ORGLIST: HMPA vs. HMPT

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From: Jack Kellum (jkellum$##$ucsd.edu)
Date: Wed Jun 23 1999 - 17:21:01 EDT

I'm trying to do geminal dialkylation on the beta-carbon of aspartic acid.
I've got the protective group strategies finally worked out so that
alkylation at this site is selective (as opposed to alpha-carbon, via
Rapoport methodology) but I'm not able to obtain yields above 35-40%. I'm
using 2 eq. LHMDS, 2 eq. ethyl iodide in THF at -78°C and warming to 0°C.

I would now like to try a cosolvent to avoid enolate aggregation and
hopefully increase reactivity of this substitution reaction. I've seen
references for both HMPA and HMPT as facilitators of this process but I'm
not sure if one is preferable over the other. Does anyone out there have
experience/knowledge of the pros and cons of these two compounds? Are they
interchangeable? Are their toxicity reasons for using one over the other?
Does one form a more stable/less hindered enolate? Remember, I want
*di*alkylation, not mono so diastereoselecitivity is not an issue.

Any and all germane opinions are welcome.

Thanks

*Author's note: The above message was originally posted to the sci.chem and
sci.chem.organic.synthesis newsgroups on 6/18/99. I have since determined,
through the help of many colleagues, that HMPA and HMPT are *not* acronyms
for the same compound although they are often confused this way in the
literature. In fact HMPT [hexamethylphosphorous triamide, (Me2N)3P] is a
reducing agent and is not useful for enhancing substitution reactions. HMPA
[hexamethylphosphoramide, (Me2N)2P=O] is the appropriate choice for this
type of reaction.

I would nevertheless appreciate any advice/suggestions from the collective
synthetic community.

Thank You

Jack Kellum
6215 Pacific Hall
Department of Chemistry and Biochemistry
University of California, San Diego
9500 Gilman Drive
La Jolla, CA, 92093-0343
Phone: (858) 534-2425
fax: (858) 534 - 0202
email: jkellum$##$ucsd.edu


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