C O M M U N I C A T I O N S
Scheme 1. Asymmetric Resolution of rac-1aa
Biologically Functional Molecules”, Basic Area (B) No. 14350473,
and The 21st Century COE Program from the Ministry of Education
Culture, Sports, Science and Technology, Japan.
Supporting Information Available: Experimental procedures and
spectral data. This material is available free of charge via the Internet
at http://pubs.acs.org.
References
(
1) Blomquist, A. T.; Liu, L. H.; Bohrer, J. C. J. Am. Chem. Soc. 1952, 74,
643-3647.
3
(2) For reviews, see: (a) Marshall, J. A. Acc. Chem. Res. 1980, 13, 213-
2
18. (b) Nakazaki, M.; Yamamoto, K.; Naemura, K. Top. Curr. Chem.
1
984, 125, 1-25. (c) Schl o¨ gl, K. Top. Curr. Chem. 1984, 125, 27-62.
(
d) Eliel, E. L.; Wilen, S. H.; Mander, L. N. In Stereochemistry of Organic
Compounds; Wiley: New York, 1994; pp 1172-1175.
a
(3) For representative studies on planar chiral cycloalkenes, see: (a) Cope,
Reagents and conditions: (a) (R,R)-8 (5 mol %), m-CPBA (2.0 equiv),
A. C.; Howell, C. F.; Knowles, A. J. Am. Chem. Soc. 1962, 84, 3190-
NMO, CH2Cl2, -78 °C; (b) (+)-Ipc2BH (1.2 equiv), THF, -50 to -10
3191. (b) Cope, A. C.; Ganellin, C. R.; Johnson, H. W., Jr. J. Am. Chem.
°
C; then NaO2H.
Soc. 1962, 84, 3191-3192. (c) Cope, A. C.; Mehta, A. S. J. Am. Chem.
Soc. 1964, 86, 5626-5630. (d) Cope, A. C.; Banholzer, K.; Keller, H.;
Pawson, B. A.; Whang, J. J.; Winkler, H. J. S. J. Am. Chem. Soc. 1965,
Scheme 2. Chirality Transmission of (R)-1aa
8
8
8
7, 3644-3649. (e) Cope, A. C.; Pawson, B. A. J. Am. Chem. Soc. 1965,
7, 3649-3651. (f) Binsch, G.; Roberts, J. D. J. Am. Chem. Soc. 1965,
7, 5157-5162. (g) Manor, P. C.; Shoemaker, D. P.; Parkes, A. S. J.
Am. Chem. Soc. 1970, 92, 5260-5262. (h) Marshall, J. A.; Konicek, T.
R.; Flynn, K. E. J. Am. Chem. Soc. 1980, 102, 3287-3288. (i) Inoue, Y.;
Matsushima, E.; Wada, T. J. Am. Chem. Soc. 1998, 120, 10687-10696.
(
j) Hoffmann, R.; Inoue, Y. J. Am. Chem. Soc. 1999, 121, 10702-10710
and references cited therein. Recently, chiral silacycloheptene has been
synthesized: (k) Krebs, A.; Pforr, K.-I.; Raffay, W.; Th o¨ lke, B.; K o¨ nig,
W. A.; Hardt, I.; Boese, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 159-
1
60. (l) Krebs, A.; Th o¨ lke, B.; Pforr, K.-I.; K o¨ nig, W. A.; Scharw a¨ chter,
K.; Grimme, S.; V o¨ gtle, F.; Sobanski, A.; Schramm, J.; Hormes, J.
Tetrahedron: Asymmetry, 1999, 10, 3483-3492. For reactions involving
planar chiral cyclic intermediate, see: (m) Wharton, P. S.; Johnson, D.
W. J. Org. Chem. 1973, 38, 4117-4121. (n) Gauvreau, D.; Barriault, L.
J. Org. Chem. 2005, 70, 1382-1388.
(
4) For recent reports on planar chirality of medium-sized ring containing
central chirality, see: (a) Sudau, A.; M u¨ nch, W.; Nubbemeyer, U. J. Org.
Chem. 2000, 65, 1710-1720. (b) Nubbemeyer, U. Eur. J. Org. Chem.
2001, 1801-1816 and referencess cited therein. (c) Deiters, A.; M u¨ ck-
Lichtenfeld, C.; Fr o¨ hlich, R.; Hoppe, D. Chem.sEur. J. 2002, 8, 1833-
a
Reagents and conditions: (a) dimethyldioxirane, acetone-CH2Cl2, 0 °C,
9
1%; (b) 9-BBN, THF, reflux, then NaO2H, 68%; (c) tBuLi, TMEDA,
1842.
hexane, -78 °C to rt, 78%; (d) PdCl2(PhCN)2 (cat.), CH2Cl2, rt, 82%.
(
5) (a) Tomooka, K.; Komine, N.; Nakai, T. Tetrahedron Lett. 1998, 39,
5
513-5516. (b) Tomooka, K.; Yamamoto, K.; Nakai, T. Angew. Chem.,
With these promising results in hand, next we examined the
kinetic resolution of rac-1a with asymmetric epoxidation and
hydroboration. The epoxidation with chiral (salen)Mn(III) complex
Int. Ed. 1999, 38, 3741-3743. (c) Tomooka, K.; Wang, L. F.; Okazaki,
F.; Nakai, T. Tetrahedron Lett. 2000, 41, 6121-6125.
(
6) Marshall, J. A.; Lebreton, J. J. Org. Chem. 1988, 53, 4108-4112.
(7) Ether 1a was prepared from neryl acetate in four steps by a slight
modification of the procedure described by Marshall (ref 6); see the
Supporting Information.
1
7
8
afforded enantioenriched (S)-1a (70% ee) in 24% yield along
15
with an epoxide (3S,4S)-4 (68% ee, 41% yield) (Scheme 1).
Moreover, asymmetric hydroboration using (+)-Ipc
(8) The enantiopurities were determined by chiral HPLC analysis (for 1a,
1
BH (1.2 equiv)18
1b, 4, and 9) or H NMR analysis of MTPA ester (for 3a, 3b, and 7).
2
(
9) The absolute stereochemistry of (R,R)-3a was assigned by the optical
rotation of isopiperitenone, which was derived by oxidation with MnO2.
See: Anglea, T. A.; Pinder, A. R. Tetrahedron 1987, 43, 5537-5543.
in THF afforded the almost enantiopure (R)-1a (>98% ee) in 43%
yield along with an alcohol (3S,4R)-7 (89% ee) in 50% yield.
Enantioenriched 1a thus obtained is valuable as a novel type of
chiral building block. As shown in Scheme 2, (R)-1a (93% ee) can
transform to enantioenriched central chiral compounds using achiral
reagents. The epoxidation with dimethyldioxirane and the hydrobo-
ration with 9-BBN provide epoxide (3S,4S)-4 (93% ee) and alcohol
(
10) It is worth noting that Marshall and Lebreton recognized the possibility
of chirality of 1a, but measured no optical activity in the recovered material
(
10% yield) upon chiral base-promoted [2,3]-Wittig rearrangement.
(
11) Only a trace amount of racemization (<1%) was detected by chiral HPLC
analysis, when it was maintained at 25 °C in hexane for 2 weeks.
(
12) Conformational analysis of ether 1a was carried out with the MacroModel
8
.0 package and PC Spartan Pro 1.0.5. Conformational search was
performed with the Mixed MCMM/LowMode method (5000 structures)
using the MM2* force field. Further geometry optimization and the
potential energy calculation of the most stable conformers were performed
by PM3 calculation using Spartan.
(3R,4S)-7 (93% ee), respectively. Furthermore, transannular reac-
tions, such as the [2,3]-Wittig rearrangement and Pd(II)-catalyzed
19
Cope rearrangement, also proceed in a stereospecific manner,
(13) To determine the configurational stability of 1a, we carried out variable
1
temperature H NMR analyses. Significantly, no appreciable change in
which provide alcohol (R,R)-3a (93% ee) and cyclic ether (3R,4S)-9
peak shape and width was observed up to 110 °C, while at around 80 °C,
1a began to undergo the Cope rearrangement.
(93% ee), respectively. These reactions are rare examples of planar
(
14) The absolute stereochemistry of (R,R)-3b was determined by the modified
Mosher’s method. See: Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa,
H. J. Am. Chem. Soc. 1991, 113, 4092-4096.
chirality to central chirality transmission.
In summary, we have described a discovery of the first example
of a purely planar chiral cyclic ether and its chirality transformation.
These new classes of planar chiral heterocyclic compounds are
potentially useful as a novel type of chiral building block, chiral
ligand, and a key component of chiral reagents. Further work is in
progress to expand the planar chirality concept to other heterocyclic
molecules.
(
15) The absolute stereochemistry of 4, 7, and 9 was deduced from the
configuration of 1a and the steric course of the reactions.
(16) The structure of 6 was determined by X-ray crystallography; see the
Supporting Information. It is worth noting that the nine-membered carbon
framework of the X-ray crystal structure of diepoxide 6 is found to be
superimposable to the framework of the calculated conformation of ether
1a. It shows the validity of the proposed conformation of 1a.
(
(
(
17) Palucki, M.; McCormick, G. J.; Jacobsen, E. N. Tetrahedron Lett. 1995,
36, 5457-5460.
18) Brown, H. C.; Desai, M. C.; Jadhav, P. K. J. Org. Chem. 1982, 47, 5065-
Acknowledgment. This research was supported in part by a
Grant-in-Aid for Scientific Research on Priority Areas (A) “Ex-
ploitation of Multi-Element Cyclic Molecules” and “Creation of
5069.
19) Overman, L. E.; Renaldo, A. F. Tetrahedron Lett. 1983, 24, 3757-3760.
JA053347G
J. AM. CHEM. SOC.
9
VOL. 127, NO. 35, 2005 12183