Synthesis of α-necrodol: Unexpected formation of a cyclopropene

Article abstract of DOI:10.1021/jo961780q

Significant 1,3-induction in intramolecular alkylidene C-H insertion is reported. Thus, exposure of ketone I to the lithium salt of (trimethylsilyl)diazomethane provides a 2.4:1.0 ratio of IIa and IIIa, which are deprotected to α-necrodol IIb and the epimeric IIIb. The 1,3-insertion product cyclopropene IV was also formed.

Full text of DOI:10.1021/jo961780q

J . Org. Chem. 1997, 62, 1687-1690
1687
Syn th esis of r-Necr od ol: Un exp ected F or m a tion of a
Cyclop r op en e
Douglass F. Taber* and Han Yu
Department of Chemistry and Biochemistry University of Delaware Newark, Delaware 19716
Received September 17, 1996X
Significant 1,3-induction in intramolecular alkylidene C-H insertion is reported. Thus, exposure
of ketone I to the lithium salt of (trimethylsilyl)diazomethane provides a 2.4:1.0 ratio of IIa and
IIIa , which are deprotected to R-necrodol IIb and the epimeric IIIb. The 1,3-insertion product
cyclopropene IV was also formed.
In tr od u ction
steps from camphoric anhydride. No subsequent syn-
thetic work has been reported.4
The intramolecular alkylidene carbene insertion has
recently been developed as a method for constructing
cyclopentenes.1 However, the diastereoselectivity of me-
thylene insertion is still a issue that must be resolved.
In our earlier paper,1k the diastereoselectivity of 1,2-
induction, in which the target methylene was adjacent
to the established chiral center, was studied. We now
report significant 1,3-induction of relative configuration
on methylene insertion. This has allowed the diastereo-
selective synthesis of R-necrodol 2b, a monoterpene
alcohol isolated from the defensive spray of the red-lined
carrion beetle.2
Com p u ta tion a l An a lysis. The key questions in the
synthesis were whether the alkylidene carbene would
insert into a methylene group that was deactivated5 by
a â-oxygen and, if the insertion were successful, whether
the desired trans cyclopentene would be a major product.
Our analysis of the transition states for this cyclization
is outlined below.
R-Necrodol (2b ) was first synthesized3 by Meinwald
and co-workers in 1990. In that initial synthesis, the
cyclopentene skeleton of 2b was derived over several
X Abstract published in Advance ACS Abstracts, March 1, 1997.
(1) For references to cyclopentene construction by intramolecular
C-H insertion by an alkylidene carbene, see: (a) Karpf, M.; Dreiding,
A. S. Helv. Chim. Acta 1979, 62, 825. (b) Gilbert, J . C.; Giamalva, D.
H.; Weerasooriya, U. J . Org. Chem. 1983, 48, 5251. (c) Gibert, J . C.;
Giamalva, D. H.; Baze, M. E. J . Org. Chem. 1985, 50, 2557. (d) Ochiai,
M.; Kunishima, M.; Nagao, Y.; Fuji, K.; Shiro, M.; Fujita, E. J . Am.
Chem. Soc. 1986, 108, 8281. (e) Gilbert, J . C.; Giamalva, D. H. J . Org.
Chem. 1992, 57, 4185. (f) Ochiai, M.; Uemura, K.; Masaki, Y. J . Am.
Chem. Soc. 1993, 115, 2528. (g) Schildknegt, K.; Bohnstedt, A. C.;
Feldman, K. S.; Sambandam, A. J . Am. Chem. Soc. 1994, 116, 93. (h)
Kunishima, M.; Hioki, K.; Tani, S.; Kato, A. Tetrahedron Lett. 1994,
35, 7253. (i) Williamson, B. L.; Tykwinski, R. R.; Stang, P. J . J . Am.
Chem. Soc. 1994, 116, 93. (j) Kim, S.; Cho, C. M. Tetrahedron Lett.
1994, 35, 8405. (k) Taber, D. F.; Meagley, R. P. Tetrahedron Lett. 1994,
35, 7909. (l) Taber, D. F.; Walter, R.; Meagley, R. P. J . Org. Chem.
1994, 59, 6014. (m) Taber, D. F.; Sahli, A.; Yu, H.; Meagley, R. P. J .
Org. Chem. 1995, 60, 6571. (n) Ohira, S.; Okai, K.; Moritani, T. J .
Chem. Soc., Chem. Commun. 1995, 36, 1537. (o) Ohira, S.; Noda, I.;
Mizobata, T.; Yamato, M. Tetrahedron Lett. 1995, 36, 3375. (p) Ohira,
S.; Sawamoto, T.; Ymato, M. Tetrahedron Lett. 1995, 36, 1537. (q)
Ohira, S.; Yamasaki, K.; Nozaki, H.; Yamato, M.; Nakayama, M.
Tetrhadron Lett 1995, 36, 8843. (r) Taber, D. F.; Christos, T. E.; Hodge,
C. N. J . Org. Chem. 1996, 61, 2081. (s) Taber, D. F.; Meagley, R. P.;
Doren, D. J . J . Org. Chem. 1996, 61, 5723.
As we have recently reported,1s,6,7 the transition state
for the alkylidene insertion can be approximated by
establishing a “weak” bond (meaningful in Mechanics)7
between the carbene carbon and the target H-atom.
Following this analysis, transition states A and B would
lead to the trans diastereomer, while transition states C
(4) For the references to the syntheses of â-necrodol and epi-â-
necrodol, see: (a) Oppolzer, W.; Schneider, P. Helv. Chim. Acta 1986,
69, 1817. (b) Trost, B. M.; Braslau, R. Tetrahedron Lett. 1988, 29, 1231.
(c) Schulte-Elte, K. H.; Pamingle, H. Helv. Chim. Acta 1989, 72, 1158.
(5) Stork, G.; Nakatani, K. Tetrahedron Lett. 1988, 29, 2283.
(6) For an RHF approximation of the insertion transition state, see
our Web site at “http://valhalla.chem.udel.edu/alkylidene.html”. The
lead graphic in this document depicts the calculated orbital overlap
in the C-H insertion transition state. The RHF approximation is also
available electronically (see the Supporting Information).
(7) (a) Molecular mechanics calculations were carried out using the
program Mechanics, implemented on a Tektronix CAChe workstation
interfaced with a Silicon Graphics Indigo workstation. This code is
based on the MM2 molecular mechanics code of Allinger, with
extensions provided by the CAChe group. Full documentation is
available from Oxford Molecular, Beaverton, OR. (c) For a detailed
analysis of the electronic structure of alkylidenes (vinylidenes) and of
the rearrangement to the corresponding alkyne, see: Gallo, M. M.;
Hamilton, T. P.; Schaefer, H. F., III. J . Am. Chem. Soc. 1990, 112,
8714.
(2) (a) Eisner, T.; Meinwald, J . Psyche 1982, 89 , 357. (b) Eisner,
T.; Deyrup, M.; J acobs, R.; Meinwald, J . J . Chem. Ecol. 1986, 12, 1407.
(c) Meinwald, J . Ann. N. Y. Acad. Sci. 1986, 471, 197. (d) Roach, B.;
Eisner, T.; Meinwald, J . J . Org. Chem. 1990, 55, 4047.
(3) J acobs, R. T.; Feutrill, G. I.; Meinwald, J . J . Org. Chem. 1990,
55, 4051.
S0022-3263(96)01780-X CCC: $14.00 © 1997 American Chemical Society

1688 J . Org. Chem., Vol. 62, No. 6, 1997
Taber and Yu
Sch em e 1a
time. This addition was more efficient in the presence
of a catalytic amount of copper(I) bromide.12
Syn th esis of r-n ecr od ol. Ketone 1 was converted
to the transient alkylidene carbene following our modi-
fications1k,l of the Ohira protocol. Thus, treatment of the
DME solution of (trimethylsilyl)diazomethane with n-
butyllithium in hexane at -60 °C resulted in a slurry of
[(trimethylsilyl)diazomethyl]lithium that was allowed to
warm until just homogeneous. This solution was chilled
again to -40 °C before addition of ketone 1. Under these
conditions, insertion proceeded to give the trans-cyclo-
pentene 2a :cis-cyclopentene 3a in a 2.4:1.0 ratio, in 41%
total yield. Deprotection then gave R-necrodol 2b and
the cis diastereomer 3b in the same 2.4:1.0 ratio.13 By
TLC, 13C NMR, 1H NMR, IR, and mass spectra, the
synthetic material was identical to that originally re-
ported.
Cyclop r op en e F or m a tion . The yield from the cy-
clization of ketone 1 was unusually low. In fact, we
isolated another product from the cyclization in 41%
yield. This was determined to be the unexpected cyclo-
propene 8.14 At least two factors may accelerate 1,3-
insertion in this case. On the one hand, insertion into a
methine CH is more facile than insertion into a methyl-
ene CH.1b,c Further, the target CH for 1,5-insertion in
this case is deactivated by a â-oxygen.5
a
Key: (a) LiAlH4, THF; (b) benzyl bromide, NaH, THF; (c)
Swern; (d) 1,2-epoxy-3-phenoxypropane, N,N-dimethylhydrazine,
2-propanol; (e) LDA, MeI, THF; (f) MeMgBr, CuBr (cat.), THF;
(g) (trimethylsilyl)diazomethane, BuLi, DME; (h) Na/NH3, THF.
J ones13a has reported a similarly substituted cyclopro-
pene with 13C chemical shifts for the alkene CH at δ 110.2
and for the quaternary alkene carbon at δ 130.2.15 Our
usual 13C pulse sequence puts methylene and quaternary
carbons “up” and methine and methyl carbons “down”.
However, the signal at δ 110.0 for 8 was “up”. HETCOR
analysis established that this signal correlated with the
1H alkene signal at δ 6.51. This anomaly is due to the
CH coupling constant, an unusually high 218 Hz.16
and D would lead to the cis diastereomer. The relative
energies after minimization of these transition-state
models were compared. The results indicate that the
transition state A leading to the trans product is more
stable than the nearest competitor that would lead to the
1,3-cis product by (a modest) 1.0 kcal/mol.
In both transition state A and transition state B, one
of the substituents is pseudoaxial on the intermediate
“cyclohexene”. It is striking that both of these transition
states are predicted to be more stable than C, in which
both substituents are pseudoequatorial. The key to this
difference is in the gauche interactions of these substit-
uents with the gem-dimethyl groups between them. In
C, the gauche interactions are maximized.
P r ep a r a tion of k eton e 1. Starting with commer-
cially available 3,3-dimethylglutaric anhydride 4 (Scheme
1), reduction by LiAlH4 followed by monobenzylation led
to the primary alcohol 5. After Swern oxidation,8 the
aldehyde was converted to the nitrile 6 using the method
developed by Ikeda and co-workers.9,10 Alkylation of 611
proceeded smoothly to provide the monomethylated ni-
trile 7 as the only product.
Converting the nitrile 7 to ketone 1 was not successful
using MeLi addition. When MeMgBr was used instead
of MeLi, the ketone was formed in acceptable yield but
only with a large excess of the reagent and a long reflux
Con clu sion
Although it is certainly not yet a rigorously quantita-
tive analysis, it is encouraging that our computational
approach to understanding the transition state for in-
tramolecular alkylidene CH insertion was successful in
predicting the preference for a trans product from the
cyclization of ketone 1. The observation of competing 1,3-
insertion may open a new route to cyclopropenes.
Exp er im en ta l Section 17
3,3-Dim eth yl-5-p h en ylm eth oxy-1-p en ta n ol (5). To a
flask containing LiAlH4 (1.1 g, 30.2 mmol) in THF (100 mL)
at 0 °C was added dropwise over 20 min 3,3-dimethylglutaric
(12) Weiberth, F. J .; Hall, S. S. J . Org. Chem. 1987, 52, 3901.
(13) The ratio of products from the cyclization was determined by
integration of the 1H NMR spectrum of the crude product mixture.
(14) For leading references to cyclopropene construction, see: (a)
Likhotvorik, I. R.; Brown, D. W.; J ones, M. J . Am. Chem. Soc. 1994,
116, 6175. (b) Boese, R.; Blaser, D.; Billups, W. E.; Haley, M. M.; Luo,
W.; Arney, B. E. J . Org. Chem. 1995, 59, 8125. (c) Baldwin, J . E.;
Villarica, K. A. J . Org. Chem. 1995, 60, 186. (d) Kurek-Tyrlik, A.;
Minksztym, K.; Wicha, J . J . Am. Chem. Soc. 1995, 117, 1849.
(15) As the arene carbons dominated the 13C spectrum in this area,
we were unable to confirm this signal for 8.
(8) Manusco, A. J .; Huang, S. L.; Swern, D. J . J . Org. Chem. 1978,
43, 2480.
(9) Ikeda, I.; Machii, Y.; Okahara, M. Synthesis 1978, 301.
(10) Almost any monosubstituted epoxide should work in this
procedure. The original authors used ethylene oxide and propylene
oxide.
(16) We have found that the 13C signals of terminal alkynes also
are “up”. Again, the C-H coupling constant in this case is large, 230
Hz.
(11) Edstrom, E.; Livinghouse, T. J . Chem. Soc., Chem. Commun.
1986, 279.
(17) For general experimental procedures, see: Taber, D. F.; Houze,
J . B. J . Org. Chem. 1994, 59, 4004.

Synthesis of R-Necrodol
J . Org. Chem., Vol. 62, No. 6, 1997 1689
anhydride (3.6 g, 25.2 mmol) in 20 mL of THF. The mixture
was warmed to rt overnight, and then was carefully quenched
with 1 mL of water. The mixture was stirred for 10 min, 10%
aqueous NaOH (1 mL) was added dropwise over 10 min, the
mixture was stirred for another 10 min, and then 2 mL of
water was added. After filtration with EtOAc (3 × 20 mL),
the combined filtrate was dried (K2CO3) and concentrated to
give 2.9 g of diol.
4,4-Dim et h yl-3-m et h yl-6-(p h en ylm et h oxy)-2-h exa n -
on e (1). To a stirred solution of nitrile 7 (413 mg, 1.79 mmol)
and MeMgBr (0.66 mL of 3.0 M in ether, 2.0 mmol) in 5 mL of
THF was added CuBr (5 mg, 0.03 mmol), and the mixture was
refluxed at 80 °C under nitrogen for 24 h. The mixture was
cooled to ambient temperature, and then 5 mL of water was
cautiously added, followed by 5 mL of 15% aqueous HCl. This
mixture was maintained at 100 °C for 3 h. After the mixture
was cooled to rt, 10 mL of EtOAc was added, the layers were
separated, and the aqueous layer was extracted twice more
with 10 mL portions of EtOAc. The combined organic extract
was dried (Na2SO4) and concentrated. The black residue was
chromatographed to afford ketone 1 (337 mg, 1.36 mmol, 76%
yield from 7) as a colorless oil: TLC Rf (10% EtOAc/petroleum
ether) ) 0.40; 1H NMR δ 7.35-7.30 (m, 5H), 4.48 (s, 2H), 3.53
(t, J ) 6.5 Hz, 2H), 2.54 (q, J ) 7.1 Hz, 1H), 2.12 (s, 3H), 1.73-
1.62 (m, 2H), 1.02 (d, J ) 7.1 Hz, 3H), 0.98 (s, 3H), 0.95 (s,
3H); 13C NMR δ down 128.3, 127.6, 127.5, 54.4, 32.0, 25.0, 24.7,
12.1; up 213.2, 138.5, 73.0, 67.1, 39.5, 34.9; IR (cm-1) 2967,
2877, 2366, 1710, 1457, 1364, 1102; MS (m/z) 157 (6), 142 (6),
141 (18), 125 (9); HRMS calcd for C16H24O2 248.1776, found
248.1775.
3-[(P h en ylm eth oxy)m eth yl]-1,4,4,5-tetr a m eth ylcyclo-
p en ten e (2a a n d 3a ). Under nitrogen, n-BuLi (0.55 mL of
2.1 M in hexane, 1.15 mmol) was added dropwise at -60 °C
to (trimethylsilyl)diazomethane (0.57 mL, 2.0 M in hexane,
1.15 mmol) in DME (1.5 mL). After 5 min at -60 °C, the dry
ice bath was removed, and the mixture was allowed to warm
until it turned homogeneous. The mixture was then cooled
to -40 °C, and ketone 1 (141 mg, 0.57 mmol) in 1 mL of DME
was added dropwise over 5 min. The solution was stirred at
-30 to -40 °C for another 45 min and then warmed to -10
°C over 2 h. The mixture was quenched with 5 mL of
saturated aqueous NH4Cl at -10 °C, the layers were then
separated, and the aqueous layer was extracted with EtOAc
(3 × 5 mL). The combined organic extract was dried (Na2SO4)
and concentrated, and the residue was chromatographed to
give the cyclopentenes 2a and 3a and cyclopropene 8 (61 mg,
0.25 mmol, 83% yield) in a 2.4:1.0:3.4 ratio, followed by 66 mg
of ketone 1.
To a cold solution (0 °C) of diol (2.9 g, 22.0 mmol) in 70 mL
of THF was added NaH (1.1 g, 24.2 mmol, 60% in mineral oil).
After the reaction subsided, benzyl bromide (4.5 g, 26.4 mmol)
was added. The mixture was stirred overnight and then was
quenched with water (20 mL) and extracted with CH2Cl2 (2 ×
20 mL). The combined organic extract was dried (Na2SO4) and
concentrated. The residue was chromatographed to give the
alcohol 5 (2.6 g, 11.7 mmol, 46% yield from anhydride) as a
clear yellow oil: TLC Rf (20% EtOAc/petroleum ether) ) 0.18;
1H NMR δ 7.33-7.30 (m, 5H), 4.48 (s, 2H), 3.65 (t, J ) 6.1 Hz,
2H), 3.53 (t, J ) 7.1 Hz, 2H), 2.14 (bs, 1H), 1.61 (t, J ) 6.1 Hz,
2H), 1.53 (t, J ) 7.1 Hz, 2H), 0.92 (s, 6H); 13C NMR δ down
128.3, 127.6, 127.5, 27.9; up 138.9, 73.0, 67.3, 59.4, 44.4, 41.1,
31.6; IR (cm-1) 3393, 2956, 2930, 2869, 1453, 1366, 1101; MS
(m/z) 113 (19), 108 (21), 107 (49), 91 (100); HRMS calcd for
C
14H22O2 222.1620, found 222.1624.
3,3-Dim et h yl-5-(p h en ylm et h oxy)p en t a n en it r ile (6).
DMSO (1.1 mL, 15.7 mmol) was added slowly at -78 °C to a
solution of oxalyl chloride (1.3 g, 10.2 mmol) in 50 mL of
CH2Cl2. After the reaction subsided, alcohol 5 (1.8 g, 7.9 mmol)
in 10 mL of CH2Cl2 was added dropwise. The mixture was
kept at -78 °C for 1 h, and then triethylamine (4.0 mL, 39.4
mmol) was added dropwise and the reaction mixture was
warmed slowly to rt. Water (10 mL) was added, the layers
were separated, and the aqueous layer was extracted with
CH2Cl2 (2 × 10 mL). The combined organic extract was dried
(Na2SO4) and concentrated to give the crude aldehyde.
1,2-Epoxy-3-phenoxypropane (3.0 g, 19.8 mmol) was added
to a solution of N,N-dimethylhydrazine (0.57 g, 9.5 mmol) in
2-propanol (4 mL). The flask containing the mixture was
closed tightly and heated to 50 °C for 3 h. The above fresh
aldehyde in 4 mL of 2-propanol was added to this mixture at
rt and then stirred at rt for an additional 3 h. 2-Propanol was
evaporated in vacuo, and the residue was chromatographed
to give 1.2 g (5.4 mmol, 68% yield from 5) of nitrile 6 as a pale
2a was separated from cyclopropene 8 by preparative TLC
as a pale yellow oil: Rf (2% EtOAc/petroleum ether) ) 0.72;
1H NMR δ 7.27-7.17 (m, 5H), 5.17-5.14 (m, 1H), 4.42 (s, 2H),
3.43-3.34 (m, 2H), 2.48-2.40 (m, 1H), 2.04-2.01 (m, 1H), 1.57
1
(s, 3H), 0.89 (s, 3H), 0.85 (s, 3H), 0.78 (d, J ) 7.2 Hz, 3H); 13
C
yellow oil: TLC Rf (10% EtOAc/petroleum ether) ) 0.40; H
NMR δ 7.35-7.24 (m, 5H), 4.45 (s, 2H), 3.53 (t, J ) 6.3 Hz,
2H), 2.28 (s, 2H), 1.67 (t, J ) 6.3 Hz, 2H), 1.06 (s, 6H); 13C
NMR δ down 128.3, 127.5, 127.4, 27.1; up 138.1, 118.6, 73.0,
66.7, 40.3, 32.5, 30.7; IR (cm-1) 2962, 2933, 2872, 2242, 1454,
1370, 1103; MS (m/z) 231 (14), 217 (16), 181 (30), 167 (24),
131 (19), 119 (34), 111(12); HRMS calcd for C14H19NO 217.1467,
found 217.1469. Anal. Calcd for C14H19NO: C, 77.38; H, 8.81.
Found: C, 77.30; H, 9.06.
NMR δ down 128.3, 127.5, 127.3, 124.2, 53.4, 52.8, 24.5, 24.0,
15.3, 12.6; up 144.5, 138.2, 73.1, 71.1, 43.0.
3a was separated from cyclopropene 8 by preparative TLC
as a pale yellow oil: Rf (2% EtOAc/petroleum ether) ) 0.72;
1H NMR δ 7.27-7.17 (m, 5H), 5.17-5.14 (m, 1H), 4.41 (s, 2H),
3.32-3.23 (m, 2H), 2.48-2.40 (m, 1H), 2.04-2.01 (m, 1H), 1.50
(s, 3H), 1.01 (s, 3H), 0.78 (d, J ) 7.2 Hz, 3H), 0.66 (s, 3H); 13
C
NMR δ down 128.3, 127.5, 127.3, 124.3, 54.6, 52.9, 29.3, 17.7,
3,3-Dim eth yl-2-m eth yl-5-(p h en ylm eth oxy)p en ta n en i-
tr ile (7). n-BuLi (14.6 mL of 1.25 M in hexane, 18.2 mmol)
was added dropwise at -78 °C to diisopropylamine (2.1 g, 20.6
mmol) in THF (20 mL). After the mixture was stirred at -78
°C for 15 min, nitrile 6 (2.5 g, 11.4 mmol) in 2 mL of THF was
added quickly. The solution was stirred for another 7 min at
-78 °C, and then MeI (2.6 g, 18.2 mmol) was added dropwise.
The mixture was stirred at -78 °C for 1 h and then stirred at
rt for another hour. The mixture was poured into ice-cold 10%
aqueous HCl (20 mL), and then water (20 mL) and EtOAc (20
mL) were added. The layers were separated, and the aqueous
layer was extracted with EtOAc (3 × 20 mL). The combined
organic extract was dried (Na2SO4) and concentrated, and the
residue was chromatographed to give the methylated nitrile
7 (2.2 g, 9.5 mmol, 84% yield) as a pale yellow oil: TLC Rf
(10% EtOAc/petroleum ether) ) 0.40; 1H NMR δ 7.28-7.17
(m, 5H), 4.39 (s, 2H), 3.45 (t, J ) 6.7 Hz, 2H), 2.51 (q, J ) 7.2,
1H), 1.60 (dt, J ) 2.4 Hz, J ) 6.7 Hz, 2H), 1.13 (d, J ) 7.2 Hz,
3H), 0.97 (s, 3H), 0.94 (s, 3H); 13C NMR δ down 128.3, 127.5,
127.4, 36.1, 25.0, 24.2, 12.9; up 138.2, 122.1, 73.0, 66.6, 38.7,
34.6; IR (cm-1) 2966, 2361, 2237, 1454, 1368, 1104; MS (m/z)
231 (10), 110 (14), 107 (35); HRMS calcd for C15H21NO
231.1623, found 231.1619.
15.3, 13.0; up 144.5, 138.2, 73.1, 71.9, 43.0.
2a + 3a : IR (cm-1) 2961, 2869, 1454, 1362, 1112, 1028; MS
(m/z) 153 (20), 136 (55), 135 (11), 124 (14), 123 (100), 121 (25);
HRMS calcd for C17H24O 244.1827, found 244.1819.
8 was separated from cyclopentenes 2a and 3a by prepara-
tive TLC as a clear oil: Rf (2% EtOAc/petroleum ether) ) 0.67;
1H NMR δ 7.25-7.12 (m, 5H), 6.51 (s, 1H), 4.39 (s, 2H), 3.42
(t, J ) 7.9 Hz, 2H), 1.90 (s, 3H), 1.55 (dt, J ) 2.4, 7.9 Hz, 2H),
0.90 (s, 3H), 0.63 (s, 3H), 0.61 (s, 3H); 13C NMR δ down 128.3,
127.6, 127.4, 27.3, 27.0, 21.0, 11.1; up 138.7, 110.0 (see text),
72.9, 68.2, 40.1, 37.2, 28.8; IR (cm-1) 2959, 2866, 1765, 1454,
1363, 1101, 1028; MS (m/z) 153 (15), 123 (18), 135 (11), 110
(14), 109 (31); HRMS calcd for C17H24O 244.1827, found
244.1838.
3-(Hydr oxym eth yl)-1,4,4,5-tetr am eth ylcyclopen ten e (2b
a n d 3b). To 25 mL of liquid ammonia at -78 °C was added
sodium metal (30 mg, 1.3 mmol) in small pieces. Cyclopentene
2a and 3a (70 mg, 0.29 mmol) in 5 mL of THF was added to
the above dark blue solution. The mixture was stirred at -78
°C for 15 min, and then solid NH4Cl (50 mg) was added to
quench the reaction. The mixture was warmed to rt over 1 h
and then was diluted with 10 mL of water and 10 mL of EtOAc.
The phases were separated, and the aqueous layer was

1690 J . Org. Chem., Vol. 62, No. 6, 1997
Taber and Yu
extracted with EtOAc (3 × 5 mL). The combined organic
extract was dried (Na2SO4) and concentrated. The residue was
chromatographed to give cyclopentenes 2b and 3b (40 mg, 0.26
mmol, 89% yield from 2a and 3a ) in a 2.4:1.0 ratio as a pale
yellow oil: TLC Rf (15% EtOAc/petroleum ether) ) 0.45.
2b: 1H NMR δ 5.22-5.21 (m, 1H), 3.65-3.44 (m, 2H), 2.36-
2.24 (m, 1H), 2.18-2.07 (m, 1H), 1.65 (d, J ) 1.3 Hz, 3H), 0.98
(s, 3H), 0.89 (s, 3H), 0.84 (d, J ) 7.5 Hz, 3H); 13C NMR δ down
123.1, 56.4, 52.2, 24.9, 23.6, 15.2, 11.9; up 145.7, 63.1, 43.0.
3b: 1H NMR δ 5.22-5.21 (m, 1H), 3.65-3.44 (m, 2H), 2.36-
2.24 (m, 1H), 2.18-2.07 (m, 1H), 1.65 (d, J ) 1.3 Hz, 3H), 1.04
(s, 3H), 0.86 (d, J ) 7.5 Hz, 3H), 0.79 (s, 3H). 13C NMR δ down
123.2, 57.6, 53.1, 30.5, 18.3, 15.2, 13.6; up 145.2, 63.7, 43.1.
2b + 3b: IR (cm-1) 3384, 2961, 2870, 1459, 1364, 1260,
1018; MS (m/z) 154 (11), 139 (16), 123 (100), 121 (22), 119 (17);
HRMS calcd for C17H24O 154.1358, found 154.1380.
Ack n ow led gm en t. We thank the donors of the
Petroleum Research Fund, adminstered by the Ameri-
can Chemical Society, for support of this work. We also
thank R. P. Meagley for helpful discussions and M. D.
Bruch for assistance with NMR.
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C spectra
for all new compounds (14 pages). An RHF approximation of
the insertion transition state is also available electronically.
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
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J O961780Q