Leo Szilard
Harmless
Posts: 20
Registered: 10-5-2015
Location: USA
Member Is Offline
Mood: No Mood
|
|
Enolate formation from Grignard
Good day. I am a new member and I apologize if I have overlooked any existing posts about this topic.
I have been thinking a lot about carbonyl chemistry, and more specifically enolates. LDA is a non-nucleophilic base that is useful for preparing
kinetic enolates (for directed aldol reactions for example). I wonder why a sufficiently bulky alkyllithium or Grignard cannot accomplish the same
thing. Can anyone cite any cases where a Grignard or alkyllithium has been used to successfully form a kinetic enolate with little or no carbonyl
addition?
A similar question relates to diisopropylamide. LDA is the go-to base for forming kinetic enolates. Would amide anion readily form from treating
iPr2NH with a Grignard (e.g. t-butylmagnesium bromide)? I suspect this reaction would work just fine (based on pKa), but then the next question is:
would this bromomagnesium diisopropylamide have similar regiochemistry and basicity as LDA? I am interested in finding an alternative to LDA that can
be prepared with something more mild than an alkyllithium.
I have a memory of seeing some papers that discuss using bromomagnesium diisopropylamide in the formation of silyl enol ethers (sorry I can't cite any
specific examples), but I want to find something relating to general enolate chemistry.
I would appreciate some other opinions about this.
|
|
|
Chemosynthesis
International Hazard
Posts: 1071
Registered: 26-9-2013
Member Is Offline
Mood: No Mood
|
|
Grignards can form enolates, particularly if sterics of either substrate are prohibitive to nucleophilic attack. Given the support of the claim here,
I am assuming one of their citations has an example for you: http://www.organic-chemistry.org/namedreactions/grignard-rea...
Edit- found better. Try the following:
Chem Soc (1977) 162
Tetrahedron (1980) 36, pp227
J. Org. Chem., (1961), 26(9), pp3162
Without further reading, I'd have to give E/Z enolate stereoselectivity some thought... or do you mean selection of the ambident carbon from which the
hydrogen is abstracted?
Seems J. Org. Chem, (2009), 74, pp1353-1355 tentatively answers at least one of those for you.
[Edited on 10-5-2015 by Chemosynthesis]
|
|
|
Leo Szilard
Harmless
Posts: 20
Registered: 10-5-2015
Location: USA
Member Is Offline
Mood: No Mood
|
|
I think the stereochemistry is a more interesting question. If a carbonyl substrate has a heteroatom with lone pairs bonded to the beta carbon, you
can get good chelation control with LDA. I wonder if magnesium would give a similar result. Does the fact that the magnesium is bonded to a halogen
(in the case of a grignard) pose a problem with chelation?
As far as the regiochemistry (selection of the ambient carbon that loses a proton): is it correct that sterics are the main factor?
Thanks for your your input!
|
|
|
Chemosynthesis
International Hazard
Posts: 1071
Registered: 26-9-2013
Member Is Offline
Mood: No Mood
|
|
I was always taught that for regiochemistry, sterics are king. They will also play a role in the addition of the Grignard and intermediate formation
with Cram's Rule and various expansions such as Felkin-Ahn, but I don't know what factors to compare for choosing the correct model to hypothesize a
particularly good answer to your questions, which are very interesting. I am not best person to reply, but I believe solvent selection will also play
a role in how much of a factor this is, as not only does this affect basicity, but Schlenk equilibrium can be Grignard specific, which while
fascinating, is not very convenient from an optimization perspective. Hope I have been helpful. I am very interested in hearing about your experiments
and if you run across any reasoning behind product expectation. I will try to remember to look into this a bit further, but it is not my specialty.
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
