Re: ECHET96 Article 081

Bob Gawley (
Sat, 13 Jul 1996 10:36:17 -0500

>Dear Professor Gawley,
>I was not surprised that you have found 'additional stabilisation (of the
>organolithium) by the double bond'. This tallies with our results on
>anionic cyclizations (JACS, 1996, 5322) and those of Bailey (JACS, 1991,
>5720) and recently Hoffmann (JCSPT2, 1995, 1953) who has NMR evidence of
>Li-pi coordination. What is surprising is the extent of retention with
>benzylbromide. If the N-allyl-2-lithiopyrrolidine is indeed more
>kinetically stable than the N-methyl analogue then it would be less prone
>to undergo single electron transfer with benzylbromide and may explain why
>racemic products no longer result. It is more difficult to explain the
>difference between benzylbromide and alkylhalides.
>Do you think that the initial interaction of all electrophiles (including
>alkylhalides) is via coordination to the lithium? If so, then the more
>reactive benzylbromide may react rapidly with retention, whereas the less
>reactive alkylhalides transfer to the opposide face (maybe for steric
>reasons due to the possible dimeric organolithium?).
>It would be interesting to discover the result with allylbromide or
>electrophiles of reactivity intermediate between benzylbromide and
>Iain Coldham
>Dr Iain Coldham
>Department of Chemistry, University of Exeter,
>Stocker Road, Exeter EX4 4QD
>Phone 01392 263465 (44 1392 263465); Fax 01392 263434
>ECHET96. Conference home page: using
>Netscape, Mosaic, etc.
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>To unsubscribe from this list, send the message UNSUBSCRIBE ECHET96 to

Dear Professor Coldham:

Thank you for your comments. Obviously, the reaction of benzyl bromide with
the lithio-pyrrolidine to give the product having retention of
configuration was a surprise. (Actually, I didn't believe it - so Silvio
actually did an independent synthesis by a literature route to prove me
wrong!) We didn't have the result with the allyl bromide in time to include
in the paper, but the product is racemic. So the table in Scheme 4 may be
amended. This difference also suggests something unique about the benzyl
group (could it be Li coordination to the aromatic ring?).

Regarding your question about the coordination of electrophiles to the
lithium, I honestly don't know. A year ago, I thought I did (ref. 9). At
that time, I figured only carbonyl electrophiles coordinated to lithium,
and since they gave inversion, that alkyl halides did not. This benzyl
bromide result (with the N-allyl pyrrolidine) doesn't fit that scenario, so
there is more here than meets the eye. Regarding your suggestion about
reactivity, etc., there may be something to the aggregation business, but
experiments to clarify that have not been done yet. (Have you done any?)

We have some pretty good evidence that SET may play a role in these
reactions. (I had postulated that SET was the reason for obtention of
racemic products in ref. 9). If the N-methyl pyrrolidine is alkylated with
cyclopropylmethyl bromide, two alkylation products are formed: the
cyclopropylmethyl product and a (ring opened) 3-butenyl product. The ee of
the former is unknown but the latter is racemic. Thus a 'pseudo-allylic'
alkyl halide alkylates (at least partly) by SET. Also, addition of
benzophenone to the lithio-N-methyl pyrrolidine gives a blue color and the
benzophenone ketyl can be seen by ESR. So the oxidation potential of the
organolithium may be an important factor as well.

In short, there is an awful lot of detail that we just don't know! One
factor I didn't mention is the role of the nitrogen: I have a strong
suspicion (but no evidence other than crystal structure Boche did a couple
of years ago) that the lithium bridges both carbon and nitrogen. I think
that your suggestion about pi bonding to the lithium also has some merit.
Unraveling all of this should be fun. Please keep me posted on your own


Bob Gawley

Robert E. Gawley
Department of Chemistry
University of Miami
P. O. Box 249118
Coral Gables, Florida 33124-0431
Phone: 305-284-3279
FAX: 305-284-4571

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