OC tidbits #7

Mose et al. (Jørgensen lab) [Nature Chemistry]

There are whole bunch of messy electrocyclic reactions in the paper and nice projections explaining diastereoselectivity. They made me nostalgic about reading OC texbooks.

mose_et_al

Hugelshofer and Magauer [JACS]

Want something even cooler, here’s a dyotropic reaction! Characterizing the side-products must have been a lot of fun. As well as monitoring the progress (the major undesired product had the same Rf as the starting material, and good luck with crude NMR). Heads up from amphoteros.

hugelshofer

Hall, Roche, and West [OL]

Was this reversible photo-switch discovered by accidentally shining a wrong UV lamp onto the final product?  The authors say it was expected. [Note: UVA = 350 nm; UVC = 254 nm]. TOC graphic:

ol-2016-03689z_0005

Chen et al. (Yu lab) [ACIE]

OK, enough electrocyclic reactions. Here’s some C-H activation work from Jin-Quan Yu lab. From [phthalimide-protected] alanine to [phthalimide-protected] substituted phenylalanines in one step! The conditions are somewhat peculiar though. A lot of silver (and quite a lot of palladium) was consumed for this to happen.

yu

Shi, Jiang, and Tian [JOC]

Tellurium is not very popular among chemists (and even less among anybody else for that matter), so each successful use of it is worth attention. The authors of this paper managed to find an application for sodium hydrotelluride. As an excuse they wrote this last sentence of discussion: ‘Reduction of the α-azido ketone 31 with PPh3, as in the Staudinger reduction, followed by stirring in air could not deliver 34 in our hands.’
tellurium
Another unusual thing in the paper is the open call for collaborations: ‘For now, gram scale of 30 and more than 100 mg of 34 [12,12′-azo-13,13′-diepi-Ritterazine N] are available for any interested collaborators.’ I felt obliged to spread the word.

OC tidbits #6

Nicolaou et al. (JACS)

Nicolaou et al. does some medicinal chemistry on prostaglandins. Take a look at this Bobbit‘s salt protocol for deprotection/oxidation combo. It seems like they overload the reaction, compared to the original paper, which used 3 equivalents of the oxidant, but who cares if it works?

Bobbit_Nicolaou

Moragas et al (ACIE)

Unprecedented (c) sigmatropic rearrangement of aziridines into sulfoximines.

Stockman_rearrangement

And De Kimpe’s rearrangement for comparison.

deKimpe_rearrangement

Li et al (ACIE)

I’m not sure I would buy the proposed mechanism for the conversion below. The authors skip ‘−H2‘ step and get away with it by simply writing “the imine intermediate 44 […] underwent tautomerization and a key decarboxylation to generate 45 with higher oxidation state.” Something else is clearly happening under that −CO2 arrow and it’s not mere tautomerization.

Hamigerans-proposed-numbers

Wappes et al (ACIE)

So similar, yet so different halogens. I guess, NaF won’t give anything useful under these conditions.

halogens-NHTs

 

OC tidbits #5

Kawamura et al. (Baran lab, Nature)

A paper with a very straightforward title, “Nineteen-step total synthesis of (+)-phorbol” (neither “concise”, nor “efficient”, “elegant” nor any other vague adjective)  was published by Baran lab.

The step that impressed me the most was oxidation of compound 7. Chemo-, regio-, and stereoselectivity of this reaction was “easily predictable based on 100 years of C–H oxidation literature”, according to follow-up blog post, but I wonder how many chemists in the world would bet for this reaction to work so cleanly. Before reading the publication, of course.

TFDO-multistep

Koh et al. (Hoveyda lab, Nature)

Expanding horizons of the metathesis reaction, Hoveyda lab teamed up with Schrock and developed a new catalyst and synthetic methodology for terminal Z-haloalkenes.

metathesis

Battilocchio, Feist et al (Nat Chem)

Remember Morken reaction? I was daydreaming about streamlining it into bond-by-bond stitching of complex compounds. Turns out that Steven Ley was looking in the same direction, although through slightly different chemistry.

sLey

Yang et al. (Org Lett)

mol_gymnastics-ok

A nice example of ‘molecular gymnastics’ (proposed mechanism is quite a funny thing). Heads up from amphoteros blog.

Potter et al (JOC)

Safety first! Opt for hydrosulfate salt next time you prepare a diazotransfer reagent. I didn’t have problems with hydrochloride before, but will better give a try to hydrosulfate.

jo-2016-00177a_0004

Adamo et al (Science)

…but hurry up with your diazotransfer, otherwise machines will soon do it for you! A fridge-sized synthesizer of known pharmaceuticals was constructed by chemists and engineers in MIT. Check out more detailed (and realistic) coverage by Derek Lowe.

 

OC tidbits #4

Büschleb et al. (ACIE)

A collection of OC tidbits selected by Hanessian and Overman groups. Featuring a dozen of natural products, each full of densely-packed stereocenters; 29 oldschoolishly lengthy synthetic schemes including three hundred intermediates that undergo all sorts of electrocyclic reactions and crazy cascades. Read in limited quantities to prevent overexcitement.

And, of course, I liked this guy (or girl?) at the frontispiece (the only thing one can get for free from Angewandte preview without subscription) in high-energy conformation overcoming some activation barrier.

completedSyn

Nicolaou et al (JACS)

KCN loves gold.

nicolaou-2

Picado et al. (JOC)

Turning failures into victories: if the reaction works, it’s just another row in a table. If it doesn’t, it can be a whole new paper!

joc-fail

Pan, Qin et al. (Org Lett)

A question without answer: how come this stereochemistry

panqin.png

… given this:

panqin2.png

 

Patil et al. (JOC)

Simplicity is the new beauty (via orgchem.by).

oximes

Mishra and Biswas (JOC)

Another example of beautiful simplicity.

mishra.png

Babij, McCuscer et al. (OPR&D)

Expanded list of chemical shifts for commond (and not so common but green) solvents [open access!]

op-2015-00417r_0006

 

 

OC tidbits #3

Giantassio, Lopchuk et al. (Baran lab) (Science)

As the legend goes, people from Pfizer approached Phil Baran and told him “You know, we figured out what our problem is. We need more propellers on our molecules.” Phil said “OK,  sounds like a good project” and put two grad students on it. Results: the 3-in-1 Science paper, with propellers spinning on every amine, SI, which is longer than my PhD thesis, and happy Pfizer counting cash.

slide1
Propellers everywhere! Source

By the way, Baran lab has a cold room for synthesis.

cold_room

 Qi et al. (Porco lab) (JACS)

Electrocyclic reactions are always fun, especially when 2 in 1. See the paper for stereoselective one.

electrocyclic

Schuler et al. (Nat Chem)

How to monitor progress of Bergman cyclization at 1.66 yoctomole scale? Atomic force microscopy is the answer.

reverse-bergman-cyclisation_nchem_2438_auproof-toc_630m

Zhao, Ming et al. (Org Lett)

Looks trivial until you try to push the electrons. The side-product hints at the mechanism.

zhao

Feng et al. (Tet Lett)

Another magic reaction candidate for debunking? Thanks sash-2003 for heads up.

1-s2-0-s0040403916300089-fx1

And before you rush to check it, they do report detection of molecular hydrogen in the gas mixture coming from the reaction.

hydrogen

 

 

OC tidbits #2

Zhu et al (Buchwald lab) (NChem)

Another great reaction that I was thinking to dedicate a separate post for but will never manage. Just check out this teaser scheme: two steps, two distant stereocenters, great chemoselectivity, and so drug-like!

Buchwald_CuH.png

Thanh Binh Nguyen (OPR&D)

Brilliant batch-washing of NMR tubes in a vacuum dessicator that has already got some good publicity in the blogosphere but probably won’t get too many citations. In theory, nothing can stop you from applying the same technique to any other glassware that has a solid bottom (flasks, beakers, etc.).

nmr-tubes
This is how vacuum washing works

 Williams & Trauner (ACIE)

Guess the name reaction (step c).

step-c

But the paper is worth checking not because of this step.

Newcomb et al (Ferreira lab): (JACS)

Some tips on increasing (E,E) yield:

tributylphosphine_isomerization

Just a nice example of sigmatropic rearrangement:

cyclic-rearrangement

 

OC tidbits #1

Despite deromantizing total synthesis I do like organic chemistry and do feel aesthetic pleasure from synthetic schemes and mechanisms [note for my future employer, I do enjoy the bench work, too!]. Also, since high school and undergrad years I still have weak spot for org-chem puzzles. So Below are some little nuggets (subjective, of course) from the recent OC papers that I found interesting.

  • From Popov et al (Somfai lab) (ACIE):

  1. Try to figure out the mechanismacie9-10
  2. Try to explain the difference in chemoselectivity (and what’s going on with that Ts group by the way?).acie10-11acie10-12

 

  • From Hamasaki et al (Kochi lab) (JACS)

Can you guess the mechanism for this one?

chain-walking-nowarning

  • Dream big!

All multi-ton processes start from the small scale, check this cute Kugelrohr apparatus setup by Thiyagarajan et al. for processing of biomass-derived furans (The white stuff in the middle is a zeolite catalyst; ACIE)

kugelrohr.png