Ruthenium-catalyzed homo Diels-Alder [2 + 2 + 2] cycloadditions of alkynyl phosphonates with bicyclo[2.2.1]hepta-2,5-diene

Article abstract of DOI:10.1021/jo2010928

Ruthenium-catalyzed homo Diels-Alder [2 + 2 + 2] cycloadditions between alkynyl phosphonates and bicyclo[2.2.1]hepta-2,5-diene were studied. The observed reactivity was found to be dependent on the presence of the phosphonate moiety. The Ru-catalyzed cycloaddition was compatible with a variety of aromatic and aliphatic substituted alkynyl phosphonates, providing the corresponding phosphonate substituted deltacyclenes in low to good yields (up to 88%).

Full text of DOI:10.1021/jo2010928

NOTE
pubs.acs.org/joc
Ruthenium-Catalyzed Homo DielsÀAlder [2 + 2 + 2] Cycloadditions of
Alkynyl Phosphonates with Bicyclo[2.2.1]hepta-2,5-diene
Tanner J. Kettles, Neil Cockburn, and William Tam*
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry, University of Guelph, Guelph,
Ontario, Canada N1G 2W1
S Supporting Information
b
ABSTRACT: Ruthenium-catalyzed homo DielsÀAlder [2 + 2 + 2]
cycloadditions between alkynyl phosphonates and bicyclo[2.2.1]hepta-2,5-
diene were studied. The observed reactivity was found to be dependent on
the presence of the phosphonate moiety. The Ru-catalyzed cycloaddition
was compatible with a variety of aromatic and aliphatic substituted alkynyl
phosphonates, providing the corresponding phosphonate substituted delta-
cyclenes in low to good yields (up to 88%).
he homo-DielsÀAlder (HDA) cycloaddition is described as
Scheme 1. Literature Examples of Transition-Metal-Catalyzed
HDA Cycloaddition of Alkynes
T
[2 + 2 + 2] cycloaddition resulting in the formation of
tetracyclic structures of considerable strain known as deltacy-
clanes. These reactions have been reported to occur both
thermally and with transition-metal catalysis.1 Typically, the
HDA cycloaddition between bicyclic alkenes and alkynes has
been explored en route to highly substituted fused polycyclic
intermediates in natural product synthesis.2 The use of transition
metals to catalyze this reaction has been well documented, and
cycloadditions involving alkynyl dienophiles have been pro-
moted by cobalt,3 cobaltÀzinc,4 and ruthenium5 catalysts,
Scheme 1. For example, using the Ru(II) catalyst (NBD)RuCl2
(PPh3)2, Tenaglia performed the HDA cycloaddition between
norbornadiene and a variety of symmetrical and unsymmetrical
disubstituted alkynes, and good yields at 90 °C for 5À60 h were
achieved.5a
Scheme 2. Ruthenium-Catalyzed [2 + 2] Cycloadditions be-
tween Bicyclic Alkenes and Alkynyl Phosphonates
In the past decade our research group has extensively inves-
tigated ruthenium catalyzed [2 + 2] cycloadditions between
bicyclic alkenes and a wide range of alkynes yielding a variety
of cyclobutene adducts.6,7 Recently we reported on [2 + 2]
cycloadditions between bicyclic alkenes and electron deficient
alkynyl phosphonates catalyzed by Cp*RuCl(COD), these sub-
strates were found to be less reactive than other heteroatom
containing alkynes, requiring relatively long reaction time and a
higher reaction temperature, Scheme 2.8
To achieve a faster rate of reaction, optimization studies of the
various reactions parameters were undertaken, including screen-
ing of a variety of solvents. When polar aprotic NMP was used as
a solvent it was found that the expected [2 + 2] cycloadduct was
not formed; instead, only the [2 + 2 + 2] HDA cycloadduct was
observed. This is the first example of a homo-DielsÀAlder
cycloaddition involving alkynyl phosphonates and the only het-
eroatom-substituted alkyne other than silicon to undergo this
mode of reaction.3f,4a,4b In this paper, we report our studies of the
homo-DielsÀAlder [2 + 2 + 2] cycloadditions between alkynyl
phosphonates and bicyclo[2.2.1]hepta-2,5-diene (norbornadiene)
catalyzed by Cp*RuCl(COD).
Vinyl phosphonates have been found to be important biomo-
lecules in metabolic processes, as anticancer and antiviral drugs,
and as antibacterial and antifungal compounds.9 The phospho-
nate group can also be modified by established procedures to a
wide variety of other phosphorus groups including phosphines.10
The selective fragmentation of homo-DielsÀAlder cycloadducts
into diquinanes is also well established.2 The formation of a HDA
cycloadduct containing a vinyl phosphonate is thus desirable, and
investigations into the observed ruthenium catalyzed [2 + 2 + 2]
HDA cycloaddition were further pursued.
Received: June 9, 2011
Published: July 06, 2011
r
2011 American Chemical Society
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|

The Journal of Organic Chemistry
NOTE
Table 1. Optimization of Solvent and Temperature for
Ru-Catalyzed HDA [2 + 2 + 2] Cycloaddtions of Norbornadiene
1 with 1-Phenylethynyl Phosphonate 8a
Table 2. Screening of Ruthenium Catalysts for HDA [2 + 2 +
2] Cycloaddtions of Norbornadiene 1 with 1-Phenylethynyl
Phosphonate 8a
yielda (%)
yielda (%)
entry
T (°C)
solvent
NMP
9a
0b
10a
entry
catalyst
9a
10a
1
2
100
150
160
160
160
160
160
160
100
100
0
0
1
2
3
4
5
6
7
8
9
Cp*RuCl(COD), 7
Cp*RuCl(COD), AgOTf
[Cp*Ru(CH3CN)3]+ PF6
[RuCl2(CO)3]2
92
5b
0
0
NMP
70b
92
53
69
0b
0c
55b
7b
0b
0b
0c
0c
0c
0
À
3
NMP
0
4
DMF
12
12
9
0
5
mesitylene
diglyme
DMSO
ethylene glycol
dioxane
neat
CpRuCl(COD)
RuCl2(COD)
25
8
6
7
0
RuCl2(PPh3)3
0
8
0c
0
CpRuCl(PPh3)2
0
9
0
60d
71d
no catalyst
0
a Yield by quantitative 31P NMR with internal P(OMe)3. b Starting
alkyne observed in the 31P NMR spectrum. c Only starting alkyne
observed in the 31P NMR spectrum.
10
0
a Yield by quantitative 31P NMR with internal P(OMe)3. b Starting
alkyne observed in 31P NMR spectrum. Starting alkyne and decom-
c
position of alkyne observed in 31P NMR spectrum. d The reaction
mixture was stirred for 240 h, see ref 8.
Scheme 3. Attempted Cycloadditions of Substituted
Acetylenes without a Phosphonate Functionality
The observed HDA [2 + 2 + 2] cycloaddition between alkynyl
phosphonate 8a, synthesized by our previously reported
method,8 and norbornadiene 1 was optimized. The optimization
experiments were performed with a 2 h reaction time and were
monitored by 31P NMP. Initially a series of solvents and
temperatures were screened for their ability to promote the
previously described HDA [2 + 2 + 2] cycloaddition, table 1. No
evidence of any reaction was observed at temperatures below
100 °C; however, once the temperature was elevated to 150 °C
the homo-DielsÀAlder cycloadduct was observed, though some
starting alkyne was still present (entries 1 and 2). The desired
cycloadduct was achieved in 92% yield, and complete consump-
tion of starting alkyne was observed at 160 °C with NMP (entry
3). To evaluate the effect of solvent, a variety of other high-
boiling solvents were screened at 160 °C (entries 3À8). Both
DMF and mesitylene yielded the HDA adduct 9a in lower yields
and reduced selectivity with the observation of 12% [2 + 2]
adduct 10a (entries 4 and 5). Diglyme, DMSO, and ethylene
glycol (entries 6À8) were all noneffect. Using dioxane as solvent
or running the reaction neat in norbornadiene 1, only [2 + 2]
cycloadduct 10a was formed.8 NMP was found to be the optimal
solvent to promote the formation of homo-DielsÀAlder adduct
9a in high yield.
(entry 5) interestingly led to the observation of only [2 + 2]
cycloadduct 10a in 25%; similarly, replacing the Cp* ligand with
Cl (entry 6) yielded 10a as the sole adduct in 8%. The
replacement of the COD ligand with phosphine (entries 7
and 8) eliminated reactivity toward either cycloadduct, and only
unreacted starting alkyne was observed; these systems are
most similar to the (NBD)RuCl2(PPh3)2 catalyst used by
Tenaglia for HDA reaction of disubstituted alkenes and nor-
bornadiene.5a A control experiment with no catalyst was also
conducted (entry 9), and only unreacted alkynyl phosphonate
was observed.
After initial optimization studies, the reaction conditions were
applied to other alkynes to demonstrate whether the phospho-
nate functionality was a necessity to achieve the observed HDA
cycloaddition, Scheme 3. A quick screen of substituted acetylenes
resulted in the exclusive formation of [2 + 2] cycloadducts,8
suggesting that the HDA [2 + 2 + 2] cycloaddition is unique to
the electronics of phosphonate-substituted alkynes when
Cp*RuCl(COD) is used as the catalyst.
A variety of ruthenium catalysts were screened and the results
are shown in table 2. Entry 2 shows that addition of silver triflate
to Cp*RuCl(COD) (to generate a cationic active ruthenium
species) greatly reduced the yield of HDA adduct 9a. Another
cationic Ru species examined (entry 3) was able to exclusively
generate the desired HDA adduct 9a in moderate yield but still
was less effective than Ru catalyst 7. Entry 4, a ruthenium dimer,
achieved exclusive formation of the HDA adduct 9a, however, in
only 7% yield. Replacing the Cp* ligand of Ru catalyst 7 with Cp
A variety of alkynyl phosphonates were prepared to better
understand the electronic and steric factors influencing the
observed ruthenium-catalyzed HDA [2 + 2 + 2] cycloadditions
between alkynyl phosphonates and bicyclic alkenes. All alkynes
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NOTE
Scheme 4. Thermal Decomposition of Homo-DielsÀAlder
Table 3. Ru-Catalyzed HDA [2 + 2 + 2] Cycloadditions of
Norbornadiene 1 with Alkynyl Phosphonates 8aÀs
Cycloadduct 9g
entry
alkyne
R1
R
time (h)
yielda (%)
1
2
8a
8b
8c
8d
8e
8f
Et
Me
Ph
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Ph
2
88
were readily prepared from deprotonation of commercially
available terminal alkynes using LDA or LHMDS followed by
trapping the resulting carbanion with a chlorophosphonate.8 The
following examples of Ru-catalyzed HDA [2 + 2 + 2] cycloaddi-
tions of both aliphatic and aromatic substituted alkynyl phos-
phonates were heated for no longer than 6 h, even if not all
starting alkynyl phosphonate had been consumed. It was found
that prolonged heating could lead to decomposition of both the
starting alkynyl phosphonate and the HDA adduct. The decom-
position involved removal of the phosphonate moiety; this was
observed most readily with alkyne 8g (R = p-MeO-C6H4). A
series of degradation studies in which alkyne 8g and HDA
cycloadduct 9g were heated separately at 160 °C for 2 days both
in the presence and absence of ruthenium catalyst 7 were carried
out. In all cases, the alkynes and cycloadducts showed decom-
position; the phosphonate-free HDA cycloadduct 13 was iso-
lated from the decomposition of the HDA cycloadduct 9g,
Scheme 4. To confirm the observed degradation product 13 is
from HDA cycloadduct 9g and not produced by the HDA [2 + 2
+ 2] cycloaddition of a degraded alkyne, the terminal acetylene
analogue of alkynyl phosphonate 8g was exposed to the opti-
mized reaction conditions, and no reaction was observed. On the
basis of these observations, reaction time was limited to no more
than 6 h to limit any degradation of substrates.
Ph
4.5
2
73
0 (24)b
3
Ph
4
p-Tol
m-Tol
o-Tol
5
60
5
6
37
6
5
71
7
8g
8h
8i
p-MeO-C6H4
m-MeO-C6H4
o-MeO-C6H4
p-CF3-C6H4
m-CF3-C6H4
o- CF3-C6H4
3-thiophene
H
5
64
8
5
74
9
4.5
5
61
10
11
12
13
14
15
16
17
18
19
8j
57
8k
8l
5
57
5
53
8m
8n
8o
8p
8q
8r
8s
4
48
0 (29)b
5.5
6
nBu
64
Cy
tBu
5
36
6
14c
0 (15)b
0d
CH2OH
4
CH2CH2OH
5
a Yield of isolated cycloadduct after column chromatography. b Isolated
yield of [2 + 2] adduct; no HDA cycloadduct observed. c Cycloadduct
isolated as inseparable mixture with unreacted alkyne. d No reaction was
observed.
Alkynyl phosphonates 8aÀt were subjected to optimal con-
ditions in the presence of norbornadiene 1, and the outcomes of
the attempted cycloadditions are presented in Table 3. The first
few substrates presented in Table 3 examine the effect of
changing the substituents of the phosphonate moiety, R1
(entries 1À3). Decreasing the size of R1 led to a decreased yield
and increased reaction time, and dimethyl phosphonate (R1 =
Me, entry 2) produced the desired HDA adduct 9b in 73% over
4.5 h compared to 88% of 9a in 2 h (R1 = Et, entry 1). The effect
of increasing steric bulk and replacing an aliphatic group with an
aromatic functionality on the phosphonate is demonstrated by
diphenyl phosphonate 8c (R1 = Ph, entry 3). The resulting
cycloadduct of the diphenyl phosphonate 8c was not the homo-
DielsÀAlder cycloadduct; instead, 24% of the corresponding [2
+ 2] cycloadduct was isolated. The effects of alkyne substitution
were examined with several examples of aromatic alkynyl phos-
phonates, and these were found to be compatible with the
optimized reaction conditions. However, all reactions required
increased reaction times and achieved lower yields than diethyl
1-phenylethynyl phosphonate, 8b (entry 2). Examining the
effects of aromatic substituents, a series ortho-, meta-, and para-
substituted diethyl 1-phenylethynyl phosphonates were synthe-
sized, including methyl-substituted (R = CH3-C6H4, entries
4À6), methoxy-substituted (R = MeO-C6H4, entries 7À9),
and trifluoromethyl-substituted (R = CF3-C6H4, entries
10À12). The biggest degree of variation in yield within a series
was seen with the methyl-substituted compounds 8dÀf. Sub-
stitution at the para position produced a 60% yield (entry 4), a
meta methyl group yielded only 37% isolated product (entry 5),
and an ortho substituent gave a good yield of 71% (entry 6).
These are interesting results compared to our previous studies of
the [2 + 2] cycloadditions between alkynyl phosphonates and
bicyclic alkenes in which it was observed that a p-methyl
substituent produced an 83% yield, whereas an o-methyl sub-
stituent gave a much lower yield of 8%.8 Methoxy-substituted
phenylethynyl phosphonates 8gÀi (entries 7À9) gave compar-
able yields as the methyl-substituted substrates 8dÀf; however,
the relative reactivity of ortho, meta, para substitution appears to
follow an opposite trend. The highest yield was observed with a
m-methoxy substituent (74%, entry 8), the para (entry 7) and
ortho (entry 9) gave slightly lower yields of 64% and 61%,
respectively. Finally, the effects of a strong electron-withdrawing
group, trifluoromethyl, on the phenylethynyl phosphonate were
examined. Yields were comparable but in general slightly lower
than was observed for both methyl and methoxy substituents;
furthermore, the location of substitution had minimal effect on
the observed reactivity. Yields of 57%, 57%, and 53% were
achieved with p-, m-, and o-trifluoromethyl-substituted pheny-
lethynyl phosphonates 8jÀl (entries 10À12), respectively. A
heteroatom-containing aromatic alkynyl phosphonate 8m was
synthesized and subjected to the HDA cycloaddition conditions
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NOTE
(R = 3-thiophene, entry 13). Diethyl 3-thiophene-ylethynyl
phosphonate 8m underwent the desired HDA [2 + 2 + 2]
cycloaddition with norbornadiene in moderate yield, 48%; in our
[2 + 2] studies, this alkynyl phosphonate also showed reduced
reactivity relative to phenyl-substituted alkynyl phosphonates as well.8
With a number of aromatic substituted alkynyl phosphonates
found to be compatible with the optimized reaction conditions, a
variety of aliphatic substrates were prepared to further expand the
scope of the reaction. Terminal diethyl ethynyl phosphonate 8n
(R = H, entry 14) was found to exclusively produce the [2 + 2]
cycloadduct in 29%; this demonstrates an important difference from
the cobalt catalyzed HDA [2 + 2 + 2] cycloadditions between
alkynes and bicyclic alkenes, developed by Lautens, which demon-
strated high yields of HDA adducts from terminal alkynes.3f Alkynyl
phosphonates 8oÀq are representative of aliphatic substituents
possessing primary, secondary, and tertiary carbons at the pro-
pargylic position of the alkynyl phosphonates (entries 15À17). The
highest yield was obtained with a primary aliphatic group 8o (R =
nBu, entry 15), 64%, which was comparable to the substituted
aromatics (entries 3À12) but still less than diethyl 1-phenylethynyl
phosphonate 8a (entry 1). Increasing substitution of the aliphatic
center to a secondary carbon 8p (R = Cy, entry 16) lowered the
yield to 36%; in contrast, during our [2 + 2] studies this alkynyl
phosphonate did not proceed to react at all, whereas the primary
alkynyl phosphonate (R = nBu) provided a moderate yield of the
respective cycloadduct.8 Continuing with this trend, a tertiary
recorded on a 400 MHz spectrometer. Chemical shifts for 31P NMR
spectra are reported in parts per million (ppm) from phosphoric acid
with trimethylphosphite as the external standard (trimethylphosphite: δ
141.0 ppm). Alkynyl phosphonates 8aÀt were prepared by our pre-
viously reported method.8
General Procedure for Ruthenium-Catalyzed Homo-DielsÀ
Alder [2 + 2 + 2] Cycloadditionswith Norbornadiene (Table 3,
Entry 1). A mixture of alkynyl phosphonate 8a (46.2 mg, 0.194 mmol)
and norbornadiene (61.7 mg, 0.700 mmol) was prepared in an oven-dried
screw-cap vial. The vial was purged with nitrogen and taken into the
drybox where Cp*RuCl(COD) (4.8 mg, 0.013 mmol) and NMP
(0.8 mL) were added, and the vial was sealed. The reaction mixture was
stirred outside the glovebox at 160 °C for 2À6 h. The crude product was
purified by flash chromatography to yield the corresponding cycloadduct
(ethyl acetate/hexanes mixture).
Deltacyclene 9a (Table 3, Entry 1). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9a (56.6 mg, 0.171 mmol, 88%) as a yellow oil: Rf 0.15
(EtOAc/hexanes 1:1); IR (CH2Cl2, NaCl) 2974 (m), 2931 (m), 1492
(w), 1266 (m), 1164 (w), 1029 (s), 964 (m), 738(m) cmÀ1; 1H NMR
(CDCl3, 400 MHz) δ 7.55À7.53 (m, 2H), 7.36À7.28 (m, 3H),
4.00À3.84 (m, 4H), 3.11 (br d, 1H, J = 1.4 Hz), 3.01 (br d, 1H, J =
1.4 Hz), 2.26 (s, 1H), 1.81 (td, 1H, J = 4.7, 1.0 Hz), 1.64À1.59 (m, 4H),
1.15 (t, 3H, J = 7.1 Hz), 1.10 (t, 3H, J = 7.1 Hz); 13C NMR (APT,
CDCl3,100 MHz) δ 163.0 (d, J = 10.7 Hz), 136.3 (d, J = 4.3 Hz), 128.3
(d, J = 193.6 Hz), 128.2, 128.1, 127.8, 61.4 (d, J = 5.8 Hz), 61.2 (d, J = 5.5
Hz), 56.3, 56.1, 53.4 (d, J = 11.8 Hz), 32.6, 25.7, 23.8, 23.3 (d, J = 3.4
Hz), 16.1 (m, 2C); 31P NMR (CDCl3, 160 MHz) δ 17.36; HRMS (EI)
calcd [M+] for C19H23O3P m/z 330.1385, found 330.1391.
Deltacyclene 9b (Table 3, Entry 2). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9b (45.9 mg, 0.152 mmol, 73%) as a pale yellow crystalline
solid: Rf 0.14 (EtOAc/hexanes 1:1); IR (CH2Cl2, NaCl) 2951 (m), 1491
(w), 1244 (m), 1182 (w), 1030 (s), 944 (m), 766 (m) cmÀ1; 1H NMR
(CDCl3, 400 MHz) δ 7.55À7.53 (m, 2H), 7.36À7.30 (m, 3H), 3.58
(d, 3H, J = 11.2 Hz), 3.51 (d, 3H, J = 11.3 Hz) 3.09 (br d, 1H, J = 1.5 Hz),
3.02 (br d, 1H, J = 1.5 Hz), 2.27 (s, 1H), 1.82 (td, 1H, J = 4.7, 1.2 Hz),
1.64À1.60 (m, 4H); 13C NMR (APT, CDCl3, 100 MHz) δ 163.9 (d, J =
10.8 Hz), 136.1 (d, J = 4.1 Hz), 128.4, 127.9, 127.8, 127.0 (d, J = 194.7
Hz), 56.3 (d, J = 6.5 hz), 56.1, 53.3 (d, J = 11.6 Hz), 52.1 (d, J = 5.8 Hz),
51.8 (d, J = 5.6 Hz), 32.6, 25.7, 23.7, 23.3 (d, J = 3.4 Hz); 31P NMR
(CDCl3, 160 MHz) δ 20.37; HRMS (EI) calcd [M+] for C17H19O3P m/
z 302.1072, found 302.1071.
t
alkynyl phosphonate 8q (R = Bu, entry 17) was found also to
exclusively undergo the HDA [2 + 2 + 2] cycloaddition, though the
highest yield achieved was only 14%. Furthermore, the product
could not be separated from unreacted starting alkynyl phospho-
nate, and attempts to consume all alkyne through prolonged heating
or adjusting reactant equivalents were unsuccessful. The observed
trend of decreasing reactivity with increasing propargylic substitu-
tion was also observed in studies of cobalt-catalyzed HDA [2 + 2 +
2] cycloadditions between norbornadiene and acetylenes.3b
Finally, the reaction conditions were applied to alkynyl
phosphonates containing propargylic and homopropargylic al-
cohols 8r,s (entries 18,19). These substrates were found to be
quite incompatible with the optimized reaction conditions; for
example, propargylic alcohol 8r gave the [2 + 2] cycloadduct
exclusively in 15% yield (entry 18). Increasing the chain length by
a carbon to produce homopropargylic alkynyl phosphonate 8r
gave no evidence of reaction by 31P NMR (entry 19).
In conclusion, we have demonstrated the first examples of
ruthenium-catalyzed homo-DielsÀAlder [2 + 2 + 2] cycloaddi-
tions between alkynyl phosphonates and bicyclic alkenes. The
reaction was found to be dependent on the phosphonate present;
dimethyl and diethyl phosphonates underwent the desired HDA
cycloaddition, whereas diphenyl phosphonates only achieved the
[2 + 2] mode of cycloaddition. Furthermore, our reaction
conditions were compatible with a variety of aromatic and
aliphatic substituents in low to good yields. Investigations with
substituted bicyclic alkenes in addition to the exploration of the
intramolecular variant of this reaction are currently underway in
our laboratory. Finally, exploration of cyclopropane ring-open-
ings toward phosphonate substituted deltacyclenes could further
enhance the scope and applicability of this reaction.
Cycloadduct 10c (Table 3, Entry 3). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 10c (19.4 mg, 0.046 mmol, 24%) as a pale brown solid: Rf
0.64 (EtOAc/hexanes 1:1); IR (CH2Cl2, NaCl) 3060 (m), 2976 (m),
2937 (m), 1591 (s), 1489 (s), 1189 (s), 1071 (m), 966 (s), 738
(m) cmÀ1; 1H NMR (CDCl3, 400 MHz) δ 7.96 (dd, 2H, J = 7.9, 2.4
Hz), 7.44À7.19 (m, 11H), 7.16À7.12 (m, 2H), 6.19 (br t, 2H, J = 1.64
Hz), 2.83À2.81 (m, 1H), 2.71 (br d, 2H, J = 1.52 Hz), 2.57 (d, 1H, J =
3.72 Hz), 1.33 (d, 1H, J = 9.6 Hz), 1.27 (d, 1H, J = 10.1 Hz); 13C NMR
(APT, CDCl3,100 MHz) δ 164.6, 150.5 (d, J = 4.8 Hz), 150.3 (d, J = 4.8
Hz), 136.1, 135.4, 132.1, 130.3, 129.8 (2), 129.7, 128.6, 128.2, 126.5
(d, J = 181.9 Hz), 125.0 (d, J = 5.0 Hz), 120.6 (d, J = 4.5 Hz), 120.4 (d, J =
4.8 Hz), 45.6 (d, J = 33.3 Hz), 43.8 (d, J = 9.63 Hz), 39.7, 39.3, 39.1; 31P
NMR (CDCl3, 160 MHz) δ 3.11 HRMS (EI) m/z calcd for C27H23O3P
[M+] 426.1385, found 426.1391.
Deltacyclene 9d (Table 3, Entry 4). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9d (38.9 mg, 0.113 mmol, 60%) as an amber-yellow oil: Rf
0.27 (EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2954 (m), 2925 (m),
’ EXPERIMENTAL SECTION
1
General Information. All reactions were carried out in an atmo-
1492 (w), 1244 (m), 1026 (s), 961 (m), 765 (w) cmÀ1; H NMR
1
sphere of dry nitrogen or argon. H, 13C, and 31P NMR spectra were
(CDCl3, 400 MHz) δ 7.54 (d, 2H, J = 8.1 Hz), 7.14 (d, 2H, J = 7.9 Hz),
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NOTE
4.01À3.85 (m, 4H), 3.09 (br d, 1H, J = 1.8 Hz), 3.00 (s, 1H), 2.34
(s, 3H), 2.24 (s, 1H), 1.80 (td, 1H, J = 4.7, 1.0 Hz), 1.63À1.57 (m, 4H),
1.17 (t, 3H, J = 7.1 Hz), 1.12 (t, 3H, J = 7.1 Hz); 13C NMR (APT,
CDCl3,100 MHz) δ 163.1 (d, J = 10.9 Hz), 138.2, 133.3 (d, J = 4.4 Hz),
128.4, 128.0 (d, J = 1.3 Hz), 127.2 (d, J = 193.7 Hz), 61.3 (d, J = 5.4 Hz),
61.1 (d, J = 5.4 Hz), 56.1 (d, J = 12.7 Hz), 56.0 (d, J = 2.6 Hz), 53.3 (d, J =
12.0 Hz), 32.6, 25.5, 23.7, 23.1 (d, J = 3.5 Hz), 21.2, 16.1 (t, 2C, J = 6.7
Hz); 31P NMR (CDCl3, 160 MHz) δ 17.662 Hz; HRMS (EI) calcd
[M+] for C20H25O3P m/z 344.1541, found 344.1549.
(d, J = 6.7 Hz), 61.5 (d, J = 5.8 Hz), 61.2 (d, J = 5.5 Hz), 56.2, 56.1, 55.3
(d, J = 8.6 Hz), 53.6 (d, J = 11.6 Hz) 32.7, 25.7, 23.8, 23.3 (d, J = 3.4 Hz),
16.2 (m, 2C); 31P NMR (CDCl3, 160 MHz) δ 17.753; HRMS (EI) calcd
[M+] for C20H25O4P m/z 360.1490, found 360.1497.
Deltacyclene 9i (Table 3, Entry 9). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9i (41.3 mg, 0.115 mmol, 61%) as a yellow oil: Rf 0.22
(EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2978 (m), 2931 (m), 1587
(w), 1486 (w), 1246 (s), 1164 (w), 1028 (s), 962 (m), 753 (m) cmÀ1
;
Deltacyclene 9e (Table 3, Entry 5). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9e (26.6 mg, 0.077 mmol, 37%) as an amber-yellow oil: Rf
0.26 (EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2980 (m), 2929 (m),
1H NMR (CDCl3, 400 MHz) δ 7.34 (dd, 1H, J = 7.5, 1.7 Hz), 7.28À7.24
(m, 1H), 6.91 (td, 1H, J = 7.5, 0.9 Hz), 6.86 (d, 1H, J = 8.2 Hz),
3.96À3.78 (m, 7H), 3.03 (br d, 1H, J = 1.8 Hz), 2.92 (br d, 1H, J = 2.0
Hz), 2.24 (s, 1H), 1.74 (td, 1H, J = 4.7, 1.1 Hz), 1.64À1.56 (m, 4H), 1.11
(t, 3H, J = 7.1 Hz), 1.06 (t, 3H, J = 7.0 Hz); 13C NMR (APT, CDCl3,100
MHz) δ 162.2 (d, J = 10.0 Hz), 156.5, 130.9, 129.6 (d, J = 195.3 Hz),
129.4, 126.2 (d, J = 4.0 Hz), 120.0, 110.2, 61.3 (d, J = 5.8 Hz), 61.0 (d, J =
5.5 Hz), 56.7À56.1 (m, 2C), 55.2 (d, J = 8.9 Hz), 52.1 (d, J = 12.4 Hz),
32.7, 25.1, 23.4, 23.0 (d, J = 3.4 Hz), 16.1 (d, 2C, J = 3.4 Hz); 31P NMR
(CDCl3, 160 MHz) δ 17.717; HRMS (EI) calcd [M+] for C20H25O4P
m/z 360.1490, found 360.1502.
1
1481 (w), 1238 (m), 1027 (s), 962 (s), 788 (m) cmÀ1; H NMR
(CDCl3, 400 MHz) δ 7.34 (br s, 2H), 7.22 (t, 1H, J = 7.7 Hz), 7.10 (d,
1H, J = 7.6 Hz), 4.01À3.85 (m, 4H), 3.09 (br d, 1H, J = 1.3 Hz), 2.99 (s,
1H), 2.35 (s, 3H), 2.24 (s, 1H), 1.80 (br td, 1H, J = 3.5 Hz, 0.9 Hz),
1.63À1.59 (m, 4H), 1.15 (t, 3H, J = 7.1 Hz), 1.11 (t, 3H, J = 7.1 Hz); 13C
NMR (APT, CDCl3,100 MHz) δ 163.2 (d, J = 10.8 Hz), 137.2, 136.2 (d,
J = 4.3 Hz), 128.9, 128.7 (d, J = 1.3 Hz), 127.7, 127.0, 125.2 (d, J = 1.3
Hz), 61.4 (d, J = 5.8 Hz), 61.1 (d, J = 5.7 Hz), 56.2 (d, J = 8.1 Hz), 56.1
(d, J = 1.4 Hz), 53.3 (d, J = 12.0 Hz), 32.6, 25.6, 23.7, 23.2 (d, J = 3.5 Hz),
21.3, 16.1 (t, 2C, J = 6.7 Hz); 31P NMR (CDCl3, 160 MHz) δ 17.890;
HRMS (EI) calcd [M+] for C20H25O3P m/z 344.1541, found 344.1549.
Deltacyclene 9f (Table 3, Entry 6). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9f (45.6 mg, 0.132 mmol, 71%) as an amber-yellow oil: Rf
0.27 (EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2980 (m), 2930 (m),
Deltacyclene 9j (Table 3, Entry 10). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9j (42.1 mg, 0.106 mmol, 57%) as a light amber oil: Rf 0.33
(EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2982 (m), 2942 (m), 1445
(w), 1325 (s), 1243 (m), 1025 (s), 963 (m) cmÀ1; 1H NMR (CDCl3,
400 MHz) δ 7.64 (d, 2H, J = 8.3 Hz), 7.58 (d, 2H, J = 8.3 Hz), 4.04À3.83
(m, 4H), 3.12 (br d, 1H, J = 1.4 Hz), 3.00 (s, 1H), 2.28 (s, 1H), 1.85 (td,
1H, J = 4.7, 1.1 Hz), 1.65À1.61 (m, 4H), 1.18 (t, 3H, J = 7.0 Hz), 1.13 (t,
3H, J = 7.1 Hz); 13C NMR (APT, CDCl3,100 MHz) δ 161.3 (d, J = 10.4
Hz), 139.9, 131.0 (d, J = 193.1 Hz), 129.8, 128.4 (d, J = 1.7 Hz), 124.7
(q, J = 3.8 Hz), 124.1 (d, J = 272.0 Hz) 61.6 (d, J = 5.1 Hz), 61.4 (d, J =
5.5 Hz), 56.5 (d, J = 7.2 Hz), 56.2 (d, J = 16.8 Hz), 53.6 (d, J = 11.4 Hz),
32.6, 26.0, 23.9, 23.4 (d, J = 3.4 Hz), 16.2 (t, 2C, J = 7.0 Hz); 31P NMR
(CDCl3, 160 MHz) δ 16.54; HRMS (EI) calcd [M+] for C20H22O3F3P
m/z 398.1259, found 398.1250.
Deltacyclene 9k (Table 3, Entry 11). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9k (44.3 mg, 0.111 mmol, 57%) as a light amber oil: Rf 0.28
(EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2982 (m), 2942 (m), 1445
(w), 1325 (s), 1243 (m), 1025 (s), 963 (m) cmÀ1; 1H NMR (CDCl3,
400 MHz) δ 7.76À7.74 (m, 2H), 7.54 (d, 1H, J = 7.9 Hz), 7.46 (t, 1H, J
= 7.7 Hz), 4.03À3.89 (m, 4H), 3.13 (br d, 1H, J = 1.4 Hz), 3.01 (br s,
1H), 2.29 (s, 1H), 1.85 (td, 1H, J = 3.7, 0.9 Hz), 1.66À1.62 (m, 4H),
1.15 (q, 6H, J = 7.0 Hz); 13C NMR (APT, CDCl3,100 MHz) δ 161.1,
137.0 (d, J = 4.3 Hz), 131.5, 130.7 (d, J = 197.0 Hz), 128.3 (2), 124.7
(m, 2C), 124.2, 61.5 (d, J =5.7 Hz), 61.3 (d, J= 5.7 Hz), 56.5 (d, J=7.2 Hz),
56.1 (d, J = 16.7 Hz), 53.5 (d, J = 11.5 Hz), 32.6, 25.1, 23.8, 23.4, 16.0
(m, 2C); 31P NMR (CDCl3, 160 MHz) δ 16.66; HRMS (EI) calcd [M+]
for C20H22O3F3P m/z 398.1259, found 398.1255.
Deltacyclene 9l (Table 3, Entry 12). The crude product was
purified by column chromatography (EtOAc/hexanes 7:3) to provide
cycloadduct 9l (40.8 mg, 0.102 mmol, 53%) as a light amber oil: Rf 0.29
(EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2984 (m), 2933 (m), 1446
(w), 1317 (s), 1264 (m), 1034 (m), 962 (m), 734 (m) cmÀ1; 1H NMR
(CDCl3, 400 MHz) δ 7.65 (d, 1H, J = 7.8 Hz), 7.48 (t, 1H, J = 7.3 Hz),
7.39 (t, 1H, J = 7.6 Hz), 7.21 (d, 1H, J = 7.5 Hz), 3.94À3.73 (m, 4H),
3.04 (br d, 1H, J = 1.7 Hz), 2.85 (s, 1H), 2.38 (s, 1H), 1.81 (br t, 1H, J =
4.3 Hz), 1.66À1.45 (m, 4H), 1.11 (t, 3H, J = 7.0 Hz), 1.02 (t, 3H, J = 7.0
Hz); 13C NMR (APT, CDCl3,100 MHz) δ 161.1, 136.6, 132.4 (d, J =
196.0 Hz), 131.1, 128.3, 127.2, 125.9 (2), 124.2 (d, J = 273.8 Hz), 61.2
(d, J = 5.8 Hz), 61.1 (d, J = 6.0 Hz), 57.8 (m, 2C), 51.7 (d, J = 12.7 Hz),
32.4, 25.8, 23.4, 22.6 (d, J = 3.5 Hz), 16.1 (m, 2C); 31P NMR (CDCl3,
160 MHz) δ 15.80; HRMS (EI) calcd [M+] for C20H22O3F3P m/z
398.1259, found 398.1267.
1
1484 (w), 1236 (m), 1028 (s), 963 (s), 735 (m) cmÀ1; H NMR
(CDCl3, 400 MHz) δ 7.21À7.09 (m, 4H), 3.93À3.65 (m, 4H), 3.08 (d,
1H, J = 1.9 Hz), 2.80 (d, 1H, J = 2.1 Hz), 2.35 (s, 1H), 2.30 (s, 3H), 1.80
(br td, 1H, J = 4.7, 1.2 Hz), 1.68À1.52 (m, 4H), 1.09 (t, 3H, J = 7.0 Hz),
1.05 (t, 3H, J = 7.1 Hz); 13C NMR (APT, CDCl3,100 MHz) δ 163.6 (d, J
= 10.6 Hz), 137.4, 135.2, 130.8 (d, J = 194.5 Hz), 129.6, 128.2, 127.6,
125.1, 61.2 (d, 2C, J = 5.9 Hz), 57.4 (m), 56.9 (m), 52.6 (d, J = 12.9 Hz),
32.5, 25.5, 23.4, 22.7 (d, J = 3.56 Hz), 20.1, 16.0 (m, 2C); 31P NMR
(CDCl3, 160 MHz) δ 17.079; HRMS (EI) calcd [M+] for C20H25O3P
m/z 344.1541, found 344.1549.
Deltacyclene 9g (Table 3, Entry 7). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9g (53.0 mg, 0.148 mmol, 64%) as a yellow oil: Rf 0.33
(EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2983 (s), 2925 (m), 1608
(m), 1508 (s), 1443 (w), 1266 (s), 1032 (s), 962 (s), 742 (s) cmÀ1; 1H
NMR (CDCl3, 400 MHz) δ 7.55À7.52 (m, 2H), 6.88À6.85 (m, 2H),
4.02À3.87 (m, 4H), 3.81 (s, 3H), 3.08 (br d, 1H, J = 1.9 Hz), 3.00 (br d,
1H, J = 1.9 Hz), 2.22 (s, 1H), 1.78 (td, 1H, J = 4.7, 1.1 Hz), 1.62À1.53
(m, 4H), 1.18 (t, 3H, J = 7.1 Hz), 1.14 (t, 3H, J = 7.1 Hz); 13C NMR
(APT, CDCl3,100 MHz) δ 162.7 (d, J = 11.0 Hz), 159.7, 129.7, 128.7 (d,
J = 4.4 Hz), 126.0 (d, J = 193.9 Hz), 113.2, 61.4 (d, J = 5.5 Hz), 61.1 (d, J
= 5.4 Hz), 56.1À55.9 (m, 2C), 55.3, 53.4 (d, J = 11.8 Hz), 32.7, 25.4,
23.8, 23.0 (d, J = 3.4 Hz), 16.2 (t, 2C, J = 6.7 Hz); 31P NMR (CDCl3, 160
MHz) δ 18.335; HRMS (EI) calcd [M+] for C20H25O4P m/z 360.1490,
found 360.1501.
Deltacyclene 9h (Table 3, Entry 8). The crude product was
purified by column chromatography (EtOAc/hexanes 1:1) to provide
cycloadduct 9h (51.9 mg, 0.144 mmol, 74%) as a yellow oil: Rf 0.34
(EtOAc/hexanes 3:2); IR (CH2Cl2, NaCl) 2980 (s), 2932 (s), 1600
(m), 1488 (m), 1243 (s), 1162 (m), 1027 (s), 964 (s), 789 (m) cmÀ1
;
1H NMR (CDCl3, 400 MHz) δ 7.30À7.24 (m, 2H), 7.14 (d, 1H, J = 7.6
Hz), 6.88 (dd, 1H, J = 2.0, 8.2 Hz), 4.06À3.90 (m, 4H), 3.87 (s, 3H),
3.14 (s, 1H), 3.05 (s, 1H), 2.29 (s, 1H), 1.85 (br t, 1H, J = 4.2 Hz),
1.67À1.62 (m, 4H), 1.21 (t, 3H, J = 7.1 Hz), 1.15 (t, 3H, J = 7.1 Hz);
13C NMR (APT, CDCl3,100 MHz) δ 162.9 (d, J = 10.6 Hz), 159.1,
137.6 (d, J = 4.2 Hz), 128.8, 128.5 (d, J = 193.4 Hz), 120.4, 114.5, 113.4
6955
dx.doi.org/10.1021/jo2010928 |J. Org. Chem. 2011, 76, 6951–6957

The Journal of Organic Chemistry
NOTE
Deltacyclene 9m (Table 3, Entry 13). The crude product was
purified by column chromatography (EtOAc/hexanes 7:3) to provide
cycloadduct 9m (43.7 mg, 0.130 mmol, 48%) as a yellow crystalline
solid: Rf 0.28 (EtOAc/hexanes 7:3); IR (CH2Cl2, NaCl) 3054 (m), 2985
(m), 1492 (w), 1265 (s), 1164 (w), 1025 (s), 966 (m), 738 (s) cmÀ1; 1H
NMR (CDCl3, 400 MHz) δ 7.68 (br d, 1H, J = 1.96 Hz), 7.50 (dd, 1H, J
= 1.04, 5.08 Hz), 7.21À7.19 (1H, m), 4.03À3.86 (m, 4H), 3.02 (s, 2H),
2.14 (s, 1H), 1.72 (br t, 1H, J = 4.66 Hz), 1.57 (s, 2H), 1.52 (br t, 1H, J =
4.56 Hz), 1.46 (br t, 1H, J = 4.65 Hz), 1.16 (dt, 6H, J = 7.04, 11.3 Hz);
13C NMR (APT, CDCl3,100 MHz) δ 160.6, 131.7 (d, J = 196.2 Hz),
128.6, 128.3, 125.5, 124.9, 61.4 (d, J = 5.4 Hz), 61.3 (d, J = 5.4 Hz), 55.9,
55.7 (m), 53.4 (d, J = 11.4 Hz), 32.7, 25.3, 24.1, 22.6, 16.2 (m, 2C); 31P
NMR (CDCl3, 160 MHz) δ 18.04; HRMS (EI) calcd [M+] for
C17H21O3PS m/z 336.0949, found 336.0939.
(t, 6H, J = 7.0 Hz), 1.26 (s, 9H); 13C NMR (APT, CDCl3,100 MHz) δ
175.5, 124.3 (d, J = 191.9 Hz), 61.0 (d, 2C, J = 5.5 Hz), 53.1, 53.7, 53.5,
35.3, 32.5, 30.2, 24.8, 23.1, 22.7, 16.4 (m, 2C); 31P NMR (CDCl3,
160 MHz) δ 18.997; HRMS (EI) calcd [M+] for C17H27O3P m/z
310.1698, found 310.1692.
Cycloadduct 10r (Table 3, Entry 18). The crude product was
purified by column chromatography (EtOAc/hexanes 7:3) to provide
cycloadduct 10r (13.6 mg, 0.048 mmol, 15%) as a light yellow oil: Rf 0.19
(EtOAc/hexanes 7:3); IR (CH2Cl2, NaCl) 3386 (s), 2979 (m), 1628
(m), 1444 (w), 1231 (m), 1163 (s), 1024 (s), 968 (s) cmÀ1; 1H NMR
(CDCl3, 400 MHz) δ 6.08 (t, 2H, J = 2.7 Hz), 5.24 (t, 1H, J = 5.6 Hz),
4.36À4.32 (m, 2H), 4.16À4.04 (m, 4H), 2.39 (s, 1H), 2.51 (s, 1H), 2.40
(s, 2H), 1.44 (d, 1H, J = 9.3 Hz), 1.38 (d, 1H, J = 9.3 Hz), 1.33 (t, 6H, J =
7.1 Hz); 13C NMR (APT, CDCl3, 100 MHz) δ 171.3 (d, J = 11.2 Hz),
135.7, 135.3, 129.3 (d, J = 197.1 Hz), 62.1 (d, J = 5.7 Hz), 62.0 (d, J = 5.8
Hz), 61.4, 45.9 (d, J = 31.3 Hz), 43.0 (d, J = 8.1 Hz), 39.5, 38.9, 37.8, 16.4
(d, J = 6.3 Hz), 16.3 (d, J = 6.4 Hz); 31P NMR (CDCl3, 160 MHz) δ
12.38; HRMS (CI) calcd for C14H21O4P [M + H]+ 285.1256 m/z,
found 285.1261 m/z.
Cycloadduct 10n (Table 3, Entry 14). The crude product was
purified by column chromatography (EtOAc/hexanes 7:3) to provide
cycloadduct 10n (28.4 mg, 0.123 mmol, 29%) as a pale yellow oil: Rf 0.23
(EtOAc/hexanes 7:3); IR (CH2Cl2, NaCl) 3053(m), 2983 (m),
1
1448(w), 1264 (s), 1026 (s), 968 (m), 896 (w), 738 (s) cmÀ1; H
Deltacyclene 13 (Scheme 4). Deltacyclene 9g (28.1 mg, 0.078
mmol) and NMP (1.0 mL) were added to a screw cap vial in the
glovebox and sealed. The mixture was stirred outside of the glovebox at
160 °C for 48 h. The crude product was purified by column chroma-
tography (EtOAc/hexanes 7:3) to provide deltacyclene 13 (2.4 mg,
0.011 mmol, 14%) as a light yellow crystalline solid: Rf 0.78 (EtOAc/
hexanes 7:3); IR (CH2Cl2, NaCl) 2926 (m), 2855 (m), 1597 (w), 1492
(w), 1175 (w), 913 (s) cmÀ1, 1H NMR (CDCl3, 400 MHz) δ 7.37À7.35
(m, 2H), 6.86À6.84 (m, 2H), 6.23 (d, 1H, J = 2.8 Hz), 3.80 (s, 3H), 3.02
(s, 1H), 2.69 (s, 1H), 2.08 (s, 1H), 1.75À1.72 (m, 1H), 1.60À1.59 (m,
2H), 1.40À1.39 (m, 2H); 13C NMR (APT, CDCl3,100 MHz) δ 158.5,
147.7, 129.6, 127.2, 126.0, 125.9, 113.9, 113.8, 56.5, 55.3, 50.0, 49.3, 32.7,
25.4, 24.2, 22.2; HRMS (EI) calcd [M+] for C16H16O m/z 224.1201,
found 224.1209.
NMR (CDCl3, 400 MHz) δ 7.06 (d, 1H, J = 4.6 Hz), 6.13 (t, 2H, J = 5.5
Hz), 4.09 (dquin, 4H, J = 2.5, 7.2 Hz), 2.59 (s, 2H), 2.48À2.46(m, 2H),
1.45 (d, 1H, J = 9.2 Hz), 1.36 (s, 1H), 1.33 (t, 6H, J = 7.1 Hz); 13C NMR
(APT, CDCl3,100 MHz) δ 153.8 (d, J = 7.4 Hz), 140.5 (d, J= 180.3 Hz),
135.9, 135.5, 61.7 (t, 2C, J = 5.3 Hz), 46.7 (d, J = 9.5 Hz), 46.1 (d, J = 31.8
Hz), 39.5, 38.4, 38.1, 16.5 (dd, 2C, J = 2.4, 6.3 Hz); 31P NMR (CDCl3,
160 MHz) δ 9.843; HRMS (EI) calcd [M+] for C13H19O3P m/z
254.1072, found 254.1066.
Deltacyclene 9o (Table 3, Entry 15). The crude product was
purified by column chromatography (EtOAc/hexanes 7:3) to provide
cycloadduct 9o (43.7 mg, 0.141 mmol, 64%) as a light yellow oil: Rf 0.40
(EtOAc/hexanes 7:3); IR (CH2Cl2, NaCl) 2963(m), 2930 (m), 1445
(w), 1243 (m), 1057 (s), 1029 (s) cmÀ1; 1H NMR (CDCl3, 400 MHz)
δ 4.07À3.93 (m, 4H), 2.78 (br d, 1H, J = 1.52 Hz), 2.62 (br d, 1H, J =
1.92 Hz), 2.60À2.45 (m, 2H), 1.99 (s, 1H), 1.67 (td, 1H, J = 4.6, 0.8 Hz),
1.56À1.50 (m, 2H), 1.47À1.39 (m, 2H), 1.37À1.32 (m, 4H), 1.28 (td,
6H, J = 1.9, 7.0 Hz), 0.89 (t, 3H, J = 7.2 Hz); 13C NMR (APT,
CDCl3,100 MHz) δ 169.3 (d, J = 13.6 Hz), 126.2 (d, J = 195.1 Hz), 61.0
(d, 2C, J = 4.5 Hz), 56.5 (d, J = 7.0 Hz), 54.0 (d, J = 18.5 Hz), 51.3 (d, J =
12.7 Hz), 32.5, 30.9 (d, J = 2.2 Hz), 30.1 (d, J = 3.2 Hz), 25.0, 23.2, 22.7,
22.5 (d, J = 3.5 Hz), 16.4 (d, 2C, J = 6.2 Hz), 14.0; 31P NMR (CDCl3,
160 MHz) δ 18.48; HRMS (EI) calcd [M+] for C17H27O3P m/z
310.1698, found 310.1703.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra of all
S
b
new compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Deltacyclene 9p (Table 3, Entry 16). The crude product was
purified by column chromatography (EtOAc/hexanes 7:3) to provide
cycloadduct 9p (39.9 mg, 0.191 mmol, 36%) as a yellow oil: Rf 0.28
(EtOAc/hexanes 7:3); IR (CH2Cl2, NaCl): 2930 (m), 2856 (m), 1266
(s), 1166 (w), 1027 (s), 962 (m), 735 (m) cmÀ1; 1H NMR (CDCl3, 400
MHz) δ 4.06À3.94 (m, 4H), 3.04 (br td, 1H, J = 11.1, 2.8 Hz), 2.78 (br
d, 2H, J = 2.2 Hz), 1.92 (s, 1H), 1.72À1.61 (m, 4H), 1.60À1.56 (m, 2H),
1.52 (d, 2H, J = 5.8 Hz), 1.41À1.37 (m, 1H), 1.31À1.24 (m, 12H); 13C
NMR (APT, CDCl3,100 MHz) δ 173.5, 123.6, 61.0 (m, 2C), 56.4 (d, J =
6.9 Hz), 51.0 (d, J = 12.7 Hz), 50.7, 39.0 (d, J = 3.0 Hz), 32.6, 31.8, 26.1,
25.9, 25.1, 23.1, 22.9 (d, J = 3.6 Hz), 16.4 (d, 2C, J = 6.6 Hz); 31P NMR
(CDCl3, 160 MHz) δ 18.83; HRMS (EI) calcd [M+] for C19H29O3P m/
z 336.1854, found 336.1850.
Deltacyclene 9q (Table 3, Entry 17). The crude product was
purified by column chromatography (EtOAc/hexanes 7:3) to provide
cycloadduct 9q (8.9 mg, 0.028 mmol, 14%) as a yellow oil: Rf 0.38
(EtOAc/hexanes 7:3). Isolated as an impure product (∼3:1 starting
alkyne 8q/HDA adduct 9q) from 1H NMR: IR (CH2Cl2, NaCl) 2982
(m), 1458 (w), 1266 (s), 1028 (s), 970 (m), 735 (s) cmÀ1; 1H NMR
(CDCl3, 400 MHz) δ 4.08À4.00 (m, 4H), 2.93 (br d, 1H, J = 1.8 Hz),
2.88 (br d, 1H, J = 1.7 Hz), 1.90 (br s, 1H), 1.73 (br s, 1H), 1.66 (td, 1H,
J = 4.6, 1.0 Hz), 1.55À1.5 (m, 2H), 1.43 (td, 1H, J = 4.5, 1.8 Hz), 1.31
Corresponding Author
*E-mail: wtam@uoguelph.ca.
’ ACKNOWLEDGMENT
This work was supported by Merck Frosst Centre for Ther-
apeutic Research and the Natural Sciences and Engineering
Research Council of Canada (NSERC). N.C. thanks the Ontario
Government for a postgraduate scholarship (OGS).
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