Transition metal–catalyzed alkyl-alkyl bond formation #chempaperaday 289

A short and nice review of alkyl-alkyl coupling chemistry. As you may know, it is more challenging than sp2 coupling.




http://science.sciencemag.org/content/356/6334/eaaf7230

Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty-Chemicals Manufacturing #chempaperaday 263

This is a minireview where the authors focused on the implementation of metathesis catalysts "in specialty-chemicals and pharmaceutical manufacturing". I think it is a very useful review. In particular, I like the details like the effect of impurity (and what they are). These impurities are not only coming from the previous steps or starting materials but they are also some of the undesired side-products of metathesis. Early metals such as Mo and W tend to cleave and make new bonds. So, as you can imagine there is a lot more going on these reactions. 

There is also nice table where you can see a long list of ring closing metathesis (RCM) catalysts and their industrial application. Finally, there are several examples of RCM, the challenges and some nice discussion about their activity and selectivity. 

http://onlinelibrary.wiley.com/wol1/doi/10.1002/anie.201506846/abstract

Lewis Acidity of Organofluorophosphonium Salts #chempaperaday 187-188

The paper I read was "Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor that was published in Science. The second one is the "perspective" by F.Gabbai in the same issue. 

Caputo, C. B.; Hounjet, L. J.; Dobrovetsky, R.; Stephan, D. W., Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor. Science 2013, 341 (6152), 1374-1377.

Gabbaï, F. P., Lewis Acids with a Difference. Science 2013, 341 (6152), 1348-1349.

I pretty much knew nothing about hydrodefluorination until I read these papers. Now I know some. Really difficult research but it's not very popular yet. So, there is a lot of opportunities in this area of research.

Whittlesey, M. K.; Peris, E., Catalytic Hydrodefluorination with Late Transition Metal Complexes. ACS Catalysis 2014, 4 (9), 3152-3159

Epoxidation #chempaperaday 167-177

Sharpless, Jacobsen, Shi

Comp.Org.Syn. 1991, 389
JOC 1986, 1922
JACS 1991, 113
JACS 1991, 106
JACS 1990, 2801
JACS 1991, 7063
TL 1990, 7345
Science 1997, 936
JACS 2002, 1307
JACS 1996, 9806
JACS 1997, 11224

Dihydroxylation #chempaperaday 159-166

Sharpless, Upjohn

JACS 1976, 1986
TL 1976, 1973
JACS 1980, 4263
JACS 1988, 10986
JACS 1989, 1123
JOC 1976, 766
TL 1990, 2999
JOC 1992, 2768

Hydrogenation #chempaperaday 144-158

Selected examples and mechanisms below:

Wilkinson, Crabtree, Knowles

JCS CC 1973, 629
JCS CC 1968, 1445
JACS 1977, 5946
JACS 1977, 2576
Science 1982, 401
JACS 1987, 1746

Noyori:

JACS 1987, 1596
JACS 1995, 1017
JACS 1995, 2675
JACS 2001, 7473
JACS 1995, 7562
JACS 1997, 8338
ACIE 2001, 2818
JOC 2003, 1998
JACS 2013, 2604

Asymmetric and Catalytic Conjugate Addition Reactions #chempaperaday 134-143

JACS 1979, 4236
ACIE 1998, 2099
Tetrahedron 1989, 349
JACS 2000, 1826
Chem.Rev. 2012, 2339
Chem.Soc.Rev. 2009, 1039
JACS 2005, 6877
JACS 2008, 446
JACS 2010, 14315
ACS Catalysis 2012, 95

C-H Activation #chempaperaday 125-133

Selected examples:

JACS 2004, 2300
JACS 2010, 14530
JACS 2004, 9542
Tetrahedron 2006, 11483
ACIE 2005, 2112
JACS 2009, 11234
JACS 2010, 14092
JACS 2012, 12002
JACS 2013, 1978

Buchwald-Hartwig Coupling #chempaperaday 109-124

Chem.Lett. 1983, 927
JACS 1994, 7901
ACIE 1995, 1348
TL 1995, 3609
JACS 2006, 3584
ACIE 1998, 2046
JOC 1999, 5575
JOC 2000, 1158
ACIE 2008, 6338
JACS 2008, 6586
JACS 2009, 11049
JACS 2006, 2180
JACS 2007, 10354
TL 1997, 6367
JACS 2006, 2180
ACIE 2011, 9943

Heck, Tsuji-Trost, Sonogashira Reactions #chempaperaday 101-109

Time to update the blog. Here are some examples from selected papers:

JACS 1992, 10091
TL 1994, 3453
JOC 1994, 2685
JOC 1994, 5583
TL 1993, 2505
JACS 1991, 1417
TL 1992, 2589
JACS 1999, 3543
JACS 1999, 7410

Suzuki Coupling #chempaperaday 85-95

These are the papers that we're required to read for the organometallic chemistry (not exactly, but anyway) course I am taking. The topic is Suzuki coupling and some examples of it. Since I've read them all, it's time to share and record.

Chem.Rev. 1995, 2457
ACIE 2001, 4544
JOC 1999, 23
JOC 1994, 639
JACS 2000, 4020
JACS 2002, 9346
JACS 2005, 4685
ACIE 2004, 1871
JACS 2001, 10099
JACS 2002, 13662
ACIE 2003, 5749

Stille coupling #chempaperaday 72-84

In this post, I will give you the papers I have read about Stille coupling and some total synthesis papers where Stille coupling used. Some of them are among the mist important papers on the topic.

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Book: "The Chemistry of Phosphorus"

I have been reading this book slowly for about two months now. It is such a rare book that I was not able to find it online. So, I took notes carefully during the time I have kept it. Unfortunately, I have to give it back tomorrow to the library I borrowed it from.

http://johnemsley.com/books/chemistry_of_phosphorus.html

Although the book is really old (published in 1976), it is fascinating how much you can learn about phosphorus. Phosphorus has always impressed me (the other element impresses me is technetium)! After all, the whole life depends on it! Why did life evolve around phosphorus? It really bothers me.

One of the most interesting things I learned from this book is the "increase in enthalpy of 3.3 kJ/mol per pm decrease in bond length (0.8 kcal/mol per 0.01 A)."

"bond angles are always narrower in phosphine derivatives than in their nitrogen counterpart" This one is not counterintuitiv but I wanted to write here.

- PH3 has a small s-character than PI3 !

To tie it up I will paraphrase: In PH3, the lone pair is less available than in NH3. Because, 3s orbital is somehow buried between 3p orbitals.You can compare the basicity and of amines and phosphines to see this effect.

This book is a great source and looks like the most serious attempt to explain the chemistry of phosphorus with in-depth discussions, useful data and tables showing several trends in phosphorus chemistry and reactions. I wish I owned a copy. So, if you ever want to buy me a present, you can try to find one for me!

Synthesis of Zykadia (ceritinib)

I think I saw it on the net this morning that a drug named Zykadia (ceritinib) was approved by FDA. It is a lung cancer drug for patients who were already treated by another drug (crizotinib). Anyway, according to the press release it is an "anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells." 

I just wondered what the molecule looked like and searched for the structure and not surprisingly I found it. 

http://www.medchemexpress.com/product_pic/LDK378.gif

Then I wondered how it was synthesized and tried to google the synthesis. Surprisingly, this came up:

http://www.yaopha.com/2013/06/08/chemical-structure-and-synthesis-of-zykadia-ceritinib-novartis-breakthrough-therapy-for-lung-cancer/

Assuming that the website and the synthesis is legit, I want to say that I find the synthesis really easy compared to some syntheses I have seen on one of my favorite apps Chemistry by Design.

Update on Clayden's Organic Chemistry textbook "challenge"

As I mentioned in this post, I am trying to finish reading and understanding Clayden's organic chemistry textbook until the end of May 2014. Thanks to spring break, I was able to gain some more speed and today I have finished Chapter 26. Since there are 53 chapters, I thought it would be nice to write about my studies so far. 

Anyway, as you can understand from my blog's header and posts I am way more interested in inorganic chemistry than organic chemistry. But, organic chemistry knowledge is essential in inorganic chemistry too. Firstly, I want to design and synthesize ligands. In fact, I want to prepare a new AND useful ligand on my own. Without knowing the basics and details of organic chemistry, there is no way I can do this. Moreover, without organic chemistry, there is no way that I can even understand and appreciate the use/synthesis of some ligands that are already published. Having finished  Wade's textbook, I realized that I needed to learn more. Also, I know I am not so good at organic chemistry. So, I decided to be better at it with Clayden's.

First of all, my thoughts about the book mentioned in that post haven't changed. I am not an organic chemist, but as a student (the target reader of the book) I still find the book not organized for my educational purposes. It is very common to come across some reagent, reaction or even a functional group in the early chapters without learning anything about them first. Usually, there is a note saying that "...covered in Chapter X." When I compare it to my favorite organic chemistry textbook (Wade's), I still think this book doesn't follow the usual sequence (from simple to difficult). 

I did every single practice problem in the book. Most of the time, I really enjoyed the problems and I am planning to write some blogposts on some mechanisms. My favorite problems and examples are the ones that give or ask you the mechanisms of real drug syntheses. It's great to see that I can understand and design the same syntheses for some drugs. Organic chemistry is really cool! To my surprise, I was able to do ~70% of the problems without much effort. So, I am better than I had expected. Some problems that involve certain agents were really hard for me. Because, if you don't know which one to choose, you will have to go and seek help in tables or chapters. One thing I realized about myself is that I can make some educational guesses, but when it comes to mechanisms I sometimes choose wrong steps although I can draw the right product in the end. I think some problems have more than one routes, and sometimes I am just wrong but lucky. 

I have never done anything about protecting groups at the school, so Chapter 25 took me a while to understand. It's not hard but it was new to me.

Overall (26 chapters), this book is great and I am sure I will always use this book in my future career.

So, now I am ready to go to ACS Dallas and when I come back, I will go on studying. I also decided to read organic chemistry papers too. Maybe they will help me to pick up some tricks. Also I will be able to see more syntheses. Feel free to suggest me readings too.

By the way I did not give up #chempaperaday. In fact, I still read papers but the point of that challenge was that I had decided to read "extra" papers. Right now, I am only reading inorganic chemistry textbooks, books and publications. So, it won't be fair to post those papers.

Another challenge - Clayden's Organic Chemistry Textbook

This semester I have a lot of "free" time. I have only two courses. So, I spend most of my time by reading, studying and finishing my research (at least trying).

One of the MANY goals I set is to try to fully understand Clayden's organic chemistry textbook. Throughout my studies, I have used this book as a reference and source. But, all my attempts to really read it failed due to its unusual (for me) order of chapters and subjects. I know it is a great book, but I still don't like the way it was designed. But, having finished all the organic, inorganic and physical chemistry courses, I know that I can understand much more than I previously did. I am also sure that this will help me in graduate school (if I end up being in one).

Burgi-Dunitz Angle

We all learn nucleophilic attack on aldehydes and ketones in organic chemistry courses. To be honest, I have never wondered the angle of the attack. I always thought that the nucleophile should attack perpendicular to the C=O bond axis. The reason I was thinking like this was that the R groups should cause steric hindrance and make the attack less likely at any other angle. I thought the electron rich bond and the lone pairs on oxygen couldn't have much effect on the attack. Looks like I was quite wrong. I should have considered hybridization and molecular orbitals too. To be clear, you can see the way I thought the attack happens below:

Last night,  I learned that nucleophiles attack the carbon at ~107 degrees to the C=O bond axis. So, my curiosity took me to the original paper by Burgi and Dunitz. 

http://pubs.acs.org/doi/abs/10.1021%2Fja00796a058

I read the paper a few times and here is what I learned:

1. As the nucleophile attacks, the R groups bend and C-O bond becomes longer.

2. As the nucleophile approaches even more, RRCO becomes even more nonplanar. Looks like sp2 hybridized carbon becomes sp3 hybridized. 

One of the R's in aldehydes is hyrdogen. This also explains why aldehydes are more reactive than ketones. They have less steric hindrance in the system. (This is one of the reasons.)

I think this is the way it happens:

From molecular orbital theory approach; the electrons in the HOMO of the nucleophile interact with the antibonding orbital (LUMO) of the C=O bond. Both the bonding and antibonding orbitals are occupied now. This breaks the Pi bond and the electrons move to the most electronegative atom (oxygen) in the bond.