Reduction of adamantanone: Face selection induced by 4-Halo and 4,9-Dihalo substitution

Full text of DOI:10.1021/jo9601066

J . Org. Chem. 1996, 61, 4157-4160
4157
literature. Thus, McKervey5 reported that the sodium
borohydride reduction of 1-Br gives exclusively
4-Brssurely a consequence of the size of the bromine
atom. The same group also reported6 that the reduction
of 1-OH with lithium aluminum hydride yields coaxial
4-OH in a 19:1 excess over isomer 5-OH; both H-bonding
and the size of the 4-hydroxy group may have contributed
to this result. More pertinent to our present purpose is
the fact that the same reduction of adamantane-2,4-dione
(3) gave 4-OH, 5-OH, and 7-OH in a ratio of 45:39:16,
respectively (note that 5- and 6-X are identical when X
is OH). From these data, one can readily calculate that
in this reduction 3 must initially have given 2-X and 1-X
in the surprisingly modest ratio of 53:47, respectively,
and even more startling, that 2-OH must give 5-X in
excess over 7-X by a margin of 70:30. Evidently, an
equatorial 4-hydroxy substituent does not direct this
nucleophile to the zu face at C-2, and even a carbonyl
group at C-4 can only barely manage this. Duddeck
published one report7 that 2-F with zinc borohydride gave
6-F and 7-F in a 2:1 ratio and another8 mentioning a 2:3
ratio (the latter paper also reported a 2:1 ratio for 4-F
and 5-F from 1-F). The solvolyses of various sulfonate
esters of 4-7-X has been studied by Grob, and his work
provided an additional motive for the study reported
herein: the effect of equatorial 4-substituents on the
solvolysis rate of both syn- and anti-2-sulfonate esters is
even smaller than that of 5-substituents. This finding
led Grob to question our interpretation that hypercon-
jugation is responsible for the effect of 5-substituents.9
Red u ction of Ad a m a n ta n on e: F a ce
Selection In d u ced by 4-Ha lo a n d 4,9-Dih a lo
Su bstitu tion
Mira Kaselj and William J . le Noble*
Department of Chemistry, State University of New York,
Stony Brook, New York 11794
Received J anuary 17, 1996
Our studies1 of the stereochemistry of addition and
elimination as well as those of several other groups2 have
been based largely on the reactions of 2-adamantylidenes
bearing substituents in the 5- and/or 7-positions.3 In
these probes, the two faces at C-2 are thereby rendered
electronically different while steric equivalence is main-
tained. We find that attack of all reagents at C-2 occurs
at the zu face if an electron-withdrawing substituent is
located at C-5, while we interpret as an indication that
transition state hyperconjugation4 controls the stereo-
chemistry. Since the product or rate ratios are usually
rather modest, the though arose that, perhaps, substan-
tially more robust effects might be expected from sub-
stituents located at C-4 and C-9. In the axial positions
of these secondary carbons, substituents will clearly
influence face selection at C-2 sterically, but in the
equatorial ones, they should not.
There are a few scattered data on nucleophilic addition
to 4-substituted adamantanones 1-X, 2-X, and 3 in the
(1) First observation: le Noble, W. J .; Chiou, D.-M.; Okaya, Y.
Tetrahedron Lett. 1978, 1961. Recent examples: (a) Kaselj, M.; Adcock,
J . L.; Luo, H.; Zhang, H.; Li.H.; le Noble, W. J . J . Am. Chem. Soc.
1995, 117, 7088. (b) Lau, J .; Gonikberg, E. M.; Hung, J .-t.; le Noble,
W. J . J . Am. Chem. Soc. 1995, 117, 11421. (c) Gonikberg, E. M.; le
Noble, W. J . J . Org. Chem. 1995, 60, 7751.
(2) (a) Tabushi, I.; Aoyama, Y. J . Org. Chem. 1973, 38, 3447. (b)
Dekkers, A. W. J . D.; Verhoeven, J . W. Tetrahedron 1973, 29, 1691.
(c) Bone, J . A.; Pritt, J . R.; Whiting, M. C. J . Chem. Soc., Perkin Trans.
2 1975, 1447. (d) Grob, C. A.; Bolleter, M.; Kunz, W. Angew. Chem.,
Int. Ed. Engl. 1980, 19, 708. (e) Lantvoev, V. I. Russ. J . Org. Chem.
(Engl. Transl.) 1980, 16, 1409. (f) Hummelen, J . C. Thesis, University
of Groningen, 1985, p 86. (g) Nelsen, S. F.; Kapp, D. L.; Akaba, R.;
Evans, D. H. J . Am. Chem. Soc. 1986, 108, 6863. (h) Finne, E. S.;
Gunn, J . R.; Sorensen, T. S. J . Am. Chem. Soc. 1987, 109, 7811. (i)
Laube, T.; Stilz, H. U. J . Am. Chem. Soc. 1987, 109, 5876. (j)
Fukunishi, K.; Kohno, A.; Kojo, S. J . Org. Chem. 1988, 53, 4369. (k)
Fernandez, M. J .; Galvez, E.; Lorente, A.; Iriepa, I.; Soler, J . A. J .
Heterocycl. Chem. 1989, 26, 307. (l) Kovalev, V. V.; Rosov, A. K.;
Shokova, E. A.; Luzikov, Y. M.; Savel’ev, Y. I. Bull. Chem. Ser. USSR
(Engl. Transl.) 1988, 463. (m) Goncharov, A. V.; Panov, V. N.; Maleev,
A. A.; Potekhin, K. A.; Kurkutova, E. N.; Struchkov, Y. T.; Palulin, V.
A.; Zefirov, N. S. Doklady (Engl. Transl.) 1991, 318, 148. (n) Burgess,
K.; van der Donk, W. A.; J arstfer, M. B.; Ohlmeyer, M. J . J . Am. Chem.
Soc. 1991, 113, 6139. (o) J ohnson, R. A.; Herr, M. E.; Murray, M. C.;
Chidester, C. G.; Han, F. J . Org. Chem. 1992, 57, 7209. (p) Vinkovic,
V.; Mlinaric-Majerski, K.; Marinic, Z. Tetrahedron Lett. 1992, 33, 7441.
(q) Huang, X. L.; Dannenberg, J . J . J . Am. Chem. Soc. 1993, 115, 6017.
(r) Adcock, W.; Clark, C. I.; Trout, N. A. Tetrahedron Lett. 1994, 35,
297. (s) Huang, X.; Bennet, A. J . J . Chem. Soc., Perkin Trans. 2 1994,
1279. (t) Chung, W.-S.; Liu, Y.-D.; Wang, N.-J . J . Chem. Soc., Perkin
Trans. 2 1995, 581. (u) Herrman, R.; Kirmse, W. Liebigs Ann. Chem.
1995, 699.
A weak point in all of these observations and conclu-
sions is that an equatorial 4-substituent affects only one
of the four bonds vicinal and periplanar to the trigonal
center, whereas a 5-substituent equally influences two
of them. Furthermore, while a 5-substituent is well
aligned with these two vicinal bonds with a dihedral
angle of 180°, a 4-substituent is geminal to one of these
(i.e., with an angle of 109°). We felt that it would be
difficult to assess the relative weight of these two
arguments unless data could be produced with a 2,4,9-
trisubstituted system with the 4- and 9-substituents
(5) Cuddy, B. D.; Grant, D.; McKervey, M. A. J . Chem. Soc. C 1971,
3173.
(6) McKervey, M. A.; Faulkner, D.; Hamill, H. Tetrahedron Lett.
1970, 1971.
(7) Duddeck, H.; Islam, M. R. Tetrahedron 1981, 37, 1193.
(8) Duddeck, H.; Islam, M. R. J . Fluorine Chem. 1984, 25, 371.
Professor Duddeck has now privately informed us that the information
contained in ref 7 is correct, according to his original spectra and in
agreement with our own experiments.
(9) Grob, C. A.; Wang, G.; Yang, C. Tetrahedron Lett. 1987, 28, 1247.
See also: Yang, C.; Grob, C. A. 206th National Meeting of the American
Chemical Society, Chicago, IL, Fall 1993; Abstract ORGN 399.
(3) As in our previous papers, we have for the sake of convenience
named all compounds except 12 as numbered in the text. The terms
axial (ax) and equatorial (eq) refer to the six-membered ring defined
by C-1-5 and C-9.
(4) Cieplak, A. S. J . Am. Chem. Soc. 1981, 103, 4540.
S0022-3263(96)00106-5 CCC: $12.00 © 1996 American Chemical Society

4158 J . Org. Chem., Vol. 61, No. 12, 1996
Notes
Sch em e 1
F igu r e 1. ORTEP diagram showing the structure and con-
figuration of compound 12. The numbering refers to the tables
in the supporting information.
Ta ble 1. P r od u ct Distr ibu tion in th e Red u ction of 1, 2,
3, a n d 8
% product
reducing
compd
agenta
4-X 5-X 6-X 7-X Z-13 E-13
ref
b
3
LiAlH4
45 39
16
70
6
6
c
8
b
1-OH LiAlH4
2-OH LiAlH4
95
5
b
30
33 67
1-F
1-F
2-F
2-F
2-F
1-Br
1-Br
2-Br
8
Zn(BH4)2
NaBH4
100
0
this work
7
8
this work
6
this work
this work
this work
Zn(BH4)2
Zn(BH4)2
NaBH4
33 67
60 40
33 67
d
NaBH4
99
NaBH4
NaBH4
NaBH4
100
0
equatorial. No such substituted adamantanes were
known, however.10
24 76
14
86
We were able to obtain at least modest samples of 8
by means of a route employing a 2-fold application of the
Wynberg method of substituting a second proximal
secondary center in adamantanone.11 For purposes of
comparison, we also prepared samples of 1- and 2-Br and
of 1- and 2-F. The synthesis is outlined in Scheme 1 (the
attempted conversion of the unprotected dione 3 into the
corresponding monotosylhydrazone was not successful).
Three insertion products 9-11 are possible; all three
were obtained, and in the ratio of 1:1.5:1.8, respectively.
They were separated by means of column chromatogra-
phy. The assignment by means of 13C NMR was straight-
forward since the numbers of resonances are 9, 8, and
12, respectively. We note here in passing that 10 has
been described in its unprotected ketone form by Bald-
win.12 We also note that the bromination of 9 gave a fair
yield of dibromo lactone 12 via oxidative cleavage of one
of the ether linkages (a known process13); all four of the
a
All reactions are done in methanol at 0 °C unless otherwise
noted. In refluxing ether. c Calculated from data in ref 6. At
room temperature.
b
d
possible monobromo lactones had been reported by Dud-
deck.14 Lactone 12 does not form by bromination of 9:
the ether cleavage occurs first. The structure and
configuration of 12 were proven by means of an X-ray
diffraction experiment (see Figure 1).22 This byproduct
can be avoided by doing the hydrolysis first, but bromin-
ation of the 4,9-didehydroadamantanone so obtained then
also gives a substantial amount of the ax,eq isomer of 8.
The steric requirements of the ketal moiety are appar-
ently such that only the eq,eq isomer can form when the
bromination is done first.
The reductions were done with sodium borohydride in
methanol at 0 °C (Table 1). The product ratios were
determined by means of 1H NMR; the published H and
1
13C NMR spectra are in agreement with ours for both
the ketones 1-2-F and -Br6,7,15 and alcohols 4-7-F and
-Br.7,8,16-18 The assignments of (E)- and (Z)-13 were made
by means of the unseparated mixture; the addition of
Eu(fod)3 clearly resulted in a downfield shift of the CHBr
(10) The only 4,9-substituted adamantanone known is the 4-ax,9-
eq-dibromoadamantan-2-one obtained in 4% yield in the reaction of
hydrobromic acid with 7-ax-bromo-4-oxohomoadamantan-5-one: Dud-
deck, H.; Brosch, D. J . Org. Chem. 1985, 50, 5401.
(11) Udding, A. C.; Strating, J .; Wynberg, H. Tetrahedron Lett. 1968,
1345.
(12) Baldwin, J . E.; Fogelsong, W. D. J . Am. Chem. Soc. 1968, 90,
4303. See also: (b) Murray, R. K.; Morgan, T. K.; Babiak, K. A. J .
Org. Chem. 1975, 40, 1079. (c) Murray, R. K.; Morgan, T. K. J . Org.
Chem. 1975, 40, 2642. (d) Teager, D. S.; Murray, R. K. J . Org. Chem.
1993, 58, 5548.
(13) Deno, N. C.; Potter, N. H. J . Am. Chem. Soc. 1967, 89, 3550,
3555.
(14) Duddeck, H.; Kaiser, M. Z. Naturforsch. 1982, 37B, 1672.
(15) Snatzke, G.; Eckhardt, G. Chem. Ber. Bunsen Ges. 1968, 101,
2010.
(16) Duddeck, H.; Wolff, P. Org. Magn. Reson. 1977, 9, 528.
(17) Duddeck, H. Tetrahedron 1978, 34, 247.
(18) Farcasiu, D.; von R. Schleyer, P. Tetrahedron Lett. 1973, 3835.

Notes
J . Org. Chem., Vol. 61, No. 12, 1996 4159
chromatography (silica, 200-400 mesh; petroleum ether:acetone
) 10:1); the products were identified by 1H and 13C NMR.6,15
Reflux of a cyclohexane solution of a mixture of 1- and 2-Br with
silver fluoride gave a mixture of 1- and 2-F, which was likewise
separated by column chromatography, with the products again
being identified by means of their known NMR spectra.7,8,16-18
P r ep a r a tion of th e Eth ylen e Keta ls of 4,9-, 4,10-, a n d 4,6-
Did eh yd r oa d a m a n ta n -2-on e (8-10). A solution of 3 (1.0 g,
6.5 mmol), p-toluenesulfonic acid monohydrate (20 mg), and
ethylene glycol (0.37 mL, 6.5 mmol) in benzene (45 mL) was
heated to reflux in a Dean-Stark dehydration apparatus for 7
h. The solution was allowed to cool, washed with 40 mL of 10%
sodium chloride solution, and dried over magnesium sulfate.
After removal of the solvent, 1.2 g of the monoketal was obtained
(88%). Recrystallization from chloroform/hexane at -80 °C gave
white crystals: mp 35 °C; IR 2922 (s), 2856 (m), 1720 (s), 1123
(m), 1083 (m), 1030 (m); 1H NMR δ 3.72 (m, 4H), 2.28 (d, 2H, J
) 15.8 Hz), 2.10 (td, 1H, J ) 2.9, 10.3 Hz), 1.94 (d, 1H, J ) 12.3
Hz), 1.82-1.60 (m, 8H); 13C NMR δ 213.01 (CO), 111.24 (COO),
64.21 and 63.97 (CH2O), 55.59, 44.89, 35.68 and 25.71 (CH),
38.29, 36.85, 33.14 and 31.43 (CH2); MS m/ z 208 (M+), 190 (M+
H2O); HRMS fd 208.1100, calcd 208.1099.
protons in the latter compound much larger than those
in the E-isomer.
We find that both 1-F and 1-Br direct the reagent
completely to the remote face of the ketone, so that the
steric factor evidently dominates the electronic oneseven
in the case of the small fluorine atom (we include
electrostatic repulsion between nucleophile and halogen
unshared electrons in this factor). While this is not
greatly surprising, the results with an equatorial sub-
stituent are unexpected. Thus, the effect of an equatorial
4-fluoro substituent on the face selectivity is only barely
larger than that of a 5-substituent (60:4019). It is also
curious that the effect of an equatorial 4-fluoro substitu-
ent is less than that of a bromine atom in that position.
Such a bromine atom does have a somewhat greater
effect than one at C-5, but the increase is not impressive.
Even with a second bromine at C-9, the Z-alcohol is still
a substantial portion of the product.
These results cannot be reconciled with the single idea
that 4-substituents deactivate only one vicinal bond
rather than two as a 5-substituent does. While that fact
may play a role, it cannot be the lone or even principal
one, since if that were the case, a very much larger effect
would have been expected from the second equatorial
bromine at C-9. The observed product ratio is not even
twice that of a single bromine (86/14 < (76/24)2). The
best explanation of these data as well as of Grob’s is that
alignment is the more critical factor: pure anti-
periplanarityswith a dihedral angle between the inter-
acting bonds close to 180°sis needed for the maximum
transmission of a substituent effect to a remote site
The product (1.2 g) was converted into the corresponding
tosylhydrazones by treatment with tosylhydrazine (1.4 g, 6.0
mmol) in methanol (10 mL) at room temperature for 4 h.
A
mixture of the cis- and trans-tosylhydrazones precipitated; it was
isolated by filtration and drying (1.9 g, 92%): IR 3221 (s), 2925
(s), 1328 (s), 1164 (s), 1034 (s); 1H NMR δ 7.78 (d, 4H, J ) 8
Hz), 7.25 (d, 4H, J ) 8 Hz), 3.94-3.65 (m, 8H), 2.95 (s, 2H),
2.49 (s, 2H), 2.38 (s, 6H), 2.10-1.92 (m, 4H), 1.80-1.50 (m, 16H);
13C NMR, δ 167.75 and 166.15 (CdN), 143.64 and 143.60 (CNH),
135.52 and 135.40 (CMe), 129.43, 129.40, 127.92 and 127.78 (aryl
CH), 111.06 and 110.99 (COO), 64.88, 64.58 and 64.05 (CH2O),
47.54, 41.08, 38.03, 36.74, 36.30, 30.47, 26.21 and 26.17 (CH),
37.84, 37.08, 36.56, 35.23, 34.09, 33.66, 33.61 and 32.49 (CH2),
21.61 (CH3). Treatment of small quantities of this mixture (200
mg, 0.57 mmol) with 50% sodium hydride (30 mg, 0.63 mmol)
in dry tetrahydrofuran (1.5 mL) at room temperature for 2 h
afforded the tosylhydrazone sodium salts. After drying, pyroly-
sis at 170 °C yielded 25 mg (23%) of a 1:1.5:1.8 mixture of 9, 10,
and 11. Column chromatography on basic alumina with ligroin
(60-80 °C):ether (0-20%) gave pure samples of all three
compounds.
through single bonds (extended hyperconjugation).
A
similar notion (“double hyperconjugation”) has been
advanced by Adcock20 to account for certain features in
the NMR spectra of 2,5-disubstituted adamantanes.
Paddon-Row et al.21 have found that the presence of even
a single s-cis “kink” severely retards electron transfer in
otherwise completely s-trans carbon frameworks. We are
presently searching for evidence of chemical effects of
even more remote substituents in rigid systems.
Eth ylen e k eta l of 4,9-d id eh yd r oa d a m a n ta n -2-on e (9): mp
30-31 °C; IR 3035 (w), 2928 (s), 2855 (m), 1116 (s), 1033 (s); 1H
NMR δ 3.89 (m, 4H), 2.03 (s, 2H), 1.76 (s, 1H), 1.70 (s, 4H), 1.39-
1.30 (m, 4H), 1.15 (t, 1H, J ) 7.4 Hz); 13C NMR, δ 122.46 (COO),
65.05 and 63.35 (CH2O), 36.91 (C-1,3), 28.96 (C-8,10), 27.95 (C-
6), 24.16 (C-7), 17.96 (C-4,9), 17.64 (C-5); MS m/ z 192 (M+), 125,
99; HRMS fd 192.1150, calcd 192.1149.
Exp er im en ta l Section
IR spectra were measured in KBr pellets; absorptions are
given in cm-1. All NMR spectra were recorded in CDCl3 at 250
MHz (1H) or at 63 MHz (13C). High-resolution mass spectra were
recorded in the Mass Spectrometry Laboratory at the University
of Illinois. The signals are assigned below only where the
identities of the nuclei are obvious; the 13C signals are grouped
according to the outcome of DEPT experiments. The prepara-
tions of 4-hydroxyadamantan-2-one and adamantan-2,4-one
have been described.6 A mixture of the known bromoadaman-
tanes 1- and 2-Br was obtained by heating a solution of a
mixture of the two epimeric 4-hydroxyadamantan-2-ones in 62%
hydrobromic acid to reflux and separated by means of column
Eth ylen e k eta l of 4,10-d id eh yd r oa d a m a n ta n -2-on e (10):
mp 36-37 °C; IR 3015 (w), 2920 (s), 2860 (m), 1410 (m), 1110
(s); 1H NMR δ 4.05-3.85 (m, 4H), 2.20 (s, 2H), 2.12-2.02 (m,
1H), 1.92-1.67 (m, 5H), 1.50-1.37 (m, 3H), 1.28 (tt, 1H, J )
1.7, 7.8 Hz); 13C NMR, δ 108.94 (COO), 64.43 (CH2O), 52.64 (C-
6), 35.58 (C-1), 31.88 (C-8,9), 30.57 (C-5,7), 27.64 (C-4,10), 26.80
(C-3); MS m/ z 192 (M+), 163, 149, 137, 112, 99; HRMS fd
192.1150, calcd 192.1149.
Eth ylen e k eta l of 4,6-d id eh yd r oa d a m a n ta n -2-on e (11):
1
IR 3020 (w), 2932 (s), 2863 (m), 1120 (s), 1037 (m); H NMR, δ
3.93-3.75 (m, 4H), 2.29 (d, 1H, J ) 12.4 Hz), 2.19 (bs, 2H), 2.12-
2.00 (m, 1H), 1.87 (d, 1H, J ) 11.7 Hz), 1.80 (td, 1H, J ) 2.5,
12.5 Hz), 1.67 (s, 1H), 1.58-1.32 (m, 4H), 1.20 (t, 1H, J ) 7.5
Hz); 13C NMR, δ 109.73 (COO), 64.20 and 64.06 (CH2O), 49.34,
31.54 and 27.37 (CH2), 40.27, 35.33, 30.69, 23.76, 22.34 and 20.55
(CH); MS m/ z 192 (M+), 125, 99; HRMS fd 192.1150, calcd
192.1149.
(19) Cheung, C. K.; Tseng, L. T.; Lin, M.-h.; Srivastava, S.; le Noble,
W. J . J . Am. Chem. Soc. 1986, 108, 1598.
(20) (a) Adcock, W.; Iyer, V. S. J . Org. Chem. 1988, 53, 5259. (b)
Adcock, W.; Krstic, A. R.; Duggan, P. J .; Shiner, V. J .; Coope, J .;
Ensinger, M. W. J . Am. Chem. Soc. 1990, 112, 3140. (c) Adcock, W.;
Coope, J .; Shiner, V. J .; Trout, N. A. J . Org. Chem. 1990, 55, 1411. (d)
Adcock, W.; Trout, N. A. J . Org. Chem. 1991, 56, 3229. See also: (e)
Hrovat, D. A.; Borden, W. T. J . Org. Chem. 1992, 57, 2519. (f) Vinkovic,
V.; Mlinaric-Majerski, K.; Marinic, Z. Tetrahedron Lett. 1992, 33, 7441.
(b) McKinley, A. J .; Ibrahim, P. N.; Balaji, V.; Michl, J . J . Am. Chem.
Soc. 1992, 114, 10631.
(21) Kroon, J .; Oliver, A. M.; Paddon-Row, M. N.; Verhoeven, J . W.
Rec. Trav. Chim. Pays-Bas 1988, 107, 509.
(22) The author has deposited atomic coordinates for 12 with the
Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
4-eq,9-eq-Dibr om oa d a m a n ta n -2-on e (8). Bromine (0.016
mL, 0.31 mmol) was added to a solution of 9 (60 mg, 0.31 mmol)
in CCl4 (1.5 mL) at -20 °C. After 2 h, the solvent was
evaporated, and recrystallization of the residue from chloroform/
hexane gave 45 mg (45%) of white crystals that were identified
as 2-ax,10-ax-dibromo-4-oxahomoadamantan-5-one (12, ax with
respect to the six-membered rings), mp 147 °C. The mother
liquor yielded a residual oil which was purified by passing
through a column of neutral alumina. Elution with ligroin (60-
80 °C):ether (8:2) gave the pure ketal of 8 (12 mg, 11%): mp
101-102 °C (an additional experiment showed that there was

4160 J . Org. Chem., Vol. 61, No. 12, 1996
Notes
no reaction of this ketal with bromine, indicating that bromin-
ation occurs first); IR 2944 (s), 2860 (m), 1223 (m), 1115 (s), 1034
(s); H NMR, δ 4.60 (s, 2H), 3.95 (s, 4H), 2.29 (bs, 2H), 2.24 (s,
Red u ction Exp er im en ts. Sodium borohydride (1.5 mg) was
added to a stirred solution of 8 (10 mg, 0.03 mmol) in methanol
(1 mL) at 0 °C. After 3 h, the mixture was poured into an
ammonium chloride solution and extracted with chloroform. The
combined extracts were dried over magnesium sulfate. Evapo-
ration left a solid mixture of (E)- and (Z)-13: IR 3520-3100 (m),
1
1H), 2.13 (s, 2H), 2.04 (s, 2H), 1.88 (d, 2H, J ) 13.1 Hz), 1.75 (s,
1H); 13C NMR, δ 110.10 (COO), 64.73 and 64.64 (CH2O), 53.42
and 43.99 (C-1,3,4,9), 42.04 (C-5), 29.51 (C-8,10), 25.62 (C-7),
25.53 (C-6); MS m/ z 354, 352, 350 (1:2:1, M+), 273, 271 (1:1,
M+ - Br), 229, 227 (1:1, M+ - C2H4BrO), 191 (M+ - HBr2). 12:
IR 2936 (m), 2865 (m), 1735 (s), 1168 (s), 1077 (s); 1H NMR δ
4.58 (bs, 2H), 4.41 (s, 1H), 3.39 (d, 1H, J ) 5.5 Hz), 2.65-2.50
1
2923 (s), 2865 (m), 1108 (s); H NMR δ 4.89 (s, H-4,9(Z)), 4.32
(s, H-4,9(E)), 4.25 (s, H-2(Z)), 3.91 (s, H-2(E)), 2.48-1.50 (m,
22H); 13C NMR δ (E) 72.26 (C-2), 53.22 (C-4,9), 41.99, 41.36 and
26.21 (C-1,3,5,7), 31.13 and 26.15 (C-6,8,10), (Z) 75.89 (C-2),
53.69 (C-4,9), 43.08, 41.68 and 25.71 (C-1,3,5,7), 29.69 and 26.01
(m, 2H), 2.44-2.25 (m, 3H), 2.17 (s, 1H), 1.95-1.74 (m, 2H); 13
C
NMR δ 172.48 (C-5), 75.70 (C-3), 49.58, 48.55, 47.41 and 41.62
(CH), 30.10, 26.19 and 22.91 (CH2), 25.05 (C-8); MS m/ z 201,
199 (1:1, M+ - CBrOO), 119. The X-ray diffraction experiment
was done with Mo KR radiation, and 1039 reflections were
collected. The full set of data and results are shown in the
supporting information.
(C-8,10); MS m/ z 312, 310, 308 (1:2:1, M+), 294, 292, 290 (M+
-
H2O), 231, 229 (1:1, M+ - Br), 213, 211 (1:1, M+ - BrH2O).
Integration of the well-separated H-4,9 peaks showed that the
ratio of isomers was E:Z ) 86:14. A duplicate experiment gave
the identical result. The assignment of configuration rests on
the effect of Eu(fod)3 on the 1H NMR spectrum of the mixture:
plots of the chemical shifts against the amounts of Eu(fod)3
added were linear (r ) 0.997), and the slopes (in arbitrary units)
were as follows: (E) H-4,9, 3.25; H-2, 4.38; (Z) H-4,9, 1.63; H-2,
8.25. The reductions of 1- and 2-Br and of 1- and 2-F were
carried out in the same way but on a somewhat larger scale (0.24
mmol). The isomer ratios were determined by integration of the
H-4 signals in the 1H NMR spectra; the spectral data were in
agreement with those published.7,8,16-18
A solution of the ketal (12 mg, 0.03 mmol) in 88% formic acid
(1.2 mL) was heated to 65 °C for 20 min, diluted with water,
and extracted with pentane:ether ) 8:2. The combined extracts
were dried over magnesium sulfate. Removal of the solvent gave
8 as a white solid (8.5 mg, 81%): mp 131-132 °C; IR 2928 (s),
2861 (m), 1735 (s), 1712 (s), 898 (m); 1H NMR δ 4.35 (s, 2H),
2.82 (s, 2H), 2.65 (d, 2H, J ) 11 Hz), 2.48 (s, 1H), 2.37 (s, 2H),
1.95-1.83 (m, 3H); 13C NMR δ 208.81 (C-2), 53.44 and 50.88
(C-1,3,4.9), 41.85 (C-5), 34.76 (C-8,10), 26.34 (C-7), 25.08 (C-6);
MS m/ z 310, 308, 306 (1:2:1, M+), 229, 227 (M+ - Br), 201, 199
(1:1, M+ - CBrO), 119; HRMS fd 305.9255, calcd 305.9255.
Alternatively, 9 could be hydrolyzed first, as described above,
to give the 4,9-didehydroadamantanone as a white solid melting
above 130 °C: IR 3050 (w), 2916 (s), 1728 (s); 1H NMR δ 2.53 (s,
2H), 1.90-1.72 (m, 7H), 1.53-1.37 (m, 3H); 13C NMR δ 215.91
(C-2), 41.19 (C-1,3), 33.71 (C-8,10), 26.52 (C-6), 24.87 (C-7), 14.90
(C-5), 12.75 (C-4,9); MS m/ z 148 (M+), 120 (M+ - CO), 105, 91,
79. Bromination of this compound as described above gave two
4,9-dibromoadamantanones in the ratio of 70:30. The main
product was identified by its mass spectrum and GC retention
time as 8; the minor product is assumed to be the eq,ax isomer
from the similarity of its GC retention time and almost identical
mass spectrum; the main difference is that the minor isomer
has a much larger 227/199 peak ratio.
Ack n ow led gm en t. The National Science Founda-
tion supported this work. We are indebted to Professor
J oseph Lauher for the X-ray diffraction study.
Su p p or tin g In for m a tion Ava ila ble: IR, 1H and 13C NMR,
and mass spectral data for all compounds mentioned in the
Experimental Section (61 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
J O9601066