new way to aryl grignards

[otto]

this might be of interest to some bees:

"Preparation and Reactions of Functionalized Arylmagnesium Reagents", Synthesis 2002, No 4, p 565-569.

in this paper various aryl grignards are made via transmetallation, e.g. isopropylmagnesium bromide is reacted w/ aryl iodides to give the corresponding arylmagnesium compounds. those compounds were then reacted following different reaction schemes.
transmetallation is fast (1 hour) at -20 deg and is surprisingly compatible w/ ester, nitrile or imine function. that means, your aromatic molecule may bear such groups w/out affecting the reaction at this temp.

now bees! iodinate any promising arene (DiMeO-benzene!), and according to the paper, problems in making grignards are past.
then crosscoupling w/ allylbromide or reaction w/ bromoacetone...

otto

p.s. the article is accessible via internet! look at www.thieme-connect.com (or .de, don't remember), then subscribe a for a trial account.

[Antoncho]

I got the article - if someone's interested, i can mail it to him.

A dry, argon flushed, 500 mL round-bottom flask, equipped with a
magnetic stirring bar and a 200 mL dropping funnel, was charged
with magnesium turnings (10.8 g, 450 mmol), which were covered
with anhyd THF (50 mL). Then 2-bromopropane (18.5 g, 150
mmol) was added dropwise at r.t. in THF (200 mL). After stirring
overnight, the dropping funnel was replaced by a rubber septum. To
separate the reagent from the remaining magnesium turnings, the
Grignard solution was transferred via a transfer-needle into another
dry, argon flushed, 500 mL Schlenk flask equipped with a rubber
septum. For storage of the iso-propylmagnesium bromide solution,
the rubber septum was replaced by a glass stopper. The concentra-tion
of i-PrMgBr was determined by the method of Paquette.

A dry and argon flushed 50 mL round-bottom flask, equipped with
a magnetic stirring bar, was charged with methyl 4-iodobenzoate (2:
788 mg, 3 mmol) in anhyd THF (6 mL) and cooled to –20 °C. i-PrMgBr
(6.2 mL, 0.54 M in THF, 3.3 mmol) prepared as described
above, was slowly added. After 1 h, the exchange was complete (as
indicated by GC analysis of reaction aliquots).

The rate of the iodine-magnesium exchange is significantly slower than the iodine-lithium exchange,8 and it is observed that the nature of the aromatic or heteroaromatic ring strongly influences the rate of the exchange. The more electron-poor the aromatic ring, the faster is the exchange reaction. Also, the presence of chelating groups ortho- to the carbon-halogen bond strongly accelerates the exchange and allows the bromine-magnesium exchange to take place under milder conditions than usual. In general, iodine-magnesium exchange reactions are considerably faster than the corresponding bromine-magnesium exchange (Scheme 2).


So... as you can see, the conditions will have to bee optimized for methoxylated (electron-rich) rings - but, perhaps, that would bee even better - like doing the rxn at RT??

Anyway, i think this all is pretty cool

Antoncho