Comments on: 9-Isocyanopupukeanane

By: jayashree

jayashree — Mon, 15 Mar 2010 08:05:12 +0000

I would like to know whether activating Pd- catalysts with ACids during Hydrogenation and especially -debenzyltion would result in increasing the activity of the catalyst & also the raactionrate and speed of the reaction???Could you cite some references to that effect??

By: Sergio

Sergio — Tue, 22 Dec 2009 03:23:59 +0000

Imho there are some ambiguity describing scheme3. TosMic should have been used for homologation of the acid before chlorination and friedel crafts, otherwise one would end up with 4 membered ring? It should be like: acid–homologation with tosmic–methylation–chlorination–friedel crafts. You write: “The free acid was then chlorinated to the acid chloride, and a bit of Lewis-acid allowed ring-closure onto the proximal aryl position”. And only after that you say: A bit of alkylation with TOSMIC (hydrolysing the nitrile and methylating) and methyl iodide provided enough carbon to get on with things”. One can not notice your latter remark:)

By: Oz

Oz — Mon, 14 Dec 2009 05:16:37 +0000

Great post Paul,

It was great to have a look back at Corey 30 years ago. The route is brilliant. I’m loving your blog.

By: milkshake

milkshake — Mon, 07 Dec 2009 03:24:08 +0000

no but one has to be gentle. Straight TFA up to 40C is tolerated even with 2,3,4-trialkyl pyrroles. I am not so sure what TESH would do – indoles can be reduced to indolines under similar conditions, thats why peptide chemists use iPr3SiH as a scavanger because it would not reduce tryphtophanes.

One can easily end up with assortment of funny bright-colored oligomers when the pyrrole has no electron-withdrawing substituents and if one pushes too much

By: Gui

Gui — Sun, 06 Dec 2009 23:09:09 +0000

One last thing, shouldn´t pyrrole polimerize in acidic conditions???

By: Gui

Gui — Sun, 06 Dec 2009 23:03:03 +0000

That is a good suggestion. You can check it out here

Angew.Chem,.Int.Ed.Engl, 1999, 2934-2936
or
Tetthedron Lett.,1991, 32, 2083-2086
Hope it helps!

By: milkshake

milkshake — Sun, 06 Dec 2009 20:45:54 +0000

It coul be, I accidentally once hydrogenated amide of 5-(TMS-ethynyl)-2-furoic acid all the way down to TMS-ethyl-tetrahydrofuroic piece on Pd-C.
Although I have seen porphyrine people doing hydrogenolysis of benzyl ester of pyrrole-2-carboxylic acid (with three alkyls on 3,4,5-positions) without a problem.

I suppose you could try triethyl silane and TFA in DCM because the ester in the 5-position should make pyrrole slightly less el rich and hence less likely to crap up in acidic conditions. I used TFA in similar system.

Then there is borane-DMS which should leave your ester unharmed if you dont push too much.

Whats in the 2-position of your C=C that you are trying to hydrogenate?

By: Gui

Gui — Sun, 06 Dec 2009 20:12:14 +0000

What have you been using that hasn´t worked? So as to rule out

By: InfMP

InfMP — Sun, 06 Dec 2009 20:02:52 +0000

Milkshake or anyone:
speaking of hydrogenation of aromatics, I`m having trouble hydrogenating a 1,1-disub-double bond (methyl and 2-pyrrolo). I think my pyrrole is being reduced by the PdC H2 because the TLC becomes non-UV active mixtures. There is an ester at the C5 position too.

What catalyst, homo or hetero should I try ?

By: The Next Phil McGroin

The Next Phil McGroin — Sat, 05 Dec 2009 20:56:38 +0000

good to know, thanks