Convenient access to functionalized vinylcyclopentenols from alkynyloxiranes

Article abstract of DOI:10.1021/jo062107w

β,γ-Alkynyl aldehydes, generated in situ by treatment of alkynyloxiranes with a catalytic amount of Sc(OTf)₃ or BF ₃· OEt₂, are effectively trapped by a variety of allyl nucleophiles to afford homopropargylic homoallylic a

Full text of DOI:10.1021/jo062107w

SCHEME 1. General Approach to Carbocyclic Dienes
Convenient Access to Functionalized
Vinylcyclopentenols from Alkynyloxiranes
Letian Wang, Matthew L. Maddess, and Mark Lautens*
80 St. George Street, DaVenport Research Laboratories,
Department of Chemistry, UniVersity of Toronto, Toronto,
Ontario M5S 3H6, Canada
Several methods for the preparation of â,γ-alkynyl aldehydes
are known,6 but they are reported to be quite sensitive,7 and
the direct approach outlined in Scheme 1 would avoid their
isolation and simplify experimental protocols. The resulting
homopropargylic homoallylic alcohols should be of value for
other applications given the easily differentiated double bond
and triple bond in the molecule and the numerous types of
reactions 1,6-enynes are known to undergo.8 This report
summarizes our efforts to affect a rearrangement/allylation-
crotylation sequence on alkynyloxiranes and the subsequent
conversion to functionalized carbocyclic dienes via enyne
metathesis.
mlautens@alchemy.chem.utoronto.ca
ReceiVed October 11, 2006
A series of aryl-, alkyl-, and silylalkynyloxiranes were
prepared according to modified literature protocols.9 In contrast
to many terminal 2-vinyloxiranes,3 the alkynyloxiranes prepared
in our study could be purified by flash chromatography and
generally exhibited good stability. The simple 4-phenyl-
substituted substrate 1 was selected for optimization in reactions
with tetraallyltin and potassium allyltrifluoroborate.10
Of the Lewis acids screened, BF3‚OEt2 and Sc(OTf)3 emerged
as the most efficient catalysts for this transformation in accord
with previous observations.3 The addition of Sc(OTf)3 to a
mixture of 1 and tetraallyltin in THF was effective (Table 1,
entry 1). However, these conditions were not general with other
substrates, and a variety of different LA, solvent, and temper-
ature protocols were studied (Table 1). When appropriate
modifications were made, yields employing tetraallyltin were
moderate to good for a range of substrates (Table 1). In general,
electron-rich systems where rearrangement should be favored
afforded higher yields of the desired products (10 to 12) than
the electron-deficient systems (Table 1, entries 1-3, vs entries
â,γ-Alkynyl aldehydes, generated in situ by treatment of
alkynyloxiranes with a catalytic amount of Sc(OTf)3 or BF3‚
OEt2, are effectively trapped by a variety of allyl nucleophiles
to afford homopropargylic homoallylic alcohols in good yield
and selectivity. Such products are used as substrates for the
synthesis of functionalized vinylcyclopentenols via enyne
metathesis.
We report on a two-step method to prepare alkylidene
cyclopentanes abstaining from alkynyloxiranes and using an
enyne metathesis1 as a key step. In recent years, enyne
metathesis (bond reorganization) employing a variety of metal
catalysts has emerged as an efficient method for the preparation
of this motif from readily available precursors. Functionalized
dienes which contain a hydroxyl group in close proximity are
of interest as stereocontrol in subsequent cycloadditions is often
possible.2
Our previous experience3 with the Lewis acid (LA) catalyzed
in situ generation,4 and trapping, of â,γ-alkenyl aldehydes from
2-vinyloxiranes led us to speculate that an analogous transfor-
mation applied to alkynyloxiranes might readily afford the
desired precursors to the functionalized carbocyclic dienes
(Scheme 1) that would be useful in Diels-Alder reactions.5
(5) (a) Diels, O.; Alder, K. Justus Liebigs Ann. Chem. 1928, 460, 98.
For reviews, see: (b) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.;
Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668. (c) Oppolzer,
W. In ComprehensiVe Organic Synthesis; Trost, B. M., Flemming, T., Eds.;
Pergamon: Oxford, 1991; Vol. 5, p 315.
(6) (a) Viala, J.; Santelli, M. J. Org. Chem. 1988, 53, 6121. (b) Michaud,
S.; Wavrin, L.; Viala, J. Synth. Commun. 2002, 32, 1563. (c) Barbot, F.;
Miginiac, P. Synthesis 1983, 651. (d) Corey, E. J.; Lansbury, P. T. J. Am.
Chem. Soc. 1983, 105, 4093. (e) Jain, S. C.; Dussourd, D. E.; Conner,
W. E.; Eisner, T.; Guerrero, A.; Meinwald, J. J. Org. Chem. 1983, 48, 2266.
(f) Corey, E. J.; Wright, S. W. J. Org. Chem. 1990, 55, 1670.
(7) Wavrin, L.; Viala, J. Synthesis 2002, 326. (b) Roush, W. R.; Park,
J. C. Tetrahedron Lett. 1991, 32, 6285.
(1) For reviews, see: (a) Diver, S. T.; Giessert, A. J. Chem. ReV. 2004,
104, 1317. (b) Mori, M. Top. Organomet. Chem. 1998, 1, 133. (c) Poulsen,
C. S.; Madsen, R. Synthesis 2003, 1.
(2) For illustrative examples, see: (a) Fisher, M. J.; Hehre, W. J.; Kahn,
S. D.; Overman, L. E. J. Am. Chem. Soc. 1988, 110, 4625. (b) Barriault,
L.; Thomas, J. D. O.; Clement, R. J. Org. Chem. 2003, 68, 2317.
(c) Fensterbank, L.; Malacria, M.; Sieburth, S. McN. Synthesis 1997, 8,
813. (d) Bols, M.; Skrydstrup, T. Chem. ReV. 1985, 95, 1253.
(3) (a) Racemic allylation and crotylation: Lautens, M.; Ouellet, S. G.;
Raeppel, S. Angew. Chem., Int. Ed. 2000, 39, 4079. (b) Enantioselective
allylation: Lautens, M.; Maddess, M. L.; Sauer, E. L. O.; Ouellet, S. G.
Org. Lett. 2002, 4, 83. (c) Racemic and enantioselective propargylation:
Maddess, M. L.; Lautens, M. Org. Lett. 2005, 7, 3557.
(8) For a review, see: (a) Corinne, A.; Olivier, B.; Malacria, M. Chem.
ReV. 2002, 102, 813. For typical applications, see: (b) Pauson-Khand
reaction: Blanco-Urgoiti, J.; Anorbe, L.; Perez-Serrano, L.; Dominquez,
G.; Perez-Castells, J. Chem. Soc. ReV. 2004, 33, 32. (c) [4 + 2 + 2]
cycloadditions: Evans, P. A.; Baum, E. W.; Fazal, A. N.; Pink, M. Chem.
Commun. 2005, 63 and references cited therein. (d) Diver, S.; Giessert, A.
Chem. ReV. 2004, 104, 1317.
(9) Details are provided in the Supporting Information.
(4) For additional examples, see: (a) Hertweck, C.; Boland, W. J. Org.
Chem. 2000, 65, 2458. (b) Bideau, F. L.; Gilloir, F.; Nilsson, Y.; Aubert,
C.; Malacria, M. Tetrahedron 1996, 52, 7487. (c) Wipf, P.; Xu, W. J. Org.
Chem. 1993, 53, 825.
(10) Potassium allyl and crotyl triflouroborates are readily prepared air-
and moisture-insensitive solids; see: (a) Batey, R. A.; Thadani, A. N.; Smil,
D. V. Tetrahedron Lett. 1999, 40, 4289. (b) Thadani, A. N.; Batey, R. A.
Org. Lett. 2002, 4, 3827.
10.1021/jo062107w CCC: $37.00 © 2007 American Chemical Society
Published on Web 02/07/2007
1822
J. Org. Chem. 2007, 72, 1822-1825

TABLE 1. Allylation of in Situ Generated â,γ-Alkynyl Aldehydes
SCHEME 2. Asymmetric Allylation
yielda (%)
entry compd
R
prod solvent
A
solvent
B
1
2
3
4
5
6
7
8
9
1
2
3
4
5
6
7
8
9
Ph
10
11
12
13
14
15
16
THF
Et2O
THF
THF
THF
THF
Et2O
Et2O
Et2O
92 CH2Cl2 71
79b CH2Cl2 73
83b CH2Cl2 70
67b CH2Cl2 67
45b CH2Cl2 49
65b CH2Cl2 71
71c CH2Cl2 77
51c CH2Cl2 49
Turning our attention to the application of these products,
we subjected the enynes to Grubbs’ second-generation catalyst
under microwave conditions14,15 and were pleased to observe
the formation of the desired functionalized dienes (Table 3). In
general, substrates lacking an allylic methyl group proceeded
in high yield after 5 min (Table 3, entries 1-5). An electron-
deficient silyl-substituted substrate (18) returned unreacted
starting material even with an extended reaction time (Table 3,
entry 6). The crotylated substrates (Table 3, entries 6-11)
bearing an allylic methyl group reacted at a significantly
decreased rate. Electron-withdrawing substitutents on the alkyne
exacerbated this trend, giving moderate product yields (Table
3, entries 7-9 and 11). Fortunately, in most cases (Table 3,
entries 7-10), the remainder of the mass balance is starting
material. Only the electron-rich aliphatic crotylated substrate
(26) gave full conversion after 10 min of heating. In some cases,
catalyst loading and reaction temperature can be decreased and
others overcome problems associated with chelation of the Boc
moiety with the metathesis catalyst.16 For example, treatment
of the BOC protected analogue of 10 (41) with 1 mol % of
Grubbs’ II catalyst at 100 °C in a sealed tube was sufficient to
yield the desired enyne product (42) in 93% isolated yield.
In summary, alkynyl epoxides are effectively converted to
â,γ-alkynyl aldehydes by treatment with a catalytic amount of
Lewis acid. In situ trapping with variety of allyl nucleophiles
affords homopropargylic homoallylic alcohols in moderate to
good yields, and as single diastereomers in the case of
crotylation. An enantioselective version has been demonstrated
for allylation which allows for formation of enantioenriched
products of either antipode. The products are useful for the rapid
construction of a variety of carbocyclic dienes. Further study
of utilizing the hydroxyl functionality to control facial selectivity
in Diels-Alder reactions is underway.
p-MeO-C6H4
m-Me-C6H4
p-CN-C6H4
p-NO2-C6H4
p-Cl-C6H4
C6H13
TBDPSO(CH2)3 17
TBDPS 18
48
Et2O 61b
a Isolated yield. b 15 mol % BF3‚OEt2 used in place of Sc(OTf)3.
c Reaction started at -78 °C then warmed to 0 °C.
4-6). The silyl terminated substrate (9) was noticeably less
reactive (Table 1, entry 9). In contrast, the alkyl systems (7
and 8) required lower temperatures in ether to give acceptable
yields of the homopropargylic homoallylic alcohols (16 and 17).
Reaction with potassium allyltrifluoroborate was best con-
ducted in dichloromethane and afforded the desired products
(10-18) in comparable yields to tetraallyltin with Sc(OTf)3 as
catalyst. The one exception was the 4-silyl-substituted alkynyl-
oxirane, which failed to give more than a trace of product under
the optimized conditions. Employing a combination of BF3‚
OEt2 and Et2O resolved this issue and afforded 18 in reasonable
yield (Table 1, entry 9). Once again, electron-rich systems (Table
1, entries 1-3) performed best.
Extension to crotylation was easily accomplished by switching
from potassium allyltrifluoroborate to either potassium (E)- or
(Z)-crotyltrifluoroborate (Table 2). Either syn- or anti-addition
products can be prepared for a range of substrates (Table 2,
entries 1, 3, 5, 7, and 9 vs entries 2, 4, 6, 8, and 10, respectively).
1
The products (19 - 28) were all single diastereomers by H
NMR, consistent with the documented cyclic transition state
for these nucleophiles.10 In contrast to the allylation chemistry,
BF3‚OEt2 and Sc(OTf)3 are often interchangeable, and in some
cases, diethyl ether was found to be a superior solvent system
(Table 2, entries 5-10). The silyl-terminated alkynyloxirane
(9) remains a problematic substrate and affords the desired
products (27 and 28) in low yield. Based on our previous
Experimental Section
(()-2-(Phenylethynyl)oxirane (1)17 (General Procedure A).
To a solution of phenylacetylene (8.0 mL, 72.8 mmol) in Et3N (50
mL) were added CuI (138 mg, 0.72 mmol), Pd(Ph3P)2Cl2 (156 mg,
0.22 mmol), and vinyl bromide (8.0 mL, F ) 1.52 at 4 °C, 114
mmol). After being stirred for 16 h at 50 °C, the mixture was
allowed to cool to rt and then filtered through a pad of Celite with
Et2O (100 mL). The ether solution was washed with water (3 ×
100 mL), dried over Na2SO4, and concentrated in vacuo. The crude
residue was then taken up in CH2Cl2 (150 mL) and cooled to 0 °C,
and m-CPBA (33 g, 134 mmol) was added. After 30 min, the
success3b with allylB(Ipc)2 (29) for asymmetric allylation of
11
â,γ-ethylenic aldehydes, we tested this reagent with the corre-
sponding alkynyl analogues. No reaction was observed at low
temperature (-78 °C) consistent with a marked decrease of
reactivity of alkynyloxiranes versus the corresponding 2-vinyl-
oxiranes. It proved necessary to increase the reaction temperature
to effect an efficient reaction, and at 20 °C the desired product
((S)-10) is isolated in good yield (Scheme 2). Unfortunately the
enantioselectivity is lower as a result of the increase in reaction
temperature consistent with the result in allylation of â,γ-
ethylenic aldehydes with allylB(Ipc)2.12,13
(14) For examples of microwave-assisted metathesis reactions, see: (a)
Balan, D.; Adolfsson, H. Tetrahedron Lett. 2004, 45, 3089. (b) Garbacia,
S.; Desai, B.; Lavastre, O.; Kappe, C. O. J. Org. Chem. 2003, 68, 9136.
For a review, see: Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J.
Tetrahedron 2001, 57, 9225.
(15) Control experiments using microwave vials under thermal conditions
indicated no appreciable difference in reaction yield or rate.
(16) For other examples of oxygen chelation effects in metathesis events,
see: Maddess, M. L.; Lautens, M. Org. Lett. 2004, 6, 1883 and references
cited therein.
(11) Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401.
(12) Either antiopode is readily accessible by modification of the
nucleophile, ent-32 gave (R)-10 in 83% yield and 77% ee.
(13) The absolute configuration may be predicted from analogy with
previous results. Compound 32 is known to give re face attack, while ent-
32 provides the enantiomer; see: (a) Brown, H. C.; Jadhav, P. K. J. Am.
Chem. Soc. 1983, 105, 2092. (b) Vulpetti, A.; Gardner, M.; Gennari, C.;
Bernardi, A.; Goodman, J. M.; Paterson, I. J. Org. Chem. 1993, 58, 1711.
(17) Eisch, J. J.; Galle, J. E. J. Org. Chem. 1990, 55, 4835.
J. Org. Chem, Vol. 72, No. 5, 2007 1823

TABLE 2. Crotylation of in Situ Generated â,γ-Alkynyl Aldehydes
a Isolated yields.
reaction mixture was warmed to rt, stirred for 12 h, and then poured
into a beaker that contained satd aq NaHCO3 (200 mL) and ice
(100 mL) and stirred for 10 min. The organic layer was isolated
and washed with Na2S2O8 (50 mL) and then brine (100 mL). After
concentration in vacuo, the crude residue was purified by flash
chromatography to afford 1 (yield ) 48%).
(()-7-Phenylhept-1-en-6-yn-4-ol (10) (General Procedure B).
To a cooled (0 °C) solution of 1 (186.3 mg, 1.0 mmol) and
potassium allyltrifluoroborate (222 mg, 1.5 mmol) in CH2Cl2 was
added Sc(OTf)3 (98 mg, 0.2 mmol). After the mixture was stirred
for 15 min, additional potassium allyltrifluoroborate (222 mg, 1.5
mmol) was added, and then the reaction mixture warmed to rt where
it was stirred for 2 h. Ether (10 mL) was added, and the organics
were washed with satd aq NaHCO3 (10 mL) and then brine (10
mL). After drying with Na2SO4 and concentration in vacuo, the
crude residue was purified by flash chromatograpy to afford 10
(yield ) 71%): 1H NMR (400 MHz, CDCl3) δ 7.45-7.40 (m, 2H),
7.31-7.27 (m, 3H), 5.87 (ddt, J ) 17.2, 10.0, 6.8 Hz, 1H), 5.22-
5.13 (m, 2H), 3.95-3.85 (m, 1H), 2.66 (dd, J ) 16.8, 5.6 Hz, 1H),
2.61 (dd, J ) 16.8, 6.4 Hz, 1H), 2.50 - 2.42 (m, 1H), 2.40-2.31
(m, 1H), 2.24 (d, J ) 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 134.4, 131.9, 128.5, 128.2, 123.6, 118.6, 83.2, 83.3, 69.6, 41.0,
27.8; FTIR (neat) ν 3382, 3077, 2907, 2228, 1641, 1598, 1490,
1442, 1070, 917, 756 cm-1; HRMS (m/z) calcd for C13H13O (EI,
M - H+) 185.0966, found 185.0971.
(4S)-7-Phenylhept-1-en-6-yn-4-ol ((S)-10). To a solution of 1
(100 mg, 0.69 mmol) and Sc(OTf)3 (25.6 mg, 0.05 mmol) in Et2O
(2 mL) was added 29 (0.77 M in ether, 2.08 mL, 1.6 mmol). The
reaction mixture was stirred at rt for 1 h and then quenched by the
sequential addition of 3 N NaOH (1 mL) and 30% H2O2 (1 mL,
warning! effervescence upon addition). After being stirred for 14
h at rt, the reaction contents were transferred to a separatory funnel
with satd aq NH4Cl (20 mL) and Et2O (25 mL). The organic layer
was isolated, the aqueous layer was extracted 2× with Et2O (15
mL), and the combined organics were dried with MgSO4, filtered,
and concentrated in vacuo. The crude residue was purified by flash
chromatography to afford (S)-10 (yield ) 89%): HPLC (CHIRAL-
CEL OD, 1 mL/min, 95 Hex/5 i-PrOH, 30 °C, 1 µL injection) tR1
) 16.3 min (minor), tR2 ) 32.6 min (major); ee ) 83%. For other
characterization data, see above.
(()-7-(4-Methoxyphenyl)hept-1-en-6-yn-4-ol (11). To a cooled
(0 °C) solution of 2 (174.2 mg, 1.0 mmol) and tetraallyltin (168
1824 J. Org. Chem., Vol. 72, No. 5, 2007

TABLE 3. Enyne Metathesis of Homopropargylic Homoallylic
Alcohols
CDCl3) δ 7.38-7.43 (m, 2H), 7.26-7.33 (m, 2H), 5.81 (ddt, J )
17.2, 10.7, 7.0 Hz, 1H), 5.08-5.18 (m, 2H), 3.66-3.73 (m, 1H),
2.65 (ddd, J ) 16.8, 10.3, 5.7 Hz, 1H), 2.43-2.50 (m, 1H), 2.04
(bsd, J ) 4.8 Hz, 1H), 1.13 (d, J ) 6.9 Hz 3H); 13C NMR (75
MHz, CDCl3) δ 140.5, 131.8, 128.4, 128.1, 123.6, 115.9, 86.5, 83.3,
73.3, 43.1, 26.0, 15.1; FTIR (neat) ν 3425, 3078, 2972, 1639, 1598,
1490, 1043, 916, 755 cm-1; HRMS (m/z) calcd for C19H19OSi (EI,
M) 200.1198, found 200.1201.
substrate
R
product
(3S*,4S*)-7-(4-Chlorophenyl)-3-methylhept-1-en-6-yn-4-ol (23)
(General Procedure E). To a cooled (0 °C) solution of 6 (178.6
mg, 1.0 mmol) and potassium Z-crotyltrifluoroborate (243 mg, 1.5
mmol) in Et2O was added BF3‚OEt2 (19 µL, 0.15 mmol). After the
mxture was stirred for 15 min, additional potassium (Z)-crotylltri-
fluoroborate (243 mg, 1.5 mmol) was added, and then the reaction
mixture warmed to rt where it was stirred for 2 h. Ether (10 mL)
was added, and the organics were washed with satd NaHCO3 (10
mL) and then brine (10 mL). After drying with Na2SO4 and
concentration in vacuo, the crude residue was purified by flash
chromatograpy to afford 23 (yield ) 66%): 1H NMR (300 MHz,
CDCl3) δ 7.31 (d, J ) 3.4 Hz, 2H), 7.24 (d, J ) 3.4 Hz, 2H),
5.85-5.73 (m, 1H), 5.19-5.09 (m, 2H), 3.73-3.66 (m, 1H), 2.71-
2.52 (m, 2H), 2.48-2.42 (m, 1H), 2.00 (d, J ) 5.1 Hz, 1H), 1.11
(d, J ) 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 140.4, 134.1,
133.1, 128.8, 122.1, 116.1, 87.7, 82.1, 73.3, 43.1, 26.0, 15.1; FTIR
(neat) ν 3418, 2965, 2930, 2234, 1640, 1604, 1489, 1462, 1418,
1398, 1091, 1014, 919, 828 cm-1; HRMS (m/z) calcd for C14H15-
ClO (EI, M+) 234.0811, found 234.0805.
time
(min)
entry
S
R1
R2
P
yielda-c (%)
1
2
3
4
5
6
7
8
9
10 Ph
H
H
H
H
H
H
Me
H
Me
Me
H
H
H
H
H
H
H
H
Me
H
5
5
5
5
5
10
10
5
10
10
10
30
31
32
33
34
35
36
37
38
39
40
94
92
86
93
11 p-MeO-C6H4
12 m-Me-C6H4
13 p-CN-C6H4
16 C6H13
76
18 TBDPS
64b
41b
32b
43b
86
22 p-CN-C6H4
23 p-Cl-C6H4
24 p-Cl-C6H4
26 C6H13
10
11
H
Me
27 TBDPS
46c
a Yields are isolated yields. b Incompletion. c Complex mixture
µL, 0.70 mmol) in Et2O (2.0 mL) was added BF3‚OEt2 (19 µL,
0.15 mmol). After 2 h, aq KF (2 M, 2 mL) and satd aq NaHCO3
(5 mL) were added, and the mixture was stirred for 12 h at rt. The
reaction mixture was filtered through a pad of Celite with ether
(20 mL), and the organics were washed with water (10 mL) and
then dried with Na2SO4. After filtration and concentration in vacuo,
the crude residue was purified by flash chromatography to afford
11 (yield ) 79%): 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J ) 9.2
Hz, 2H), 6.83 (d, J ) 9.2 Hz, 2H), 5.87 (ddt, J ) 17.6, 10.4, 7.2
Hz, 1H), 5.23 - 5.14 (m, 2H), 3.94 - 3.85 (m, 1H), 3.81 (s, 3H),
2.64 (dd, J ) 16.4, 5.2 Hz, 1H), 2.59 (dd, J ) 16.4, 6.4 Hz, 1H),
2.50 - 2.42 (m, 1H), 2.39 - 2.31 (m, 1H), 2.05 (d, J ) 4.8 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 159.5, 134.4, 133.2, 118.5,
115.7, 114.1, 84.4, 83.1, 69.6, 55.5, 41.0, 27.9; FTIR (neat) ν 3405,
2926, 2049, 1607, 1510, 1248, 1033, 832 cm-1; HRMS (m/z) calcd
for C14H16O2 (EI, M +) 216.1150, found 216.1154.
(()-7-(3-Methylphenyl)hept-1-en-6-yn-4-ol (12) (General Pro-
cedure C). To a cooled (0 °C) solution of 3 (158.2 mg, 1.0 mmol)
and tetraallyltin (168 µL, 0.70 mmol) in THF (2.0 mL) was added
BF3‚OEt2 (19 µL, 0.15 mmol). After 2 h, aq KFaq (2 M, 2 mL) and
satd aq NaHCO3 (5 mL) were added, and the mixture was stirred
for 12 h at rt. The reaction mixture was filtered through a pad of
Celite with ether (20 mL), and the organics were washed with water
(10 mL) and then dried with Na2SO4. After filtration and concentra-
tion in vacuo, the crude residue was purified by flash chromatog-
raphy to afford 12 (yield ) 83%): 1H NMR (300 MHz, CDCl3) δ
7.26-7.10 (m, 4H), 5.94-5.80 (m, 1H), 5.23-5.15 (m, 2H), 3.93-
3.87 (m, 1H), 2.64-2.61 (m, 2H), 2.51-2.35 (m, 1H), 2.32 (s,
3H), 2.04 (d, J ) 4.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 138.1,
134.4, 132.5, 129.0, 128.9, 128.3, 123.3, 118.5, 85.7, 83.5, 69.6,
40.9, 27.8, 21.4; FTIR (neat) ν 3388, 2922, 1602, 1485, 1047, 917,
783 cm-1; HRMS (m/z) calcd for C14H17O (EI, M + H+) 201.1279,
found 201.1279.
(()-3-(1-Phenylvinyl)cyclopent-3-en-1-ol (30) (General pro-
cedure F). A microwave vial equipped with a stir bar was charged
with 10 (37 mg, 0.2 mmol) along with tricyclohexylphosphine-
[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][ben-
zylidine]ruthenium(IV) dichloride (8.5 mg, 0.01 mmol, 5 mol %).
The resulting mixture was diluted with PhCH3 (0.7 mL), and a cap
was affixed and then crimped to seal the vessel. The reaction was
then heated to 160 °C employing microwave heating (30 s prestir)
and held for 5 min. After the reaction vessel had cooled, it was
opened, and the reaction contents were loaded directly upon a
column of silica gel and purified by flash chromatography to afford
30 (yield ) 94%): 1H NMR (300 MHz, CDCl3) δ 7.35-7.30 (m,
5H), 5.55 (brs, 1H), 5.20 (s, 1H), 5.14 (s, 1H), 4.68-4.60 (m, 1H),
2.95 (dd, J ) 16.2, 6.3 Hz, 1H), 2.81 (dd, J ) 18.3, 6.3 Hz, 1H),
2.61 (d, J ) 16.2 Hz, 1H), 2.44 (d, J ) 18.3 Hz, 1H), 1.87 (brs,
1H); 13C NMR (75 MHz, CDCl3) δ 146.4, 141.7, 141.2, 128.7,
128.2, 128.1, 127.5, 72.0, 43.7, 43.2; FTIR (neat) ν 3354, 3057,
2924, 1681, 1589, 1494, 1043 cm-1; HRMS (m/z) calcd for
C13H14O2 (EI, M + O, oxidation product) 202.0994, found
202.0990.
Acknowledgment. We thank Merck Frosst Canada, the
Ontario Research and Development Challenge Fund (ORDCF),
NSERC (Canada), and the University of Toronto for financial
support of this work. L.W. thanks the University of Toronto
for financial support. M.M. thanks NSERC (Canada) and the
Sumner Foundation for financial support.
(3S*,4S*)-3-Methyl-7-phenylhept-1-en-6-yn-4-ol (19) (General
Procedure D). To a cooled (0 °C) solution of 1 (168.3 mg, 1.0
mmol) and potassium (Z)-crotyltrifluoroborate (243 mg, 1.5 mmol)
in CH2Cl2 was added Sc(OTf)3 (98 mg, 0.20 mmol). After the
mixture was stirred for 15 min, additional potassium (Z)-crotyll-
trifluoroborate (243 mg, 1.5 mmol) was added and then the reaction
mixture warmed to rt where it was stirred for 2 h. Ether (10 mL)
was added, and the organics were washed with satd aq NaHCO3
(10 mL) and then brine (10 mL). After drying with Na2SO4 and
concentration in vacuo, the crude residue was purified by flash
chromatograpy to afford 19 (yield ) 72%): 1H NMR (300 MHz,
Supporting Information Available: Full characterizations of
compounds (1-9, 13-18, 20-22, 24-28, and 31-42) are included.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO062107W
J. Org. Chem, Vol. 72, No. 5, 2007 1825