J. Am. Chem. Soc. 1998, 120, 8551-8552
8551
Scheme 1. [1,2]-Wittig Rearrangement Where Chelation Sets
Stereospecificity of the 1,2-Wittig Rearrangement:
How Chelation Effects Influence Stereochemical
Outcome
the Stereochemistry of the Newly Formed Alcohol3
Robert E. Maleczka, Jr.,* and Feng Geng
Department of Chemistry
Michigan State UniVersity
East Lansing, Michigan 48824
ReceiVed May 18, 1998
Scheme 2. [1,2]-Wittig Rearrangement with “Normal”
Since its discovery the rearrangement of R-metalated ethers,
particularly the [2,3]-Wittig rearrangement, has been the subject
of intensive mechanistic and synthetic investigations.1 Relative
to the [2,3]-shift, the [1,2]-Wittig rearrangement has received
relatively little publicity. Most studies of the [1,2]-Wittig have
been mechanistic in origin, resulting in the widely accepted theory
that the reaction proceeds via a radical pair dissociation-
recombination mechanism.2
Inversion of Configuration at the Metal Terminus6
Several years ago, Schreiber3 reported an important observation
on the stereospecific nature of this rearrangement (Scheme 1).
Deprotonation of 1 resulted in “synthetically useful levels” of
the [1,2]-rearrangement product that was heavily biased toward
the syn isomer 3. Schreiber postulated that the product arose
from bond reorganization via a diradical transition state in which
a lithium tether 2 sets up the syn stereochemistry. Another
surprising feature of this rearrangement was the high level of
retention (94%) at the migrating center.
Scheme 3
This observation became more interesting upon Cohen’s4 and
Bru¨ckner’s5 recent evidence that [1,2]-Wittig rearrangements
proceeded with inversion of the lithium-bearing terminus. Nakai6
addressed this question and showed clearly that the [1,2]-Wittig
rearrangement of enantiodefined R-alkoxylithium species proceeds
with retention of the migrating center and with inversion of the
lithium-bearing terminus (Scheme 2). In these examples, the
stereochemistry of the product alcohols is not the result of
chelation control, but rather decided by the configuration of the
stannane precursor.
Scheme 4
While there is little argument with either mechanistic explana-
tion for the observed stereochemistries, it is important to note
that the enantiodefined stannanes studied by Nakai did not hold
the possibility of rearrangement under chelation control.7 We
found it intriguing to consider substrates with an ether oxygen
capable of coordinating with the lithium of the stereodefined
lithium terminus. In such substrates the appropriate stereochem-
ical combination could put Schreiber’s mechanism in stereo-
chemical conflict with the results of Nakai, Cohen, and Bru¨ckner
(Scheme 3). We therefore sought to prepare and study such
substrates to provide a deeper understanding of the [1,2]-Wittig
rearrangement. We believed that knowledge of the stereochemical
influences imparted by these two mechanistic pathways would
allow the discovery of new reaction conditions which should
enable the practitioner to predict and control the stereochemical
course of the [1,2]-Wittig rearrangement. Such reaction control
would be of considerable value as it would represent a means
for the selective construction of either syn- or anti-1,3 polyols,
via a common reaction manifold.
Our preliminary experiments began with the preparation of the
enantiodefined stannanes 6, 9, 10, and 11. The syntheses of these
compounds paralleled established procedures8 and involved the
displacement of the known enantiodefined stannyl mesylates9 (R)-
13 and (S)-13 by the alkoxides of erythro and threo forms of
1-C-phenyl-2,3-O-isopropylidene-D-glycerol10 (Scheme 4). This
method provided the desired stannanes in 87% yield and in greater
(1) (a) Nakai, T.; Mikami, K. Chem. ReV. 1986, 86, 885-902. (b) Marshal,
J. A. In ComprehensiVe Organic Synthesis; Pattenden, G., Ed.; Pergamon:
London, 1991; Vol. 3, pp 975-1014.
(2) (a) Scha¨fer, H.; Scho¨llkopf, U.; Walter, D. Tetrahedron Lett. 1968,
2809-2814, and references therein. (b) Evans, D. A.; Baillargeon, D. J.
Tetrahedron Lett. 1978, 3315, 3315-3322. (c) Azzena, U.; Denurra, T.;
Melloni, G.; Piroddi, A. M. J. Org. Chem. 1990, 55, 5532-5535. (d) Tomooka,
K.; Yamamoto, H.; Nakai, T. J. Am. Chem. Soc. 1996, 118, 3317-3318. (e)
Tomooka, K.; Yamamoto, H.; Nakai, T. Liebigs Ann. Chem. 1997, 1275-
1281.
1
than 95% de as judged by the H NMR.
Once model compounds 6, 9, 10, and 11 were in hand, the
[1,2]-Wittig rearrangement reaction was investigated. Compound
6 was first exposed to n-BuLi in 30% THF/hexanes, the same
solvent system employed by Schreiber. The reaction gave a 64%
(3) (a) Schreiber. S. L.; Goulet, M. T. Tetrahedron Lett. 1987, 28, 1043-
1046. (b) Goulet, M. T. Ph.D. Thesis, Yale University, 1988.
(4) Verner, E. J.; Cohen, T. J. Am. Chem. Soc. 1992, 114, 375-377.
(5) Hoffmann, R.; Bru¨ckner, R. Chem Ber. 1992, 125, 1957-1963.
(6) (a) Tomooka, K.; Igarashi, T.; Nakai, T. Tetrahedron Lett. 1993, 34,
8139-8142. (b) Tomooka, K.; Igarashi, T.; Nakai, T. Tetrahedron 1994, 50,
5927-5932.
(8) Tomooka, K.; Igarashi, T.; Watanabe, M.; Nakai, T. Tetrahedron Lett.
1992, 33, 5795-5798.
(9) Matteson, D. S.; Tripathy, P. B.; Sarkar, A.; Sadhu, K. M. J. Am. Chem.
Soc. 1989, 111, 4399-4402 and references therein.
(10) (a) Ohgo, Y.; Yoshimura, J.; Kono, M.; Sato, T. Bull. Chem. Soc.
Jpn. 1969, 42, 2957-2961. (b) Mulzer, J.; Angermann, A. Tetrahedron Lett.
1983, 24, 2843-2846.
(7) Nakai has reported chelation-controlled rearrangements of racemic lithio
species (see ref 2e).
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