Phosphate of ketone, ester and amide

Triflate of ketone ester and amides are useful reagent for pd coupling.
When triflate is unstable (ex. lactone or lactam), phosphate can be used (PO(OPh)2Cl).
It has better stability, stable on silica gel.

Then pd coupling can happen as triflate on phosphate.

Finally, another accident revealed the source.

Something happened during an overnight refluxing methanol rxn.

There are the clues I found:

1. somehow the red alcohol in the thermometer became un-continuous. there are gas between the red-alcohol.

2. the hot plate was cold although the knob is still on the right position. Restarted the hotplate returned the heat.

3. What is more, the mineral oil bath became darker than before.
4. although cooling water is running, half of the methanol was gone. (open container reaction)


My conclusion is the hot plate is bad. It heated up to a very high temperature sometime in the night! The high temperature exceeded the range of the thermometer and destroyed it. Also it darkened the mineral oil.
This hotplate is the same one I used for the other accident! SEE PIC!
the mechanism of controlling temp of this kind of hot plate is by a electromagnetic relay. I can hear the "click" sound when it started to heat. When the temp reached a preset value, the clicking sound became intense.
It is not reliable. Never use this kind of hotplate!

Pd catalyzed coupling of halides with enolates

Some players:
James Cook, Buchwald, Hartwig,
Josep Bonjoch...

progress:
intermolecular: enolates from ketone, ester, amide, nitrile; halides can be Ar-X, vinyl bromide.
intramolecular: enolates from ketone, ester, nitrile, halides can be Ar-x, vinyl bromide/iodide.

You may notice intramolecular amide coupling is missing.
The reason is obvious that strong base is needed to deprotonate the amide which can cause server side reactions. In the intermolecuar situation, this can be avoided by exchange the strong lithium enolate of amide with Zinc enolate as done by Hartwig.

Intramolecular epoxide openings

From :
Douglass F. Taber,* Lee J. Silverberg, and Edward D. Robinson
J. Am. Chem. SOC. 1991,113,6639-6645


1. nitrile anion opening and sulfone anions.

2.Nucleophilic allylic silanes have been employed, under acid-catalyzed conditions, ln
intramolecular epoxide openings.

3. Finally, StorkM has shown that ketone and ester enolates can be used to open allylic epoxides,
to form cyclohexane derivatives.

4. The only other enolate-based opening of an epoxide has been that reported by Negishi.31

(31)Z hang, Y.;M iller, J. A.; Negishi, E.-I.J . Org. Chem. 1989,54,2 043.

protection of tertiary amine while epoxidize an alkene.

1. use NaHSO3 to reduce the amine oxide.

tert-amine can be oxidized by mcpba to amine oxide. by using NaHSO3, the oxide can be reduced to tert-amine again. So use 2 eq. mcpba , then treated with NaHSO3.

2. TFA protection.
use TFA to convert the tert-amine to TFA salt which prevented oxidation.
after mcpba, use K2CO3 to remove TFA.
this method is not good to acid sensitive compound.

preparation of methanoli HCl

very expensive if you buy it from aldrich.
easy to make.
you need HCl gas cylinder or you can prepare it from con. sulfuric acid and NaCl ( add sulfuric acid into NaCl and stirring).

then you bubble HCl gas to MeOH. heat will be generated so an ice bath can be used.
by weighing the MeOH before and after, the concentration can be easily calculated.
In my case, I can easily reach 6N .

Once again, another lab accident.

This time it is a sealed tube reaction.
solvent is methanolic HCl (about 3-6 M, 10 ml). ace galssware 50 ml seal tube (max. 60 psi) with teflon cap.
temp is only 80-90 C. magnetic stirring.
after about 5 hr, somehow, the teflon cap was unscrewed (by itself !) and popped up to the ceiling of the fume hood along with all the solvents and reactants.

the reaction was not supposed to generate any gas.
the solution was green, which was not observed in a previous run.
the magnetic stir bar was broken after the explosion. magnetic metal inside can be seen.
Luckily, nobody get injured because of a protection shield we have.
Also nothing got broken. the seal tube is still intact and looks ok.

what is going on?
I guess the defective magnetic stir bar was the reason, which generated H2 gas in the presence of HCl. this is also explained why the color is green.

What is interesting is I still can not image how the tight teflon cap managed to unscrew itself.
In an early similar accident I had half a year ago, the sealed tube was just destroyed by the inside pressure.