Tow a r d th e Develop m en t of a Str u ctu r a lly Novel Cla ss of Ch ir a l
Au xilia r ies. Con for m a tion a l P r op er ties of th e Ald ol Ad d u cts of
Oxa d ia zin on es: Obser va tion of Un u su a l Sh ield in g Effects†
J ames R. Burgeson,‡ Matthew K. Renner,§ Ingo Hardt,§ Gregory M. Ferrence,‡
J ean M. Standard,*,‡ and Shawn R. Hitchcock*,‡
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, and
Pfizer Global Research, 3565 General Atomics Court, San Diego, California 92121
hitchcock@xenon.che.ilstu.edu
Received October 9, 2003
Asymmetric aldol reactions were conducted with the titanium enolate of N3-hydrocinnamoyl-3,4,5,6-
tetrahydro-2H-1,3,4-oxadiazin-2-one to afford aldol adducts 5a -j. The dominant product of the
1
asymmetric aldol reaction was the non-Evans syn adduct as determined by H NMR spectroscopy
and X-ray crystallography. When evaluating the 1H NMR spectra of adducts 5a -j, a highly shielded
signal with an average chemical shift of 0.05 ppm was observed. This signal was readily determined
to be the C5-methyl group of the oxadiazinone. It is presumed that the overall conformation adopted
by the aldol adducts in solution places an aromatic ring of the N3-substituent in close proximity to
the C5-methyl group. An investigation of this conformational preference is conducted employing
1H NMR spectroscopy, X-ray crystallography, and computational methods.
In tr od u ction
The asymmetric aldol addition reaction continues to
be a synthetic process of great interest.1 This is primarily
due to the fact that the aldol reaction can be manipulated
to generate either syn or anti adducts,2,3 which are
valuable intermediates in the synthesis of many natural
products. A great variety of methods have emerged over
the last 25 years that are capable of achieving high
selectivities for one isomer or another. These methods
include the use of stoichiometric chiral auxiliaries and
substoichiometric asymmetric catalysts.4 Catalytic meth-
ods are proving to be very effective, but chiral auxiliaries
F IGURE 1. Oxadiazinones as chiral auxiliaries.
† Part of this work was presented at the 225th National Meeting of
the American Chemical Society, New Orleans, LA, March 23-27, 2003;
Abstract No. 450-ORGN (J .R.B.).
still remain as a viable means for obtaining chiral,
nonracemic aldol adducts. We have recently reported on
the application of a (1R,2S)-ephedrine-based 3,4,5,6-
tetrahydro-2H-1,3,4-oxadiazin-2-one (oxadiazinone) as a
chiral auxiliary in the titanium-mediated asymmetric
aldol addition reaction (Figure 1).5
‡ Illinois State University.
§ Pfizer Global Research.
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10.1021/jo035481u CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/09/2004
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