LETTER
Enantioselective Synthesis of Cyclohexenylalkenes by Asymmetric Deprotonation
1295
tuting two complementary options. In the latter case, reac-
tion was successfully adapted to the synthesis of chiral
functionalized dienes 6 using one-pot nonaflation-Heck
coupling protocol. We currently investigate whether the
described method is generally applicable to plane-sym-
metrical cyclic ketones. The resulting enantiomerically
highly enriched dienes should be very useful chiral build-
ing blocks for cycloadditions, Michael reactions or other
additions to the 1,3-diene system.
544. As a chiral induction in nonaflation or Heck-coupling
step seems to be very unlikely, we infer the enantiomeric
excess of 3 (at least 89%) from that of the product 6a.
(
10) The quality of n-Bu NF is essential to achieve good yields in
4
the transformation of trimethylsilyl enol ethers into enol
nonaflates. To this end, we applied drying of the commercially
available solutions with freshly activated molecular sieves
4 Å (M. Webel, Dissertation, Technische Universität Dresden
2000) or used n-Bu NF solution in the presence of thoroughly
4
dried KF powder (I. M. Lyapkalo, H.-U. Reissig, M. Webel,
Eur. J. Org. Chem. 2001, submitted for publication).
(
(
11) The kinetic deprotonation was performed as described in
3
e
Acknowledgement
Ref. followed by addition of the neat NfF at -105 °C for 10
min and gradual warming up to ambient temperature
overnight.
Generous support by the Deutsche Forschungsgemeinschaft, the
Alexander von Humboldt Foundation (research fellowship for
I. M. L.) and the Fonds der Chemischen Industrie is most gratefully
acknowledged. We thank Prof. H. Moretto (Bayer AG, Leverkusen)
for generous donations of nonafluorobutanesulfonyl fluoride.
12) Enol nonaflates have occasionally been shown to be very
efficient components in Heck coupling reactions, for example,
see: (a) S. Bräse, A. de Meijere, Angew. Chem. 1995, 107,
2741 2743; Angew. Chem. Int. Ed. Engl. 1995, 34, 2545.
(
b) S. Bräse, Synlett 1999, 1654 1656. We applied the
1
0
conditions as described previously by us (Ref. )
References and Notes
(13) A good consistency in the optical rotatory power magnitudes
of both samples was observed: [ ] = -111.2 and -109.5 (both
c = 1.20, CHCl3).
14) We failed to observe separate NMR signals of the
(
1) R. Shirai, M. Tanaka, K. Koga, J. Am. Chem. Soc. 1986, 108,
43 545.
2) Reviews: (a) P. J. Cox, N. S. Simpkins, Tetrahedron:
Asymmetry 1991, 2, 1 25. (b) K. Koga, Pure Appl. Chem.
D
5
(
(
diastereomers prepared by LiAlH reduction of
4
enantiomerically enriched 6a followed by acylation of the
resultant alcohol with Mosher’s chloride.
1994, 66, 1487 1492. (c) P. O’Brien, J. Chem. Soc., Perkin
Trans. 1 1998, 1439 1457 and references cited therein.
3) (a) H. Izawa, R. Shirai, H. Kawasaki, H.-d. Kim, K. Koga,
Tetrahedron Lett. 1989, 30, 7221 7224. (b) J. Leonard, D.
Ouali, S. K. Rahman, Tetrahedron Lett. 1990, 31, 739 742.
(
(
15) M. Webel, H.-U. Reissig, Synlett 1997, 1141 1142.
16) Typical procedure 3 6a: Thoroughly ground potassium
fluoride (0.100 g, 1.72 mmol) was dried at 210 220 ºC (0.03
mbar) for 1 h (kugelrohr apparatus), allowed to cool to r.t., and
(
(
3
c) M. Majewski, R. Lazhny, Tetrahedron Lett. 1994, 35,
653 3656. (d) T. Momose, M. Toshima, N. Toyooka, Y.
Hirai, C. H. Eugster, J. Chem. Soc., Perkin Trans. 1 1997,
307 1313. (e) I. Vaulont, H.-J. Gais, N. Reuter, E. Schmitz,
THF (0.50 ml) and 1.05 M n-Bu NF in THF (0.05 mL, 0.05
4
1
0
mmol) were subsequently added (see Ref. ). The resulting
suspension was vigorously stirred at r.t. for 20 min under Ar-
atmosphere before cooling to -78 ºC. (S)-3 (0.226 g, 1.00
mmol, 89% ee) and NfF (0.363 g, 1.20 mmol) were
1
R. K. L. Ossenkamp, Eur. J. Org. Chem. 1998, 805 826.
1
,3a,d
(
(
4) The reaction was successfully developed in both internal
and successive3e quenching modes, most commonly with
subsequently added at -78 ºC. The mixture was then gradually
warmed up to r.t. and stirred overnight (15 17 h). To the
resulting solution containing (S)-4, were subsequently added
R SiCl.
3
5) The configuration of the stereogenic center was assigned as
S) by analogy with the silyl enol ether 3 whose absolute
LiCl (0.15 g, 3.50 mmol), Et N (0.36 g, 3.50 mmol), Pd(OAc)
(
3
2
1
(11 mg, 0.05 mmol), DMF (1.5 mL) and methyl acrylate
configuration was strictly determined to be (S), see Ref.
6) E. Hirsch, S. Hünig, H.-U. Reissig, Chem. Ber 1982, 115,
(
0.129 g, 1.50 mmol). The reaction flask was then flushed with
(
(
1
5
argon for 2 3 min, tightly closed again and heated with
vigorous stirring at 73 75 ºC (bath temperature) for 3 h.
Aqueous workup, hexane extraction followed by column
3
687 3696. Also see Ref.
7) K. Sugasawa, M. Shindo, H. Noguchi, K. Koga, Tetrahedron
Lett. 1996, 37, 7377 7380. A successive quenching with
3
e
chromatography (gradient elution: hexane hexane/Et O
Me SiCl as described in Ref. was applied.
2
3
20:1) provided (S)-6a (189 mg, 85% yield. 89% ee) as
(
8) This workup results in clean separation of (R,R’)-bis(1-
phenylethyl)amine from the silyl enol ether 3. An addition of
excess of KOH to the aqueous phase followed by extraction
with hexane allows quantitative recovery of the enantiopure
amine.
colourless crystals, mp 43 46 °C, [ ] = -109.3 (c = 1.18,
D
1
3
CHCl ) (cf. Ref. ). For analytical data of rac-6a see:
3
W. J. Scott, M. R. Peña, K. Swärd, S. J. Stoessel, J. K. Stille,
J. Org. Chem. 1985, 50, 2302 2308.
(
9) Optical rotation: [ ]365 = -209.6, [ ] = -65.7 (c = 1.22 in
D
C H ), 89% ee. There is some divergence between optical
6
6
Article Identifier:
1437-2096,E;2001,0,08,1293,1295,ftx,en;G11101ST.pdf
rotatory power magnitudes reported for enantiomerically pure
1
3
, for details see Ref. and C. M. Cain, R. P. C. Cousins, G.
Coumbarides, N. S. Simpkins, Tetrahedron 1990, 46, 523
Synlett 2001, No. 8, 1293–1295 ISSN 0936-5214 © Thieme Stuttgart · New York