ORGANIC
LETTERS
1999
Vol. 1, No. 1
31-33
Chirality Transfer from Carbon to
Nitrogen to Carbon via Cyclic
Ammonium Ylides
Kevin W. Glaeske and F. G. West*
Department of Chemistry, UniVersity of Utah, 315 South 1400 East, Rm. Dock,
Salt Lake City, Utah 84112-0850
Received March 22, 1999
ABSTRACT
Cyclic ammonium salts 2 were prepared by diastereoselective quaternization of nitrogen in the corresponding proline or threonine derivatives.
Upon treatment with base, salts 2 underwent [1,2]- or [2,3]-shift to 3 with moderate to complete stereospecificity. The overall process entails
chirality transfer from the original r carbon to the neighboring nitrogen and then back to the carbon.
Chirality transfer from carbon to carbon via sigmatropic
rearrangements is a well-established approach in asymmetric
synthesis.1 However, transfer of stereochemical information
from a chiral heteroatom to carbon is much less common.
While sulfur ylides have enjoyed considerable attention in
this area,2 several examples involving base-induced rear-
rangements of chiral quaternary ammonium salts also have
been reported.3 Our observation of high levels of stereose-
lectivity in the rearrangement of a metallocarbene-derived
spirocyclic ammonium ylide,4 along with those of Clark5 and
McMills,6 prompted our interest in exploring N f C chirality
transfer under more controlled conditions. In particular, we
were interested in forming a quaternary ammonium salt of
known configuration before generating the short-lived ylide.
Here we describe preliminary results of chirality transfer by
[1,2]- or [2,3]-shift of several cyclic ammonium ylides
stereogenic at nitrogen.
We chose to limit our initial focus to cyclic ylides with
exocyclic migrating groups, since these cases seemed most
likely to preserve the stereochemical information during
migration from N to C. We envisaged fast recombination of
(1) (a) Hill, R. K. In ComrehensiVe Organic Synthesis; Trost, B. M.,
Fleming, Eds.; Pergamon: Oxford, 1991; Vol. 5, Chapter 7.1. (b) Bru¨ckner,
R. In ComrehensiVe Organic Synthesis; Trost, B. M., Fleming, Eds.;
Pergamon: Oxford, 1991; Vol. 6, Chapter 4.6.
(6) Wright, D. L.; Weekly, R. M.; Groff, R.; McMills, M. C. Tetrahedron
Lett. 1996, 37, 2165.
(2) (a) Trost, B. M.; Hammen, R. F. J. Am. Chem. Soc. 1973, 95, 962.
(b) Kurth, M. J.; Hasan, T. S.; Olmstead, M. M. J. Org. Chem. 1990, 55,
2286. (c) Cagle, P. C.; Arif, A. M.; Gladysz, J. A. J. Am. Chem. Soc. 1994,
116, 3655.
(3) (a) Hill, R. K.; Chan, T.-H. J. Am. Chem. Soc. 1966, 88, 866. (b)
Brewster, J. H.; Jones, R. S., Jr. J. Org. Chem. 1969, 34, 354. (c) Hiroi,
K.; Nakazawa, K. Chem. Lett. 1980, 1077. (d) Stara´, I. G.; Star’y, I.; Tich’y,
M.; Za´vada, J.; Hanus, V. J. Am. Chem. Soc. 1994, 116, 5084. For an
especially relevant study involving stereoselective [2,3]-shifts of configu-
rationally stable N-allyl-2-lithiopyrrolidines and -pyrrolidinium salts, see:
(e) Gawley, R. E.; Zhang, Q.; Campagna, S. J. Am. Chem. Soc. 1995, 117,
11817.
(7) Corey, E. J.; Link, J. O. J. Org. Chem. 1991, 56, 442.
(8) General Procedure for Salt Formation: Preparation of 2a. MeI (3.73
mL, 60 mmol) was added neat to 1a (6.57 g, 30 mmol), and the mixture
was stirred for 1 h. Excess MeI was removed under reduced pressure, and
the brown residue (4:1 crude mixture of diastereomers) was dissolved in
CH2Cl2 (150 mL) and layered with Et2O (200 mL). Three recrystallizations
(CH2Cl2/Et2O) provided 8.37 g (77%) of 2a as white needles: mp 140-
141 °C; [R]22D ) -41.9° (c ) 0.25, CH2Cl2); IR (KBr) 2976, 1757, 1446
1
cm-1; H NMR (CDCl3, 300 MHz) δ 7.63-7.59 (m, 2H), 7.54-7.44 (m,
3H), 5.46 (dd, 1H, J ) 9.0, 9.0 Hz), 5.35 (d, 1H, JAB ) 12.9 Hz), 5.09 (d,
1H, JAB ) 12.9 Hz), 4.54 (app. q, 1H, J ) 10.8 Hz), 3.85 (s, 3H), 3.43
(ddd, 1H, J ) 10.5, 8.1, 1.8 Hz), 3.16 (s, 3H), 2.83-2.70 (m, 1H), 2.50-
2.12 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ 167.2, 133.7, 131.5, 130.0,
128.9, 72.1, 66.8, 64.9, 54.3, 45.3, 25.0, 19.1. Anal. Calcd for C14H20-
INO2: C, 46.55; H, 5.58; N, 3.88. Found: C, 46.64; H, 5.59; N, 3.85.
(4) (a) West, F. G.; Naidu, B. N. J. Am. Chem. Soc. 1994, 116, 8420.
(b) Naidu, B. N.; West, F. G. Tetrahedron 1997, 53, 16565.
(5) Clark, J. S.; Hodgson, P. B. Tetrahedron Lett. 1995, 36, 2519.
10.1021/ol9905349 CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/17/1999