C O M M U N I C A T I O N S
Table 2. Asymmetric [2,3]-Sigmatropic Rearrangement of Amines
is dictated by the chiral ligand. Attempts to verify this reaction
pathway by subjecting complexes C and D to D2O before workup
resulted in no deuterium incorporation, the reason for which we
are currently favoring the mechanism outlined in Scheme 3.
1a
ee (%)d
entry
amine
yield (%)b
anti:sync
anti:syn
1
2
3
4
5
6
7
8
9
1b
1c
1d
1e
1f
1g
1h
1ii
1j
3b/82
3c/85
3d/70
3e/71
3f/52
h
3h/92
3i/65j
3j/64
3k/80
79:21
20:80
88:12f
29:71f
95:5f
96 (2R,3R):75 (2R,3S)e
82 (2R,3R):98 (2R,3S)e
93:n.d.f,g
98:99f
99:n.d.f,g
67:33
30:70
97:77f
94:88f
96f
In conclusion, we have developed the first asymmetric Lewis
acid-mediated [2,3]-sigmatropic rearrangement of allylic ammonium
ylides. We are currently investigating the scope of this transforma-
tion as well as its application in total synthesis, and the results will
be presented in due course.
10
1k
99f
a For experimental conditions, see Supporting Information. b Isolated
yield of diastereomeric mixture. c Determined by 1H NMR analysis of the
crude product. d For determination of enantiomeric excess, see Supporting
Information. e The absolute configuration was established via chemical
correlation; see Supporting Information. f Stereochemistry assigned by
analogy with the rearrangements of 1b. g n.d. ) not determined. h Gave 5
in 72% yield and 61% ee. i E:Z 1:10, reaction run at -20 °C. j With 14%
recovered starting material.
Acknowledgment. This work was supported financially by the
Swedish Research Council and the Knut and Alice Wallenberg
foundation. We are grateful to Dr. T. Privalov for ab initio
calculations.
Scheme 3. Kinetically Controlled Stereoselection in the
Rearrangement of 1b
Supporting Information Available: Experimental procedures, data
for new compounds, and computational details. This material is
References
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(2R,3R)-anti-3b (R1 ) Me). Reaction of B is disfavored due to
steric interactions between the allyl moiety and the adjacent N-Ts
group, and B will thus isomerize to A followed by rearrangement.13
In this scenario, (2R,3S)-syn-3b is formed from the endo complex
corresponding to A, which should experience a destabilizing
interaction between the internal vinylic C-H moiety and the
proximal sulfonamide moiety, thus accounting for the observed anti:
syn-selectivity. This also explains the results with 1g; both the exo
and endo complexes corresponding to A will experience severe
steric interactions, and consequently, the [1,2]-rearrangement af-
fording 5 becomes the favored pathway.
In contrast to this kinetically controlled stereoselection, a
thermodynamic pathway can be envisioned. Formation of A and B
followed by rearrangement will give oxazaborolidines C and D,
respectively. Of these, C is thermodynamically favored, and its
hydrolysis will give (2R,3R)-anti-3b (R1 ) Me).14 Equilibration of
D under the basic reaction conditions results in E that after work
up will afford (2R,3S)-syn-3b (R1 ) Me). In this scenario, the anti:
syn-selectivity is controlled by the initial rate for the formation of
A and B, while the absolute stereochemistry at C2 in the product
(5) Workman, J. A.; Garrido, N. P.; Sanc¸on, J.; Roberts, E.; Wessel, H. P.;
Sweeney, J. B. J. Am. Chem. Soc. 2005, 127, 1066-1067.
(6) Blid, J.; Brandt, P.; Somfai, P. J. Org. Chem. 2004, 69, 3043-3049.
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Kessar, S. V.; Singh, P.; Kaul, V. K.; Kumar, G. Tetrahedron Lett. 1995,
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(9) Care must be taken in order to exclude the formed HBr; see Supporting
Information.
(10) The ligand could be recovered almost quantitatively; see Supporting
Information.
(11) Other solvents (Et2O, THF, or PhMe) did not improve the yield or
enantiomeric excess.
(12) The corresponding endo complexes are omitted for clarity.
(13) Equilibration of diastereomeric oxazaborolidines has been described
previously, see: Vedejs, E.; Fields, S. C.; Lin, S.; Schrimpf, M. R. J.
Org. Chem. 1995, 60, 3028-3034. Equilibration before deprotonation and
rearrangement can also be envisioned.
(14) Oxazaborolidine C (R1 ) H) is 10 kcal/mol more stable than D (R1 ) H)
at the B3LYP/6-31G* level of calculation. For computational details, see
Supporting Information.
JA0510562
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J. AM. CHEM. SOC. VOL. 127, NO. 26, 2005 9353