Structure-reactivity in relationships in oxidative carbon-carbon bond forming reactions: A mild and efficient approach to stereoselective syntheses of 2,6-disubstituted tetrahydropyrones

Article abstract of DOI:10.1021/ja046125b

Homobenzylic ethers with pendent enol acetate nucleophiles undergo highly efficient cleavage reactions followed by 6-endo cyclizations to form 2,6-disubstituted tetrahydropyrones with excellent stereocontrol at room temperature in the presence of the mild oxidant ceric ammonium nitrate. Cyclizations proceed through either stabilized or nonstabilized oxocarbenium ions. Structure-reactivity relationships are presented to provide a predictive guide for the design of radical cation cleavage processes. Unique sequences for preparing cyclization substrates based on stereoselective Lewis acid mediated acetal openings have been developed for the synthesis of complex substrates that are suitable for applications to the synthesis of biologically active natural products.

Full text of DOI:10.1021/ja046125b

SUPPORTING INFORMATION
Structure-Reactivity Relationships in Oxidative Carbon-Carbon Bond Forming
Reactions: A Mild and Efficient Approach to Stereoselective Syntheses of 2,6-
Disubstituted Tetrahydropyrones
Lijun Wang, John R. Seiders, II, and Paul E. Floreancig*
Department of Chemistry
University of Pittsburgh
Pittsburgh, PA 15260
General Experimental
1
13
Proton ( H NMR) and carbon ( C NMR) nuclear magnetic resonance spectra were
recorded on Bruker Avance 300 spectrometers at 300 MHz and 75 MHz, respectively; or
Bruker Avance 500 spectrometers at 500 MHz and 125 MHz if specified. The chemical
shifts are given in parts per million (ppm) on the delta (δ) scale. The solvent peak or the
internal standard tetramethylsilane were used as reference values. High resolution and
low resolution mass spectra were recorded on a VG 7070 spectrometer. Infrared (IR)
spectra were collected on a Mattson Gygnus 100 spectrometer. Optical rotations were
measured on a Perkin-Elmer 241 polarimeter. Analytical thin layer chromatography
(
TLC) was performed on E. Merck pre-coated (25 nm) silica gel 60F-254 plates. Flash
column chromatography was preformed using ICN SiliTech 32-63 60Å silica gel.
Reagent grade ethyl acetate and hexanes (commercial mixture) were purchased from EM
Science and used as is for chromatography. Reagent grade methylene chloride (CH Cl ),
2
2
1
,2 dichloroethane (DCE) and acetonitrile (CH CN) were distilled from CaH . Reagent
3
2
grade 1,2 dimethoxyethane (DME) was distilled from Na/benzophenone. Diethyl ether
Et O) and tetrahydrofuran (THF) were dried by passing through aluminum drying
(
2
column. All reactions were run under a nitrogen (N ) atmosphere unless otherwise noted.
2
Ph
Ph
a-c
OH
SiMe
3
OC
8 17
H
OC
8
H
17
MeO
MeO
7
16
Reagents and conditions
a) TsCl, Et N, CH Cl . b) Lithium acetylide, ethylenediamine complex, DMSO, 0 °C to rt. c) n-BuLi,
40 °C to rt, then ICH SiMe , rt to 55 °C
3
2
2
2
-
3
[8-(4-methoxyphenyl)-7-octyloxy-8-phenyloct-2-ynyl]trimethylsilane (16)
S1

To 1-methoxy-4-(2-octyloxy-1-phenylhept-6-ynyl)benzene (200.0 mg, 0.492 mmol) in
THF (5 mL) at – 30 °C was added n-butyl lithium (1.6 M, 0.738 mmol, 0.500 mL). The
mixture was then stirred at – 30 °C for 15 min and warmed to 0 °C for 15 min.
Iodomethyl trimethylsilane (158.0 mg, 0.738 mmol) was then added dropwise. The
reaction flask was then covered in aluminum foil and heated to 55 °C for 12 h. The
reaction mixture was then cooled to room temperature and quenched by the addition of
water (1 mL). The mixture was then extracted with EtOAc (2x) and the combined organic
layers were washed with water and brine, dried over (Na SO ), filtered and concentrated
2
4
under reduced pressure. The resulting residue was then purified via flash column
chromatography (3% EtOAc in hexanes) to provide the desired product (173.1 mg, 82%):
1
H NMR (300 MHz, CDCl ) δ 7.36 (d, J = 7.2 Hz, 2H), 7.26 (t, J = 7.1, 3H), 7.17 (d, J =
3
8
6
.3 Hz, 2H), 6.81 (d, J = 8.7 Hz, 2H), 3.96-3.84 (m, 2H), 3.77 (s, 3H), 3.35 (dt, J = 8.7,
.4 Hz, 1H), 3.03 (dt, J = 8.7, 6.6 Hz, 1H), 2.06-1.94 (m, 2H), 1.63-1.48 (m, 4H), 1.39 (t,
1
3
J = 2.5 Hz, 2H), 1.33-1.12 (m, 12H), 0.88 (t, J = 7.1 Hz, 3H), 0.06 (s, 9H); C NMR (75
MHz, CDCl ) δ 158.3, 143.2, 135.5, 129.7, 129.3, 128.3, 127.9, 126.3, 114.1, 82.5, 78.9,
3
7
4.5, 55.5, 32.4, 32.1, 30.4, 29.7, 26.4, 25.7, 22.9, 19.4, 14.4, 7.2, -1.8: HRMS (EI) calcd
+
for C H O Si (M ) 492.3424, found 492.3418.
3
2
48
2
1
-Octyloxy-2-vinylidene-cyclopentane (17)
To 16 (50.0 mg, 0.101 mmol) in CH CN (5 mL) at room temperature was
3
8 17
C H O
added NaHCO (100.0 mg, 1.20 mmol). The mixture was then stirred for 10
3
1
7
min and CAN (138.4 mg, 0.252 mmol) was added. The reaction mixture was
then allowed to stir for 1.5 h and filtered through a silica plug. The filtrate was then
concentrated under reduced pressure. The resulting residue was then purified via flash
column chromatography (5% EtOAc in hexanes) to provide the desired product (10.6 mg,
1
4
7%): H NMR (300 MHz, CDCl ) δ 4.77 (td, J = 6.1, 1. Hz, 2H), 4.29 (s, 1H), 3.56 (dt,
3
J = 9.3, 6.8 Hz, 1H), 3.36 (dt, J = 9.3, 6.6 Hz, 1H), 2.53-2.51 (m, 1H), .29-2.31 (m, 1H),
1
.85-1.78 (m, 4H), 1.53-1.51 (m, 4H), 1.28-1.25 (m, 12H), 0.88 (t, J = 6.5 Hz, 3H).
Ph
[
8-benzyloxy-9-(4-methoxyphenyl)-9-phenylnona-
SiMe3
1
,2-dienyl]trimethylsilane (22):
H NMR (300 MHz, CDCl ) δ 7.20-7.40 (m, 10H),
.00-7.10 (m, 2H), 6.82 (d, J = 8.5 Hz, 50% of 2H),
OBn
MeO
1
3
22
7
6
4
3
2
.81 (d, J = 8.5 Hz, 50% of 2H), 4.85-4.90 (m, 1H), 4.69 (app dq, J = 1.4, 6.8 Hz, 1H),
.43 (d, J = 10.9 Hz, 1H), 4.20 (d, J = 10.9 Hz, 1H), 4.01-4.06 (m, 2H), 3.78 (2 singlets,
1
3
H), 1.89-1.93 (m, 2H), 1.27-1.58 (br, 6H), 0.09 (s, 9H); C NMR (75 MHz, CDCl ) δ
3
10.1, 158.2, 143.4, 143.0, 138.7, 135.1, 134.5, 130.3, 129.5, 129.1, 128.6, 128.3, 128.0,
S2

1
2
27.5, 126.3, 114.0, 113.7, 83.4, 82.6, 72.6, 55.8, 55.7, 55.3, 32.8, 32.6, 29.9, 27.9, 25.0,
-
1
4.9, -0.6; IR (neat) 2929, 1936, 1510, 1247, 839, 697 cm ; HRMS (EI) calcd for
+
C H O Si (M ) 484.2797, found 484.2806.
3
2
40
2
(
2-ethynylcyclohexyloxymethyl)benzene (23)
1
H NMR (300 MHz, CDCl ) δ 7.14-7.34 (m, 5H), 4.62-4.49 (d, J = 12.3 Hz,
3
BnO
~
50% of 1H), 4.59 (s, ~50% of 2H), 4.58 (d, J = 12.3 Hz, ~50% of 1H), 3.30-
23
3
.37 (m, 1H), 2.92 (br s, 43% of 1H), 2.41-2.48 (m, 57% of 1H), 1.94 (m, 1H,
1
3
alkyne proton), 1.11-1.9 (m, 8H); C NMR (75 MHz, CDCl ) δ 139.1, 128.5, 127.9,
3
1
2
27.8, 127.6, 87.0, 85.0, 79.4, 77.0, 71.4, 70.8, 70.2, 69.5, 35.2, 32.9, 30.6, 30.3, 29.9,
-
1
9.6, 28.6, 24.1, 23.7, 22.1; IR (neat) 3305, 2934, 2858, 2114, 1443, 1097, 735, 697 cm ;
+
HRMS (EI) calcd for C H O (M - H) 213.1279, found 213.1275.
15
17
1
-[2-(tert-Butyldimethylsilyloxy)-1-phenyl-9-
trimethylsilylnona-7,8-dienyl]-4-methoxybenzene
(24)
Ph
SiMe3
OTBS
MeO
1
24
H NMR (300 MHz, CDCl ) δ 7.26-7.42 (m, 7H), 6.85
3
(
d, J = 8.4 Hz, 2H), 4.90-4.95 (m, 1H), 4.73 (q, J = 6.8
Hz, 1H), 4.31-4.34 (m, 1H), 3.98-4.02 (m, 1H), 3.78 (2 singlets, 3H), 1.93-1.97 (m, 2H),
.33-1.54 (m, 6H), 0.83 (2 singlets, 9H), 0.15 (s, 9H), -0.01 (2 singlets, 3H), -0.45 (2
1
1
3
singlets, 3H); C NMR (75 MHz, CDCl ) δ 210.2, 158.2, 142.7, 142.8, 135.5, 134.1,
3
1
5
2
30.9, 129.8, 129.7, 128.9, 128.3, 128.2, 126.1, 113.8, 113.7, 83.4, 82.7, 76.3, 75.9, 55.9,
5.6, 55.3, 35.7, 35.5, 30.0, 28.0, 26.0, 24.3, 24.2, 23.9, 18.1, -0.6, -4.2, -5.3; IR (neat)
929, 2852, 1936, 1511, 1248, 1096, 836, 698 cm .
-1
tert-Butyl-(2-ethynylcyclohexyloxy)dimethylsilane (25)
1
H NMR (300 MHz, CDCl ) δ 3.76-3.80 (m, 50% of 1H), 3.61-3.65 (m, 50%
3
TBSO
of 1H), 2.56-2.60 (m, 50% of 1H), 2.29-2.35 (m, 50% of 1H), 2.04 (d, J =
.4 Hz, 50% of 1H), 2.01 (d, J = 2.4 Hz, 50% of 1H), 1.80-1.90 (m, 2H),
.64-1.75 (m, 2H), 1.45-1.53 (m, 2H), 1.26-1.34 (m, 2H), 0.90 (2 singlets, 9H), 0.09 (s,
25
2
1
6
-1
H); IR (neat) 2924, 2853, 2166, 1731, 1465, 1244, 835 cm .
2
-(4-methoxyphenyl)-3-octyloxy-2-phenyltetrahydropyran (26)
C H17O
8
MeO
To 7 (50.0 mg, 0.125 mmol) in DCE (2 mL) were added NaHCO3
O
(
100.0 mg, 1.20 mmol) and DDQ (56.9 mg, 0.250 mmol). The reaction
was then stirred at room temperature for 3 hours and filtered through a
silica plug. The filtrate was then concentrated under reduced pressure.
The resulting residue was then purified via flash column
26
S3

1
chromatography (5% EtOAc in hexanes) to provide ether 26 (27.0 mg, 55%): H NMR
(
300 MHz, CDCl ) δ 7.60-7.56 (m, 2H), 7.36-7.17 (m, 5H), 6.84-6.78 (m, 2H), 3.82-3.78
3
(
1
m, 1H), 3.79 (s, 3H), 3.62-3.60 (m, 2H), 3.36-3.33 (m, 1H), 2.85-2.83 (m, 1H), 1.98-
.95 (m, 4H), 1.55-1.53 (m, 2H), 1.29-1.23 (m, 12H), 0.89 (t, J = 6.7 Hz, 3H); C NMR
1
3
(
300 MHz, CDCl ) δ 158.3, 158.1, 145.8, 143.9, 137.5, 135.3, 129.5, 128.4, 127.8, 127.2,
3
1
2
26.7, 126.4, 113.2, 82.4, 82.2, 81.5, 70.7, 62.2, 55.2, 31.9, 29.9, 29.4, 29.3, 26.2, 26.1,
-
1
5.8, 25.5, 23.8, 22.7, 14.2; IR (neat) 2928, 2855, 1509, 1249, 1080, 1036 cm ; HRMS
+
(EI) calcd for C H O (M ) 396.2664, found 396.2676.
26
36
3
2
-hexyl-4-(4-methoxybenzyl)-[1,3]dioxolane
O
To 3-(4-methoxyphenyl)propane-1,2-diol (3.32 g, 18.25 mmol) in
benzene (30 mL) were added freshly distilled heptanal (2.08 g,
O
MeO
6 13
C H
28
1
8.25 mmol, 2.54 mL) and p-TsOH (10 mg). The reaction mixture
was then warmed to reflux and stirred for 15 h, while removing water via a Dean-Stark
trap. After cooling to room temperature, the reaction was neutralized by the addition of
Et N (2 mL) and the solvent was removed under reduced pressure. The resulting residue
3
was then purified via flash column chromatography (5% EtOAc in hexanes) to provide
1
the desired product (4.27 g, 84%): H NMR (300 MHz, CDCl ) δ 7.14 (d, J = 8.5 Hz,
3
2
4
7
H), 6.85 (d, J = 8.5 Hz, 2H), 5.02 (t, J = 4.8 Hz, 0.35H), 4.91 (t, J = 4.7 Hz, 0.65H),
.28 (p, J – 6.7 Hz, 0.48H), 3.84 (dd, J = 7.7, 7.0 Hz, 0.74H), 3.78 (s, 3H), 3.62 (dd, J =
.7, 6.2 Hz, 0.73H), 3.55 (appt t, J = 4.3 Hz, 0.45H), 2.96 (dd, J = 13.8, 6.3 Hz, 1H), 2.73
(
0
dd, J = 13.8, 7.0 Hz, 1H), 1.73-1.66 (m, 2H), 1.46-1.42 (m, 2H0, 1.33-1.29 (m, 8H),
1
3
.93-0.88 (m, 3H); C NMR (75 MHz, CDCl ) δ 158.0, 129.9, 129.2, 113.6, 104.7,
3
1
2
03.9, 76.3, 69.6, 68.8, 54.8, 38.8, 38.2, 33.9, 31.4, 28.9, 23.6, 22.2, 13.8; IR (neat) 2929,
-
1
858, 1612, 1513, 1441, 1248, 1037 cm ; HRMS (EI) calcd for C H O (M+) 278.1882,
1
7
26
3
found 278.1883.
3
-(4-methoxyphenyl)-2-(1-prop-2-ynylheptyloxy)-propan-1-ol
OH
To 2-hexyl-4-(4-methoxybenzyl)-[1,3]dioxolane (3.00 g, 10.7
O
MeO
C6H13
mmol) and allenyltributyltin (4.25 g, 12.9 mmol, 3.84 mL) in
CH Cl (50 mL) at -78 °C was added TiCl (2.44 g, 12.9 mmol, 1.41 mL) rapidly. The
2
2
4
reaction was then stirred at -78 °C for 15 min and methanol (2 mL) was added slowly.
The mixture was then poured into water and extracted with EtoAc (2x). The combined
organic layers were then washed with water and 10% aqueous KF, dried over Na SO ,
2
4
filtered and concentrated under reduced pressure. The resulting residue was then purified
via flash column chromatography (15-20% EtOAc in hexanes) to provide the desired
1
product (2.86 g, 84%): H NMR (300 MHz, CDCl ) δ 7.13 (d, J = 8.5 Hz, 2H), 6.83 (d, J
3
S4

=
8.5 Hz, 2H), 3.79 (s, 3H), 3.67-3.60 (m, 2H), 3.55-3.37 (m, 2H), 2.89 (dd, J = 13.7, 5.9
Hz, 1H), 2.73 (dd, J = 13.7, 7.1 Hz, 1H), 2.23 (dd, J = 5.7, 2.6 Hz, 2H), 1.99 (t, J = 2.6
Hz, 1H), 1.85-1.81 (m, 1H), 1.70-1.56 (m, 2H), 1.30-1.28 (m, 10H), 0.89 (t, J = 6.9 Hz,
1
3
3
5
1
3
H); C NMR (75 MHz, CDCl ) δ 158.2, 130.5, 130.3, 113.9, 81.4, 80.0, 70.0, 63.7,
3
5.3, 37.3, 34.3, 31.8, 29.4, 25.5, 24.5, 22.7, 14.2; IR (neat) 3453, 3308, 2929, 2857,
612, 1512, 1465, 1247, 1038 cm ; HRMS (EI) calcd for C H O (M+) 318.2195, found
18.2198.
-1
2
0
30
3
1
-methoxy-4-[2-(1-prop-2-ynylheptyloxy)-pent-3-enyl]-
benzene
To 3-(4-methoxyphenyl)-2-(1-prop-2-ynylheptyloxy)-propan-1-ol
1.00 g, 3.14 mmol) in CH Cl (10 mL) at 0 °C was added
O
MeO
6 13
C H
30
(
2
2
NaHCO (2.63 g, 31.4 mmol). The mixture was then stirred for 10 min and Dess-Martin
3
periodinane (1.73 g, 4.08 mmol) was added. The reaction mixture then slowly warmed to
room temperature and stirred for 1.5 h, filtered to remove insoluble materials and
concentrated under reduced pressure. The resulting residue was then taken up in DME (5
mL) and 5-ethylsulfonyl-1-phenyl-1H-tetrazole (971.0 mg, 4.08 mmol) was added. The
mixture was then cooled to -60 °C and KHMDS (919.0 mg, 4.61 mmol) in DME (10 mL)
was added over 45 min via syringe pump. The reaction was then stirred at -60 °C for 12
h and the quenched by the addition of water while warming to room temperature. The
mixture was then extracted with EtOAc (2x). The combined organic layers were then
washed with water and brine, dried over Na SO , filtered and concentrated under reduced
2
4
pressure. The resulting residue was then purified via flash column chromatography (3%
1
EtOAc in Hexanes) to provide the desired product (191.8 mg, 19%): H NMR (300
MHz, CDCl ) δ 7.11 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 5.50 (dq, J = 15.3, 6.4
3
Hz, 1H), 5.32 (dd, J = 15.3, 8.3 Hz, 1H), 3.86 (q, J = 7.5 Hz, 1H), 3.79 (s, 3H), 3.45-3.39
(
m, 1H), 2.83 (dd, J = 13.7, 7.0 Hz, 1H), 2.66 (dd, J = 13.7, 6.1 Hz, 1H), 2.25-2.12 (m,
2
8
1
H), 1.93 (t, J = 2.5 Hz, 1H), 1.67 (d, J = 6.2 Hz, 3H), 1.56-1.41 (m, 4H), 1.29-1.27 (m,
1
3
H), 0.89 (t, J = 6.6 Hz, 3H); C NMR (75 MHz, CDCl ) δ 157.8, 131.9, 130.8, 130.6,
3
13.2, 81.8, 80.4, 74.0, 69.5, 55.1, 41.8, 34.5, 31.8, 29.1, 25.3, 23.5, 22.6, 17.6, 14.1; IR
-
1
(
neat) 3310, 2931, 2857, 1512, 1247, 1039 cm ; HRMS (EI) calcd for C H O (M+)
2
2
32
2
3
28.2402, found 328.2393.
Acetic acid 3-[1-(4-methoxybenzyl)-but-2-enyloxy]-1-
methylenenonyl ester (31)
To 1-methoxy-4-[2-(1-prop-2-ynylheptyloxy)-pent-3-enyl]-
O
MeO
H
13
C
6
OAc
31
benzene (100.0 mg, 0.30 mmol) in toluene (3 mL) were added
S5

Na CO (4.00 mg, 0.04 mmol) and acetic acid (36.0 mg, 0.60 mmol, 35.0 µL). The
2
3
mixture was then stirred at room temperature for 10 min and [Ru(p-cymene)Cl ] (6.0
2
2
mg, 0.012 mmol) and 2-trifurylphosphine (4.0 mg, 0.024 mmol). The reaction mixture
was then warmed to 80 °C and stirred for an additional 15 h. The mixture was then
cooled to room temperature and concentrated under reduced pressure. The resulting
residue was then purified via flash column chromatography (5% EtOAc in hexanes) to
2
0
1
provide the desired product (48.9 mg, 42%): [α]D = -8.3 (c = 1.4 in CHCl ); H NMR
3
(
300 MHz, CDCl ) δ 7.0 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 8.5 Hz, 2H), 5.44 (dq J = 15.3,
3
6
1
1
.1 Hz, 1H), 5.28 (ddd, J 15.3, 8.1, 1.3 Hz, 1H), 4.72 (s, 1H), 4.65 (s, 1H), 3.85-3.78 (m,
H), 3.78 (s, 3H), 3.44 (p, J = 6.3 Hz, 1H), 2.83 (dd, J = 13.5, 6.3 Hz, 1H), 2.63 (dd, J =
3.5, 6.7 Hz, 1H), 2.33 (dd, J = 14.7, 5.5 Hz, 1H), 2.20 (dd, J = 14.7, 6.6 Hz, 1H), 2.11
(
s, 3H), 1.65 (dd, J = 6.1, 1.0 Hz, 2H), 1.48-1.39 (m, 2H), 1.28-1.25 (m, 8H), 0.89 (t, J =
1
3
6
1
1
.2 Hz, 3H); C NMR (75 MHz, CDCl ) δ 168.9, 157.8, 153.7, 132.4, 103.6, 130.3,
3
28.3, 113.3, 103.4, 80.2, 72.8, 55.1, 41.7, 38.7, 34.9, 31.8, 29.1, 25.4, 22.6, 21.0, 17.5,
-
1
4.0; IR (neat) 2930, 2857, 1758, 1512, 1369, 1039 cm ; HRMS (EI) calcd for
(
C H O ) 388.2613 found 388.26022.
2
4
36
4
O
2-hexyl-6-propenyltetrahydropyran-4-one (32)
To acetic acid 3-[1-(4-methoxybenzyl)-but-2-enyloxy]-1-
methylenenonyl ester (48.0 mg, 0.12 mmol) in DCE (2.2 mL) was
O
6 13
C H
32
added NaHCO (100.0 mg, 1.19 mmol) and 4Å molecular sieves (100.0
3
mg). The mixture was then stirred at room temperature for 10 min and CAN (275.0 mg,
0
.50 mmol) in CH CN (1.2 mL) was added dropwise. The reaction was then stirred for an
3
additional 30 min and filtered through a silica plug. The filtrate was then concentrated
under reduced pressure and purified via flash column chromatography (5% EtOAc in
2
0
hexanes) to provide the desired product (21.5 mg, 80%): [α]D = -2.3 (c = 0.9 in CHCl );
3
1
H NMR (300 MHz, CDCl ) δ 5.75 (dqd, J = 15.3, 6.3, 0.8 Hz, 1H), 5.56 (ddq, J = 15.3,
3
6
6
.2, 1.5 Hz, 1H), 4.09-4.01 (m, 1H), 3.64-3.56 (m, 1H), 2.38-2.20 (m, 4H), 1.74 (d, J =
1
3
.3 Hz, 3H), 1.29-1.26 (m, 10H), 0.88 (t, J = 6.6, 3H); C NMR (75 MHz, CDCl )
3
δ 207.4, 130.4, 128.4, 47.8, 47.7, 36.4, 31.7, 29.1, 25.1, 22.6, 17.7, 14.0; IR (neat) 2928,
-1
2
857, 1721 cm ; HRMS (EI) calcd for C H O (M+) 224.1776, found 224.1759.
1
4
24
2
Acetic acid 3-[1-(4-methoxybenzyl)-pent-2-enyloxy]-1-
methylenenonyl ester (33)
O
To 1-methoxy-4-[2-(1-prop-2-ynylheptyloxy)hex-3-enyl]benzene
MeO
H13C6 OAc (243.0 mg, 0.71 mmol) in toluene (3 mL) was added Na CO3
2
33
(
12.0 mg, 0.11 mmol) and acetic acid (85.0 mg, 1.40 mmol, 85.0
S6

µL). The mixture was then stirred at room temperature for 10 min and [Ru(p-
cymene)Cl ] (17.3 mg, 0.028 mmol) and tri-2-furyl phosphine (13.1 mg, 0.056 mmol)
2
2
were added. The reaction mixture was then warmed to 80 °C and stirred for an additional
5 h. The mixture was then cooled to room temperature and concentrated under reduced
pressure. The resulting residue was then purified via flash column chromatography (5%
1
2
0
EtOAc in hexanes) to provide the desired product (182.5 mg, 64%): [α]D = -7.4 (c = 1.0
1
in CHCl ); H NMR (300 MHz, CDCl ) δ 7.0, (d, J = 8.5 Hz, 2H), 6.79 (d, J = 8.5 Hz,
3
3
2
1
5
1
H), 5.46 (dt, J = 10.9, 7.3 Hz, 1H), 5.19 (dd, J = 10.9, 9.5 Hz, 1H), 4.76 (s, 1H), 4.71 (s,
H), 4.30 (q, J = 7.9 Hz, 1H), 3.78 (s, 3H), 3.41 (p, J = 6.1 Hz, 1H), 2.87 (dd, J = 13.3,
.8 Hz, 1H), 2.57 (dd, J = 13.3, 7.6 Hz, 1H), 2.34 (dd, J = 14.7, 8.9 Hz, 1H), 2.27 (dd, J =
4.7, 6.4 Hz, 1H), 2.11 (s, 3H), 1.86 (dq, J = 14.7, 7.1 Hz, 1H), 1.73 (dq, J = 14.7, 7.4
Hz, 1H), 1.43-1.34 (m, 2H), 1.33-.125 (m, 8H), 0.88 (t, J = 6.9 Hz, 3H), 0.74 (t, J = 7.5
1
3
Hz, 3H); C NMR (75 MHz, CDCl ) δ 169.1, 158.0, 153.8, 134.5, 130.7, 130.5, 130.2,
3
1
13.5, 103.8, 74.6, 73.7, 55.3, 41.7, 38.9, 35.1, 31.9, 29.3, 25.5, 22.7, 21.2, 20.9, 14.2; IR
-
1
(
neat) 2931, 2857, 1758, 1665, 1612, 1464, 1246, 1196, 1038 cm ; HRMS (EI): calcd for
+
C H O (M ) 402.2770, found 402.2754.
2
5
38
4
O
2-but-1-enyl-6-hexyltetrahydropyran-4-one (34)
To 33 (100.0 mg, 0.25 mmol) in DCE (2.4 mL) was added NaHCO3
13 (200.0 mg, 2.38 mmol) and 4Å molecular sieves (200 mg). The mixture
was then stirred at room temperature for 10 min and CAN (544.0 mg,
O
3
6
C H
4
0
.99 mmol) in CH CN (1.5 mL) was added dropwise. The reaction mixture was then
3
stirred at room temperature for an additional 30 min and filtered through a silica plug.
The filtrate was then concentrated under reduced pressure, and the resulting residue was
purified via flash column chromatography (3% EtOAc in Hexanes) to provide the desired
2
0
1
product (41.1 mg, 70%): [α]D = -2.5 (c = 0.9 in CHCl ); H NMR (300 MHz, CDCl ) δ
3
3
5
1
2
.58 (dtd, J = 10.9, 7.4, 0.9 Hz, 1H), 5.40 (ddt, J = 10.9, 7.6, 1.4 Hz, 1H), 4.38 (dddd, J =
2.4, 7.6, 5.3, 0.8 Hz, 1H), 3.62 (dtd, J = 11.2, 4.7, 2.6 Hz, 1H), 2.40-2.24 (m, 2H), 2.16-
.00 (m, 2H), 1.75-1.62 (m, 2H), 1.58-1.40 (m, 2H), 1.38-1.25 (m, 8H), 0.99 (t, J = 7.5
13
Hz, 3H), 0.87 (t, J = 6.9 Hz, 3H); C NMR (75 MHz, CDCl ) δ 207.3, 135.3, 128.2, 73.1,
3
4
1
8.0, 47.7, 36.4, 31.7, 29.1, 28.8, 25.1, 22.9, 22.5, 21.3, 14.1; IR (neat) 2959, 2939, 2858,
-1
+
722 cm ; HRMS (EI) calcd for C H O (M ) 238.1933, found 238.1936.
1
5
26
2
Acetic acid 3-[1-(4-methoxybenzyl)-3-methylbut-2-enyloxy]-1-
methylenenonyl ester (35)
To 1-methoxy-4-[4-methyl-2-(1-prop-2-ynyl-heptyloxy)pent-3-
O
MeO
H13C6 OAc enyl]benzene (63.0 mg, 0.18 mmol) in toluene (2 mL) was added
35
S7

Na CO (2.5 mg, 0.48 mmol) and acetic acid (18.0 mg, 0.36 mmol, 17.0 µL). The
2
3
mixture was then stirred at room temperature for 10 min and [Ru(p-cymene)Cl ] (3.8
2
2
mg, 0.007 mmol) and tri-2-furylphosphine (2.7 mg, 0.014 mmol) were added. The
reaction mixture was then warmed to 80 °C and stirred for an additional 16 h. The
mixture was then cooled to room temperature and concentrated under reduced pressure.
The resulting residue was then purified via flash column chromatography (4% EtOAc in
2
0
hexanes) to provide the desired product (28.1 mg, 39%): [α]D = -7.7 (c = 0.7 in CHCl );
3
1
H NMR (300 MHz, CDCl ) δ 7.07 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 8.6 Hz, 2H), 5.02 (d,
3
J = 9.3 Hz, 1H), 4.75 (s, 1H), 4.69 (s, 1H), 4.23-4.16 (m, 1H), 3.78 (s, 3H), 3.40 (p, J =
5
1
.9 Hz, 1H), 2.84 (dd, J = 13.3, 5.9 Hz, 1H), 2.55 (dd, J = 13.3, 7.4 Hz, 1H), 2.37 (dd, J =
4.6, 5.6 Hz, 1H), 2.24 (dd, J = 14.6, 6.5 Hz, 1H), 2.11 (s, 3H), 1.67 (s, 3H), 1.48-1.47
1
3
(
m, 2H), 1.37 (s, 3H), 1.30-1.18 (m, 8H), 0.89 (t, J = 6.4 Hz, 3H); C NMR (75 MHz,
CDCl ) δ 168.7, 157.9, 153.8, 134.7, 130.9, 130.8, 126.6, 113.7, 103.4, 75.6, 73.2, 55.2,
3
4
1
1.7, 38.8, 29.2, 25.6, 25.3, 22.6, 21.0, 17.9, 14.0; IR (neat) 2929, 2856, 1758,
-1
+
512,1052 cm ; MS: m/z(%): 281 (12) [C H O ].
1
7
29
3
O
2
-hexyl-6-(2-methylpropenyl)tetrahydropyran-4-one (36)
To 35 (28.0 mg, 0.06 mmol) in DCE (2.0 mL) was added NaHCO3
60.0 mg, 0.71 mmol) and 4Å molecular sieves (60 mg). The mixture
was then stirred at room temperature for 10 min and CAN (152.0 mg,
.27 mmol) in CH CN (1.0 mL) was added dropwise. The reaction mixture was then
O
C6H13
(
36
0
3
stirred at room temperature for an additional 30 min and filtered through a silica plug.
The filtrate was then concentrated under reduced pressure, and the resulting residue was
purified via flash column chromatography (3% EtOAc in hexanes) to provide the desired
2
0
1
product (11.4 mg, 80%): [α]D = -2.3 (c = 0.6 in CHCl ); H NMR (300 MHz, CDCl ) δ
3
3
5
.25 (d, J = 7.8 Hz, 1H), 4.29 (dd, J = 14.0, 7.9 Hz, 1H), 3.66-3.57 (m, 1H), 2.40-2.20
(
m, 4H), 1.76 (s, 3H), 1.69 (s, 3H), 1.53-1.37 (m, 2H), 1.33-1.26 (m, 8H) 0.88 (t, J = 6.8
1
3
Hz, 3H); C NMR (75 MHz, CDCl ) δ 207.4, 137.3, 124.5, 74.1, 48.0, 47.8, 36.5, 31.7,
2
(
3
-
1
9.6, 29.1, 25.6, 25.2, 22.5, 18.4, 14.0; IR (neat) 2928, 2857, 1720, 1052 cm ; HRMS
+
EI): calcd for C H O (M ) 238.1932 found 238.1935.
15
26
2
Acetic acid 3-[4-(tert-butyldimethylsilanyloxy)-1-(4-
methoxybenzyl)but-2-enyloxy]-1-methylenenonyl ester (37)
OTBS
O
MeO
H
13
C
6
OAc
T o
ynylheptyloxy)pent-2-enyloxy] dimethylsilane (89.7 mg, 0.195
mmol) in toluene (2 mL) was added Na CO (3.3 mg, 0.031 mmol) and acetic acid (23.0
tert-butyl-[5-(4-methoxyphenyl)-4-(1-prop-2-
37
2
3
mg, 0.39 mmol, 20.0 µL). The mixture was then stirred at room temperature for 10 min
S8

and [Ru(p-cymene)Cl ] (4.0 mg, 0.007 mmol) and tri-2-furylphosphine (3.0 mg, 0.014
2
2
mmol) were added. The reaction mixture was then warmed to 80 °C and stirred for an
additional 15 h. The reaction was then cooled to room temperature and concentrated
under reduced pressure. The resulting residue was then purified via flash column
chromatography (5% EtOAc in hexanes) to provide the desired product (45.4 mg, 45%):
2
0
1
[
α]D = -7.5 (c = 0.5 in CHCl ); H NMR (300 MHz, CDCl ) δ 7.09 (d, J = 8.6, Hz, 2H),
3
3
6
.79 (d, J = 8.6 Hz, 2H), 5.58-5.47 (m, 2H), 4.72 (s, 1H), 4.64 (s, 1H), 4.12 (d, J = 2.8
Hz, 2H), 3.95 (app q, J = 6.6 Hz, 1H), 3.78 (s, 3H), 3.42 (p, J = 5.7 Hz, 1H), 2.83 (dd, J =
3.5, 6.5 Hz, 1H), 2.65 (dd, J = 13.5, 6.5 Hz, 1H), 2.32 (dd, J = 14.7, 5.5 Hz, 1H), 2.21
dd, J = 14.7, 6.4 Hz, 1H), 2.11 (s, 3H), 1.47-1.37 (m, 2H), 1.30-1.25 (m, 8H), 0.90 (s,
1
(
9
1
3
H), 0.91-0.89 (m, 3H), 0.05 (s, 3H), 0.04 (s, 3H); C NMR (75 MHz, CDCl ) δ 168.8,
3
1
57.9, 153.7, 132.2, 130.6, 130.5, 113.4, 103.4, 98.2, 79.6, 73.5, 62.9, 55.1, 46.8, 41.8,
3
2
8.4, 34.9, 31.8, 29.3, 25.8, 25.4, 22.6, 21.0, 20.6, 18.3, 14.0, -5.2; IR (neat) 2954, 2929,
-
1
+
856, 1758, 1512, 1463, 1248, 1196, 1108 cm ; HRMS (EI): calcd for C H O Si (M -
2
6
41
5
C H ) 461.2723, found 461.2718.
4
9
O
O
2-[3-(tert-butyldimethylsilanyloxy)propenyl]-6-
hexyltetrahydropyran-4-one (38)
13 To 37 (45.0 mg, 0.08 mmol) in DCE (2.2 mL) was added
TBSO
6
C H
38
NaHCO (90.0 mg, 1.07 mmol) and 4Å molecular sieves (90.0
3
mg). The mixture was then stirred at room temperature for 10 min and CAN (190.0 mg,
.34 mmol) in CH CN (1.0 mL) was added dropwise. The reaction mixture was then
0
3
stirred at room temperature for an additional 10 min and filtered through a silica plug.
The filtrate was then concentrated under reduced pressure, and the resulting residue was
purified via flash column chromatography (5% EtOAc in hexanes) to provide the desired
2
0
1
product (24.2 mg, 79%): [α]D = -2.2 (c = 1.0 in CHCl ); H NMR (300 MHz, CDCl ) δ
3
3
5
2
2
0
4
1
.84 (dt, J = 15.5, 3.8 Hz, 1H), 5.76 (dd, J = 15.5, 4.9 Hz, 1H), 4.20 (dd, J = 3.8, 1.1 Hz,
H), 4.14-4.08 (m, 1H), 3.66-3.57 (m, 1H), 2.46-2.41 (m, 2H), 2.40-2.37 (m, 1H), 2.30-
.21 (m, 1H), 1.75-1.70 (m, 1H), 1.59-1.50 (m, 1H), 1.30-1.26 (m, 8H), 0.92 (s, 9H),
1
3
.93-0.90 (m, 3H), 0.08 (s, 6H); C NMR (75 MHz, CDCl ) δ 207,3, 131.4, 128.7, 63.0,
3
7.8, 36.4, 31.8, 29.2, 26.0, 25.3, 22.6, 18.5, 14.1, -5.1; IR (neat) 2929, 2856, 1722, 1254,
-1
+
057 cm ; HRMS (EI): calcd for C H O Si (M ) 354.2590, found 354.2553.
2
0
38
3
Acetic acid-3-[1-(4-methoxybenzyl)allyloxy]-1-methylenenonyl
ester (39):
To 1-methoxy-4-[2-(1-prop-2-ynyl-heptyloxy)but-3-enyl]benzene
O
MeO
C H
6
13
39
(
0.95 g, 3.01 mmol) in toluene (15 mL) were added Na CO (51.0
2
3
S9

mg, 0.48 mmol) and acetic acid (0.36 g, 6.02 mmol, (35.0 µL). The mixture was then
stirred at room temperature for 10 min and [Ru(p-cymene)Cl ] (74.8 mg, 0.12 mmol)
2
2
and tri-2-furylphosphine (55.9 mg, 0.24 mmol) were added. The reaction mixture was
then warmed to 80 °C and stirred for an additional 16 h. The mixture was then cooled to
room temperature and concentrated under reduced pressure. The resulting residue was
then purified via flash column chromatography (3% EtOAc in hexanes) to provide the
1
desired product (699.0 mg, 62%): H NMR (300 MHz, CDCl ) δ 7.10 (d, J = 8.5 Hz,
3
2
1
H), 6.81 (d, J = 8.5 Hz, 2H), 5.73-5.60 (m, 1H), 5.11 (d, J = 10.2 Hz, 1H), 5.03 (d, J =
7.2 Hz, 1H), 4.73 (s, 1H), 4.66 (s, 1H), 3.90 (q, J = 6.7 Hz, 1H), 3.79 (s, 3H), 3.45 (p, J
=
=
5.6 Hz, 1H), 2.84 (dd, J = 13.5, 6.4 Hz, 1H), 2.66 (dd, J = 13.5, 6.7 Hz, 1H), 2.35 (dd, J
14.7, 5.6 Hz, 1H), 2.22 (dd, J = 14.7, 6.5 Hz, 1H), 2.11 (s, 3H), 1.45-1.43 (m, 2H),
1
3
1
1
3
.30-1.25 (m, 8H), 0.88 (t, J = 6.3 Hz, 3H); C NMR (75 MHz, CDCl ) δ 168.9, 157.9,
53.6, 139.2, 130.6, 130.2, 1117.0, 113.3, 103.5, 80.7, 73.4, 55.1, 41.5, 38.3, 34.8, 31.7,
0.9, 29.2, 25.3, 22.6, 21.0, 14.0; IR (neat) 2930, 2857, 1757, 1665, 1465, 1247, 1038
3
-1
+
cm ; HRMS (EI): calcd for C H O (M ) 374.2457, found 374.2461.
23
34
4
Acetic acid-3-[1-(4-methoxy-3-nitrooxybenzyl)allyloxy]-1-
methylenenonyl ester (40)
To 39 (50.0 mg, 14 mmol) in DCE (2.2 mL) were added
O NO
2
O
MeO
C
6
H
13
40
NaHCO (100.0 mg, 1.19 mmol) and 4Å molecular sieves (100.0
3
mg). The mixture was then stirred at room temperature for 15 min and CAN in CH CN
3
(
1.0 mL) was added dropwise. The reaction was then stirred for an additional 20 min and
passed through a silica plug. The filtrate was then concentrated under reduced pressure,
and the resulting residue was purified via flash column chromatography (20% EtOAc in
1
hexanes) to provide the nitrated product (12.0 mg, 19%): H NMR (300 MHz, CDCl ) δ
3
7
8
.71 (s, 1H), 7.37 (d, J = 8.5 Hz, 1H), 6.98 (d, J = 8.5 Hz, 1H), 5.63 (ddd, J = 17.3, 10.2,
.3 Hz, 1H), 5.15 (d, J = 10.2 Hz, 1H), 5.07 (d, J = 17.3 Hz, 1H), 3.94 (s, 3H), 3.94-3.89
(
m, 1H), 3.44 (p, J = 6.0 Hz, 1H), 2.83 (dd, J = 13.7, 6.9 Hz, 1H), 2.73 (dd, J = 13.7, 5.6
Hz, 1H), 2.31 (dd, J = 14.6, 5.7 Hz, 1H), 2.21 (dd, J = 14.6, 6.3 Hz, 1H), 2.11 (s, 3H),
1
3
1
.44-1.42 (m, 2H), 1.26-1.24 (m, 8H), 0.88 (t, J = 5.8 Hz, 3H); C NMR (75 MHz,
CDCl ) δ 168.9, 153.4, 151.4, 138.7, 135.6, 130.7, 126.8, 117.7, 112.9, 103.6, 79.9, 73.4,
3
+
5
3
6.5, 41.0, 38.4, 34.8, 31.7, 29.2, 25.2, 22.6, 21.0, 14.0; MS: m/z(%): 389 (6) [M - NO ],
2
+
60 (6) [M - CH NO ].
3
2
4
-(4-methoxyphenyl)-4-methylpentane-1,3-diol
OH
To 2-(4-methoxyphenyl)-2-methylhex-5-en-3-ol (3.09 g, 14.0
OH
MeO
mmol) in CH Cl (30 mL) at – 78 °C was gently bubbled O (g) for
2
2
3
42
S10

2
0 min. The solution was then purged with nitrogen, and MeOH (30 mL) was added
followed by NaBH (2.65 g, 70.3 mmol). The reaction mixture was then warmed to 0 °C,
4
and the reaction mixture was slowly warmed to room temperature. After stirring at room
temperature for 12 h, the reaction was quenched by the careful addition of water. The
CH Cl and MeOH were then removed under reduced pressure, and the aqueous layer
2
2
was extracted with EtOAc (2x). The combined organic layers were then washed with
water and brine, dried over Na SO , filtered and concentrated under reduced pressure.
2
4
The resulting residue was then purified via flash column chromatography (80% EtOAc in
1
hexanes) to provide the desired product (2.13 g, 68%): H NMR (300 MHz, CDCl ) δ
3
7
.30 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.83-3.78 (m, 3H), 3.80 (s, 3H), 2.35
1
3
(
s, 1H), 1.61-1.56 (m, 2H), 1.33 (s, 3H), 1.30 (s, 3H); C NMR (75 MHz, CDCl ) δ
3
1
2
58.0, 138.7, 127.6, 113.8, 80.3, 62.6, 55.3, 41.9, 32.8, 24.4, 23.4; IR (neat) 3396, 2963,
-
1
+
836, 1737, 1513, 1464, 1250, 1035 cm ; HRMS (EI) calcd for C H O (M ) 224.1412,
1
3
20
3
found 224.1416.
2
-hexyl-4-[1-(4-methoxyphenyl)-1-methylethyl]-[1,3]dioxane
To 4-(4-methoxyphenyl)-4-methylpentane-1,3-diol (1.59 g, 6.8
mmol) in benzene (15 mL) were added p-TsOH (10 mg) and freshly
distilled heptanal (778.4 mg, 6.8 mmol, 0.95 mL). The reaction
mixture was then warmed to reflux and stirred for 15 h, while
O
O
MeO
6 13
C H
43
removing water via a Dean-Stark trap. After cooling to room temperature, the reaction
mixture was neutralized by the addition of Et N (2 mL), and the solvent was removed
3
under reduced pressure. The resulting residue was then purified via flash column
1
chromatography (5% EtOAc in hexanes) to afford the desired product (1.75 g, 80%): H
NMR (300 MHz, CDCl ) δ 7.31 (d, J = 8.9 Hz, 2H), 6.84 (d, J = 8.9 Hz, 2H), 4.48 (t J =
3
5
.1 Hz, 1H), 4.02 (ddd, J = 11.2, 4.8, 1.3 Hz, 1H), 3.79 (s, 3H), 3.63 (dd, J = 12.1, 2.5
Hz, 1H), 3.53 (dd, J = 12.1, 2.1 Hz, 1H), 2.41-2.20 (m, 1H), 1.64-1.57 (m, 4H), 1.34 (s,
1
3
3
H), 1.32 (s, 3H), 1.03 (dq, J = 11.6, 2.2 Hz, 2H), 0,89 (t, J = 6.7 Hz, 3H); C NMR (75
MHz, CDCl ) δ 157.7, 138.8, 127.7, 113.2, 102.3, 84.1, 66.7, 55.1, 40.6, 35.0, 31.8, 29.1,
3
2
8.7, 25.9, 23.9, 22.8, 22.5, 14.0; IR (neat) 2956, 2856, 1513, 1465, 1250, 1185, 1036
-1
+
cm ; HRMS (EI) calcd for C H O (M ) 320.2351, found 320.2346.
20
32
3
4
-(4-methoxyphenyl)-4-methyl-3-(1-prop-2-
OH
ynylheptyloxy)pentan-1-ol
O
MeO
To 2-hexyl-4-[1-(4-methoxyphenyl)-1-methylethyl]-[1,3]-dioxane
C H
6
13
(
200.0 mg, 0.62 mmol) in CH Cl (6 mL) at – 78 °C were added
2
2
TiCl /Ti(i-PrO) (6:5) in CH Cl (9 mL) over 2h (via syringe pump). The reaction mixture
4
4
2
2
S11

was then quenched by the dropwise addition of MeOH (1 mL), and poured directly into
water. The mixture was then extracted with EtOAc (2x). The combined organic layers
were then washed with water, 10% aqueous KF and brine, dried over Na SO filtered, and
2
4
concentrated under reduced pressure. The resulting residue was then purified via flash
column chromatography (15% EtOAc in hexanes) to provide the desired product as a
1
1
7
1
9:1 mixture of separable diastereomers (191.5 mg, 86%): H NMR (300 MHz, CDCl ) δ
3
.31 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H), 3.67 (dd, J = 6.9, 4.6 Hz,
H), 3.52-3.49 (m, 2H), 3.31 (p, J = 5.8 Hz, 1H), 2.27 (dd, J = 5.2, 2.6 Hz, 2H), 1.99 (t, J
=
2.6 Hz, 1H), 1.76-1.75 (m, 2H), 1.68-1.57 (m, 4H), 1.36 (s, 3H), 1.30 (s, 3H), 1.30-1.27
1
3
(
m, 6H), 0.89 (t, J = 6.8 Hz, 3H); C NMR (75 MHz, CDCl ) δ 157.8, 140.1, 127.6,
3
1
2
13.4, 82.3, 81.6, 70.1, 61.1, 55.3, 42.3, 34.4, 33.3, 31.9, 29.5, 27.9, 26.2, 25.3, 23.9,
-
1
3.5, 22.7, 14.2; IR (neat) 3309, 2955, 2857, 1513, 1465, 1250, 1037 cm ; HRMS (EI)
+
calcd for C H O (M ) 360.2664, found 360.2674.
23
36
3
tert-butyl-[4-(4-methoxyphenyl)-4-methyl-3-(1-prop-2-
ynylheptyloxy)pentyloxy] dimethylsilane
OTBS
O
MeO
To
4-(4-methoxyphenyl)-4-methyl-3-(1-prop-2-
6 13
C H
ynylheptyloxy)pentan-1-ol (325.4 mg, 0.90 mmol) in DMF (3
mL) were added imidazole (134.7 mg, 1.98 mmol) and DMAP (30 mg) at 0 °C. The
mixture was then stirred for 5 min and TBSCl (149.0 mg, 0.99 mmol) and the cold bath
was removed. The reaction mixture was then stirred at room temperature for 1.5 h, and
quenched by the addition of water. The mixture was then extracted with EtOAc (2x). The
combined organic layers were then washed with water and brine dried over Na SO ,
2
4
filtered and concentrated under reduced pressure. The resulting residue was then purified
via flash column chromatography (5% EtOAc in hexanes) to provide the desired product
1
(
363.7 mg, 85%): H NMR (300 MHz, CDCl ) δ 7.30 (d, J = 8.8 Hz, 2H), 6.84 (d, J =
3
8
3
.8 Hz, 2H), 3.80 (s, 3H), 3.60 (dd, J = 6.4, 3.8 Hz, 1H), 3.50 (p, J = 6.3 Hz, 1H), 3.42-
.38 (m, 1H), 3.33-3.28 (m, 1H), 2.32 (dq, J = 16.7, 2.7 Hz, 1H), 2.20 (dd, J = 16.7, 2.7
Hz, 1H), 1.97 (t, J = 2.7 Hz, 1H), 1.45-1.38 (m, 4H), 1.34 (s, 3H), 1.31 (s, 3H), 1.34-1.30
1
3
(
m, 8H), 0.92 (t, J = 5.0 Hz, 3H), 0.88 (s, 9H), -0.01 (s, 3H), -0.03 (s, 3H); C NMR (75
MHz, CDCl ) δ 157.5, 140.0, 127.6, 113.2, 81.9, 80.3, 75.7, 69.6, 60.6, 55.1, 42.0, 35.3,
3
3
2
4
3.9, 31.8, 29.4, 26.8, 25.9, 25.1, 23.2, 22.6, 18.2, 14.0, -5.4, -5.5; IR (neat) 3312, 2954,
+
857, 1611, 1513, 1464, 1251, 1086, 1039, 833; HRMS (EI) calcd for C H O Si (M )
3
3
46
2
74.3497, found 474.3508.
S12

Acetic acid 3-[1-[2-(tert-butyldimethylsilanyloxy)ethyl]-2-(4-
methoxyphenyl)-2-methylpropoxy]-1-methylenenonyl ester
OTBS
OAc
O
MeO
(
44)
T o
ynylheptyloxy)pentyloxy] dimethylsilane (363.0 mg, 0.76 mmol)
in toluene (5 mL) were added Na CO (13.0 mg, 0.12 mmol) and acetic acid (46.0 mg,
13 6
H C
4
tert-butyl[4-(4-methoxyphenyl)-4-methy-3-(1-prop-2-
4
2
3
0
.76 mmol, 46.0 µL). The mixture was then stirred at room temperature for 10 min and
[
Ru(p-cymene)Cl ] (18.7 mg, 0.03 mmol) and tri-2-furylphosphine (14.2 mg, 0.06
2
2
mmol) were added. The reaction mixture was then warmed to 80 °C and stirred for an
additional 20 h. The mixture was then cooled to room temperature and concentrated
under reduced pressure. The resulting residue was then purified via flash column
chromatography (5% EtOAc in hexanes) to provide the desired product (194.0 mg, 48%):
1
H NMR (300 MHz, CDCl ) δ 7.28 (d, J = 8.6 Hz, 2H), 6.83 (d, J = 8.6 Hz, 2H), 4.79 (s,
3
1
(
4
h), 4.75 (s, 1H), 3.79 (s, 3H), 3.54 (dd, J = 7.1, 3.3 Hz, 1H), 3.42-3.28 (m, 3H), 2.42
dd, J = 14.7, 5.1 Hz, 1H), 2.29 (dd, J = 14.7, 6.9 Hz, 1H), 2.11 (s, 3H), 1.59-1.48 (m,
H), 1.33 (s, 3H), 1.27 (s, 3H), 1.33-1.27 (m, 8H), 0.91-0.85 (m, 3H), 0.85 (s, 9H), -0.03
1
3
(
s, 3H), -0.06 (s, 3H); C NMR (75 MHz, CDCl ) δ 169.2, 157.8, 154.1, 140.5, 127.9,
3
1
2
10.7, 103.8, 80.2, 76.1, 61.1, 55.4, 42.6, 38.2, 35.8, 34.0, 32.1, 29.7, 26.9, 25.2, 23.8,
-
1
2.9, 21.4, 14.3, -5.0: IR (neat) 2955, 2929, 1755, 1513, 1251, 1194 cm ; HRMS (EI)
+
calcd for C H O Si (M ) 477.3036, found 477.3027.
27
45
5
O
O
2-[2-(tert-butyldimethylsilanyloxy)ethyl]-6-
hexyltetrahydropyran-4-one (45)
C6H13 To 44 (30.0 mg, 0.056 mmol) in DCE (1.2 mL) were added
TBSO
45
NaHCO (60.0 mg, 0.7 mmol) and 4 Å molecular sieves (60.0 mg).
3
The mixture was then stirred at room temperature for 10 min and CAN (122.0 mg, 0.22
mmol) in CH CN (0.5 mL) was added dropwise. The reaction was then stirred for an
3
additional 20 min and filtered through a silica plug. The filtrate was then concentrated
under reduced pressure. The resulting residue was then purified via flash column
chromatography (7% EtOAc in hexanes) to provide the desired product (16.8 mg, 88%):
1
H NMR (500 MHz, CDCl ) δ 3.86-3.75 (m, 3H), 3.60-3.56 (m, 1H), 2.40 (d, J = 14.2
3
Hz, 2H), 2.31-2.22 (m, 2H), 1.86-1.82 (m, 1H), 1.77-1.74 (m, 2H), 1.52-1.50 (m, 2H),
1
3
1
.33-1.28 (m, 8H), 0.92 (s, 9H), 0.92-0.89 (m, 3H), 0.08 (s, 6H); C NMR (75 MHz,
CDCl ) δ 207.6, 73.6, 58.9, 48.0, 39.4, 36.5, 31.7, 29.1, 25.9, 25.3, 22.5, 14.0, -5.3; IR
3
-
1
+
(
neat) 2930, 2856, 1723, 1470, 1252, 1093 cm ; HRMS (EI) calcd for C H O Si (M -
1
9
37
3
H): 341.2512, found 341.2520.
S13

MeO
O
H
a-f
O
MeO
MeO
H
13
C
6
Reagents and Conditions
a) Methallyllithium, THF, -78 °C. b) O
3
, CH
2
Cl
2
, -78 °C, then Ph
3
2
P, rt. c) Et BOMe,
THF, -78 °C, then NaBH . d) Heptanal, p-TsOH, C H , reflux. e) Allenyltributyltin,
4
6 6
4 4 2 2
TiCl /Ti(Oi-Pr) (3:1), CH Cl , -78 °C. f) NaH, DMF, then MeI.
Acetic acid 3-{3-methoxy-1-[1-(4-methoxyphenyl)-1-methyl]butoxy}-1-
methylenenonyl ester (46)
To 1-methoxy-4-[4-methoxy-1,1-dimethyl-2-(1-methylbut-3-ynyloxy)pentyl]benzene
(
45.5 mg, 0.12 mmol) in toluene (3 mL) were added Na CO (2.1 mg, 0.02 mmol) and
2
3
acetic acid (14.0 mg, 0.24 mmol, 14.0 µL). The mixture was then stirred at room
temperature for 10 min and [Ru(p-cymene)Cl ] (3.1 mg, 0.005 mmol) and tri-2-
2
2
furylphosphine (2.4 mg, 0.01 mmol) were added. The reaction mixture was then warmed
to 80 °C and stirred for an additional 15 h. The mixture was then cooled to room
temperature and concentrated under reduced pressure. The resulting residue was then
purified via flash column chromatography (4% EtOAc in hexanes) to provide the desired
1
product (33.1 mg, 63.4%): H NMR (300 MHz, CDCl ) δ 7.26 (d, J = 8.5 Hz, 2H), 6.82
3
(
(
(
8
1
2
d, J = 8.5 Hz, 2H), 4.76 (s, 1H), 4.75 (s, 1H), 3.78 (s, 3H), 3.52 (p, J = 5.7 Hz, 1H), 3.45
t, J = 4.9 Hz, 1H), 3.17 (s, 3H), 2.70-2.63 (m, 1H), 2.44 (dd, J = 14.7, 6.8 Hz, 1H), 2.32
dd, J = 14.7, 5.7 Hz, 1H), 1.55-1.46 (m, 4H), 1.32 (s, 3H), 1.26 (s, 3H), 1.28-1.25 (m,
1
3
H), 0.92-0.87 (m, 6H); C NMR (75 MHz, CDCl ) δ 168.9, 157.6, 154.1, 139.9, 127.8,
3
13.1, 103.1, 80.9, 75.4, 73.7, 56.0, 55.1, 42.4, 40.0, 38.7, 33.1, 31.8, 29.6, 26.7, 25.1,
-
1
2.9, 21.1, 19.0, 14.0: IR (neat) 2929, 2858, 1758, 1513, 1465, 1250, 1038 cm ; (HRMS)
+
(
EI) calcd for C H O (M - C H O) 299.2222, found 299.2214.
17
31
4
10 13
2
-hexyl-6-(2-methoxypropyl)tetrahydropyran-4-one (47)
O
OMe
To 46 (33.1 mg, 0.076 mmol) in DCE (1.2 mL) were added NaHCO3
O
C
6
H
13 (66.0 mg, 0.78 mmol) and 4Å molecular sieves (66.0 mg). The mixture
47
was then stirred at room temperature for 15 min and CAN (167.0 mg,
0
.30 mmol) in CH CN (0.5 mL) was added dropwise. The reaction mixture was then
3
stirred for an additional 15 min and filtered through a silica plug. The filtrate was then
concentrated under reduced pressure and the resulting residue was purified via flash
column chromatography (6% EtOAc in Hexanes) to provide the desired product (19.4
1
mg, 100%): H NMR (300 MHz, CDCl ) δ 3.83-3.76 (m, 1H), 3.63-3.53 (m, 1H), 3.33
3
(
1
s, 3H), 2.35 (ddt, J = 12.6, 7.7, 1.9 Hz, 2H), 2.25-2.16 (m, 2H), 1.73-1.63 (m, 2H), 1.54-
1
3
.44 (m, 2H), 1.32-1.28 (m, 8H), 1.17 (d, J = 6.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H); C
MeO
S14
O
M O

NMR (75 MHz, CDCl δ 207.5, 73.7, 73.1, 56.3, 48.2, 48.1, 44.2, 36.4, 31.7, 29.0, 25.4,
3
-
1
2
2.6, 19.4, 14.0; IR (neat) 2929, 2857, 1721, 1091 cm ; HRMS (EI) calcd for C H O
1
5
28
3
+
(M ) 256.2038, found 256.2035.
Acetic acid 3-{3-methoxy-1-[1-(4-methoxyphenyl)-1-methylethyl]butoxy}-1-
methylenenonyl ester (48)
MeO
To 1-methoxy-4-[4-methoxy-1,1-dimethyl-2-(1-methylbut-3-
ynyloxy)pentyl]benzene (33.0 mg, 0.08 mmol) in toluene (2 mL)
were added Na CO (1.2 mg, 0.0012 mmol) and acetic acid (9.6
O
2
3
MeO
H
13
C
6
OAc
mg, 0.16 mmol, 16 µL). The mixture was then stirred at room
48
temperature for 10 min and [Ru(p-cymene)Cl ] (2.0 mg, 0.003
2
2
mmol) and tri-2-furylphosphine (1.6 mg, 0.006 mmol) were added. The reaction mixture
was then warmed to 60 °C and stirred for an additional 15 h. The mixture was then
cooled to room temperature and concentrated under reduced pressure. The resulting
residue was then purified via flash column chromatography (5% EtOAc in hexanes) to
1
provide the desired product (14.9 mg, 43%): H NMR (300 MHz, CDCl ) δ 7.28 (d, J =
3
8
.8 Hz, 2H), 6.83, (d, J = 8.8 Hz, 2H), 4.78 (s, 1H), 4.74 (s, 1H), 3.79 (s, 3H), 3.71 (dd, J
=
=
9.0, 1.9 Hz, 1H), 3.34-3.26 (m, 2H), 3.21 (s, 3H), 2.62 (dd, J = 14.4, 4.9 Hz, 2.16 (dd, J
14.4, 7.7 Hz, 1H), 2.11 (s, 3H), 1.51-1.47 (m, 1H), 1.45-1.42 (m, 3H), 1.31 (s, 3H),
1
3
1
.27 (s, 3H), 1.28-1.19 (m, 8H), 1.03 (d, J = 5.9 Hz, 0.90 (t, J = 6.5 Hz, 3H); C NMR
(
75 MHz, CDCl ) δ 168.8, 157.5, 154.0, 140.5, 127.6, 113.7, 103.1, 79.5, 75.9, 72.8,
3
5
2
5.1, 54.9, 42.1, 39.8, 38.2, 34.0, 31.8, 29.6, 25.6, 25.1, 22.6, 21.1, 18.9, 14.0; IR (neat)
-
1
929, 2857, 1758, 1513, 1465, 1250, 1194, 1038 cm ; HRMS (EI): calcd for C H O
1
7
31
4
+
(M - C H O) 299.2222, found 299.2224.
1
0
13
O
2-hexyl-6-(2-methoxypropyl)tetrahydropyran-4-one (49)
To 48 (40.5 mg, 0.09 mmol) in DCE (2.2 mL) were added NaHCO3
80.0 mg, 0.95 mmol) and 4Å molecular sieves (80.0 mg). The mixture
was then stirred at room temperature for 15 min and CAN (195.0 mg,
.36 mmol) in CH CN (1.0 mL) was added dropwise. The reaction mixture was then
OMe
O
6 13
C H
(
49
0
3
stirred for an additional 10 min and filtered through a silica plug. The filtrate was then
concentrated under reduced pressure, and the resulting residue was purified via flash
column chromatography (6% EtOAc in hexanes) to provide the desired product (22.3 mg,
1
9
2
1
7%): H NMR (300 MHz, CDCl ) δ 3.73-3.66 (m, 1H), 3.56-3.46 (m, 2H), 3.31 (s, 3H),
3
.37 (ddt, J = 14.5, 9.2, 2.3 Hz, 2H), 2.26-2.17 (m, 2H), 2.02 (p, J = 6.8 Hz, 1H), 1.68-
.50 (m, 5H), 1.34-1.25 (m, 6H), 1.18 (d, J = 3.1 Hz, 3H), 0.89 (t, J = 6.9 Hz, 3H); C
1
3
NMR (75 MHz, CDCl ) δ 207.4, 74.0, 73.3, 55.9, 48.0, 47.9, 42.7, 36.4, 31.7 29.0, 25.3,
3
S15

-
1
2
2.5, 18.9, 14.0;IR (neat) 2929, 2857, 1721, 1375, 1091 cm ; HRMS (EI): calcd for
+
C H O (M ) 256.2038 found 256.2035.
1
5
28
3
MeO
O
Acetic acid 3-{3-methoxy-1-[1-(4-methoxyphenyl)-1-
methylethyl]butoxy}-1-methylenenonyl ester (50)
To 1-methoxy-4-[4-methoxy-1,1-dimethyl-2-(1-methylbut-3-
MeO
13 6
H C
OAc ynyloxy)pentyl]benzene (146.4 mg, 0.39 mmol) in toluene (3 mL)
50
were added Na CO (6.0 mg, 0.062 mmol) and acetic acid (46.9
2
3
mg, 0..78 mmol, 44.0 µL). The mixture was then stirred at room temperature for 10 min
and [Ru(p-cymene)Cl ] (9.0 mg, 0.015 mmol) and tri-2-furylphosphine (7.0 mg, 0.030
2
2
mmol) were added. The reaction mixture was then warmed to 60 °C and stirred for an
additional 15 h. The mixture was then cooled to room temperature and concentrated
under reduced pressure. The resulting residue was then purified via flash column
chromatography (6% EtOAc in hexanes) to provide the desired product (60.0 mg, 34%):
1
H NMR (300 MHz, CDCl ) δ 7.30 (d, J = 8.9 Hz, 2H), 6.83 (d, J = 8.9 Hz, 2H), 4.78 (s,
3
1
3
1
H), 4.73 (s, 1H), 3.79 (s, 3H), 3.64 (dd, J = 8.7, 2.4 Hz, 1H), 3.36-3.27 (m, 2H), 3.20 (s,
H), 2.39 (dd, J = 14.7, 4.9 Hz, 1H), 2.24 (dd, J = 14.7, 7.1 Hz, 1H), 2.09 (s, 3H), 1.55-
.42 (m, 4H), 1.31-1.21 (m, 8H), 1.31 (s, 3H), 1.27 (s, 3H), 1.02 (d, J = 6.0 Hz, 3H), 0.89
1
3
(
t, J = 6.9 Hz, 3H); C NMR (75 MHz, CDCl ) δ 168.9, 157.5, 153.8, 140.3, 127.7,
3
1
2
13.1, 103.5, 79.8, 72.9, 55.1, 54.9, 42.1, 39.9, 37.8, 33.2, 31.8, 29.5, 25.0, 24.7, 22.6,
-
1
1.0, 18.9, 14.0; IR (neat) 2930, 2858, 1758, 1513, 1465, 1250, 1038 cm ; HRMS (EI)
+
calcd for C H O (M - C H O) 299.2222, found 299.2224.
17
31
4
10 13
2
-hexyl-6-(2-methoxypropyl)tetrahydropyran-4-one (47)
To 50 (60.4 mg, 0.13 mmol) in DCE (2.2 mL) were added NaHCO (120.0 mg, 1.4
3
mmol) and 4Å molecular sieves (120.0 mg). The mixture was then stirred at room
temperature for 15 min and CAN (295.0 mg) in CH CN (1.0 mL) was added dropwise.
3
The reaction mixture was then stirred for an additional 15 min and filtered through a
silica plug. The filtrate was then concentrated under reduced pressure, and the resulting
residue was purified via flash column chromatography (6% EtOAc in hexanes) to provide
1
the desired product (32.1 mg, 96%): H NMR (500 MHz, CDCl ) δ 3.81-3.77 (m, 1H),
3
3
1
.62-3.55 (m, 2H), 3.33 (s, 3H), 2.35 (app. t, J = 7.6 Hz, 2H), 2.24-2.18 (m, 2H), 1.71-
.68 (m, 1H), 1.63-1.57 (m, 1H), 1.51-1.47 (m, 2H), 1.30-1.26 (m, 8H), 1.16 (d, J = 6.1
1
3
Hz, 3H), 0.89 (t, J = 6.5 Hz, 3H); C NMR (75 MHz, CDCl ) δ 207.9, 73.4, 72.9, 56.5,
3
-
4
8.1, 44.0, 36.3, 31.7, 29.0, 25.5, 22.6, 19.3, 14.1; IR (neat) 2929, 2857, 1721, 1091 cm
1
+
;
HRMS (EI): calcd for C H O (M ) 256.2038, found 256.3031.
15
28
3
S16

Acetic acid 3-{1-[1-(4-methoxyphenyl)-1-
methylethyl]allyloxy}-1-methylenenonyl ester (51)
O
MeO
To 1-[1,1-dimethyl-2-(1-methylbut-3-ynyloxy)but-3-enyl]-4-
methoxybenzene (208.2 mg, 0.607 mmol) in toluene (5 mL) was
added Na CO (10.2 mg, 0.097 mmol) and acetic acid (72.0 mg,
H13C6 OAc
1
5
2
3
1
.21 mmol, 71.0 µL). The mixture was then stirred at room temperature for 10 min and
[
Ru(p-cymene)Cl ] (14.8 mg, 0.024 mmol) and tri-2-furylphosphine (11.2 mg, 0.048
2
2
mmol) were added. The reaction mixture was then warmed to 60 °C and stirred for an
additional 18 h. The mixture was then cooled to room temperature and concentrated
under reduced pressure. The resulting residue was then purified via flash column
chromatography (4% EtOAc in hexanes) to provide the desired product (110.4 mg, 45%):
1
H NMR (300 MHz, CDCl ) δ 7.29 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H), 5.42
3
(
ddd, J = 17.2, 10.3, 8.4 Hz, 1H), 5.11 (dd, J = 10.3, 2.0 Hz, 1H), 4.99 (dd, J = 17.2, 2.0
Hz, 1H), 4.73 (s, 1H), 4.67 (s, 1H), 3.80 (s, 3H), 3.64 (d, J = 8.4 Hz, 1H), 3.40-3.32 (m,
H), 2.40 (dd, J = 14.7, 4.8 Hz, 1H), 2.19-2.07 (m, 1H), 2,12 (s, 3H), 1.56-1.16 (m, 10
1
1
3
H), 1.28 (s, 3H), 1.16 (s, 3H), 0.87 (t, J = 6.4 Hz, 3H); C NMR (75 MHz, CDCl ) δ
3
1
3
1
4
68.9, 157.4, 153.8, 134.1, 136.9, 128.0, 118.3, 112.7, 103.4, 86.6, 72.7, 55.0, 40.9, 37.8,
4.5, 31.7, 29.2, 25.1, 25.0, 22.5, 21.0, 14.0; IR (neat) 2930, 2857, 1758, 1665, 1514,
-
1
+
464, 1250, 1188, 1038 cm ; HRMS (EI) calcd for C H O (M ) 402.2770, found
2
5
38
4
02.2767.
2
-hexyl-6-vinyltetrahydropyran-4-one (52)
O
To 51 (33.0 mg, 0.08 mmol) in DCE (2.2 mL) were added NaHCO (66.0
3
mg, 0.78 mmol) and 4Å molecular sieves (66.0 mg). The mixture was
then stirred at room temperature for 15 min and CAN (190.0 mg, 0.34
O
5
6 13
C H
2
mmol) in CH CN (1.0 mL) was added dropwise. The reaction was then
3
stirred for an additional 20 min and filtered through a silica plug. The filtrate was then
concentrated and the resulting residue was purified via flash column chromatography
1
(
4% EtOAc in hexanes) to provide the desired product (12.1 mg, 70%): H NMR (300
MHz, CDCl ) δ 5.92 (ddd, J = 17.2, 10.5, 5.4 Hz, 1H), 5.32, (dt, J = 17.2, 1.3 Hz, 1H),
3
5
1
1
2
1
.21 (dt, J = 10.5, 1.2 Hz, 1H), 4.10 (dddd, J = 11.2, 6.5, 3.0, 1.2 Hz, 1H), 3.63 (dtd, J =
4.5, 4.7, 2.7 Hz, 1H), 2.47-2.39 (m, 2H), 2.38-2.21 (m, 2H), 1.73-1.67 (m, 1H), 1.60-
1
3
.52 (m 1H), 1.36-1.24 (m, 8H), 0.88 (t, J = 6. Hz, 3H); C NMR (75 MHz, CDCl ) δ
3
06.9, 137.3, 115.9, 47.8, 47.4, 36.4, 31.7, 29.1, 25.1, 22.5, 14.0; IR (neat) 2929, 2857,
-1
+
722, 1251, 1061 cm ; HRMS (EI): calcd for C H O (M ) 210.1619, found 210.1609.
1
3
22
2
S17

{
4-[1-(2-Methoxymethoxyethyl)-2-(4-methoxyphenyl)-2-
OMOM
SiMe
methylpropoxy]-2-methylenedecyl}trimethylsilane (53)
To 1-{2-[1-(2-bromoallyl)heptyloxy]-4-methoxymethoxy-1,1-
dimethylbutyl}-4-methoxybenzene (170.0 mg, 0.35 mmol) in
THF were added Pd(PPh ) (20.0 mg, 0.017 mmol) and
O
MeO
13 6
H C
3
53
3
4
trimethylsilylmethylmagnesium chloride (1.0 M in Et O, 1.75 mmol, 1.75 mL) dropwise.
2
The reaction mixture was then warmed to reflux and stirred at that temperature for an
additional 4 h. The mixture was then cooled to room temperature and the solvent was
removed under reduced pressure. The resulting residue was then purified via flash
column chromatography (5% EtOAc in hexanes) to provide the desired product (109.8
1
mg, 64%): H NMR (300 MHz, CDCl ) δ 7.30 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz,
3
2
(
1
H), 4.60-4.54 (m, 2H), 4.51-4.48 (m, 2H), 3.79 (s, 3H), 3.60-3.55 (m, 2H), 3.36-3.30
m, 2H), 3.28 (s, 3H), 2.27 (td, J = 13.1, 4.8 Hz, 1H), 1.90 (td, J = 13.1, 7.6 Hz, 1H), 1.6-
.63 (m, 2H), 1.55-1.52 (m, 4H), 1.34 (s, 3H), 1.30 (s, 3H), 1.30-1.27 (m, 6H), 0.92-0.88
1
3
(
m, 3H), 0.05 (s, 9H); C NMR (75 MHz, CDCl ) δ 157.6, 145.0, 127.7, 113.3, 109.7,
3
9
1
5
6.3, 80.1, 55.3, 55.2, 42.5, 32.33, 32.0, 29.8, 27.2, 25.3, 22.8, 14.2, -1.1; IR (neat) 2930,
-
1
+
513, 1465, 1296, 1249, 1109, 1077 cm ; HRMS (EI) calcd for C H O Si (M )
3
1
51
4
15.3557, found 515.3535.
1
-methoxy-4-{4-methoxymethoxy-1,1-dimethyl-2-[1-(2-
OMOM
O
nitrooxymethylallyl) heptyloxy]butyl}benzene (54)
To 53 (40.4 mg, 0.08 mmol) in DCE (2.5 mL) were added 4Å
ONO2 molecular sieves (80.0 mg) and NaHCO (80.0 mg, 0.9 mmol).
MeO
H13C6
3
54
The reaction mixture was then stirred for 10 min and CAN
(
89.0 mg, 0.16 mmol) in CH CN (1.2 mL) dropwise. After 5 min, the reaction mixture
3
was concentrated under reduced pressure. The resulting residue was then purified via
flash column chromatography (7% EtOAc in hexanes) to provide the nitrated product
1
(
28.7 mg, 75%): H NMR (300 MHz, CDCl ) δ 7.27 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7
3
Hz, 2H), 5.17 (s, 1H), 5.06 (s, 1H), 4.87 (s, 2H), 4.51 (s, 2H), 3.79 (s, 3H), 3.54 (dd, 6.4,
.9 Hz, 1H), 3.34-3.22 (m, 3H), 3.29 (s, 3H), 2.30 (dd, J = 14.0, 6.4 Hz, 1H), 2.20 (dd, J
14.0, 5.5 Hz, 1H), 1.75-1.65 (m, 2H), 1.44-1.36 (m, 4H), 1.32 (s, 3H), 1.28 (s, 3H),
3
=
1
3
1
1
2
.25-1.23 (m, 6H), 0.90 (t, J = 6.5 Hz, 3H); C NMR (75 MHz, CDCl ) δ 157.8, 139.9,
39.0, 127.7, 117.4, 113.3, 96.3, 80.4, 75.7, 65.7, 55.3, 42.1, 38.2, 33.2, 32.3, 31.9, 29.7,
6.1, 25.3, 24.0, 22.7, 14.2; IR (neat) 2931, 1633, 1513, 1252, 1037 cm ; HRMS (EI)
3
-
1
+
calcd for C H NO (M ) 504.2961, found 504.2921.
28
42
7
S18

S19

S20

S21

S22

S23

S24

S25

S26

S27

S28

S29

S30