had to do some reading on to understand. The Negishi Carbometalation has a very interesting mechanism. Essentially the Zirconium acts as a total theif and steals the Aluminum's methyl along with its electrons from the bond then stabilizes it with its two chlorine. It then sits down onto the alkyne similar to how you see HCl act with the negative chlorine, or in this case methyl, going to the more substituted carbon. After this the Zirconium and the Aluminum switch bonds the methyl on the Aluminum and the bond from the alkene on the Zirconium. Finnaly they add I2 to t solution, one iodine bonding to the Aluminum and one to the alkene. This explanation is pretty rough around the edges so if you want to check out the paper yourself here it is.

One of the later reactions of this paper was the Suzuki using 9-BBN. Here the 9-BBN was used to reduce the alkyne and place a steric Boron group on the terminal carbon. This step was followed with a Pd coupling with the vinyl idoide. I like the versatility of this step and its getting me to think about different ways to incorporate Boron groups into various structures.

Lots of fun Organometalics in this one.

Big Adventure in Little City

So now that I've gotten that Jackie Chan sounding title out of the way, ill get to the story.

So the plan was to play tunes and Skype untill the sun began to set, get on a city bus and take it round trip, to see the city. Soon i was wandering around the medschool looking for the South bus. Things seemed to look a little different now that it was dark and I ended up spending a decent amount of time wandering outside of the medschool. I was thrilled with that though, it worked out perfect, Saw all of the buildings from a different road which look alot prettier than the normal view. Ended up in a cove within the medschool with some very pretty locked doors, and then when i broke out of it and found the stop, the hospital helicopter was taking off (it was dark now) and it was soo coool! Snagged a video on the phone. It wasn't long untill i was hopping on the 935 bus, but before that i met a guy that was shot 4 times! The initial bus ride was awesome! It had layered rows and I got on a seat near the back which sat alot higher than the rest, to get a better view. Okay well now im going to start telling the story from someone who has already finished the trip and understands what the heck happened. At the Monroe stop the bus driver got out and got into a car that was sitting there as we pulled up. She was in that parked car for 10 minutes untill a cop walked up. I have no clue what was said, but 5 minutes later the bus rejoined its course. Soon we were driving through downtown, tall buildings, lots of lights, it was gorgeous. When we got to the downtown stop some people were exchanged and then a bus driver got on. He spoke with her for around five minutes, in what seemed to be a heated conversation. Then we headed north of the city. Lots of new unseen buildings, The beer factory from a new side, and this is where most of the people on the bus requested stops. After every one else got off, she ended up pulling into a Wegmans parking lot, behind a parked bus, announcing this is the last stop, Soon I was questioning her how this was the last stop and not a round trip back to the hospital. She said "no it doesn't work like that" and eventually just gave "whatever" as an answer. Im guessing that talk with the other bus driver may have gotten her angry. Well I got off into this unknown area and looked around noticing there was a bus stop sign. None of the routes on the sign were for south. Instead of getting stressed out I decided there were worse places to get stranded and decided to make a trip into the Wegmans, a local grocery store. There I got some delicious Mango Slices, which helped cool me down and ended up carrying me to the end of the trip. After wandering around the store and doing some munchin. Headed back to the bus stop and met a new bus driver. I asked him if he knew where I was and told him how I became stranded. We chatted for a bit and he said he was headed downtown, where i could get on another bus to go to strong. I sat on the front seat and we talked for a good bit of the bus ride, he told me alot about Rochester and that his hometown was actually very close to my own. After seeing a completely new area of the town and how freakin cool the handicapped lift for a bus is, we made it downtown. I got on the 19 like the previous bus driver instructed, but this time I made sure we were headed to Strong Hospital, He said we were headed to Strong, but that itll be a while since it goes through the University. I was exuberant! The bus ended up taking me within 2 minutes of the dorm i stay in. It was awesome!

A Versatile Route to the Tulearin Class of Macro Lactones: Synthesis of a Stereoisomer of Tulerarin A
Alexander L. Mandel, Veronique Bellosta, Dennis P. Curran and Janine Cossy.
Link to the PDF

Here is a fun little paper out of Paris. This paper really makes up for the lack of reactions you saw in the last paper, totaling about 18 (some being deprotections and protections hence the about).

The science begins with a Julia Kocienski Olefination. Here they used a Sulfone with a phenyltetrazolyl group on it to bring forth the trans alkene. The mechanism involves potassium bonding to the non conjugated carbon adjacent to the sulfone and an attack on the aldehyde. Then after a series of elimations it gives off sulfur dioxide and the phenyltetrazolyl.

After the Sharpless they used DIBAL-H to reduce the ester within the lactone into an aldehyde and then they used a methyl phosphine to afford the terminal alkene, which becomes very important later in the synthesis.

Here they used a benzylthiazolidine thione group, known as the Crimmins Chiral Auxiliary, with specific conditions in this aldol addition to attain specific stereochemistry. After that they do a simple protection and then remove the benzylthiazolidine thione group using hydroxide and peroxide.

Finally, completing the scaffolding, they carry out a ring closing metathasis using Grubbs first generation. They also attempted the reaction using other catalysts, but gave side products or did not react at all.

Some nice science, liked the Julia and seeing the Crimmins in action was nice.

Presentations

Every one has to do presentations, some people enjoy them more than others and some, it comes naturally to. There are many things people do right and people to wrong with presentations and here are my top presentation notes. You can post your keys to a good presentation in the comments.

1. Know your Audience (as best you can). Alot of times you can have a general idea of who your presenting to which should govern the amount of explanation you go into. If your explaining how there are four different base pairs to a group of biologists, they may glaze over.

2. Dont be a Robot. Have some life in the way you talk move and change from topic to topic. If you sound monotone and don't move, people will get bored and lose interest. Being a real person on stage will make you seem more confident.

3. Show what your talking about. Okay these are some things Ive underlined in the little notepad that you bring to talks.. When giving a talk its good to show where you are on a slide if you have a multi component slide. Although, during a talk a student pointed to the slide, which he was very far from, with their hand instead of using the lazer, which only showed us that his material was somewhere between the slide and the cealing. After I thought about it and realized there isn't a good way to actually point with your hand during a presentation where your slides are at a good distance from you. If you use your inside arm you end up waving your arms around and looking uneven. If you use your outside arm you are closing yourself off from the audience and talking to the board. So use a lazer!! Now for the Lazer, only use one hand to point the lazer, you'll come off looking clumsy and foolish otherwise. When actually pointing attempt to actually point and not circle, circles can draw attention and aren't as accurate.

4. Try and dress nicely. Alot of scientists arent quite the best dressers but wearing a T-shirt that looks like it might have holes in it and isn't tucked in, is almost a sign of disrespect for the talk itself.

5. Enjoy yourself! Your most likely presenting your own research! Finally an opportunity to chat about the stuff you know quite well. When people are asking questions see them as opportunities to improve your research. Their suggestions could allow you to look at your research from a different angle.

Stereoselective Synthesis of (-)-Spicigerolid
Yohan Georges, Xavier Ariza and Jordi Garcia
Link to PDF

So this was somewhat of a short paper, not having too many reactions, but when I saw the Sigmatropic rearrangement with a heteroatom there wasn't there was only one option.. Review this paper.

In the first step, they used the Carreira Procedure, where the zinc activates the C-H bond on the Alkyne. The mixture of the chiral NME and Zn give high yields of the optically active product. A good paper from Carreira referencing his techniques can be found here.

Next they did my favorite part, the sigmatropic rearrangement. Here a 3,3 Sigma rearrangment breaking a carbon oxygen bond and forming a different bond between a different oxygen and different carbon. This also seems to be more thermodynamically favorable due to the larger conjugated system in the resulting product, which in my opinion is absolutly required because the sigma could go along the other direction of the molecule since all of the oxygens have Ac protecting groups. In my opinion, a bad choice for just this reason, they could have put different protecting groups on the two alcohols after the alkyne coupling since the alcohol used in the sigma rearrangement is already protected.

Later in the paper they do another Alkyne carbonyl attack and then lindlar it to get the cis alkene. I personally would have attempted to couple it as the alkene against the carbonyl but they are the ones with the nice paper and ill give it to them for that.

The Total Synthesis of the Galbulimima Alkaloid GB 13
Lewis N, Mander and Mathhew M. McLachlant
Link to PDF

So this might not be one of the newest papers, coming from back in the day (2002) but the post on Himadrine brought me to an older paper from Movassaghi (Galbulimia Alkaloid), bringing me to an earlier synth of it.

Lots of good chemistry in this paper, a Regitz Diazo Transfer, Wolff rearrangement, Birch reduction, an Eschenmoser fragmentation, and near the end of the paper, a nice cyclization.

So an early step of theirs was the Diazo Transfer where they attacked ethyl formate and then introduced the sulfonyl azide which then was attacked and then eliminated off the formaldehyde giving the Diazo Product. Here is a good paper testing out different reactions and conditions.

Once they had the Diazo they were able to do a Wolff rearrangment. Here they used light and a silyl group to catalyze the reaction. After an acidic workup they obtained a 68% yield which isnt too bad for rearrangement chem.

In the Birch Reduction they not only brought the anisole group down to the enone but also completely pull off cyanide and keep the stereochemistry while doing so. When they initally brought in the Lithium it removed the cyano group via reduction. Then the addition of methanol and acid pushed the Birch to reducing the Anisole.

Here is the fun step where they developed the ketone and terminal alkyne. Well in the Eschenmoser fragmentation they brought in the sulfonylhydrazine in ethanol and THF which, after alot of arrow pushing, will give you the desred alkynl ketone.

Finnaly one of the last steps they bring two oximes together with a plethera of reagents. The first being the ZrCl4 and NaBH4 which looks to me like the aldoxime is converted to the amine and then nuc's the other imine. Once the ketoxime is removed they remove the hydroxy group and then protect with TFAA. Heres a link to the oxime to amine paper they cited.
(Update! Just realized this step created 2 stereocenters with 100% ee. Since they didn't use any kind of chiral molecules to help induce the choice of cis, I'm guessing it is forced into this conformation by steric repulsion the previously created stereocenters.)

Alot of Chemistry in this paper. Very glad I stumbled upon it.

Total Synthesis of (−)-Himandrine
Mohammad Movassaghi, Meiliana Tjandra and Jun Qi
Link to the PDF

So here is a great paper coming out of the Movassaghi Group over at MIT, where I was actually lucky enough to visit once. So the first thing you notice about this paper is the target molecule, a multi-ring, multi-stereocenter compound.

So this paper has plenty of good chemistry: a nice Suzuki, an intramolecular Diels Alder, a Ruthenium cross metathasis, and something Ive never seen, a DDQ oxidation.

They used the Suzuki to construct the diene with the bromo group, leading to the azetidone group addition and the Diels Alder.

The next fun step was the Ru catalyzed cross metathasis. Here they essentially added two carbons and an aldehyde which will be used in an aldol later.

This intermolecular Diels alder sets three stereocenters and closes two rings. A very nice step which is where you can start to begin to see the molecule.

Now for the DDQ oxidation. Here they ran the DDQ in water being a source of oxygen and then the DDQ oxidized the ring to bring forth some enones.

Overall it was a great read and learned alot from it.

Total Synthesis of 20-Norsalvinorin A. 1. Preparation of a Key Intermediate
Ylva E. Bergman, Roger Mulder and Patrick Perlmutter
Link to the Paper

So here's a nice little paper from the outback. Theres some good chemistry leading up to the Diels Alder which is what sets the majority of the Stereocenters and brings their molecule together. The most interesting part of their paper was the use of DBU, an amidine, where they used it to reverse a specific stereocenter.

I liked bringing in the chiral diene leading to a majority of the desired stereochemistry. As you can see they were able to coordinate the reaction of the more reactive alkene in the ring aswell.







This reaction was pretty slick in my opinion. Here they used an amidine to reverse the chirality of a carbon.
When I first saw this step I was stumped. Later, upon settling into my head I realized that its likely that the imine in the amidine is cooridinating the two adjacent oxygens leading to an aldol type of resonance. This kicked off the tertiary hydrogen which momentairly lost its chirality and then upon the disconnection of the amidine brought back the carboneal and lead to a trans-decalin type structre, which would be more favorable than its previous structure. You can also see how it would not reverse the chirality of the quaternary carbon being that it can not lose its chirality or go to the sp2 hybridization. I honestly think they could have heated the compound or maybe add a metal acting as a lewis acid but nonetheless its still very good chemistry.

New Paper from Merck Labs

Practical Synthesis of a Potent Bradykinin B₁ Antagonist via Enantioselective Hydrogenation of a Pyridyl N-Acyl Enamide

Paul D. O’Shea, Danny Gauvreau, Francis Gosselin, Greg Hughes, Christian Nadeau, Amelie Roy and C. Scott Shultz
Pdf to the paper

So it seems the Merck Lab has a little gift of science for us in the new JOC. The paper's main points were mainly comprised of a Suzuki and some Carbo acid activation, but they also threw in some fun chirality aswell.


In preparing their reagent for the Suzuki they had to induce chirality within it and although got a little steppy had very good yields and came out with product.



After this the ran the Suzuki, deprotected the amine and did the Carbo activation with EDC and HOBT.

Update: I did some more reading in the paper and the Tangphos is actually binding to the Rh catalyst so I thought I'd post the Rh Catalyst aswell.