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Supporting Information
Asymmetric Allylboration as a Surrogate for the
Enantioselective Synthesis of Allylic Amines and
Å‹
-
Amino Acids
via
Overman Rearrangement.
P. Veeraraghavan Ramachandran,* Thomas E. Burghardt, and M. Venkat Ram Reddy
Herbert C. Brown Center for Borane Research
Department of Chemistry, Purdue University
560 Oval Dr., West Lafayette, IN 47907-2084
chandran@purdue.edu
Table of Contents
Experimental Procedures and Spectral Data ....................................................................................1
I. Preparation of
Å‹
,
Ȳ
-Unsaturated Aldehydes. ..........................................................................1
II. Preparation of Homoallylic Alcohols. .................................................................................3
III. Preparation of Allylic Amides............................................................................................5
IV. Preparation of
Å‹
-Amino Acids. ..........................................................................................6
NMR Spectra....................................................................................................................................8
I. NMR Spectra of
Å‹
,
Ȳ
-Unsaturated Aldehydes .......................................................................8
II. NMR Spectra of Homoallylic Alcohols ............................................................................14
III. NMR Spectra of Allylic Amides ......................................................................................24
IV. NMR Spectra of
Å‹
-Amino Acids .....................................................................................34
Experimental Procedures and Spectral Data
Materials
: All 'allyl'boration reactions and preparation
of trichloroacetimidates were carried out under nitrogen
atmosphere. Tetrahydrofuran was distilled from sodium
benzophenone ketyl prior to use; other reagents were
purchased from commercial sources and used without
further purification. The NMR chemical shifts (
Ō
) are
reported in ppm.
I. Preparation of
Å‹
,
Ȳ
-Unsaturated
Aldehydes.
Et
2
O (3×30 mL) and dried with MgSO
4
. After removal
of the solvent under reduced pressure, the resulting
alcohol was diluted with CH
2
Cl
2
and Dess-Martin
periodinane (2.8 g, 6.6 mmol) was added. After stirring
at RT for 0.5 h, the solvent was removed; the residue
was extracted with pentane (5×30 mL) and filtered
through Celite. After evaporation of the solvent, the
obtained product was purified on silica gel (flash; 96:4
hexanes:ethyl acetate) to afford 0.7 g (4.8 mmol, 89%
yield) of
4b
.
1
H NMR (300 MHz, CDCl
3
,
Ō
): 2.57 (d,
J
=
0.72 Hz, 3H), 6.40 (dq,
J
= 1.24 Hz, 7.88 Hz, 1H), 7.40-
7.55 (m, 5H), 10.19 (d,
J
= 7.83 Hz, 1H);
13
C NMR (75
MHz, CDCl
3
,
Ō
): 16.4, 126.3, 127.3, 128.8, 130.1, 140.6,
157.7, 191.3.
OEt
1) LiAlH
4
2) DMP
89%
O
(2
E
)-3-phenyl-but-2-
enal (
4b
). To ethyl (2
E
)-3-phenylbut-2-enoate (1.0 mL,
5.4 mmol) diluted with THF (20 mL) and cooled to 0 °C
was added LiAlH
4
(1 M in THF; 9 mL, 9 mmol) and the
reaction was stirred at RT for 1 h. Excess LiAlH
4
was
quenched with water; the product was extracted with
O
Ph
1) a) EtMgBr
b) LiAlH
4
2) DMP
46%
O
OAc OEt
P
h
Ph
O
(2
E
)-3-phenyl-2-
propyl-propenal (
4c
). To ethyl 2-
[(acetyloxy)(phenyl)methyl]acrylate (4.3 g, 13.3 mmol)
S1
Ph
diluted with THF (60 mL) and cooled to –78 °C was
added ethylmagnesium bromide (3 M in Et
2
O; 5 mL, 15
mmol) and the reaction was stirred for 0.5 h at –78 °C
and 1 h at 0 °C, at which point LiAlH
4
(1 M in THF; 15
mL, 15 mmol) was added, followed by stirring at 0 °C
for 1 h. Upon quenching with H
2
O, the product was
extracted with Et
2
O (3×50 mL), washed with brine,
dried over MgSO
4
, and the solvent was removed under
reduced pressure. To the obtained crude (2
E
)-3-phenyl-
2-propylprop-2-en-1-ol diluted with CH
2
Cl
2
(60 mL)
was added Dess-Martin periodinane (6.6 g, 15.5 mmol)
and the mixture was stirred for 0.5 h at RT. The solvent
was removed; the resulting residue was extracted with
pentane (5×50 mL) and filtered through Celite. After
removal of the solvent, the obtained product was
purified on silica gel (flash; 96:4 hexanes:ethyl acetate)
to afford 1.1 g (6.1 mmol, 46% yield) of
4c
.
1
H NMR
(300 MHz, CDCl
3
,
Ō
): 0.98 (t,
J
= 7.4 Hz, 3H), 1.49-1.57
(m, 2H), 2.48-2.54 (m, 2H), 7.19 (s, 1H), 7.37-7.50 (m,
5H), 9.53 (s, 1H);
13
C NMR (75 MHz, CDCl
3
,
Ō
): 14.4,
21.7, 26.8, 128.8, 129.6, 129.7, 135.0, 143.2, 149.9,
195.7.
Ph
3
P=C-CHO
93%
O
(2
E
)-3-
pentafluorophenylprop-2-enal (
4e
).
Pentafluorobenzaldehyde (1.5 mL, 12.1 mmol) was
added to a solution of
(triphenylphosphoranylidene)acetaldehyde (3.6 g, 11.8
mmol) in toluene (120 mL) and the mixture was stirred
for 1 h at 80 °C. The solvent was removed under
reduced pressure and the product was purified on a short
plug of silica gel (flash; 98:2 hexanes:ethyl acetate) to
afford
4e
in 93% yield (2.4 g, 11.0 mmol) with a minor
toluene contamination.
1
H NMR (300 MHz, CDCl
3
,
Ō
):
6.95 (dd,
J
= 7.41 Hz, 16.47 Hz, 1H), 7.46 (d,
J
= 16.56
Hz, 1H), 9.71 (d,
J
= 7.38 Hz, 1H);
19
F NMR (282 MHz,
CDCl
3
,
Ō
): –158.87-–158.71 (m, 2F), –146.96 (t,
J
=
21.52 Hz, 1F), –136.41 (d,
J
= 12.87 Hz, 2F);
13
C NMR
(75 MHz, CDCl
3
,
Ō
): 135.2, 125.2-150.6 (m), 193.2.
O
C
6
F
5
OMe
1) TBS-Cl
2) BH
3
·SMe
2
3) DMP
4) Ph
3
P=CH-CHO
48%
(
2
E
,4
R
)-5-(
tert
-butyldimethylsilanyloxy)-4-methyl-pent-
2-enal (
4f
). To methyl (2
S
)-3-hydroxy-2-
methylpropanoate (3.0 mL, 27.1 mmol) in DMF (100
mL) cooled to 0 °C was added imidazole (1.8 g, 26.4
mmol) and
tert
-butyldimethylsilyl chloride (4.2 g, 27.8
mmol) and the mixture was stirred for 1 h at RT. The
obtained product was extracted with pentane (4×50 mL),
washed with water (4×20 mL), and concentrated under
reduced pressure. The obtained residue was diluted with
THF (100 mL), borane-dimethyl sulphide complex (12
mL, 120 mmol) was added, and the reaction was stirred
for 24 h at RT. Excess of the borane was quenched with
water, the product was extracted with Et
2
O (3×100 mL),
washed with brine, and solvent was evaporated. To the
crude alcohol diluted with CH
2
Cl
2
(100 mL) was added
Dess-Martin periodinane (14.0 g, 33.0 mmol) and the
reaction was stirred for 0.5 h at RT, then it was
concentrated under reduced pressure. The product was
extracted with pentane (3×100 mL), filtered through
Celite, and the solvents were removed in vacuo. To the
crude aldehyde diluted with toluene (60 mL) was added
(triphenylphosphoranylidene)acetaldehyde (7.5 g, 26.6
mmol) and the reaction was stirred at 80 °C for 14 h.
The crude material was purified on silica gel (9:1
hexanes:ethyl acetate) to afford 2.9 g (12.9 mmol, 48%
yield) of
4f
.
1
H NMR (300 MHz, CDCl
3
,
Ō
): 0.10 (s,
3H), 0.13 (s, 3H), 0.94 (s, 9H), 1.16 (d,
J
= 6.60 Hz, 3H),
2.70 (qn,
J
= 6.52 Hz, 1H), 3.59-3.71 (m, 2H), 6.20 (dd,
J
= 7.95 Hz, 15.75 Hz, 1H), 6.91 (dd,
J
= 6.9 Hz, 15.9
Hz, 1H), 9.58 (d,
J
= 8.10 Hz, 1H);
13
C NMR (75 MHz,
CDCl
3
,
Ō
): –5.1, 15.6, 18.6, 26.2, 39.9, 67.0, 132.6,
161.4, 194.5.
O
HO
O
Si
O
O
1) TBS-Cl
2) PCC
61%
HO
Si
O
(2
E
)-4-(
tert
-
butyldimethylsilanyloxy)but-2-enal (
4d
). To (2
Z
)-but-
2-ene-1,4-diol (10 mL, 121 mmol) diluted with DMF
(120 mL) and cooled to 0 °C was added imidazole (8.2
g, 120 mmol) and
tert
-butyldimethylsilyl chloride (18.3
g, 121 mmol) and the mixture was stirred at 0 °C for 3 h.
After addition of H
2
O (50 mL), the product was
extracted with pentane (5×100 mL), the solvent was
evaporated and the product purified on silica gel (95:5
hexanes:ethyl acetate) to afford 18.8 g (93.4 mmol,
77%) of (2
Z
)-4-(
tert
-butyl-dimethylsilanyloxy)-but-2-
en-1-ol.
1
H NMR (300 MHz, CDCl
3
,
Ō
): 0.05 (s, 6H),
0.87 (s, 9H), 2.82 (br s, 1H), 4.18 (dd,
J
= 4.29 Hz, 23.22
Hz, 2H), 5.51-5.66 (m, 2H);
13
C NMR (75 MHz, CDCl
3
,
Ō
): –5.2, 10.3, 25.9, 58.5, 59.5, 130.1, 131.0. The
monoprotected alcohol (7.7 g, 37.8 mmol) was added
rapidly to a stirring solution of pyridinium
chlorochromate (39.9 g, 184 mmol) and sodium acetate
(17.1 g, 202 mmol) in CH
2
Cl
2
(300 mL). Note:
oxidation under Dess-Martin or Swern conditions would
afford the aldehyde with
Z
stereochemistry. After 3 h at
RT the reaction was complete; the crude material was
filtered through silica gel (Et
2
O eluent), evaporated, and
purified on silica gel (97:3 hexanes:ethyl acetate) to give
6.0 g (30.2 mmol, 80%) of
4d
.
1
H NMR (300 MHz,
CDCl
3
,
Ō
): 0.04 (d,
J
= 1.23 Hz, 6H), 0.87 (d,
J
= 1.23
Hz, 9H), 4.4 (s, 2H), 6.35 (dd,
J
= 3.54 Hz, 4.71 Hz, 1H),
6.81-6.87 (m, 1H), 9.55 (d,
J
= 9.21 Hz, 1H);
13
C NMR
(75 MHz, CDCl
3
,
Ō
): –5.5, 18.3, 25.8, 62.2, 130.5,
156.5, 193.3.
HO
S2
C
6
F
5
OMe
1) PMBO-C(=O)CCl
3
2) LiAlH
4
3) DMP
4) Ph
3
P=C-CHO
23%
O
7.25 (d,
J
= 8.58 Hz, 2H), 9.51 (d,
J
= 7.92 Hz, 1H);
13
C
NMR (75 MHz, CDCl
3
,
Ō
): 15.9, 37.2, 55.3, 72.9, 113.9,
129.3, 130.1, 132.2, 159.3, 160.9, 194.3.
II. Preparation of Homoallylic Alcohols.
OH
HO
O
O
O
(2
E
,4
R
)-5-(4-methoxybenzyloxy)-4-methylpent-2-enal
(
4g
). To methyl (2
S
)-3-hydroxy-2-methylpropanoate
(3.0 mL, 27.1 mmol) in CH
2
Cl
2
(20 mL) and
cyclohexane (40 mL) cooled to 0 °C were added 4-
methoxybenzyl 2,2,2-trichloroethanimidoate (15.5 g,
54.8 mmol) and pyridinium 4-toluene sulphonate (0.4 g,
1.6 mmol) and the mixture was stirred for 14 h at RT.
The product was extracted with Et
2
O (3×50 mL) and
washed with brine. After the volatiles were removed
under reduced pressure, the product was purified on
silica gel (9:1 hexanes:ethyl acetate) to give the desired
methyl (2
S
)-3-(4-methoxybenzyloxy)-2-
methylpropanoate. To the obtained ether dissolved in
THF (50 mL) and cooled to 0 ºC was added LiAlH
4
(1.1
g, 29.0 mmol) and the reaction was stirred for 2 h at RT.
After quenching with EtOAc and water, the product was
extracted with Et
2
O (3×50 mL), washed with brine, and
concentrated under reduced pressure to furnish the
desired (2
R
)-3-[(4-methoxybenzyl)oxy]-2-
methylpropan-1-ol. To the crude alcohol diluted with
CH
2
Cl
2
(50 mL) was added Dess-Martin periodinane
(14.0 g, 33.0 mmol) and the reaction was stirred for 0.5
h at RT, then it was concentrated under reduced
pressure. The product was extracted with pentane (4×50
mL), filtered through Celite, concentrated under reduced
pressure, and purified on silica gel (9:1 hexanes:ethyl
acetate) to give (2
S
)-3-[(4-methoxybenzyl)oxy]-2-
methylpropanal in 85% yield (4.7 g, 22.6 mmol) from
the Roche ester.
1
H NMR (300 MHz, CDCl
3
,
Ō
): 1.07
(d,
J
= 7.14 Hz, 3H), 2.55-2.61 (m, 1H), 3.54-3.60 (m,
2H), 3.73 (s, 3H), 4.40 (s, 2H), 6.84 (d,
J
= 8.49 Hz, 2H),
7.20 (d,
J
= 8.46 Hz, 2H), 9.65 (s, 1H);
13
C NMR (75
MHz, CDCl
3
,
Ō
): 10.7, 46.8, 55.1, 69.7, 72.9, 113.8,
114.3, 129.2, 130.1, 159.3, 203.8. The obtained
aldehyde (0.7 g, 3.3 mmol) was added to a suspension of
(triphenylphosphoranylidene)acetaldehyde (1.0 g, 3.3
mmol) in toluene (50 mL) and the mixture was heated
for 24 h at 80 °C. Among several batches, the TLC
analysis always showed only partial product formation,
even if excess of the ylide was used, the reaction time
was extended to 48 h, the reaction was done at 110 °C,
or benzene was used as the solvent. Additionally, the
product was highly unstable and was decomposing
rapidly during purification. We believe that treatment of
the sensitive aldehyde with the ylide caused partial
racemisation of the material, which was later reflected in
low diastereoselectivity of
5g
and
6g
(Table 1, Entry 7).
4g
was obtained in 28% yield (0.21 g, 0.9 mmol) from
the aldehyde (23% from Roche ester).
1
H NMR (300
MHz, CDCl
3
,
Ō
): 1.09 (d,
J
= 6.87 Hz, 1.2H), 1.12 (d,
J
=
6.84 Hz, 1.8H), 2.66 (qn,
J
= 6.71 Hz, 0.4H), 2.77 (qn,
J
= 6.65 Hz, 0.6H), 3.37-3.44 (m, 2H), 4.45 (s, 2H), 3.80
(s, 3H), 6.34-6.83 (m, 2H), 6.88 (d,
J
= 8.58 Hz, 2H),
(1
E
,3
S
)-1-phenylhexa-1,5-dien-3-ol
(
5a
). To (–)-
B
-allyldiisopinocampheylborane (
1
; 1 M in
pentane; 24 mL, 24 mmol) diluted with Et
2
O (24 mL)
and cooled to –100 °C was added cinnamaldehyde (2
mL, 15.8 mmol) diluted with Et
2
O (5 mL) pre-cooled to
–78 °C. The mixture was stirred for 4 h, while it was
allowed to warm to –78 °C. To the reaction mixture at –
78 °C was added 3 M aq. NaOH (9 mL) and (slowly!)
30% aq. H
2
O
2
(6 mL), and the reaction was left stirring
for 14 h under positive N
2
pressure while it slowly
warmed to RT. The product was then extracted with
Et
2
O (3×50 mL), washed with brine, dried with MgSO
4
,
and the solvent was removed under reduced pressure.
Since TLC analysis showed the alcohol inseparable from
isopinocampheol (Ipc-OH), the crude material was
diluted with CH
2
Cl
2
(100 mL) and cooled to 0 °C.
Added were pyridine (3 mL, 37.2 mmol) and acetyl
chloride (3 mL, 42.2 mmol), and the mixture was stirred
for 1 h at 0 °C. The excess pyridine was quenched with
10% aq. HCl (30 mL); the product was extracted with
CH
2
Cl
2
(1×30 mL) and Et
2
O (2×50 mL), washed with
brine, and dried with MgSO
4
. Upon removal of the
solvents, the material was purified on silica gel (200:1
hexanes:ethyl acetate) to afford pure (1
S
)-1-[(
E
)-2-
phenylvinyl]but-3-enyl acetate. To the obtained acetate
diluted with methyl alcohol (50 mL) and cooled to 0 °C
was added K
2
CO
3
(1.8 g, 13.0 mmol) and the reaction
was stirred for 3 h at RT, when the mixture was
quenched with brine, the product extracted with Et
2
O,
solvent removed under reduced pressure and the residue
purified on silica gel (flash; 96:4 hexanes:ethyl acetate)
to furnish the desired pure
5a
in 73% yield (2.0 g, 11.5
mmol) and 94% ee.
1
H NMR (300 MHz, CDCl
3
,
Ō
):
2.45 (t,
J
= 6.74 Hz, 2H), 2.95 (br s, 1H), 4.37 (q,
J
= 5.91
Hz, 1H), 5.15-5.23 (m, 2H), 5.86-5.95 (m, 1H), 6.28
(dd,
J
= 6.39 Hz, 15.93 Hz, 1H), 6.63 (d,
J
= 15.99 Hz,
1H), 7.28-7.41 (m, 5H);
13
C NMR (75 MHz, CDCl
3
,
Ō
):
42.0, 71.9, 118.1, 126.6, 127.6, 128.7, 130.3, 131.9,
134.3, 136.9.
OH
(4
S
,5
E
)-6-phenylhepta-1,5-dien-4-ol
(
5b
).
1
H NMR (300 MHz, CDCl
3
,
Ō
): 1.95 (br s, 1H),
2.13 (d,
J
= 1.32 Hz, 3H), 2.42 (t,
J
= 6.48 Hz, 2H), 4.63
(q,
J
= 7.05 Hz, 1H), 5.15-5.23 (m, 2H), 5.79-5.95 (m,
2H), 7.28-7.44 (m, 5H);
13
C NMR (75 MHz, CDCl
3
,
Ō
):
16.7, 42.4, 68.4, 118.5, 126.1, 127.6, 128.5, 130.2,
134.5, 137.6, 143.1.
S3
Ph
OH
OH
Ph
Si
O
(1
E
,3
S
)-1-phenyl-2-propylhexa-1,5-
dien-3-ol (
5c
).
1
H NMR (300 MHz, CDCl
3
,
Ō
): 0.94 (t,
J
= 7.28 Hz, 3H), 1.48-1.54 (m, 2H), 1.81 (br s, 1H),
2.09-2.14 (m, 1H), 2.32-2.43 (m, 3H), 4.28 (q,
J
= 4.05
Hz, 1H), 5.16-5.20 (m, 2H), 5.81-5.87 (m, 1H), 6.58 (s,
1H), 7.20-7.28 (m, 5H);
13
C NMR (75 MHz, CDCl
3
,
Ō
):
14.5, 22.4, 30.8, 40.8, 74.5, 118.2, 125.5, 126.4, 128.2,
128.6, 134.8, 137.7, 144.4.
(4
S
,5
E
,7
R
)-8-(
tert
-
Butyldimethylsilanyloxy)-7-methyl-octa-1,5-dien-4-ol
(
5f
) was obtained through conversion to (2
R
,3
E
,5
S
)-2-
methyl-octa-3,7-diene-1,5-diol.
1
H NMR (300 MHz,
CDCl
3
,
Ō
): 0.93 (d,
J
= 6.87 Hz, 1H), 0.97 (d,
J
= 6.81
Hz, 2H), 2.24-2.32 (m, 3H), 2.80 (br s, 2H), 3.31-3.50
(m, 2H), 4.06-4.13 (m, 1H), 5.06-5.11 (m, 2H), 5.45-
5.55 (m, 2H), 5.70-5.84 (m, 1H);
13
C NMR (75 MHz,
CDCl
3
,
Ō
): 16.4, 16.7, 369.2, 39.8, 42.0, 42.1, 67.3, 71.8,
72.2, 118.0, 118.2, 133.3, 133.6, 134.1, 134.7, 134.8,
134.9 (see preparation of
5d
).
1
H NMR (300 MHz,
CDCl
3
,
Ō
): 0.03 (s, 6H), 0.88 (s, 9H), 0.99 (d,
J
= 6.87
Hz, 3H), 1.70 (br s, 1H), 2.21-2.36 (m, 3H), 3.37-3.51
(m, 2H), 4.12 (q,
J
= 6.13 Hz, 1H), 5.10-5.16 (m, 2H),
5.47-5.65 (m, 2H), 5.74-5.88 (m, 1H);
13
C NMR (75
MHz, CDCl
3
,
Ō
): –5.0, 16.8, 18.7, 26.3, 39.3, 42.4, 68.3,
72.2, 118.3, 132.2, 134.8, 134.9.
OH
OH
Si
O
(4
S
,5
E
)-7-(
tert
-
butyldimethylsilanyloxy)hepta-1,5-dien-4-ol (
5d
) was
obtained after conversion to diol: To the obtained crude
allylboration material dried thoroughly with Na
2
SO
4
,
diluted with THF (50 mL) and cooled to 0 °C was added
tetrabutylammonium fluoride (1 M in THF; 5 mL, 5
mmol) and the reaction was stirred for 2 h at RT. The
product was extracted with Et
2
O (3×50 mL) and washed
with brine; after the solvent was removed under reduced
pressure, the material was purified on silica gel (1:1
hexanes:ethyl acetate) to give 0.5 g (3.9 mmol, 70%
from aldehyde) of (2
E
,4
S
)-hepta-2,6-diene-1,4-diol.
1
H
NMR (300 MHz, CDCl
3
,
Ō
): 2.26 (t,
J
= 6.72 Hz, 2H),
3.46-3.66 (br m, 2H), 4.06 (d,
J
= 4.95 Hz, 2H), 4.13 (q,
J
= 4.03 Hz, 1H), 5.05-5.11 (m, 2H), 5.69-5.78 (m, 3H);
13
C NMR (75 MHz, CDCl
3
,
Ō
): 41.7, 62.5, 71.2, 117.9,
130.0, 133.4, 134.3. To the obtained diol diluted with
DMF (40 mL) and cooled to 0 °C was added imidazole
(0.2 g, 2.9 mmol) and
tert
-butyldimethylsilyl chloride
(0.6 g, 4.0 mmol) and the mixture was stirred at 0 °C for
1 h. After addition of H
2
O (20 mL), the product was
extracted with pentane (5×30 mL), the solvent was
evaporated and the product purified on silica gel (flash;
98:2 hexanes:ethyl acetate) to afford
5d
(0.9 g, 3.8
mmol, 68% from aldehyde; 91% ee after conversion to
cinnamyl ester).
1
H NMR (300 MHz, CDCl
3
,
Ō
): 0.05 (s,
6H), 0.89 (s, 9H), 1.93 (br s, 1H), 2.23-2.32 (m, 2H),
4.15-4.19 (m, 3H), 5.08-5.14 (m, 2H), 5.72-5.84 (m,
3H);
13
C NMR (75 MHz, CDCl
3
,
Ō
): –4.9, 18.7, 26.2,
42.2, 63.4, 71.4, 118.4, 130.5, 132.2, 134.6.
O
O
(4
S
,5
E
,7
S
)-8-(4-
methoxybenzyloxy)-7-methylocta-1,5-dien-4-ol (
5g
) (dr
2:1).
1
H NMR (300 MHz, CDCl
3
,
Ō
): 0.99 (d,
J
= 6.78
Hz, 1.2H), 1.00 (d,
J
= 6.81 Hz, 1.8H), 1.91 (br s, 1H),
2.20-2.27 (m, 2H), 2.45 (qn,
J
= 6.61 Hz, 1H), 3.21-3.34
(m, 2H), 3.76 (s, 3H), 4.08 (q,
J
= 6.21 Hz, 1H), 4.40 (s,
2H), 5.01-5.12 (m, 2H), 5.46-5.84 (m, 3H), 6.84 (d,
J
=
8.73 Hz, 2H), 7.22 (d,
J
= 8.19 Hz, 2H);
13
C NMR (75
MHz, CDCl
3
,
Ō
): 36.7, 42.2, 42.3, 72.0, 72.9, 75.0, 75.1,
114.0, 114.2, 118.2, 118.2, 128.9, 129.5, 130.9, 132.2,
134.6, 134.7, 159.4.
OH
Ph
(1
E
,3
R
,4
S
)-4-methyl-1-phenylhexa-
1,5-dien-3-ol (
7a
). To potassium
tert
-butoxide (1 M in
THF; 8 mL, 8 mmol) diluted with THF (8 mL) and
cooled to –78 °C was added
trans
-butene (2 mL, 21
mmol) and butyllithium (2.5 M in hexanes; 3.2 mL, 8.0
mmol). The mixture was stirred for 0.1 h at –78 °C,
followed by 0.3 h at –55 °C, and cooled again to –78 °C,
when a solution of (–)-
B
-
methoxydiisopinocampheylborane (4.6 g, 14.5 mmol) in
THF (5 mL) was added and the reaction was stirred for 1
h at –78 °C. Subsequently, boron trifluoride diethyl
etherate (1.0 mL, 7.9 mmol) was added and the mixture
was stirred for 0.1 h, followed by addition of
cinnamaldehyde (1.0 mL, 7.9 mmol) and stirring at –78
°C for 5 h. Since oxidative workup with aq. NaOH (3
mL) and H
2
O
2
(2.5 mL) afforded the desired alcohol
inseparable from isopinocampheol, the pure
7
was
obtained after conversion to acetate, purification, and
removal of the acetyl group (see preparation of
6a
).
1
H
NMR (300 MHz, CDCl
3
,
Ō
): 1.08 (d,
J
= 6.87 Hz, 3H),
1.92 (br s, 1H), 2.35-2.42 (m, 1H), 4.07 (t,
J
= 6.9 Hz,
OH
(1
E
,3
S
)-1-
pentafluorophenylhenylhexa-1,5-dien-3-ol (
5e
).
H
NMR (300 MHz, CDCl
3
,
Ō
): 2.01 (br s, 1H), 2.32-2.51
(m, 2H), 4.38-4.41 (m, 1H), 5.18-5.23 (m, 2H), 5.77-
5.90 (m, 1H), 6.57-6.58 (m, 2H);
19
F NMR (282 MHz,
CDCl
3
,
Ō
): –160.75-–160.58 (m, 2F), –154.05 (t,
J
=
21.04 Hz, 1F), –140.57-–140.49 (m, 2F);
13
C NMR (75
MHz, CDCl
3
,
Ō
): 42.1, 71.7, 114.3, 119.5, 133.6, 141.0,
141.2, 141.3, 136.0-146.44 (m).
1
S4
C
6
F
5
1H), 5.13-5.22 (m, 2H), 5.77-5.89 (m, 1H), 6.22 (dd,
J
=
6.84 Hz, 15.9 Hz, 1H), 6.62 (d,
J
= 15.93 Hz, 1H), 7.23-
7.42 (m, 5H);
13
C NMR (75 MHz, CDCl
3
,
Ō
): 16.4, 45.0,
76.5, 117.0, 126.8, 128.0, 128.9, 130.3, 132.0, 137.0,
140.5.
pressure and to the obtained crude material diluted with
xylenes (50 mL) was added potassium carbonate (1.7 g,
12.3 mmol) and the reaction was stirred at reflux (150
°C) for 14 h. The reaction mixture was filtered through
Celite, concentrated under reduced pressure, and
purified on silica gel (flash; hexane to 99:1
hexanes:ethyl acetate) to afford 3.2 g (10.0 mmol, 89%
yield) of
6a
as an oily substance, which slowly
crystallised upon standing.
1
H NMR (300 MHz, CDCl
3
,
Ō
): 2.87 (t,
J
= 5.89 Hz, 2H), 5.03-5.09 (m, 2H), 5.55 (dd,
J
= 5.49 Hz, 7.68 Hz, 1H), 5.65-5.91 (m, 3H), 6.90 (d,
J
=
6.48 Hz, 1H), 7.26-7.42 (m, 5H);
13
C NMR (75 MHz,
CDCl
3
,
Ō
): 36.2, 56.7, 116.1, 126.9, 128.2, 128.7, 129.0,
131.9, 135.8, 139.5, 160.6. MS (EI): 282/284 (M–Cl),
115 (C
9
H
7
+
); (CI): 318/320/322 (M+H), 157.
OH
Ph
OMEM
(1
E
,3
R
,4
R
)-4-[(2-
methoxyethoxy)methoxy]-1-phenylhexa-1,5-dien-3-ol
(
8a
). To 3-[(2-methoxyethoxy)methoxy]prop-1-ene
(1.25 g, 8.4 mmol) diluted with THF (12 mL) and
cooled to –78 °C was added
sec
-butyllithium (1.4 M in
cyclohexane; 6 mL, 8.4 mmol) and the mixture was
stirred for 1 h at –78 °C. Then, a solution of (–)-
B
-
methoxydiisopinocampheylborane (4.5 g, 14.2 mmol) in
THF (5 mL) was added and the mixture was stirred for 1
h. Subsequently, BF
3
·OEt
2
(2.6 mL, 20.5 mmol) was
added and the reaction was stirred for 0.1 h, followed by
cinnamaldehyde (1.0 mL, 7.9 mmol) and stirring for 5 h
at –78 °C. After the oxidative workup, the product was
purified on silica gel (7:3 hexanes:ethyl acetate).
1
H
NMR (300 MHz, CDCl
3
,
Ō
): 3.21 (br s, 1H), 3.37 (s,
3H), 3.51-3.52 (m, 2H), 3.63-3.66 (m, 1H), 3.81-3.84
(m, 1H), 4.06 (t,
J
= 7.14 Hz, 1H), 4.26 (t,
J
= 6.43 Hz,
1H), 4.77 (dd,
J
= 6.96 Hz, 20.07 Hz, 2H), 5.36-5.32 (m,
2H), 5.81-5.75 (m, 1H), 6.20 (dd,
J
= 6.02 Hz, 15.98 Hz,
1H), 6.69 (d,
J
= 15.93 Hz, 1H), 7.29-7.38 (m, 5H);
13
C
NMR (75 MHz, CDCl
3
,
Ō
): 59.2, 67.7, 71.9, 74.6, 81.6,
93.4, 120.0, 126.7, 127.8, 128.2, 128.7, 132.0, 134.6,
137.0.
Cl
3
C
O
NH
2,2,2-trichloro-
N
-[(1
S
,2
E
)-1-methyl-
1-phenylhexa-2,5-dienyl]acetamide (
6b
).
1
H NMR (300
MHz, CDCl
3
,
Ō
): 1.89 (s, 3H), 2.87 (t,
J
= 6.35 Hz, 2H),
5.03-5.09 (m, 2H), 5.58-5.68 (m, 1H), 5.78-5.97 (m,
2H), 6.96 (br s, 1H), 7.29-7.39 (m, 5H);
13
C NMR (75
MHz, CDCl
3
,
Ō
): 26.4, 36.6, 61.2, 76.9, 93.6, 116.3,
125.7, 126.6, 127.9, 128.7, 129.3, 134.3, 136.4, 144.0,
160.1. MS (EI): 331/333, 170 (M–NH
2
COCCl
3
), 129
(C
10
H
9
+
); (CI): 332/334/336 (M+H), 171 (M+H–
NH
2
C(= O)CCl
3
).
CCl
3
HN
O
OH
Ph
Ph
2,2,2-trichloro-
N
-[(1
S
,2
E
)-1-phenyl-2-
propylhexa-2,5-dienyl]acetamide (
6c
).
1
H NMR (300
MHz, CDCl
3
,
Ō
): 0.92 (t,
J
= 7.28 Hz, 3H), 1.4-1.45 (m,
2H), 1.84-1.89 (m, 1H), 2.09-2.14 (m, 1H), 2.88 (t,
J
=
6.71 Hz, 2H), 4.99-5.04 (m, 2H), 5.43-5.47 (m, 2H),
5.78-5.83 (m, 1H), 6.91 (d,
J
= 7.2 Hz, 2H), 7.27-7.34
(m, 5H);
13
C NMR (75 MHz, CDCl
3
,
Ō
): 14.4, 22.2,
31.7, 32.1, 59.8, 93.0, 115.5, 125.2, 127.7, 128.4, 129.1,
136.7, 138.9, 139.1, 160.8. MS (EI): 324/326 (M–HCl),
91 (C
7
H
7
+
); (CI): 360/362/364 (M
+
), 199 (M–H
2
NC(=
O)CCl
3
).
OMEM
(3
R
,4
R
,5
E
)-3-[(2-
methoxyethoxy)methoxy]-6-phenylhepta-1,5-dien-4-ol
(
8b
).
1
H NMR (300 MHz, CDCl
3
,
Ō
): 2.08 (s, 3H), 3.13
(br s, 1H), 3.37 (s, 3H), 3.52-3.55 (m, 2H), 3.67-3.72
(m, 1H), 3.82-3.87 (m, 1H), 4.04-4.12 (m, 1H), 4.47 (t,
J
=
7.5 Hz, 1H), 4.79 (dd,
J
=
7 Hz, 18.3 Hz, 2H), 5.25-
5.35 (m, 2H), 5.66-5.74 (m, 2H), 7.24-7.39 (m, 5H);
13
C
NMR (75 MHz, CDCl
3
,
Ō
): 17.2, 59.2, 67.9, 71.2, 72.0,
82.0, 93.7, 119.7, 126.2, 126.3, 127.6, 128.5, 134.6,
139.7, 143.3.
III. Preparation of Allylic Amides.
CCl
3
HN
O
CCl
3
O
Si
HN
O
2,2,2-trichloro-
N
-[(1
S
,2
E
)-1-
(
tert
-butyldimethylsilanyloxymethyl)-hexa-2,5-
dienyl]acetamide (
6d
).
1
H NMR (300 MHz, CDCl
3
,
Ō
):
0.07 (s, 6H), 0.89 (s, 9H), 2.81 (t,
J
= 6.32 Hz, 2H), 3.69
(dd,
J
= 3.55 Hz, 10.19 Hz, 1H), 3.80 (dd,
J
= 3.89 Hz,
10.07 Hz, 1H), 4.39-4.45 (m, 1H), 5.01-5.07 (m, 2H),
5.50 (dd,
J
= 6.87 Hz, 16.14 Hz, 1H), 5.70-5.87 (m, 2H),
7.16 (d,
J
= 6.75 Hz, 1H);
13
C NMR (75 MHz, CDCl
3
,
Ō
): –5.2, 18.5, 26.1, 36.6, 54.5, 64.9, 116.2, 127.3,
2,2,2-trichloro-
N
-[(1
S
,2
E
)-1-
phenylhexa-2,5-dienyl]acetamide (
6a
). To
5a
(2.0 g,
11.5 mmol) diluted with THF (60 mL) and cooled to –
42 °C (acetonitrile - dry ice bath) was added sodium
bis(trimethylsilyl)amide (1 M in THF; 1.2 mL, 1.2
mmol) and the reaction was stirred for 0.5 h, when
trichloroacetonitrile (1.7 mL, 16.9 mmol) was added.
The reaction was stirred for 0.1 h at –42 °C, and allowed
to warm to RT. The solvent was removed under reduced
S5
Ph
Ph
Â
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