Monday, June 29, 2009

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.


Saturday, June 27, 2009

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.

Friday, June 26, 2009

Total Synthesis of 20-Norsalvinorin A. 1. Preparation of a Key Intermediate
Ylva E. Bergman, Roger Muld
er 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.

Wednesday, June 24, 2009

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.