Diastereoselective manipulations of bicyclo[m.1.0]alkane derivatives. 2. Nucleophilic additions to the carbonyl carbons of bicyclot[m.1.0]alkan-2-ones

Article abstract of DOI:10.1021/jo951753k

Enantiomerically enriched bicyclo[m.1.0]alkan-2-ones having larger ring sizes between five and 16 members were prepared and subjected to additions of nucleophiles to the carbonyl carbon. Such additions were efficient and highly diastereoselective for all nucleophiles for bicycles with ring sizes greater than seven. Diastereoselectivity for these additions is rationalized by assuming early transition states and exposure of the same carbonyl face to the ring exterior in the vast majority of populated conformers for each bicyclic ketone.

Full text of DOI:10.1021/jo951753k

J . Org. Chem. 1996, 61, 2743-2752
2743
Dia ster eoselective Ma n ip u la tion s of Bicyclo[m .1.0]a lk a n e
Der iva tives. 2. Nu cleop h ilic Ad d ition s to th e Ca r bon yl Ca r bon s
of Bicyclo[m .1.0]a lk a n -2-on es1
Eugene A. Mash,* Timothy M. Gregg, and Michelle A. Kaczynski
Department of Chemistry, The University of Arizona, Tucson, Arizona 85721
Received September 25, 1995X
Enantiomerically enriched bicyclo[m.1.0]alkan-2-ones having larger ring sizes between five and
16 members were prepared and subjected to additions of nucleophiles to the carbonyl carbon. Such
additions were efficient and highly diastereoselective for all nucleophiles for bicycles with ring
sizes greater than seven. Diastereoselectivity for these additions is rationalized by assuming early
transition states and exposure of the same carbonyl face to the ring exterior in the vast majority
of populated conformers for each bicyclic ketone.
In tr od u ction
Common-ringed2 systems are frequently employed as
templates in stereocontrolled organic synthesis. Since
the number of available conformations is limited, the
reactivity of ring-bound functional groups can often be
predicted with certainty. Medium and large rings can
adopt a greater number of conformations. Despite an
early presumption that stereocontrolled manipulation of
such “floppy” rings was impossible, Still,3 Vedejs,4 and
others5 demonstrated that predictable manipulations of
medium and large rings are possible in cases where a
local conformational bias exists due to the presence of
one or more stereogenic units.
F igu r e 1. Synthesis of enantiomerically enriched cyclopropyl
ketones 3.
A limitation for medium and large carbocycles has been
the difficulty in introducing stereogenic units. We previ-
ously developed a method for diastereoselective cyclo-
propanation of 2-cycloalken-1-one ketals 1 (Figure 1).6
Thus, bicyclo[m.1.0]alkan-2-ones 3, possessing cis ring
fusion for m ) 3-14 or trans ring fusion for m ) 7-14,
are available in either enantiomeric form via hydrolyses
of the corresponding cyclopropane ketals 2. We have
undertaken computational and synthetic studies to ad-
vance our understanding of these carbocycles and to
evaluate their suitability as synthetic intermediates for
construction of complex natural products. In the preced-
ing paper the populated conformations of the set of
bicyclo[m.1.0]alkan-2-ones 3 were studied by computa-
tional methods.7 In this paper the results of studies of
nucleophilic additions to the carbonyls of several bicyclo-
[m.1.0]alkan-2-ones 3 are presented and discussed.
While considerable work on medium and large hetero-
cyclic rings has appeared, the synthetic potential of
medium and large carbocycles is less well investigated.
X Abstract published in Advance ACS Abstracts, March 1, 1996.
(1) Mash, E. A.; Kaczynski, M. A.; Dolata, D. P. Tetrahedron Lett.
1990, 31, 4565-4568.
(2) Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of
Organic Compounds; J ohn Wiley & Sons: New York, 1994; p 678.
(3) (a) Still, W. C. J . Am. Chem. Soc. 1979, 101, 2493-2495. (b) Still,
W. C.; Galynker, I. Tetrahedron 1981, 37, 3981-3996. (c) Still, W. C.
In Current Trends in Organic Synthesis; Pergamon Press: Tokyo,
J apan, 1982; pp 233-246. (d) Still, W. C.; Romero, A. G. J . Am. Chem.
Soc. 1986, 108, 2105-2106 and references cited in the above.
(4) (a) Vedejs, E.; Dolphin, J . M.; Gapinski, D. M.; Mastalerz, H. In
Current Trends in Organic Synthesis; Pergamon Press: Tokyo, J apan,
1982; pp 221-232. (b) Vedejs, E.; Wittenberger, S. J . J . Am. Chem.
Soc. 1990, 112, 4357-4364. (c) Vedejs, E. In Studies in Natural
Products Chemistry; Atta-ur-Rahman, Ed.; Elsevier: Amsterdam, 1991;
Vol. 8, pp 205-218. (d) Vedejs, E. Adv. Sulfur Chem. 1994, 1, 1-40
and references cited in the above.
Resu lts a n d Discu ssion
Enantiomerically enriched cyclopropyl ketals 2, pre-
pared as previously described,6a,8 were hydrolyzed using
aqueous HCl in methanol1 to provide bicyclic ketones 3a -
i. To each of these ketones were added one or more
nucleophiles as summarized in Table 1. In some cases
both the major and the minor product diastereomers
arising from attack of the nucleophile at opposite faces
of the carbonyl were isolated and characterized. In all
such instances but one (Table 1, entry 1) the product
diastereomers differed in polarity (R values on analytical
TLC plates ranged from 1.2 to 4.9) and were readily
(5) (a) Doskotch, R. W.; Keely, S. L.; Hufford, C. D. J . Chem. Soc.,
Chem. Commun. 1972, 1137-1138. (b) Sutherland, J . K. Tetrahedron
1974, 30, 1651-1660. (c) Corey, E. J .; Nicolaou, K. C.; Melvin, L. S. J .
Am. Chem. Soc. 1975, 97, 654-655. (d) Thies, R. W.; Boop, J . L.;
Schiedla, M.; Zimmerman, D. C.; LaPage, T. H. J . Org. Chem. 1983,
48, 2021-2024. (e) Coates, R. M.; Muskopf, J . W.; Senter, P. A. J . Org.
Chem. 1985, 50, 3541-3557. (f) Cameron, A. G.; Knight, D. W. J . Chem.
Soc., Perkin Trans. I 1986, 161-167. (g) Funk, R. L.; Ableman, M. M.;
Munger, J . D. Tetrahedron 1986, 42, 2831-2846. (h) Raucher, S.; Chi,
K.-W.; Hwang, K.-J .; Burks, J . E. J . Org. Chem. 1986, 51, 5503-5505.
(i) Takahashi, T.; Nemoto, H.; Kanda, Y.; Tsuji, J .; Fujise, Y. J . Org.
Chem. 1986, 51, 4315-4316. (j) Quinkert, G.; Heim, N.; Glenneberg,
J .; Billhardt, U.-M.; Autze, V.; Bats, J . W.; Du¨rner, G. Angew. Chem.,
Int. Ed. Engl. 1987, 26, 362-364. (k) Mehta, G.; Rao, K. S. J . Org.
Chem. 1988, 53, 425-427. (l) Schreiber, S. L.; Smith, D. B.; Schulte,
G. J . Org. Chem. 1989, 54, 5994-5996. (m) Takahashi, T. In Studies
in Natural Products Chemistry; Atta-ur-Rahman, Ed.; Elsevier: Am-
sterdam, 1991; Vol. 8, pp 175-204. (n) Deslongchamps, P. Pure Appl.
Chem. 1992, 64, 1831-1847. (o) Marshall, J . A.; Andersen, M. W. J .
Org. Chem. 1993, 58, 3912-3918. (p) Neeland, E. G.; Ounsworth, J .
P.; Sims, R. J .; Weiler, L. J . Org. Chem. 1994, 59, 7383-7394. (q)
Marshall, J . A.; Wallace, E. M.; Coan, P. S. J . Org. Chem. 1995, 60,
796-797. (r) Winkler, J . D.; Hong, B.-C. Tetrahedron Lett. 1995, 36,
683-686 and previous papers by these authors.
(6) (a) Mash, E. A.; Math, S. K.; Arterburn, J . B. J . Org. Chem. 1989,
54, 4951-4953. (b) Mash, E. A.; Torok, D. S. J . Org. Chem. 1989, 54,
250-253. (c) Mash, E. A.; Hemperly, S. B. J . Org. Chem. 1990, 55,
2055-2060. (d) Mash, E. A.; Hemperly, S. B.; Nelson, K. A.; Heidt, P.
C.; Van Deusen, S. J . Org. Chem. 1990, 55, 2045-2055.
(7) Mash, E. A.; Gregg, T. M.; Stahl, M. T.; Walters, W. P. J . Org.
Chem. 1996, 61, 2738-2742.
(8) Mash, E. A.; Nelson, K. A. Tetrahedron 1987, 43, 679-692.
0022-3263/96/1961-2743$12.00/0 © 1996 American Chemical Society

2744 J . Org. Chem., Vol. 61, No. 8, 1996
Ta ble 1. Ad d ition s of Nu cleop h iles to Ca r bon yls of Bicyclo[m .1.0]a lk a n -2-on es 3a -k
Mash et al.

Manipulations of Bicyclo[m.1.0]alkane Derivatives
J . Org. Chem., Vol. 61, No. 8, 1996 2745
8
F igu r e 3. Synthesis of (()-6a .
F igu r e 2. Nucleophilic attack on the lowest energy conform-
ers of 3a .
separated by column chromatography. In other cases
diastereoselectivity was sufficiently high so that the
minor diastereomer was not observed. In such instances
the minimal diastereomer ratio is given as >20:1, the
limit of detectability by 13C NMR spectroscopy.9
F igu r e 4. Nucleophilic attack on the lowest energy conform-
ers of 3b.
Addition of methyllithium to the carbonyl carbon of
(1R,6S)-bicyclo[4.1.0]heptan-2-one (3a ) was not stereo-
selective, and the conversion to product was low (Table
1, entry 1). Substantial amounts of starting material
were recovered, presumably because enolization was
competitive with attack at carbonyl. This result, which
is in keeping with the observation of others,10 can be
rationalized if early transition states are assumed11 since
both faces of the carbonyl are exposed to nucleophilic
attack in both populated conformers of the starting
material (see 3a -1 and 3a -2, Figure 2; percentage given
is percent of conformer population).7 The populated
conformers of the products, 4a and 4b, were found using
a Monte Carlo search strategy and MM2 minimization
techniques.7,12 The predominant product conformers,
4a -1 and 4b-1, are also depicted in Figure 2. On the basis
of the small difference in the weighted average strain
energies of 4a and 4b (Table 2), it seems likely that
neither of the initially formed lithium alkoxide products
corresponding to 4a and 4b is strongly preferred on
thermodynamic grounds.
Ta ble 2. P op u la ted Con for m er s of
2-Meth ylbicyclo[m .1.0]a lk a n -2-ols
number of
conformers
within 20 kJ
of global
number of
conformers
within 5 kJ
of global
strain energy
of global
minimum,
kJ /mol
weighted
strain
bicyclic
alcohol
energy,
kJ /mol
minimum
minimum
4a
4b
6a
6b
10a
10b
23a
23b
30a
30b
4
3
2
2
73.1
72.5
73.8
73.2
88.7
7
1
88.1
6
2
96.0
97.0
4
5
2
3
8
6
22
18
102.6
116.6
106.7
111.3
103.2
108.4
102.9
117.2
109.0
114.2
108.6
113.8
69
68
857
1032
uct alcohols 5a and 5b were assigned structures from
melting points of the known phenylurethane deriva-
tives.13 Cyclopropylcarbinols 6a and 6b were assigned
structures based on chromatographic and spectroscopic
comparisons with (()-6a prepared from racemic 1-meth-
yl-2-cyclohepten-1-ol (8) by allylic alcohol-directed Sim-
mons-Smith cyclopropanation (Figure 3).14 Structures
for alcohols 7a and 7b were assigned by analogy with
6a and 6b.
Additions to the carbonyl carbon of (1R,7S)-bicyclo-
[5.1.0]octan-2-one (3b) were more efficient and exhibited
modest diastereoselectivity (Table 1, entries 2-4). Prod-
(9) This is the signal-to-noise limit of detection. For previous use of
13C NMR in determination of diastereomer ratios, see: Hiemstra, H.;
Wynberg, H. Tetrahedron Lett. 1977, 18, 2183-2186.
(10) Ward, H. D.; Teager, D. S.; Murray, R. K. J . Org. Chem. 1992,
57, 1926-1928.
The obtention of mixtures of diastereomers for addi-
tions to 3b was consistent with its conformational
ensemble, as each face of the carbonyl is exposed to attack
in one or more of the populated conformers (e.g., Figure
4).7 However, the variation of the preferred face for
attack (hydride at the Re face of the carbonyl, methyl-
lithium and butyllithium at the Si face) underscores the
(11) (a) Kamernitzky, A. V.; Akhrem, A. A. Tetrahedron 1962, 18,
705-750 and references cited therein. (b) Houk, K. N.; Paddon-Row,
M. N.; Rondan, N. G.; Wu, Y.-D.; Brown, F. K.; Spellmeyer, D. C.; Metz,
J . T.; Li, Y.; Longarich, R. J . Science 1986, 231, 1108-1117. (c) Lowry,
T. H.; Richardson, K. S. Mechanism and Theory in Organic Chemistry,
3rd ed.; Harper & Row: New York, 1987; pp 661-693 and references
cited therein. (d) Wu, Y.-D.; Houk, K. N.; Florez, J .; Trost, B. M. J .
Org. Chem. 1991, 56, 3656-3664. (e) Eksterowicz, J . E.; Houk, K. N.
Chem. Rev. 1993, 93, 2439-2461.
(12) (a) Saunders, M. J . Am. Chem. Soc. 1987, 109, 3150-3152. (b)
Mohamadi, F.; Richards, N. G. J .; Guida, W. C.; Liskamp, R.; Lipton,
M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J . Comput.
Chem. 1990, 11, 440-467.
(13) (a) Cope, A. C.; Moon, S.; Peterson, P. E. J . Am. Chem. Soc.
1962, 84, 1935-1940. (b) Dauben, W. G.; Berezin, G. H. J . Am. Chem.
Soc. 1963, 85, 468-472.
(14) Simmons, H. E.; Cairns, T. L.; Vladuchick, S. A.; Hoiness, C.
M. Org. React. 1973, 20, 1-131.

2746 J . Org. Chem., Vol. 61, No. 8, 1996
Mash et al.
Less material was available for study of the larger cis-
fused bicyclic ketones 3d -g, so fewer experiments were
performed, but similar results were obtained. Treatment
of (1R,9S)-bicyclo[7.1.0]decan-2-one (3d ) with methyl-
lithium (Table 1, entry 11) produced exclusively cyclo-
propylcarbinol diastereomer 15a in 66% yield. This
diastereoselectivity is comparable to that reported by
Winstein for LiAlH4 reduction of racemic 3d .16 Reduc-
tions of (1S,12R)-bicyclo[10.1.0]tridecan-2-one (3e) and
(1S,15R)-bicyclo[13.1.0]hexadecan-2-one (3f) using Li-
AlH4 (entries 12 and 14) were highly diastereoselective
and efficient. Additions of vinylmagnesium bromide to
these ketones (entries 13 and 15) were highly diastereo-
selective, but less efficient, presumably due to competing
enolization. However, treatment of (1R,16S)-bicyclo-
[14.1.0]heptadecan-2-one (3g) with methyllithium (entry
16) gave a single diastereomer in excellent yield.
The tentative structural assignment for 15a is in
keeping with Winstein’s observation16 and is supported,
and the observed diastereoselectivity rationalized, by
computational studies which suggest that the Re face of
the carbonyl of 3d is exposed to the ring exterior in all
populated conformers.7 Similar conformationally con-
trolled exposures of one carbonyl face to nucleophilic
attack from the ring periphery are predicted from com-
putational modeling for ketones 3e, 3f, and 3g, and
tentative structural assignments for products 16a -20a
were made accordingly.
Our study of the larger trans-fused bicyclic ketones
included additions of methyllithium to (1R,11R)-bicyclo-
[9.1.0]dodecan-2-one (3h , Table 1, entry 17), (1S,12S)-
bicyclo[10.1.0]tridecan-2-one (3i, entry 19), (1R,13R)-
bicyclo[11.1.0]tetradecan-2-one (3j, entry 24), and (1S,15S)-
bicyclo[13.1.0]hexadecan-2-one (3k , entry 26). In each
case, generation of the tertiary cyclopropylcarbinol was
highly stereocontrolled and efficient. Similar results
were observed for LiAlH4 reductions of 3i and 3k (entries
18 and 25). Ketones 3i and 3k were also subjected to
attack by a variety of other carbanionic nucleophiles
(entries 20-23 and 27-30). In all cases the chemical
yields were high and the observed diastereoselectivities
were >20:1. These results were again rationalized by
consideration of the populated conformers of the cyclo-
propyl ketones 3h -k . In each case local conformational
anchoring results in exposure of one face of the carbonyl
to the ring exterior.7
F igu r e 5. Nucleophilic attack on the lowest energy conform-
ers of 3c.
need to evaluate competing transition states for this
ketone, in accord with the Curtin-Hammett principle.
A Monte Carlo search for the populated conformers of
product alcohols 6a and 6b revealed that the former is
less strained by approximately 8 kJ /mol (Table 2). As
the latter was the principal product, addition of meth-
yllithium to 3b must have occurred under kinetic control,
as expected.11
Previously, Winstein showed that reduction of racemic
bicyclo[6.1.0]nonan-2-one ((()-3c) using lithium alumi-
num hydride was highly diastereoselective.15 We ob-
served a similar result for LiAlH4 reduction of (1R,8S)-
3c, and in addition subjected this ketone to attack by a
wide variety of carbanionic nucleophiles (Table 1, entries
5-10). In all experiments with 3c, product yields were
high and the observed diastereoselectivities were >20:1.
In the case of phenylmagnesium bromide (entry 8), run
on a 220 mg scale, both product diastereomers could be
isolated and characterized, with the less polar product
12a predominant. The principal diastereomeric products
were tentatively assigned structures 9a -14a in keeping
with the previous assignment of structure to (()-9a .15
The observed diastereoselectivities can be rationalized
from the predominance of two conformers for 3c in which
the Re face of the carbonyl is exposed to attack by
nucleophiles approaching from the periphery of the ring
(Figure 5).7 The Si face of the carbonyl is shielded by
the transannular carbon and hydrogen atoms. Confor-
mational equilibria do not change this situation, and so
for nucleophilic additions to 3c involving early transition
states, the structures of the major products may be
predicted from the common local conformation of the
cyclopropyl ketone functional group array.
A Monte Carlo search for the populated conformers of
the products 23 and 30, derived from addition of meth-
yllithium to ketones 3i and 3k , respectively, revealed that
23a and 30a are less strained than 23b and 30b (Table
2 and Figures 6 and 7). Assuming these differences in
strain energy are reflected in the stabilities of the
corresponding initially formed lithium alkoxides, the
thermodynamically preferred diastereomers 23a and 30a
were produced in these kinetically controlled reactions.
The major products from ketones 3h -k were tentatively
assigned structures 21a -34a .
In order to establish the facial selectivity for nucleo-
philic attack, ketones 3c, 3i, and 3k were allowed to react
with an excess of lithiosulfoximine (S)-35 (Table 3).17
Given that the sulfoximine employed possessed an ee of
approximately 85%, four product diastereomers were
possible for each ketone. For 3c, a 1:10 mixture of chro-
A Monte Carlo search for the populated conformers of
the product alcohols derived from addition of methyl-
lithium to 3c revealed that the major product 10a is less
strained than 10b by approximately 14 kJ /mol (Table 2
and Figure 5). In this case, the major product diastere-
omer produced under kinetic control is also the thermo-
dynamically favored product.
(16) Poulter, C. D.; Freidrich, E. C.; Winstein, S. J . Am. Chem. Soc.
1970, 92, 4282-4288.
(17) (a) J ohnson, C. R.; Zeller, J . R. Tetrahedron 1984, 40, 1225-
1233. (b) Shiner, C. S.; Berks, A. H. J . Org. Chem. 1988, 53, 5542-
5545.
(15) Poulter, C. D.; Friedrich, E. C.; Winstein, S. J . Am. Chem. Soc.
1970, 92, 4274-4281.

Manipulations of Bicyclo[m.1.0]alkane Derivatives
J . Org. Chem., Vol. 61, No. 8, 1996 2747
Ta ble 3. Ad d ition s of Lith iosu lfoxim in e 35 to Ca r bon yls of Bicyclo[m .1.0]a lk a n -2-on es 3c, 3i, a n d 3k
F igu r e 6. Nucleophilic attack on the lowest energy conform-
ers of 3i.
F igu r e 7. Nucleophilic attack on the lowest energy conform-
ers of 3k .
matographically separable products 36a and 36b was
obtained (Table 3, entry 1). Single-crystal X-ray analysis
confirmed that the major diastereomer 36b possessed the
structure shown. Notably, the conformation of 36b
observed in the crystal closely resembles conformer 10a -
4. The structure for the minor diastereomer 36a was not
established. For ketones 3i and 3k , a kinetic preference
was observed for reaction with the predominant S enan-
tiomer of lithiosulfoximine 35 since the product ratios
observed were 32:1 and 314:1, respectively (Table 3,
entries 2 and 3). The structure of product 38a depicted
in Table 3 was established by single-crystal X-ray analy-
sis. The conformation of 38a observed in the crystal
closely resembles conformer 30a -1 (Figure 7). Crystals
of product 37a suitable for X-ray analysis have not yet
been obtained, so the structure depicted in Table 3 is
tentatively assigned. Structures of the minor adducts
37b and 38b were not established.
Con clu sion
It has been demonstrated that when enantiomerically
enriched bicyclo[m.1.0]alkan-2-ones where m g 6 are
subjected to nucleophilic attack under kinetic control,
adduct alcohols are produced in high yields and with high
degrees of diastereoselectivity. Diastereoselectivity is
predictable if one assumes early transition states which

2748 J . Org. Chem., Vol. 61, No. 8, 1996
Mash et al.
8.7, 4.0 Hz); 13C NMR δ 18.0, 22.3, 23.7, 24.0, 24.4, 25.4, 27.8,
29.6, 29.7, 30.7, 42.7, 213.0.
reflect the local conformational anchoring of the stereo-
genic cyclopropyl carbonyl functional group array. Such
conformational anchoring may facilitate diastereoselec-
tion in other carbonyl-functionalizing reactions. Studies
to explore such possibilities are currently underway.
(1S,12S)-Bicyclo[10.1.0]tr id eca n -2-on e (3i): Rf 0.34 (10%
EtOAc/hexanes); mp 35-38 °C; [R]25 -36.1° (c 3.16, CHCl3);
D
1
IR (neat) cm-1 2996, 2925, 2857, 1688; H NMR δ 0.70-0.88
(2, m), 1.23-1.79 (15, m), 1.80-2.08 (3, m), 2.25 (1, ddd, J )
13.1, 10.9, 3.2 Hz), 2.83 (1, ddd, J ) 13.1, 7.6, 3.2 Hz); 13C
NMR δ 18.5, 23.5, 23.9, 25.3, 26.2, 26.5, 27.0, 27.4, 27.7, 27.8,
32.4, 44.6, 212.1.
Exp er im en ta l Section
All reactions were performed in flame-dried glassware under
argon. Reaction mixtures were stirred magnetically. Hygro-
scopic liquids and solutions of reactive intermediates were
transferred via syringe. Reaction product solutions were
concentrated using a rotary evaporator at 30-40 mmHg.
Diethyl ether and tetrahydrofuran were distilled from sodium/
benzophenone ketyl. Dichloromethane was distilled from
CaH2. Analytical thin-layer chromatography was performed
on Merck precoated plates (0.25 mm, silica gel 60, F-254).
Visualization of spots was effected by treatment of the plate
with a 2.5% solution of anisaldehyde in ethanol containing 6%
H2SO4 and 2% acetic acid followed by charring on a hot plate.
Flash chromatography was performed on Merck silica gel 60
(230-400 mesh). Standard gravity-driven column chroma-
tography was performed on Merck silica gel 60 (70-230 mesh).
Optical rotations were measured at 589 nm. Unless noted,
all NMR spectra were recorded in CDCl3 solution. Proton and
13C magnetic resonance spectra were recorded at 250.1 and
62.9 MHz, respectively, using tetramethylsilane (0 ppm) and
the center line of the chloroform-d triplet (77.0 ppm) as
internal standards. Unless otherwise indicated, all of the
major product diastereomers were judged to be greater than
Anal. Calcd for C13H22O: C, 80.36; H, 11.41. Found: C,
80.26; H, 11.36.
(1R,13R)-Bicyclo[11.1.0]tetr a d eca n -2-on e (3j): Rf 0.37
(10% EtOAc/hexanes); 1H NMR δ 0.68-0.84 (2, m), 1.12-1.55
(16, m), 1.57-1.92 (3, m), 1.93-2.07 (1, m), 2.30 (1, ddd, J )
14.6, 8.3, 4.4 Hz), 2.80 (1, ddd, J ) 14.6, 8.7, 4.4 Hz); 13C NMR
δ 17.8, 23.8, 25.2, 26.1, 26.5, 26.6, 26.8, 27.0, 27.5, 28.0, 29.3,
32.3, 42.2, 211.7.
(1S,15S)-Bicyclo[13.1.0]h exa d eca n -2-on e (3k ): ref 18.
Nu cleop h ilic Ad d ition s. Preparations of compounds 22,
32, 34, and 36 are illustrative of the general methodology
employed.
(1S,2R,12S)-Bicyclo[10.1.0]t r id eca n -2-ol (22a ) a n d
(1S,2S,12S)-Bicyclo[10.1.0]tr id eca n -2-ol (22b). To a well-
stirred suspension of lithium aluminum hydride (29 mg, 0.77
mmol) in diethyl ether (2 mL) at -78 °C was added a solution
of 3i (75 mg, 0.38 mmol) in ether (2 mL) via cannula. The
cannula was rinsed three times with ether (1 mL). The
reaction mixture was allowed to warm to room temperature
over 3 h and then cooled to 0 °C, and the reaction was
quenched by successive additions of water (30 µL), 4 N NaOH
(30 µL), and water (90 µL). After stirring for 30 min at room
temperature, the white precipitate was removed by filtration.
Volatiles were removed in vacuo to give a white solid which
was purified by column chromatography on silica gel 60 (70-
230 mesh) eluted with 8% EtOAc/hexanes. The yield of the
less polar diastereomer 22a , Rf 0.19 (10% EtOAc/hexanes),
obtained as a white crystalline solid, mp 77-78 °C, was 70
mg (0.36 mmol, 93%). The yield of the more polar diastere-
omer 22b, Rf 0.09, also obtained as a white crystalline solid,
mp 72-74 °C, was 2 mg (0.010 mmol, 3%).
1
95% pure on the basis of H and 13C NMR analysis. Where
observed, minor product diastereomers were often character-
ized at less than 95% purity due to the small amounts of
available material. High-resolution mass spectra were re-
corded at the Nebraska Center for Mass Spectrometry, Lincoln,
NE. Elemental analyses were performed by Desert Analytics,
Tucson, AZ.
Enantiomerically enriched cyclopropyl ketals 2 were pre-
pared as previously described.6,8 These ketals were hydrolyzed
to ketones 3 with HCl in methanol as previously described.1
Spectral data are given below.
Sp ectr a l d a ta for 22a : [R]24 -113.4° (c 3.25, CHCl3); IR
D
(neat) cm-1 3321 (br), 2997, 2918, 2844; 1H NMR δ 0.08-0.19
(1, m), 0.63-0.87 (4, m), 1.18-1.75 (17, m), 1.91-2.08 (1, m),
3.92-4.00 (1, m); 13C NMR δ 9.2, 11.0, 21.0, 21.5, 22.4, 23.4,
(1R,6S)-Bicyclo[4.1.0]h ep ta n -2-on e (3a ): ref 8.
(1R,7S)-Bicyclo[5.1.0]octa n -2-on e (3b): ref 8.
(1R,8S)-Bicyclo[6.1.0]n on a n -2-on e (3c): Rf 0.30 (10%
23.9, 27, 27.6, 27.8, 32.5, 36.3, 68.0; HRMS calcd for C13H24
196.1827, found 196.1823.
O
EtOAc/hexanes); [R]24 +87.6° (c 1.03, CHCl3); IR (neat) cm-1
D
1
Sp ectr a l d a ta for 22b: 1H NMR δ 0.22-0.30 (1, m), 0.35-
0.44 (1, m), 0.58-0.84 (3, m), 1.20-1.88 (17, m), 1.95-2.09 (1,
m), 2.84-2.94 (1, m); 13C NMR δ 16.9, 21.0, 23.4, 24.1, 24.8,
25.1, 27.3 , 27.6, 28.0, 32.7, 35.6, 77.2.
2999, 2928, 2855, 1692; H NMR δ 0.58-0.82 (2, m), 1.09 (1,
dd, J ) 10.0, 5.0 Hz), 1.19-2.31 (10, m), 2.65 (1, ddd, J ) 12.2,
5.0, 4.2 Hz); 13C NMR δ 8.8, 21.6, 26.2, 26.9, 27.0, 27.2, 29.6,
45.6, 211.8.
(1S,12R)-Bicyclo[10.1.0]tr id eca n -2-on e (3e): Rf 0.46 (10%
(1S,2R,15S)-2-P h en ylbicyclo[13.1.0]h exadecan -2-ol (32a)
a n d (1S,2S,15S)-2-P h en ylb icyclo[13.1.0]h exa d eca n -2-ol
(32b). To a well-stirred solution of phenylmagnesium bromide
(0.27 mL of a 3 M solution, 0.81 mmol) in ether (2 mL) at -78
°C was added a solution of 3k (64 mg, 0.27 mmol) in ether (2
mL) via an addition funnel. The funnel was rinsed twice with
ether (0.5 mL). The reaction mixture was allowed to warm to
0 °C over 30 min, and the reaction was quenched by dropwise
addition of a saturated aqueous NH4Cl solution (5 mL). The
mixture was diluted with water (5 mL) and extracted three
times with ether (15 mL). The ether extracts were dried
(MgSO4), filtered, and concentrated in vacuo to give a colorless
oil which was purified by column chromatography on silica
gel 60 (70-230 mesh) eluted with 5% ether/hexanes. The yield
of the less polar diastereomer 32a , an oil homogeneous by TLC,
Rf 0.35 (10% EtOAc/hexanes), was 74 mg (0.24 mmol, 88%).
Diastereomer 32b (approximately 2-3 mg) was obtained as
an oil, Rf 0.21, contaminated by residue from the commercial
phenylmagnesium bromide solution.
EtOAc/hexanes); mp 56-60 °C; [R]26 +6.7° (c 0.46, CHCl3);
D
IR (neat) cm-1 2994, 2963, 2924, 2857, 1682; 1H NMR δ 0.86-
0.97 (1, m), 1.00-1.75 (17, m), 2.01 (1, m), 2.07 (1, td, J ) 7.3,
5.7 Hz), 2.43 (1, ddd, J ) 17.2, 5.7, 3.5 Hz), 2.99 (1, ddd, J )
17.2, 11.3, 2.8 Hz); 13C NMR δ 12.7, 22.1, 23.1, 23.4, 23.9, 24.0,
25.3, 26.6, 26.6, 27.1, 29.2, 42.0, 209.0.
(1S,15R)-Bicyclo[13.1.0]h exa d eca n -2-on e (3f): Rf 0.47
(10% EtOAc/hexanes); [R]26 +62.9° (c 0.41, CHCl3); IR (neat)
D
cm-1 2995, 2924, 2854, 1696; 1H NMR δ 0.91-1.00 (1, m),
1.03-1.12 (1, m), 1.12-1.53 (21, m), 1.54-1.71 (1, m), 1.76-
1.93 (1, m), 1.99 (1, td, J ) 8.2, 5.2 Hz), 2.55 (1, dt, J ) 17.9,
5.6 Hz), 2.76 (1, ddd, J ) 17.9, 8.2, 6.1 Hz); 13C NMR δ 14.7,
21.7, 25.2, 25.7, 25.9, 26.0, 26.0, 26.2, 26.8, 26.9, 27.1, 27.2,
28.2, 29.2, 43.8, 209.2
Anal. Calcd for C16H28O: C, 81.29; H, 11.94. Found: C,
81.23; H, 11.87.
(1S,16R)-Bicyclo[14.1.0]h ep ta d eca n -2-on e (3g): Rf 0.36
1
(5% EtOAc/hexanes); H NMR δ 0.88-0.97 (1, m), 1.07-1.86
Sp ectr a l d a ta for 32a : [R]25 +0.88° (c 2.51, CHCl3); IR
D
(27, m), 2.02 (1, td, J ) 7.9, 5.6 Hz), 2.49 (1, ddd, J ) 17.4,
8.4, 5.1 Hz), 2.71 (1, ddd, J ) 17.4, 8.4, 6.8 Hz); 13C NMR δ
13.6, 22.0, 25.6, 25.6, 25.9, 26.0, 26.3, 26.5, 26.6, 26.7, 27.3,
27.4, 28.0, 29.6, 43.9, 209.0.
(neat) cm-1 3470 (br), 3057, 2995, 2925, 2852, 1598; 1H NMR
δ 0.18-0.27 (1, m), 0.48-0.58 (1, m), 0.73-0.89 (1, m), 0.95-
1.62 (23, m), 1.75-2.04 (3, m), 7.18-7.37 (3, m), 7.47-7.53 (2,
m); 13C NMR δ 8.1, 14.6, 22.6, 25.7, 26.2, 26.3, 26.4, 27.1, 27.2,
(1R,11R)-Bicyclo[9.1.0]d od eca n -2-on e (3h ): Rf 0.28 (10%
1
EtOAc/hexanes); H NMR δ 0.73-0.96 (3, m), 1.08-2.06 (15,
m), 2.28 (1, ddd, J ) 13.5, 8.7, 4.3 Hz), 2.81 (1, ddd, J ) 13.8,
(18) Nelson, K. A.; Mash, E. A. J . Org. Chem. 1986, 51, 2721-2724.

Manipulations of Bicyclo[m.1.0]alkane Derivatives
J . Org. Chem., Vol. 61, No. 8, 1996 2749
27.4, 27.8, 29.2, 33.8, 43.9, 73.9, 125.4, 126.5, 128.0, 147.4;
HRMS calcd for C22H34O 314.2610, found 314.2611.
inseparable mixture consisting of recovered 3a and diastere-
omeric alcohols 4a and 4b, Rf 0.17 (30% ethyl ether/hexanes).
The latter were obtained in approximately 50% yield and in a
1:1 ratio as determined by NMR spectroscopy.
Sp ectr a l d a ta for th e m ixtu r e of 4a a n d 4b: 1H NMR δ
-0.18 (1, q, J ) 4.8 Hz), 0.30 (1, q, J ) 5.1 Hz), 0.50-0.73 (2,
m), 0.85-1.83 (24, m); 13C NMR δ 7.8, 10.0, 10.8, 12.6, 17.6,
18.8, 22.4, 22.6, 23.1, 30.3, 30.9, 34.5, 36.6, 68.7.
(1RS,2RS,7SR)-Bicyclo[5.1.0]oct a n -2-ol ((()-5a ) a n d
(1RS,2SR,7SR)-Bicyclo[5.1.0]octa n -2-ol ((()-5b). From ra-
cemic ketone 3b (178 mg, 1.43 mmol) and lithium aluminum
hydride (188 mg, 4.95 mmol) in ether at -78 °C was obtained
a separable mixture consisting of less polar and more polar
alcohols (()-5a and (()-5b, respectively. Chromatography on
silica gel 60 afforded 65 mg (0.52 mmol, 36%) of (()-5a , Rf
0.18 (30% ether/pentane), and 45 mg (0.36 mmol, 25%) of (()-
5b, Rf 0.11, as oils homgenous by TLC.
Sp ectr a l d a ta for (()-5a : 1H NMR δ 0.35-0.62 (2, m),
0.90-2.90 (10, m), 4.13-4.29 (1, m); 13C NMR δ 3.0, 14.9, 22.7,
24.9, 26.8, 28.5, 35.6, 71.2.
Sp ectr a l d a ta for (()-5b: 1H NMR δ 0.26-0.41 (1, m),
0.68-1.05 (4, m), 1.10-1.45 (2, m), 1.58-2.0 (5, m), 2.10-2.35
(1, m), 3.35 (1, m); 13C NMR δ 14.2, 14.43, 23.37, 27.86, 28.28,
31.23, 39.18, 76.48.
The phenylurethanes of (()-5a and (()-5b were prepared
as previously described13 and were found to melt at 73.5-75
°C (lit.13a mp 75.4-76 °C) and 121-122 °C (lit.13a mp 123-
124 °C), respectively.
Sp ectr a l d a ta for 32b: 1H NMR δ -0.06-0.02 (1, m), 0.09-
0.17 (1, m), 0.36-0.50 (1, m), 0.55-0.90 (2, m), 0.99-1.08 (1,
m), 1.15-2.16 (24, m), 6.80-6.98 (3, m), 7.20-7.36 (2, m).
(1S,2R,15S)-2-(1-Hexyn yl)bicyclo[13.1.0]h exa d eca n -2-
ol (34a ) a n d (1S,2S,15S)-2-(1-H exyn yl)b icyclo[13.1.0]-
h exa d eca n -2-ol (34b). To a well-stirred solution of 1-hexyne
(54 mg, 0.66 mmol) in ether (2 mL) at 0 °C was added a
solution of n-butyllithium in hexanes (0.5 mL of a 1.3 M
solution, 0.64 mmol). After 10 min the mixture was cooled to
-78 °C and a solution of 3k (51 mg, 0.21 mmol) in ether (2
mL) was added via cannula. The cannula was rinsed twice
with ether (1 mL). The reaction mixture was allowed to warm
to 0 °C over 3 h, and the reaction was quenched by dropwise
addition of a saturated aqueous NH4Cl solution (5 mL). The
mixture was diluted with water (5 mL) and extracted three
times with ether (15 mL). The ether extracts were dried
(MgSO4), filtered, and concentrated in vacuo to give a pale
yellow oil which was purified by column chromatography on
silica gel 60 eluted first with 5% and then with 10% ether/
hexanes. The yield of the less polar diastereomer 34a ,
obtained as an oil homogeneous by TLC, Rf 0.34 (10% EtOAc/
hexanes), was 62 mg (0.19 mmol, 90%). The yield of the more
polar diastereomer 34b, also obtained as an oil homogeneous
by TLC, Rf 0.07, was 1.0 mg (0.003 mmol, 1%).
Sp ectr a l d a ta for 34a : [R]25 -4.9° (c 3.08, CHCl3); IR
D
(neat) cm-1 3616, 3466 (br), 3066, 2996, 2927, 2853, 2233; 1H
NMR δ 0.20-0.30 (1, m), 0.58-0.75 (2, m), 0.81-0.97 (5, m),
1.12-1.85 (28, m), 2.21 (2, t, J ) 6.9 Hz); 13C NMR δ 7.9, 13.6,
14.2, 18.3, 21.9, 23.1, 25.7, 26.2, 26.3, 26.4, 27.1, 27.3, 28.6,
(1R,2S,7S)-2-Meth ylbicyclo[5.1.0]octa n -2-ol (6a ) a n d
(1R,2R,7S)-2-Meth ylbicyclo[5.1.0]octa n -2-ol (6b). From
ketone 3b (125 mg, 1.0 mmol) and methyllithium in ether (0.9
mL of a 1.4 M solution, 1.3 mmol) at -78 °C was obtained
124 mg (0.88 mmol, 88%) of a 2:5 mixture of product alcohols
6a and 6b as determined by 13C NMR. Chromatography on
silica gel 60 afforded 22 mg (0.16 mmol, 16%) of 6a , Rf 0.16
(20% ether/pentane), and 88 mg (0.63 mmol, 63%) of 6b, Rf
0.11, as oils homogeneous by TLC.
29.2, 30.9, 33.5, 43.3, 68.2, 83.6, 84.0; HRMS calcd for C22H38
318.2923, found 318.2919.
O
Sp ectr a l d a ta for 34b: IR (neat) cm-1 3441 (br), 2925,
2853, 2230; 1H NMR δ 0.20-0.30 (1, m), 0.75-1.02 (7, m),
1.20-1.90 (28, m), 2.15-2.28 (2, m).
(1R,2S,8S,SS)-2-[(N-Met h yl-S-p h en ylsu lfoxim id oyl)-
m eth yl]bicyclo[6.1.0]n on a n -2-ol (36b). To a well-stirred
solution of (S)-N,S-dimethyl-S-phenylsulfoximine [382 mg, 2.3
mmol, ∼85% ee, [R]25 +116° (c 4.0, MeOH), lit.17b [R]25
1
Sp ectr a l d a ta for 6a : H NMR δ 0.39-0.56 (2, m), 0.95-
1.03 (2, m), 1.20-1.96 (12, m); 13C NMR δ 4.7, 15.5, 25.0, 26.9,
D
D
27.2, 28.1, 30.4, 41.6.
-135.9° (c 4.60, MeOH) for the R enantiomer] in THF (4 mL)
at 0 °C was added a solution of n-BuLi in hexanes (1.6 mL of
a 1.2 M solution, 1.92 mmol). The solution was cooled to -78
°C, and a solution of 3c (103 mg, 0.75 mmol) in THF (2 mL)
was added via cannula. The cannula was rinsed with THF (2
× 1 mL). After 2 h, the mixture was poured into a saturated
aqueous NH4Cl solution (15 mL) and extracted with ether (2
× 25 mL). The ether was dried (MgSO4), filtered, and
concentrated in vacuo to give a yellow oil which was purified
by column chromatography on silica gel 60 (70-230 mesh)
eluted with 12% EtOAc/hexanes. The yield of the less polar
diastereomer 36a , Rf 0.11 (10% EtOAc/hexanes), obtained as
a white crystalline solid, mp 108-111 °C, was 21 mg (0.07
mmol, 9%). The yield of the more polar diastereomer 36b, Rf
0.08, also obtained as a white crystalline solid, mp 111.5-113.5
°C, was 203 mg (0.66 mmol, 88%).
1
Sp ectr a l d a ta for 6b: H NMR δ 0.34-0.53 (2, m), 0.96-
2.06 (14, m); 13C NMR δ 4.7, 16.2, 24.2, 25.9, 27.9, 28.1, 32.2,
40.3, 74.9.
(()-2-Meth ylbicyclo[5.1.0]octa n -2-ol ((()-6a ). Freshly
prepared Zn-Cu couple14 (700 mg, 11 mmol) and potassium
carbonate (350 mg, 2.5 mmol) were heated to reflux in freshly
distilled ether (3 mL). Diiodomethane (700 mg, 2.6 mmol) was
added dropwise via syringe, and the reaction mixture was
stirred for 15 min. A solution of 1-methyl-2-cyclohepten-1-ol
((()-8, 72 mg, 0.57 mmol) in ether (1 mL) was added by pipet.
The pipet was rinsed with ether (1 mL). After 3 h, the reaction
was cooled to 0 °C and 5% potassium carbonate solution (5
mL) was added. The resulting residue was filtered and
evaporated to give a pink oil which was purified on 240-400
mesh silica gel 60 eluted with ether/pentane (0-30%). The
yield of (()-6a , obtained as a colorless liquid, Rf 0.32 (40%
ether/pentane), was 42 mg (0.30 mmol, 52%).
Sp ectr a l d a ta for 36a : [R]24D +3.1° (c 1.0, CHCl3); IR (neat)
cm-1 3238 (br), 3021, 2990, 2923, 2860, 1475, 743, 690; 1H
NMR δ 0.35-0.70 (4, m), 1.36-1.92 (9, m), 2.60 (3, s), 2.70-
2.81 (1, m), 3.02 (1, d, J ) 13.8 Hz), 3.50 (1, d, J ) 13.8 Hz),
6.39 (1, s), 7.54-7.68 (3, m), 7.85-7.93 (2, m); 13C NMR δ 4.6,
17.4, 21.7, 24.6, 25.5, 25.9, 28.8, 29.1, 40.9, 66.3, 74.7, 128.9,
129.5, 133.0, 139.2.
Sp ectr a l d a ta for (()-6a : IR (neat) cm-1 3403 (br), 3070,
1
2964, 2920, 2853; H NMR δ 0.38-0.56 (2, m), 0.92-1.02 (2,
m), 1.14-1.95(12, m); 13C NMR δ 4.6, 15.6, 25.0, 26.9, 27.3,
28.2, 30.4, 41.6, 73.3.
(()-3-Hyd r oxy-3-m eth ylcycloh ep ten e ((()-8).19 To a
solution of methyllithium (7.4 mL of a 1.0 M solution, 7.4
mmol) in ether (9 mL) at -78 °C was added a solution of
2-cycloheptenone (270 mg, 2.45 mmol) in ether (2 mL) via
cannula. The cannula was rinsed twice with ether (0.5 mL).
The reaction mixture was allowed to warm to 0 °C over 2 h,
and the reaction was quenched by dropwise addition of a
saturated aqueous NH4Cl solution (10 mL). The mixture was
diluted with water (10 mL) and extracted with ether (3 × 20
mL). The ether extracts were dried (MgSO4), filtered, and
concentrated to give a colorless oil which was chromatographed
on silica gel 60 (70-230 mesh) eluted with 40% ether/pentane.
Sp ectr a l d a ta for 36b: [R]24 +32.6° (c 7.3, CHCl3); IR
D
(neat) cm-1 3240 (br), 3061, 2919, 2801, 742, 689; H NMR δ
1
0.57-0.90 (4, m), 1.36-1.65 (6, m), 1.70-1.97 (4, m), 2.61 (3,
s), 3.11 (1, d, J ) 13.7 Hz), 3.29 (1, d, J ) 13.7 Hz), 6.69 (1, s),
7.52-7.66 (3, m), 7.84-7.91 (2, m); 13C NMR δ 7.9, 16.7, 20.0,
22.9, 23.7, 26.1, 28.5, 28.6, 44.8, 67.7, 73.9, 128.8, 129.4, 132.9,
139.5; HRMS calcd for C9H14O (M - C8H11NOS) 138.1045,
found 138.1043, calcd for C8H11NOS 169.0562, found 169.0559.
The structure of 36b was established by single-crystal X-ray
analysis.20
(1R,2S,6S)-2-Meth ylbicyclo[4.1.0]h ep ta n -2-ol (4a ) a n d
(1R,2R,6S)-2-Meth ylbicyclo[4.1.0]h ep ta n -2-ol (4b). From
ketone 3a (510 mg, 4.6 mmol) and methyllithium in ether (6.4
mL of a 1.4 M solution, 9.0 mmol) at -78 °C was obtained an
(19) J efford, C. W.; Rimbault, C. G. Tetrahedron Lett. 1981, 22, 91-
94.

2750 J . Org. Chem., Vol. 61, No. 8, 1996
Mash et al.
1
The yield of (()-8, Rf 0.12 (10% Et2O/pentane), was 170 mg
(1.35 mmol, 55%).
Sp ectr a l d a ta for 12b: H NMR δ -0.30 to -0.21 (1, m),
0.49-0.60 (1, m), 0.85-1.02 (1, m), 1.14-1.30 (1, m), 1.35-
2.45 (10, m), 7.16-7.36 (3, m), 7.42-7.49 (2, m).
Sp ectr a l d a ta for (()-8: IR (neat) cm-1 3358 (br), 3011,
2965, 2924, 2856, 1651; 1H NMR δ 1.32 (3, d, J ) 2.9 Hz),
1.50-1.90 (6, m), 2.00-2.40 (3, m), 5.64 (2, dm, J ) 2.9 Hz);
13C NMR δ 24.3, 27.3, 27.5, 28.6, 40.8, 74.0, 129.1, 139.7.
(1RS,2SR,7SR)-2-Bu tylbicyclo[5.1.0]octa n -2-ol (7a ) a n d
(1RS, 2RS, 7SR)-2-Bu tylbicyclo[5.1.0]octa n -2-ol ((()-7b).
From ketone (()-3b (166 mg, 1.34 mmol) and butyllithium (2.9
mL of a 1.4 M solution in ether) at -78 °C was obtained a
separable mixture consisting of less polar and more polar
alcohols (()-7a and (()-7b, respectively. Chromatography on
silica 60 afforded 77 mg (0.42 mmol, 31%) of (()-7a , Rf 0.40
(15% EtOAc/hexanes), and 124 mg (0.68 mmol, 51%) of (()-
7b, Rf 0.30, as oils homogeneous by TLC.
(1R,2R,8S)-2-E t h en ylb icyclo[6.1.0]n on a n -2-ol (13a ).
From ketone 3c (100 mg, 0.72 mmol) and vinylmagnesium
bromide in ether (0.94 mL of a 1.0 M solution, 0.94 mmol) at
-78 °C was obtained 120 mg (0.72 mmol, 99%) of a single
diastereomeric alcohol (13a ) as an oil homogeneous by TLC,
Rf 0.55 (20% EtOAc/hexanes).
Sp ectr a l d a ta for 13a : [R]28 -43.9° (c 1.65, CHCl3); IR
D
(CHCl3) cm-1 3595, 3500 (br), 3007, 2925, 2861, 1708, 1634;
1H NMR δ 0.15-0.25 (1, m), 0.46-0.85 (3, m), 1.00 (1, s), 1.30-
1.93 (10, m), 4.97 (1, d, J ) 10.7 Hz), 5.19 (1, d, J ) 17.3 Hz),
6.04 (1, dd, J ) 17.3, 10.7 Hz); 13C NMR δ 4.2, 16.5, 21.1, 23.1,
24.1, 26.0, 28.7, 42.5, 73.4, 109.7, 148.7.
Sp ectr a l d a ta for (()-7a : 1H NMR δ 0.43-0.58 (2,m),
0.75-1.02 (4, m), 1.18-1.73 (15, m), 1.8-2.0 (1, m); 13C NMR
δ 6.10, 14.15, 15.42, 23.30, 24.77, 25.62, 25.72, 27.62, 28.75,
39.89, 43.60, 74.34.
Sp ectr a l d a ta for (()-7b: 1H NMR δ 0.44-0.54 (2, m),
0.87-0.99 (3, m), 1.00-1.10 (2, m), 1.10-1.20 (1, m), 1.20-
1.67 (12, m), 1.75, 1.91 (1, m), 2.00-2.15 (1, m); 13C NMR δ
5.03, 15.42, 14.11, 23.39, 23.83 25.72, 26.51, 26.66, 27.77,
37.78, 45.92, 76.80.
(1R,2S,8S)-2-(1-Hexyn yl)bicyclo[6.1.0]n on a n -2-ol (14a ).
From ketone 3c (90 mg, 0.65 mmol) and 1-lithiohexyne
(approximately 0.72 mmol, prepared from 90 µL of 1-hexyne
and 0.45 mL of a 1.6 M solution of n-BuLi in hexanes) in THF
at -78 °C was obtained 141 mg (0.64 mmol, 98%) of a single
diastereomeric alcohol (14a ) as an oil homogeneous by TLC,
Rf 0.66 (20% EtOAc/hexanes).
Sp ectr a l d a ta for 14a : [R]28 -62.4° (c 1.23, CHCl3); IR
D
(CHCl3) cm-1 3595, 3003, 2929, 2861, 2222; 1H NMR δ 0.35-
0.46 (1, m), 0.55-0.68 (2, m), 0.91 (3, t, J ) 6.8 Hz), 0.99-
1.10 (1, m), 1.25-1.90 (14, m), 2.04-2.16 (1, m), 2.19 (2, t, J
) 6.8 Hz); 13C NMR δ 4.5, 13.5, 16.8, 18.2, 20.6, 21.8, 23.9,
25.3, 25.5, 28.2, 30.7, 44.3, 68.7, 81.4, 87.1.
(1R,2S,8S)-Bicyclo[6.1.0]n on a n -2-ol (9a ). From ketone
3c (100 mg, 0.72 mmol) and lithium aluminum hydride (23
mg, 0.61 mmol) in ether at -78 °C was obtained 101 mg (0.72
mmol, 99%) of a single diastereomeric alcohol (9a ) as an oil
homogeneous by TLC, Rf 0.38 (20% EtOAc/hexanes).
(1R,2S,9S)-2-Meth ylbicyclo[7.1.0]decan -2-ol (15a). From
ketone 3d (30 mg, 0.2 mmol) and methyllithium in ether (0.2
mL of a 1.3 M solution, 0.26 mmol) at -78 °C was obtained
22 mg (0.13 mmol, 66%) of a single diastereomeric alcohol (15a )
as an oil homogeneous by TLC, Rf 0.48 (1% MeOH/CH2Cl2).
Sp ectr a l d a ta for 9a : [R]28 -21.7° (c 1.36, CHCl3); IR
D
(CHCl3) cm-1 3610, 3454 (br), 2994, 2915; H NMR δ 0.22-
1
0.30 (1, m), 0.50-0.70 (2, m), 0.86-0.99 (1, m), 1.15-2.00 (12,
m), 4.38-4.48 (1, m); 13C NMR δ 4.7, 15.7, 20.5, 20.7, 25.3,
25.3, 28.5, 36.4, 68.8.
Sp ectr a l d a ta for 15a : [R]28 -28.1° (c 0.32, CHCl3); IR
D
(CHCl3) cm-1 3605, 3480 (br), 3005, 2927, 2848; 1H NMR δ
-0.05-0.03 (1, m), 0.25-0.34 (1, m), 0.42-0.73 (2, m), 0.75-
1.03 (2, m), 1.18-1.36 (4, m), 1.36-1.57 (5, m), 1.60-2.15 (5,
m); 13C NMR δ 2.5, 14.5, 17.7, 23.5, 27.2, 28.6, 30.7, 31.3, 32.8,
41.7, 69.3.
(1R,2S,8S)-2-Meth ylbicyclo[6.1.0]n on an -2-ol (10a). From
ketone 3c (100 mg, 0.72 mmol) and methyllithium in ether
(0.7 mL of a 1.4 M solution, 0.98 mmol) at -78 °C was obtained
110 mg (0.71 mmol, 99%) of a single diastereomeric alcohol
(10a ) as an oil homogeneous by TLC, Rf 0.50 (20% EtOAc/
hexanes).
(1S,2R,12R)-Bicyclo[10.1.0]tr id eca n -2-ol (16a ). From
ketone 3e (88 mg, 0.45 mmol) and lithium aluminum hydride
(35 mg, 0.92 mmol) in ether at -78 °C was obtained 78 mg
(0.40 mmol, 88%) of a single diastereomeric alcohol (16a ) as
an oil homogeneous by TLC, Rf 0.21 (10% EtOAc/hexanes).
Sp ectr a l d a ta for 10a : [R]28 -26.1° (c 1.22, CHCl3); IR
D
(CHCl3) cm-1 3603, 3480 (br), 2995, 2965, 2925, 2861; 1H NMR
δ 0.18-0.26 (1, m), 0.46-0.76 (3, m), 0.86 (1, broad s), 1.25-
1.88 (13, m); 13C NMR δ 4.1, 16.2, 21.2, 24.0, 24.5, 26.0, 28.6,
34.7, 44.0, 71.4.
Sp ectr a l d a ta for 16a : [R]25 +42.7° (c 3.59, CHCl3); IR
D
(neat) cm-1 3387 (br), 3061, 2990, 2921, 2859; 1H NMR δ 0.28-
0.37 (1, m), 0.53-0.65 (1, m), 0.72-1.00 (2, m), 2.50-2.82 (19,
m), 4.04-4.14 (1, m); 13C NMR δ 6.4, 16.7, 21.9, 24.2, 24.3,
25.4, 25.7, 26.1, 26.4, 27.0, 27.1, 34.6, 69.8; HRMS calcd for
C13H24O 196.1827, found 196.1825.
(1R,2S,8S)-2-Bu tylbicyclo[6.1.0]n on a n -2-ol (11a ). From
ketone 3c (100 mg, 72 mmol) and n-butyllithium in ether (0.6
mL of a 1.6 M solution, 0.94 mmol) at -78 °C was obtained
131 mg (0.67 mmol, 92%) of a single diastereomeric alcohol
(11a ) as an oil homogeneous by TLC, Rf 0.58 (20% EtOAc/
hexanes).
(1S,2S,12R)-2-Eth en ylbicyclo[10.1.0]tr id eca n -2-ol (17a )
a n d (1S,2R,12R)-2-E t h en ylb icyclo[10.1.0]t r id eca n -2-ol
(17b). From ketone 3e (67 mg, 0.34 mmol) and vinylmagne-
sium bromide in ether (1.3 mL of a 1 M solution, 1.3 mmol) at
-78 °C was obtained a mixture consisting of less polar and
more polar diastereomeric alcohols 17a and 17b, respectively.
After chromatographic separation, the yield of 17a , obtained
as an oil homogeneous by TLC, Rf 0.52 (10% EtOAc/hexanes),
was 0.6 mg (0.003 mmol, 1%). The yield of 17b, also obtained
as an oil homogeneous by TLC, Rf 0.45, was 43 mg (0.19 mmol,
56%).
Sp ectr a l d a ta for 11a : [R]28 -31.6° (c 1.35, CHCl3); IR
D
(CHCl3) cm-1 3601, 2929, 2860, 1459, 1378, 1238, 1161, 1107,
1012, 891, 853; 1H NMR δ 0.15-0.28 (1, m), 0.45-0.71 (3, m),
0.85 (1, s), 0.91 (3, t, J ) 7.0 Hz), 1.22-1.90 (16, m); 13C NMR
δ 4.9, 14.2, 15.4, 21.0, 23.1, 23.4, 24.4, 25.9, 26.3, 28.7, 42.7,
47.5, 73.1.
(1R,2S,8S)-2-P h en ylbicyclo[6.1.0]n on a n -2-ol (12a ) a n d
(1R,2R,8S)-2-P h en ylbicyclo[6.1.0]n on a n -2-ol (12b). From
ketone 3c (220 mg, 1.6 mmol) and phenylmagnesium bromide
in ether (1.6 mL of a 3 M solution, 4.8 mmol) at -78 °C was
obtained a mixture consisting of less polar and more polar
diastereomeric alcohols 12a and 12b, respectively. After
chromatographic separation, the yield of 12a , obtained as an
oil homogeneous by TLC, Rf 0.36 (10% EtOAc/hexanes), was
310 mg (1.4 mmol, 91%). The yield of 12b, also obtained as
an oil homogeneous by TLC, Rf 0.20, was 14 mg (0.066 mmol,
4%).
Sp ectr a l d a ta for 17a : 1H NMR δ 0.13-0.29 (2, m), 0.35-
0.46 (1, m), 0.64-0.82 (3, m), 1.10-1.92 (17, m), 4.97 (1, dd, J
) 10.7, 1.1 Hz), 5.12 (1, dd, J ) 17.3, 1.1 Hz), 6.00 (1, dd, J )
17.3, 10.7 Hz).
Sp ectr a l d a ta for 17b: [R]25 +64.8° (c 1.96, CHCl3); IR
D
(neat) cm-1 3601, 3492 (br), 3059, 2921, 2860, 1634; 1H NMR
δ 0.18-0.27 (1, m), 0.51-0.64 (1, m), 0.66-0.82 (1, m), 0.85-
0.95 (1, m), 1.15 (1, s), 1.25-1.84 (19, m), 5.05 (1, dd, J ) 10.7,
1.1 Hz), 5.18 (1, dd, J ) 17.3, 1.1 Hz), 5.99 (1, dd, J ) 17.3,
10.7 Hz); 13C NMR δ: 5.7, 18.1, 22.9, 25.3, 25.5, 25.9, 26.2,
26.6, 27.6, 27.8, 39.2, 74.4, 111.1, 146.4; HRMS calcd for
C15H26O 222.1984, found 222.1981.
Sp ectr a l d a ta for 12a : [R]25 -88.1° (c 2.38, CHCl3); IR
D
(neat) cm-1 3559, 3482 (br), 3056, 2976, 2919, 2858, 1597, 732,
699; 1H NMR δ 0.34-0.54 (2, m), 0.63-0.80 (1, m), 0.99-1.10
(1, m), 1.28 (1, s), 1.42-2.00 (9, m), 2.09 m(1, ddd, J ) 13.8,
11.2, 2.9 Hz), 7.17-7.27 (1, m), 7.27-7.38 (2, m), 7.48-7.56
(2, m); 13C NMR δ 4.6, 17.4, 21.2, 24.2, 25.1, 26.1, 28.6, 44.1,
(1S,2R,15R)-Bicyclo[13.1.0]h exa d eca n -2-ol (18a ). From
ketone 3f (41 mg, 0.17 mmol) and lithium aluminum hydride
(16 mg, 0.42 mmol) in ether at -78 °C was obtained 39 mg
74.9, 124.4, 126.4, 128.0, 151.8; HRMS calcd for C15H20
216.1514, found 216.1512.
O

Manipulations of Bicyclo[m.1.0]alkane Derivatives
J . Org. Chem., Vol. 61, No. 8, 1996 2751
(0.16 mmol, 96%) of a single diastereomeric alcohol (18a ) as
an oil homogeneous by TLC, Rf 0.17 (10% EtOAc/hexanes).
bromide in ether (0.2 mL of a 3.0 M solution, 0.66 mmol) at
-78 °C was obtained a mixture consisting of less polar and
more polar diastereomeric alcohols 25a and 25b, respectively.
The yield of 25a , obtained as an oil homogeneous by TLC, Rf
0.30 (10% EtOAc/hexanes), was 97 mg (0.37 mmol, 97%). The
yield of 25b, also obtained as an oil homogeneous by TLC, Rf
0.16, was 0.5 mg (0.002 mmol, ca. 1%).
Sp ectr a l d a ta for 18a : [R]25 +3.7° (c 1.92, CHCl3); IR
D
(neat) cm-1 3357 (br), 3063, 2991, 2927, 2855; 1H NMR δ
-0.05-0.08 (1, m), 0.63-0.88 (3, m), 1.10-1.67 (25, m), 3.35-
3.48 (1, m); 13C NMR δ 8.6, 15.0, 22.3, 22.6, 25.2, 25.4, 25.9,
26.2, 26.3, 26.6, 26.7, 27.0, 27.3, 36.6, 69.7; HRMS calcd for
C16H30O 238.2297, found 238.2294.
Sp ectr a l d a ta for 25a : [R]25 -38.5° (c 2.50, CHCl3); IR
D
(neat) cm-1 3457 (br), 3057, 2996, 2925, 2847, 726, 698, 610;
1H NMR δ 0.19-0.28 (1, m), 0.56-0.66 (1, m), 0.74-0.90 (1,
m), 0.98-1.71 (17, m), 1.79 (1, td, J ) 12.8, 4.1 Hz), 1.98-
2.17 (2, m), 7.20-7.39 (3, m), 7.55-7.62 (2, m); 13C NMR δ
9.3, 13.5, 20.8, 22.8, 23.6, 24.3, 24.7, 27.4, 27.8, 28.0, 32.8, 42.4,
(1S,2S,15R)-2-E t h en ylb icyclo[13.1.0]h exa d eca n -2-ol
(19a) an d (1S,2R,15R)-2-Eth en ylbicyclo[13.1.0]h exadecan -
2-ol (19b). From ketone 3f (60 mg, 0.25 mmol) and vinyl-
magnesium bromide in THF (1.0 mL of a 1 M solution, 1.0
mmol) at -78 °C was obtained a mixture consisting of less
polar and more polar diastereomeric alcohols 19a and 19b,
respectively. The yield of 19a , obtained as an oil homogeneous
by TLC, Rf 0.44 (10% EtOAc/hexanes), was 51 mg (0.19 mmol,
76%). The yield of 19b, also obtained as an oil homogeneous
by TLC, Rf 0.19, was 0.9 mg (0.003 mmol, ca. 1%).
74.2, 125.6, 126.9, 128.1, 147.8; HRMS calcd for C19H28
272.2140, found 272.2134.
O
Sp ectr a l d a ta for 25b: 1H NMR δ 0.11-0.19 (1, m), 0.68-
0.92 (4, m), 1.15-1.95 (18, m), 7.20-7.37 (3, m), 7.45-7.50 (2,
m).
Sp ectr a l d a ta for 19a : [R]25 +52.6° (c 2.21, CHCl3); IR
D
(1S,2S,12S)-2-Eth en ylbicyclo[10.1.0]tr id eca n -2-ol (26a )
a n d (1S,2S,12S)-2-E t h en ylb icyclo[10.1.0]t r id eca n -2-ol
(26b). From ketone 3i (66 mg, 0.34 mmol) and vinylmagne-
sium bromide in THF (1.4 mL of a 1.0 M solution, 1.4 mmol)
at -78 °C was obtained a mixture consisting of less polar and
more polar diastereomeric alcohols 26a and 26b, respectively.
The yield of 26a , obtained as an oil homogeneous by TLC, Rf
0.32 (10% EtOAc/hexanes), was 69 mg (0.31 mmol, 92%). The
yield of 26b, also obtained as an oil homogeneous by TLC, Rf
0.19, was 1.6 mg (0.01 mmol, 2%).
(neat) cm-1 3603, 3488 (br), 3059, 2927, 2855, 1637; 1H NMR
δ 0.18-0.27 (1, m), 0.50-0.61 (1, m), 0.70-0.92 (2, m), 1.14
(1, s), 1.22-1.82 (24, m), 5.06 (1, dd, J ) 10.6, 1.1 Hz), 5.19 (1,
dd, J ) 17.2, 1.1), 5.98 (1, dd, J ) 17.2, 10.6); 13C NMR δ 5.6,
17.5, 21.0, 24.8, 25.0, 25.2, 25.2, 25.3, 26.5, 26.9, 27.7, 29.0,
39.2, 74.1, 111.2, 145.8; HRMS calcd for C18H32O 264.2453,
found 264.2457.
Sp ectr a l d a ta for 19b: 1H NMR δ 0.00-0.09 (1, m), 0.19-
0.28 (1, m), 0.58-0.92 (2, m), 1.15-1.70 (25, m), 5.13 (1, dd, J
) 10.5, 1.3 Hz), 5.28 (1, dd, J ) 17.1, 1.3 Hz), 5.70 (1, dd, J )
17.1, 10.5 Hz).
Sp ectr a l d a ta for 26a : [R]24 -65.0° (c 2.45, CHCl3); IR
D
(neat) cm-1 3452 (br), 3081, 2998, 2926, 2848, 1638; 1H NMR
δ 0.09-0.18 (1, m), 0.53-0.62 (1, m), 0.66-0.99 (3, m), 1.07
(1, s), 1.21-1.73 (15, m), 1.76-1.93 (1, m), 2.02 (1, ddt, J )
13.1, 9.6, 3.7 Hz), 5.06 (1, dd, J ) 10.8, 1.3 Hz), 5.28 (1, dd, J
) 17.4, 1.3 Hz), 6.03 (1, dd, J ) 17.4, 10.8 Hz); 13C NMR δ 8.8,
12.7, 20.5, 22.5, 23.5, 23.9, 24.0, 27.3, 27.8, 28.0, 32.7, 41.0,
72.7, 112.1, 145.1; HRMS calcd for C15H26O 222.1984, found
222.1988.
(1R,2R,16S)-2-Met h ylb icyclo[14.1.0]h ep t a d eca n -2-ol
(20a ). From ketone 3g (48 mg, 0.19 mmol) and methyllithium
in ether (0.18 mL of a 1.4 M solution, 0.25 mmol) at -78 °C
was obtained 48 mg (0.18 mmol, 94%) of a single diastereo-
meric alcohol (20a ) as an oil homogeneous by TLC, Rf 0.55
(20% EtOAc/hexanes).
Sp ectr a l d a ta for 20a : [R]28 -12.2° (c 0.72, CHCl3); IR
D
(CHCl3) cm-1 3603, 2995, 2927, 2855; 1H NMR δ 0.18-0.27
(1, m), 0.50-0.60 (1, m), 0.70-0.80 (2, m), 0.91 (1, s), 1.20-
1.78 (29, m); 13C NMR δ 5.4, 17.2, 22.5, 25.9, 26.3, 26.4, 26.7,
26.8, 27.1, 27.1, 27.3, 27.4, 28.1, 28.7, 29.4, 30.1, 41.8, 72.1.
(1R,2S,11R)-2-Meth ylbicyclo[9.1.0]d od eca n -2-ol (21a ).
From ketone 3h (24.5 mg, 0.14 mmol) and methyllithium in
ether (0.11 mL of a 1.4 M solution, 0.15 mmol) at -78 °C was
obtained 28 mg (0.14 mmol, 99%) of a single diastereomeric
alcohol (21a ) as an oil.
Sp ectr a l d a ta for 26b: 1H NMR δ 0.10-0.19 (1, m), 0.67-
0.92 (4, m), 1.15-1.80 (16, m), 1.93-2.08 (1, m), 2.22-2.35 (1,
m), 5.03 (1, dd, J ) 10.9, 1.4 Hz), 5.21 (1, dd, J ) 17.4, 1.4
Hz), 5.99 (1, dd, J ) 17.4, 10.9 Hz).
(1S,2R,12S)-2-(1-H exyn yl)b icyclo[10.1.0]t r id eca n -2-ol
(27a) an d (1S,2S,12S)-2-(1-Hexyn yl)bicyclo[10.1.0]tr idecan -
2-ol (27b). From ketone 3i (75 mg, 0.39 mmol) and 1-lithio-
hexyne (approximately 1.2 mmol, prepared from 178 µL of
1-hexyne and 0.90 mL of a 1.3 M solution of n-BuLi in hexanes)
in ether at -78 °C was obtained a mixture consisting of less
polar and more polar diastereomeric alcohols 27a and 27b,
respectively. The yield of 27a , obtained as an oil homogeneous
by TLC, Rf 0.37 (10% EtOAc/hexanes), was 105 mg (0.38 mmol,
97%). The yield of 27b, also obtained as an oil homogeneous
by TLC, Rf 0.20, was 1.2 mg (0.004 mmol, 1%).
Sp ectr a l d a ta for 21a : IR (CHCl3) cm-1 3605, 3466 (br),
1
3003, 2925, 2851; H NMR δ 0.03-0.11 (1, m), 0.42-0.58 (2,
m), 0.65-0.90 (3, m), 1.22-1.77 (17, m), 2.01-2.14 (1, m); 13
C
NMR δ 6.2, 15.0, 21.7, 22.6, 26.8, 26.9, 27.1, 28.0, 28.3, 28.7,
32.2, 40.8, 70.5.
(1S,2R,12S)-2-Meth ylbicyclo[10.1.0]tr id eca n -2-ol (23a ).
From ketone 3i (77 mg, 0.40 mmol) and methyllithium in ether
(2.0 mL of a 0.6 M solution, 1.2 mmol) at -78 °C was obtained
73 mg (0.34 mmol, 87%) of a single diastereomeric alcohol (23a )
as a colorless solid, mp 41-45 °C, homogeneous by TLC, Rf
0.23 (10% EtOAc/hexanes).
Sp ectr a l d a ta for 27a : [R]25 -49.2° (c 4.85, CHCl3); IR
D
(neat) cm-1 3456 (br), 2999, 2928, 2850, 2237; 1H NMR δ 0.16-
0.27 (1, m), 0.62-1.05 (7, m), 1.15-2.05 (22, m), 2.21 (2, t, J
) 6.8 Hz); 13C NMR δ 9.5, 12.7, 13.5, 18.3, 21.0, 21.9, 22.3,
23.3, 23.7, 26.5, 27.1, 27.6, 27.6, 30.8, 32.3, 41.6, 68.1, 83.3,
84.4; HRMS calcd for C19H32O 276.2453, found 276.2452.
Sp ectr a l d a ta for 27b: 1H NMR δ 0.08-0.17 (1, m), 0.58-
1.03 (7, m), 1.22-1.99 (22, m), 2.17 (2, t, J ) 6.7 Hz).
(1R,2S,13R)-2-Meth ylbicyclo[11.1.0]tr id eca n -2-ol (28a ).
From ketone 3j (36 mg, 0.17 mmol) and methyllithium in ether
(0.16 mL of a 1.4 M solution, 0.23 mmol) at -78 °C was
obtained 35 mg (0.16 mmol, 90%) of a single diastereomeric
alcohol (28a ) as an oil homogeneous by TLC, Rf 0.28 (10%
EtOAc/hexanes).
Sp ectr a l d a ta for 23a : [R]24 -89.1° (c 3.48, CHCl3); IR
D
(neat) cm-1 3417 (br), 2995, 2925, 2848; 1H NMR δ 0.02-0.12
(1, m), 0.58-0.85 (4, m), 0.98 (1, s), 1.20-1.67 (18, m), 1.70-
1.83 (1, m), 1.92-2.06 (1, m); 13C NMR δ 8.3, 12.9, 20.8, 22.5,
23.5, 24.1, 26.1, 27.3, 27.7, 28.0, 28.8, 32.7, 41.8, 70.6; HRMS
calcd for C14H26O 210.1984, found 210.1977.
(1S,2R,12S)-2-Bu tylbicyclo[10.1.0]tr id eca n -2-ol (24a ).
From ketone 3i (71 mg, 0.37 mmol) and n-butyllithium in ether
(0.85 mL of a 1.3 M solution, 1.1 mmol) at -78 °C was obtained
49.5 mg (0.2 mmol, 54%) of a single diastereomeric alcohol
(24a ) as an oil homogeneous by TLC, Rf 0.37 (10% EtOAc/
hexanes).
Sp ectr a l d a ta for 28a : [R]28 +85.2° (c 1.04, CHCl3); IR
D
(neat) cm-1 3603, 3484 (br), 3003, 2929, 2851; 1H NMR δ 0.00-
0.09 (1, m), 0.42-0.63 (3, m), 0.80-0.93 (2, m), 1.20-1.62 (20,
m), 1.67-1.80 (1, m), 1.98 (1, ddt, J ) 13.9, 9.8, 3.4 Hz); 13C
NMR δ 6.2, 14.3, 20.8, 22.6, 22.8, 24.4, 25.5, 26.3, 26.8, 27.9,
28.3, 29.5, 34.2, 43.4, 70.4.
Sp ectr a l d a ta for 24a : [R]24 -71.0° (c 2.34, CHCl3); IR
D
(neat) cm-1 3474 (br), 2994, 2928, 2849; 1H NMR δ 0.04-0.16
(1, m), 0.57-1.00 (8, m), 1.18-1.75 (22, m), 1.92-2.08 (1, m);
13C NMR δ 9.1, 12.0, 14.1, 20.5, 22.4, 23.3, 24.0, 25.4, 25.5,
27.2, 27.7, 28.1, 32.9, 39.5, 41.2, 72.2; HRMS calcd for C17H32
252.2453, found 252.2458.
O
(1S,2R,15S)-Bicyclo[13.1.0]h exa d eca n -2-ol (29a ) a n d
(1S,2S,15S)-Bicyclo[13.1.0]h exa d eca n -2-ol (29b). From
ketone 3k (53 mg, 0.22 mmol) and lithium aluminum hydride
(30 mg, 0.79 mmol) in ether at -78 °C was obtained a mixture
consisting of less polar and more polar diastereomeric alcohols
(1S,2R,12S)-2-P h en ylbicyclo[10.1.0]tr id eca n -2-ol (25a )
an d (1S,2S,12S)-2-P h en ylbicyclo[10.1.0]tr idecan -2-ol (25b).
From ketone 3i (71 mg, 0.37 mmol) and phenylmagnesium

2752 J . Org. Chem., Vol. 61, No. 8, 1996
Mash et al.
29a and 29b, respectively. The yield of 29a , Rf 0.19 (10%
EtOAc/hexanes), obtained as a white solid, mp 64-65 °C, was
51 mg (0.21 mmol, 96%). The yield of 29b, Rf 0.10, also
obtained as a white solid, was 1.4 mg (0.006 mmol, 3%).
Sp ectr a l d a ta for 37a : [R]24 -10.8° (c 8.4, CHCl3); IR
D
(neat) cm-1 3258 (br), 3061, 2996, 2925, 2848, 2803, 732, 689;
1H NMR δ -0.14-0.05 (1, m), 0.43-0.65 (2, m), 0.78-0.88 (1,
m), 0.89-1.04 (1, m), 1.12-1.66 (14, m), 1.82-1.98 (1, m),
1.99-2.09 (2, m), 2.52 (3, s), 3.08 (1, d, J ) 13.9 Hz), 3.24 (1,
d, J ) 13.9 Hz), 6.47 (1, s), 7.47-7.60 (3, m), 7.79-7.85 (2, m);
13C NMR δ 9.1, 12.7, 21.1, 22.2, 23.6, 24.0, 26.7, 27.2, 27.6,
27.8, 28.7, 32.4, 38.9, 62.3, 72.6, 128.8, 129.4, 132.9, 138.9;
HRMS calcd for C13H22O (M - C8H11NOS) 194.1671, found
194.1631, calcd for C8H11NOS 169.0562, found 169.0557.
Sp ectr a l d a ta for 29a : [R]25 -69.0° (c 0.21, CHCl3); IR
D
(neat) cm-1 3424, 3390, 3001, 2926, 2850; 1H NMR δ 0.15-
0.24 (1, m), 0.54-0.87 (4, m), 1.15-1.56 (24, m), 1.76-1.90 (1,
m), 3.85-3.93 (1, m); 13C NMR δ 7.7, 12.7, 23.5, 23.7, 25.9,
26.1, 26.3, 26.3, 27.1, 27.1, 29.2, 33.5, 36.9, 68.8; HRMS calcd
for C16H30O 238.2297, found 238.2296.
Sp ectr a l d a ta for 29b: [R]25 -8.6° (c 0.07, CHCl3); 1H
Sp ectr a l d a ta for 37b: [R]24 -23.1° (c 0.26, CHCl3); IR
D
D
NMR δ 0.29-0.37 (1, m), 0.40-0.49 (1, m), 0.60-0.85 (3, m),
1.22-1.77 (24, m), 2.76-2.86 (1, m).
(neat) cm-1 3245 (br), 3061, 2998, 2924, 2849, 2803, 746, 690;
1H NMR δ 0.35-0.45 (1, m), 0.70-1.72 (19, m), 1.79-2.06 (2,
m), 2.63 (3, s), 3.25 (1, d, J ) 13.8 Hz), 3.36 (1, d, J ) 13.8
Hz), 6.55 (1, s), 7.52-7.68 (3, m), 7.84-7.92 (2, m); 13C NMR
δ 12.3, 12.8, 19.7, 21.8, 23.2, 23.7, 24.0, 27.0, 27.6, 27.8, 28.7,
32.7, 41.7, 64.2, 72.6, 128.9, 129.5, 133.0, 139.3.
(1S,2R,15S)-2-Meth ylbicyclo[13.1.0]h exadecan -2-ol (30a).
From ketone 3k (104 mg, 0.42 mmol) and methyllithium in
ether (1.0 mL of a 1.4 M solution, 1.4 mmol) at -78 °C was
obtained 97 mg (0.38 mmol, 90%) of a single diastereomeric
alcohol (30a ) as an oil homogeneous by TLC, Rf 0.29 (10%
EtOAc/hexanes).
(1S,2R,15S,SS)-2-[(N-Met h yl-S-p h en ylsu lfoxim id oyl)-
m eth yl]bicyclo[13.1.0]h exa d eca n -2-ol (38a ). From ketone
3k (92 mg, 0.39 mmol) and lithio-(S)-N,S-dimethyl-S-phenyl-
sulfoximine (85% ee, ca. 0.96 mmol, prepared from 198 mg of
(S)-N,S-dimethyl-S-phenylsulfoximide and 0.80 mL of a 1.2 M
solution of n-BuLi in hexanes) in THF at -78 °C was obtained
a mixture consisting of less polar and more polar diastereo-
meric alcohols 38a and 38b, respectively. The yield of 38a ,
Rf 0.15 (10% EtOAc/hexanes), obtained as a colorless solid, mp
97.5-99 °C, was 157 mg (0.38 mmol, 99%). The yield of 38b,
Rf 0.11, also obtained as a colorless solid, was 0.5 mg (0.001
mmol, 0.3%).
Sp ectr a l d a ta for 30a : [R]24 -33.7° (c 1.92, CHCl3); IR
D
(neat) cm-1 3441 (br), 2923, 2853; 1H NMR δ 0.05-0.15 (1,
m), 0.46-0.60 (2, m), 0.62-0.94 (3, m), 1.10-1.61 (25, m),
1.65-1.81 (1, m); 13C NMR δ 7.1, 14.0, 22.8, 25.7, 26.2, 26.2,
26.3, 26.7, 27.0, 27.4, 27.6, 27.8, 28.2, 29.2, 33.8, 43.7, 70.2;
HRMS calcd for C17H32O 252.2453, found 252.2450.
(1S,2R,15S)-2-Bu tylbicyclo[13.1.0]h exa d eca n -2-ol (31a )
a n d (1S,2S,15S)-2-Bu t ylb icyclo[13.1.0]h exa d eca n -2-ol
(31b). From ketone 3k (58 mg, 0.25 mmol) and n-butyllithium
in ether (0.57 mL of a 1.3 M solution, 0.74 mmol) at -78 °C
was obtained a mixture consisting of less polar and more polar
diastereomeric alcohols 31a and 31b, respectively. The yield
of 31a , obtained as an oil homogeneous by TLC, Rf 0.38 (10%
EtOAc/hexanes), was 61 mg (0.21 mmol, 85%). The yield of
31b, also obtained as an oil homogeneous by TLC, Rf 0.21, was
1 mg (0.003 mmol, ca. 1%).
Sp ectr a l d a ta for 38a : [R]24 +25.1° (c 7.8, CHCl3); IR
D
(neat) cm-1 3262 (br), 3063, 2923, 2852, 2803, 733, 689; 1H
NMR δ 0.00-0.10 (1, m), 0.47-0.52 (1, m), 0.64-0.80 (2, m),
0.99-1.75 (22, m), 1.93 (1, ddm, J ) 14.4, 9.2 Hz), 2.14-2.28
(1, m), 2.59 (3, s), 3.14 (1, d, J ) 13.9 Hz), 3.27 (1, d, J ) 13.9
Hz), 6.52 (1, s), 7.54-7.68 (3, m), 7.85-7.93 (2, m); 13C NMR
δ 7.8, 14.1, 23.4, 25.5, 25.6, 25.8, 26.2, 26.4, 27.0, 27.3, 27.4,
27.6, 28.7, 28.8, 33.4, 41.0, 62.3, 72.3, 128.8, 129.4, 132.9, 139.0;
HRMS calcd for C16H28O (M - C8H11NOS) 236.2140, found
236.2142, calcd for C8H11NOS 169.0562, found 169.0560.
Sp ectr a l d a ta for 38b: 1H NMR δ 0.39-0.48 (1, m), 0.69-
1.80 (27, m), 2.62 (3, s), 3.14 (1, d, J ) 13.8 Hz), 3.40 (1, d, J
) 13.8 Hz), 6.36-6.46 (1, m), 7.54-7.65 (3, m), 7.85-7.91 (2,
m).
Sp ectr a l d a ta for 31a : [R]24 -14.5° (c 0.61, CHCl3); IR
D
(neat) cm-1 3477 (br), 2994, 2926, 2854; 1H NMR δ 0.09-0.19
(1, m), 0.48-0.60 (2, m), 0.67-0.82 (3, m), 0.91 (3, t, J ) 7.0
Hz), 1.13-1.62 (28, m), 1.74 (1, dd, J ) 16.7, 8.3 Hz); 13C NMR
(C6D6) δ 8.1, 13.4, 14.5, 22.9, 23.9, 26.0, 26.2, 26.6, 26.6, 26.7,
27.2, 27.3, 27.4, 27.9, 28.1, 29.7, 34.3, 41.0, 42.0, 71.4; HRMS
calcd for C20H38O 294.2923, found 294.2924.
Sp ectr a l d a ta for 31b: IR (neat) cm-1 3413 (br), 2925,
2853; 1H NMR δ 0.10-0.20 (1, m), 0.50-0.60 (1, m), 0.65-
1.60 (36, m).
The structure of 38a was established by single-crystal x-ray
analysis.20
(1S,2S,15S)-2-E t h e n ylb icyclo[13.1.0]h e xa d e ca n -2-ol
(33a ). From ketone 3k (91 mg, 0.39 mmol) and vinylmagne-
sium bromide in THF (1.15 mL of a 1.0 M solution, 1.15 mmol)
at -78 °C was obtained 73 mg (0.28 mmol, 72%) of a single
diastereomeric alcohol (33a ) as an oil homogeneous by TLC,
Rf 0.37 (10% EtOAc/hexanes).
Ack n ow led gm en t. Partial support of this research
by Research Corporation, by the Howard Hughes Medi-
cal Research Foundation, by the Elsa U. Pardee Foun-
dation, by the E. I. DuPont de Nemours Co., and by the
University of Arizona through the Materials Charac-
terization Program, the Department of Chemistry, and
the Office of the Vice President for Research is gratefully
acknowledged. Technical assistance from L. J . Wil-
liams, M. Bruck, M. A. Chandler, and J . A. Baron is
gratefully acknowledged.
Sp ectr a l d a ta for 33a : [R]25 -10.4° (c 2.99, CHCl3); IR
D
(neat) cm-1 3472 (br), 3080, 2995, 2925, 2853, 1638; 1H NMR
δ 0.09-0.19 (1, m), 0.38-0.48 (1, m), 0.60-0.92 (3, m), 0.98
(1, s), 1.09-1.49 (22, m), 1.54-1.65 (1, m), 1.66-1.81 (1, m),
5.01 (1, dd, J ) 10.7, 1.3 Hz), 5.17 (1, dd, J ) 17.4, 1.3 Hz),
5.91 (1, dd, J ) 17.4, 10.7 Hz); 13C NMR (C6D6) δ 8.0, 14.1,
22.8, 26.1, 26.6, 26.8, 26.9, 26.9, 26.9, 27.6, 27.8, 29.7, 34.2,
42.8, 72.4, 111.5, 145.1; HRMS calcd for C18H32O 264.2453,
found 264.2454.
Su p p or tin g In for m a tion Ava ila ble: Mass spectral frag-
ment lists, 13C NMR spectra of new cyclopropyl ketones 3 and
of the major diastereomers for compounds 4-38, and ORTEP
structures for 36b and 38a (55 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.
(1S,2R,12S,SS)-2-[(N-Met h yl-S-p h en ylsu lfoxim id oyl)-
m eth yl]bicyclo[10.1.0]tr id eca n -2-ol (37a ). From ketone 3i
(94 mg, 0.48 mmol) and lithio-(S)-N,S-dimethyl-S-phenylsul-
foximine (85% ee, ca. 1.2 mmol, prepared from 241 mg of (S)-
N,S-dimethyl-S-phenylsulfoximide and 1.0 mL of a 1.2 M
solution of n-BuLi in hexanes) in THF at -78 °C was obtained
a mixture consisting of less polar and more polar diastereo-
meric alcohols 37a and 37b, respectively. The yield of 37a ,
Rf 0.14 (10% EtOAc/hexanes), obtained as a colorless solid, mp
83-86 °C, was 167 mg (0.46 mmol, 95%). The yield of
diastereomer 37b, Rf 0.08, also obtained as a colorless solid,
mp 110-114 °C, was 5.2 mg (0.014 mmol, 3%).
J O951753K
(20) The author has deposited atomic coordinates for 36b and 38a
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.