Synthesis of 4-aminocyclohex-1-enecarboxylates from Danishefsky's diene

Article abstract of DOI:10.1055/s-2001-17706

An efficient BF₃·Et₂O mediated conversion of Diels-Alder adduct 1 of Danishefsky's diene and methyl acrylate yielded cyclohexenones 2 and 3. Subsequent reductive amination with several amines using NaBH(OAc)₃ in acetic acid medium gave 4-alkylaminocyclohex-1-enecarboxylate derivatives (4a-e) in a concise form.

Full text of DOI:10.1055/s-2001-17706

PAPER
1971
Synthesis of 4-Aminocyclohex-1-enecarboxylates from Danishefsky’s Diene
Synthesis
o
of 4-Aminoc
s
yclohex-1
e
-enecarbox
f
ylates fr
i
om
D
an
n
ishefsky’s
D
a
iene Quirante,* Xavier Vila, Josep Bonjoch*
Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028-Barcelona, Spain
Fax +34(93)4021896; E-mail: bonjoch@farmacia.far.ub.es
Received 23 April 2001; revised 18 July 2001
adducts obtained by Diels–Alder reactions between
Abstract : An efficient BF3 Et2O mediated conversion of Diels–
Alder adduct 1 of Danishefsky’s diene and methyl acrylate yielded
cyclohexenones 2 and 3. Subsequent reductive amination with sev-
eral amines using NaBH(OAc)3 in acetic acid medium gave 4-alky-
dienes other than Danishefsky’s and methyl acrylate,7 but
with poor yields or even as secondary products.8 Addi-
tionally, it is noteworthy that the reaction of 2-trimethyls-
laminocyclohex-1-enecarboxylate derivatives (4a–e) in a concise ilyloxy-1,3-butadiene and methyl propiolate is not
form.
regioselective, giving compounds of type 3 in its ethylene
acetal form in only 60% overall yield.9
Key words: aminations, Diels–Alder reactions, enones, reductions,
Danishefsky’s diene
Treatment of Diels–Alder adduct 1 with BF3 Et2O gave a
mixture of enones 2 and 3 (ratio 3:1) in nearly quantitative
yield,10 which is an improvement on previous protocols
for isolation of these compounds.11
4-Alkylaminocyclohex-1-enecarboxylates can be envis-
aged as useful starting materials for the synthesis of
bridged azabicyclic compounds. We have previously de-
scribed the only reported procedure, so far, for the prepa-
ration of these derivatives,1 consisting in the reductive
amination of monoethylene acetal of 1,4-cyclohexanedi-
one followed by a sequential deprotection of the carbonyl
group, formation of the N-Boc derivative and the corre-
sponding enol triflate and ending with a Pd assisted me-
thoxycarbonylation as the key step (Scheme 1). In this pa-
per we describe a new straightforward procedure to obtain
these compounds, based on the reductive amination of the
cyclohexenones obtained from the conversion of the Di-
els–Alder adducts formed by reaction of Danishefsky’s
diene with methyl acrylate.2
OSiMe3
CO2Me
OSiMe3
BF3 Et2O
CH2Cl2
MeO
O
MeO
CO2Me
1a, 2-Hα
1b, 2-Hβ
R1
R2
N
O
R1R2NH
+
NaBH(OAc)3
AcOH, DCE
CO2Me
CO2Me
CO2Me
2
3
4a-e
R
Boc
O
Scheme 2
N
NHR
O
ref 1
this work
Reductive amination of the mixture of enones 2 and 3 with
several amines, i.e., benzylamine, benzylmethylamine
and tryptamine, NaBH(OAc)312 in acetic acid medium af-
forded the corresponding amines 4a–c in good yield. For
amine 4a the overall yield was 70%, for the three steps
from Danishefsky’s diene. This is an improvement on the
O
O
OTf
CO2Me
CO2Me
Scheme 1
The Diels–Alder reaction between Danishefsky’s diene previously reported procedure for the synthesis of 4-ami-
and methyl acrylate was described several years ago.3 nocyclohex-1-enecarboxylates.1 Reductive amination of
However, the usefulness of the resulting -methoxy silyl the mixture of enones 2 and 3 with (S)-phenylethylamine
enol ether adduct 1 in the synthesis of other compounds and L-leucine-CO2-t-Bu, under the same conditions, gave
has been limited.4–6 In his first studies, Danishefsky trans- amines 4d and 4e as a nearly equimolecular mixture of di-
formed 1 into an ethylene acetal in situ by direct treatment astereoisomers. Absence of diastereoselectivity was also
with ethylene glycol. While conversion of 1 into a mixture observed using the more sterically demanding sodium tri-
of enones 2 and 3 has been reported by Jung5 and inciden- 2-ethylhexanoyloxyborohydride.13
tally by Spino.6 The preparation of enones 2 and 3 has also
been reported as the result of transformations of several
When using benzylamine and NaCNBH3 instead of
NaBH(OAc)3, the over reduced compound 814 was also
isolated apart from the expected 4a. The reaction with me-
thylamine failed, but the N-methyl derivative 4f could be
Synthesis 2001, No. 13, 08 10 2001. Article Identifier:
prepared by debenzylation of the tertiary amine 4b upon
1437-210X,E;2001,0,13,1971,1974,ftx,en;T02701SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1972
J. Quirante et al.
PAPER
IR (NaCl): 1737, 1661 cm–1.
Table Preparation of Compounds 4a–e
cis-Isomer 1a
Product
4a
R1
R2
H
Yield (%)
1H NMR: = 0.16 (s, 9 H, SiCH3), 2.75–2.80 (5 H), 3.25 (s, 3 H,
OCH3), 3.68 (s, 3 H, CO2CH3), 4.08 (t, 1 H, J = 5 Hz, H-2eq), 5.10
(d, 1 H, J = 5 Hz, H-3).
13C NMR: = 0.2 (SiCH3), 19.1 (C-6), 29.5 (C-5), 44.6 (C-1), 51.4
(CO2CH3), 55.9 (OCH3), 73.6 (C-2), 101.5 (C-3), 155.5 (C-4),
173.1 (CO).
Bn
73
64
47
51
50
4b
Bn
Me
H
4c
2-[3-Indolyl]ethyl
(S)-1-Phenylethyl
(S)-CH(i-Bu)CO2t-Bu
4d
H
trans-Isomer 1b
1H NMR: = 0.17 (s, 9 H, SiCH3), 2.75–2.80 (5 H), 3.28 (s, 3 H,
OCH3), 3.67 (s, 3 H, CO2CH3), 4.21 (ddd, 1 H, J = 6.5, 3.5, 2 Hz,
H-2ax), 4.95 (dt, 1 H, J = 3.5, 1.5 Hz, H-3).
4e
H
13C NMR: = 0.2 (SiCH3), 22.7 (C-6), 28.4 (C-5), 44.2 (C-1), 51.6
(CO2CH3), 55.4 (OCH3), 76.6 (C-2), 102.9 (C-3), 153.3 (C-4),
174.2 (CO).
treatment with -(chloroethyl)chloroformate and warm-
ing of the resulting carbamate in a methanol solution.
Anal. Calcd for C12H22O4Si: C, 55.78; H, 8.58. Found: C, 55.66; H,
8.54.
NHMe
NHBn
NHBn
Methyl 4-Oxocyclohex-1-ene-1-carboxylate (2) and Methyl 4-
Oxocyclohex-2-ene-1-carboxylate (3)
Silyl enol ether 1 (20.2 g, 78.3 mmol) in CH2Cl2 (148 mL) at 0 °C
was slowly added to BF3 Et2O (39.3 mL, 313 mmol) and the reac-
tion mixture was stirred for 15 min. The solvent was removed,
EtOAc (350 mL) was added, and the mixture was very slowly bas-
ified at 0 °C with K2CO3 (350 mL), and then with solid Na2CO3.
The aqueous phase was extracted with EtOAc (2 100 mL) and the
combined organic extracts were dried and concentrated to give
9.98 g (83%) of enones 2 and 3 (3:1 mixture, estimated by 1H NMR)
as a yellow oil, which was used in the next step without further pu-
rification. Separation and analytical characterisation of these two
enones has been previously reported by Jung et al.5 When working
on an 8.5 mmol scale the yield was 94%.
CO2Me
CO2Me
CO2Me
4f
5
8
Figure
If the reductive amination of the mixture of 2 and 3 was
carried out in two steps, the dienamine 515 was the only in-
termediate formed after the first step, using benzylamine.
Compound 5 in HOAc medium was reduced with
NaBH(OAc)3 in good yield (nearly the same as when re-
ductive amination was carried out in one step), while the
reduction with NaBH4 in MeOH took place in low yield
(31% from 1).
Reductive Amination of Enones 2 and 3 with Benzylamine using
NaBH(OAc)3: Methyl 4-Benzylaminocyclohex-1-ene-1-
carboxylate (4a); Typical Procedure
A solution of benzylamine (880 mL, 8.07 mmol) and enones 2 and
3 (1.13 g, 7.34 mmol) in 1,2-dichloroethane (25.6 mL) was treated
with NaBH(OAc)3 (2.33 g, 11.0 mmol) and HOAc (420 L, 7.34
mmol). The mixture was stirred at r.t. for 24 h and concentrated. The
residue was taken up in CH2Cl2 (100 mL) and washed with 10%
K2CO3 (2 75 mL). After evaporation of the organic extracts, the
residue was purified by chromatography (SiO2 Et3N, 2.5%, hex-
ane–CH2Cl2, 4:6) to give methyl 4-benzylaminocyclohex-1-ene-1-
carboxylate (4a) as a yellow oil (173 mg, 73%). Analytical data for
4a coincided with those previously reported.1
In summary, a new method for the preparation of methyl
2-alkylaminocyclohex-1-enecarboxylates has been devel-
oped.
1H and 13C NMR spectra were recorded in CDCl3 solutions at 300
MHz or at 500 MHz, and 75.4 MHz, respectively. Only NMR peak
assignments derived from two-dimensional NMR experiments are
given. IR spectra were recorded on a Nicolet 205 FT-IR spectropho-
tometer. HRMS were determined on an Autospec-VG apparatus.
TLC was performed on SiO2 (silica gel 60 F254, Merck). The spots
were located by UV light or 1% KMnO4 solution. Chromatography
refers to flash column chromatography and this was carried out on
SiO2 (silica gel 60, SDS, 230–400 mesh). All reactions were carried
out under an Ar atm with freshly distilled anhyd solvents under an-
hydrous conditions. Anhyd Na2SO4 was used for drying of organic
extracts. Microanalyses were performed at the 'Centro de Investi-
gación y Desarrollo' (CSIC), Barcelona.
MS: m/z (%) = 245 (M+, 16), 133 (79), 132 (46), 104 (10), 91 (100),
79 (9), 65 (19), 53 (10).
Methyl 4-(N-Benzyl-N-methylamino)cyclohex-1-ene-1-car-
boxylate (4b)
Benzylmethylamine (173 L, 2.17 mmol) and enones 2 and 3 (303
mg, 1.97 mmol) in 1,2-dichloroethane (6.8 mL) were treated with
NaBH(OAc)3 (626 mg, 2.96 mmol) and HOAc (124 L, 2.08
mmol). The raw material was purified by chromatography
(CH2Cl2–MeOH, 99:1) to give amine 4b as a yellow oil (328 mg,
64%).
Methyl 2-Methoxy-4-trimethylsilyloxycyclohex-3-ene-1-car-
boxylate (1)
IR (NaCl): 1715 cm–1.
To a stirred solution of trans-1-methoxy-3-trimethylsilyloxybuta-
diene16 (38.7 g, 225 mmol) in benzene (160 mL) was added methyl
acrylate (40.5 mL, 449 mmol). The reaction mixture was heated at
reflux for 48 h. The solution was concentrated to give 1 (53.3 g,
92%; 45:55 mixture of 1a and 1b, estimated by 1H NMR) as an oil,
which was used in the next step without further purification.
1H NMR: = 1.52 (qd, 1 H, J = 12, 5 Hz, H-5ax), 2.04 (dm, 1 H,
J = 11 Hz), 2.21 (s, 3 H, NCH3), 2.10–2.45 (m, 3 H), 2.57 (dm, 1 H,
J = 15 Hz), 2.75 (dddd, 1 H, J = 12, 10, 5, 2.5 Hz, H-4ax), 3.56 and
3.62 (2 d, 2 H, J = 12 Hz, CH2Ph), 3.71 (s, 3 H, OCH3), 6.95 (m, 1
H, W1/2 = 9 Hz, H-2), 7.15–7.35 (m, 5 H, Ar-H).
Synthesis 2001, No. 13, 1971–1974 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of 4-Aminocyclohex-1-enecarboxylates from Danishefsky’s Diene
1973
13C NMR: = 24.6 (C-6), 24.9 (C-5), 28.0 (C-3), 37.4 (NCH3), 51.5
(OCH3), 57.8 (C-4), 57.9 (CH2Ph), 126.8, 128.1, 128.6 (Ar-C),
129.9 (C-1), 138.6 (C-2), 139.6 (C-ipso), 167.5 (CO).
MS: m/z (%) = 259 (M+, 17), 147 (90), 146 (100), 132 (15), 97 (10),
91 (75), 83 (14), 71 (18), 70 (14), 69 (22), 67 (10), 65 (16), 60 (15),
57 (36), 56 (22), 55 (39), 53 (11).
(1:1.5 mixture of diastereoisomers, estimated by GC) as a yellow
oil.
IR (NaCl): 3370, 1727, 1715 cm–1.
1H NMR: = 0.89 and 0.93 (2 d, 3 H each, CH3), 1.30–1.50 (m, 3
H), 1.46 (s, 9 H, CH3), 1.55–2.75 (m, 6 H), 3.25 and 3.28 (2 dd, 1
H, J = 15, 7.5 Hz, NCH), 3.72 (s, 3 H, OCH3), 6.89 (m, 1 H, H-2).
HRMS: m/z calcd for C16H21NO2: 259.1572. Found: 259.1568.
13C NMR: = 22.4, 22.5, 22.6, 22,6 (CH3), 23.0, 23.5 (C-6), 24.9
(CH), 28.1 (CH3), 27.6, 29.8 (C-5), 32.4, 33.7 (C-3), 43.3 (CH2),
50.5, 50.6 (C-4), 51.5 (OCH3), 57.7 (CH), 80.9 (C), 129.8, 129.9 (C-
1), 137.4 (C-2), 167.5 (CO), 175.6, 175.7 (CO).
Anal. Calcd for C16H21NO2: C, 74.10; H, 8.16; N, 5.40. Found: C,
73.70; H, 8.28; N, 5.32.
Methyl 4-[2-(Indol-3-yl)ethylamino]cyclohex-1-ene-1-
carboxylate (4c)
MS: m/z (%) = 325 (M+, 26), 309 (24), 268 (25), 240 (27), 224
(100), 213 (55), 184 (63), 112 (60), 81 (62), 69 (95), 57 (91).
Tryptamine (813 mg, 5.07 mmol) and enones 2 and 3 (353 mg, 1.90
mmol) in 1,2-dichloroethane (13.7 mL) were treated with
NaBH(OAc)3 (1.24 g, 5.85 mmol) and HOAc (223 L, 3.90 mmol).
The raw material was purified by chromatography (SiO2·Et3N, hex-
ane–EtOAc, 2:8) to give amine 4c as a yellow oil (550 mg, 47%).
HRMS: m/z calcd for C18H31NO4: 325.2253. Found: 325.2222.
Anal. Calcd for C18H31NO4: C, 66.43; H, 9.60; N, 4.30. Found: C,
66.07; H, 9.70; N, 4.34.
IR (NaCl): 3407, 1710 cm–1.
Methyl 4-Methylamino-1-methoxycarbonylcyclohex-1-ene (4f)
To a solution of amine 4b (73 mg, 0.28 mmol) in 1,2-dichloroethane
(3 mL) was added -chloroethyl chloroformate (31 L, 0.28 mmol)
at 0 ºC. After 15 min at this temperature, the solution was heated at
reflux temperature for 1 h. The solvent was evaporated, the residue
was redissolved in MeOH (3 mL) and heated at reflux for 45 min.
Evaporation of the solvent gave a residue which was crystallised to
give the hydrochloride of 4f (46 mg, 79%) as white crystals.
1H NMR: = 1.41 (m, 1 H, H-5 ax), 1.62 (br s, 1 H, NH), 1.82–2.05
(m, 2 H), 2.00 (m, 1 H), 2.40–2.50 (m, 2 H), 2.77 (m, 1 H, H-4 ax),
2.99 (br s, 4 H, NCH2CH2), 3.71 (s, 3 H, OCH3), 6.88 (m, 1 H, W1/
2 = 11 Hz, H-2 ), 7.01 (d, 1 H, J = 2 Hz, H-2), 7.11 (td, 1 H, J = 6,
1 Hz, H-5), 7.18 (td, 1 H, J = 6, 1 Hz, H-6), 7.34 (d, 1 H, J = 8 Hz,
H-7), 7.61 (d, 1 H, J = 7.5 Hz, H-4), 8.44 (br s, 1 H, NH-indole).
13C NMR: = 23.3 (CH2-Indole), 25.9, 28.5 and 32.9 (C-3 , C-5 ,
C-6 ), 47.0 (CH2N), 51.5 (C-4 ), 52.1 (OCH3), 111.1 (C-7), 113.5
(C-3), 118.7 (C-4), 119.1 (C-5), 121.9 (C-6), 122.0 (C-2), 127.2 (C-
3a), 129.8 (C-1 ), 136.3 (C-7a), 137.6 (C-2 ), 167.5 (CO).
Mp 165–167 °C (Et2O–MeOH).
IR (KBr): 3416, 1718 cm–1.
1H NMR: = 1.93 (m, 1 H, H-5ax), 2.34 (m, 2 H), 2.50–2.85 (m, 3
H), 2.68 (s, 3 H, NCH3), 3.19 (m, 1 H, H-4ax), 3.75 (s, 3 H, OCH3),
6.84 (m, 1 H, W1/2 = 12 Hz, H-2), 9.66 (br s, 2 H, NH2).
MS: m/z (%) = 168 (68), 136 (26), 132 (11), 131 (100), 130 (37), 79
(28), 77 (11).
13C NMR: = 23.1 (C-6), 24.5 (C-5), 28.1 (C-3), 30.1 (NCH3), 51.8
(OCH3), 54.6 (C-4), 130.1 (C-1), 134.0 (C-2), 166.4 (CO).
HRMS: m/z calcd for C18H22N2O2: 298.1681. Found: 298.1670.
Methyl 4-(1-Phenylethylamino)cyclohex-1-ene-1-carboxylate
(4d)
MS: m/z (%) = 169 (9), 138 (4), 58 (4), 57 (100), 56 (11).
Anal. Calcd for C9H16ClNO2: C, 52.56; H, 7.84; N, 6.81. Found: C,
52.46; H, 7.81; N, 6.61.
(S)-1-Phenylethylamine (181 L, 1.42 mmol) and ketone 2 and 3
(199 mg, 1.29 mmol) in 1,2-dichloroethane (4.5 mL) were treated
with NaBH(OAc)3 (410 mg, 1.94 mmol) and HOAc (74 L, 1.29
mmol). The raw material was purified by chromatography
(SiO2·Et3N, hexane–CH2Cl2, 3:7) to give 171 mg (51%) of amine
4d (1:1.1 mixture of diastereoisomers, estimated by GC) as a yellow
oil.
Reductive Amination of Enones 2 and 3 with Benzylamine in
Two Steps
A mixture of benzylamine (238 L, 2.18 mmol) and enones 2 and 3
(300 mg, 1.95 mmol) in CH2Cl2 (1.5 mL) was stirred for 4 h with
activated 4 Å molecular sieves. The resulting suspension was fil-
tered through a short pad of Celite and the filtrate concentrated to
give 473 mg of methyl 4-benzylaminocyclohex-1,3-diene-1-car-
boxylate (5).
IR (NaCl): 3322, 1712 cm–1.
1H NMR: = 1.33 and 1.34 (2 d, 3 H, J = 6.5, CH3), 1.35–2.50 (m,
6 H), 2.61 (m, 1 H, H-4ax), 3.68 (s, 3 H, OCH3), 3.92 and 3.97 (2 q,
1 H, J = 6.5 Hz, CH), 6.84 (m, 1 H, H-2), 7.18–7.38 (m, 5 H, Ar-H).
IR (NaCl): 3345, 1681 cm–1.
13C NMR: = 23.0, 23.2 (C-6), 24.7, 24.9 (CH3), 27.6, 29.2 (C-5),
32.5, 33.7 (C-3), 48.8, 49.0 (C-4), 51.3 (OCH3), 54.6, 54.7 (CH),
126.2, 126.5, 126.6, 128.5 (C-o, C-m, C-p), 129.6, 129.7 (C-1),
137.4, 137.7 (C-2), 145.5, 145.6 (C-ipso), 167.3 (CO).
1H NMR: = 1.83 (br s, 1 H, NH), 2.31 and 2.54 (2 t, 4 H, J = 10
Hz, H-5, H-6), 3.70 (s, 3 H, OCH3), 4.22 (br s, 2 H, CH2Ph), 4.85
(d, 1 H, J = 6.5 Hz, H-3), 7.21 (d, 1 H, J = 6.5 Hz, H-2), 7.20–7.40
(m, 5 H, Ar-H).
MS: m/z (%) = 259 (M+, 26), 244 (14), 147 (68), 132 (24), 130 (18),
106 (20), 105 (100), 104 (28), 103 (12), 79 (35), 77 (25).
13C NMR: = 21.8 (C-6), 29.2 (C-5), 47.3 (CH2Ph), 50.8 (OCH3),
89.1 (C-3), 112.1 (C-1), 126.9, 127.3, 128.5 (C-o, C-m, C-p), 137.5
(C-ipso), 138.7 (C-2), 151.9 (C-4), 168.0 (CO).
HRMS: m/z calcd for C16H21NO2: 259.1572. Found: 259.1564.
Dienamine 5 was dissolved in 1,2-dichloroethane (6.75 mL) and
treated with NaBH(OAc)3 (620 mg, 2.93 mmol) and HOAc (134
L, 2.34 mmol). The mixture was stirred at r.t. for 24 h and concen-
trated. The residue was taken up in CH2Cl2 and washed with 10%
K2CO3. After concentration of the organic extracts, the residue was
purified by chromatography (SiO2·Et3N, 2.5%, hexane–CH2Cl2,
4:6) to give 4a as a yellow oil (306 mg, 64%).
Methyl 4-[(S)- -isobutyl-tert-butoxycarbonylmethyl)amino]cy-
clohex-1-ene-1-carboxylate (4e)
L-Leucine-tert-butyl ester (221 mg, 0.99 mmol), ketones 2 and 3
(102 mg, 0.66 mmol) and Et3N in 1,2-dicloroethane (1.5 mL) were
treated with NaBH(OAc)3 (210 mg, 0.99 mmol) and HOAc (38 L,
0.66 mmol) for 72 h. The raw material was purified by chromatog-
raphy (hexane–EtOAc, 1:1) to give 108 mg (50%) of amine 4e
Synthesis 2001, No. 13, 1971–1974 ISSN 0039-7881 © Thieme Stuttgart · New York

1974
J. Quirante et al.
PAPER
(8) Potman, R. P.; Janssen, N. J. M. L.; Scheeren, J. W.; Nivard,
R. J. F. J. Org. Chem. 1984, 49, 3628.
Acknowledgement
Support for this research was provided by the DGICYT (Spain)
through Grant PB97-0877. Thanks are also due to the DURSI (Ca-
talonia) for Grant 1999SGR-00078 and a fellowship to X.V.
(9) Audrain, H.; Skrydstrup, T.; Ulibarri, G.; Riche, C.;
Chiaroni, A.; Grierson, D. S. Tetrahedron 1994, 50, 1469.
(10) It is assumed that methanol is eliminated concurrently with
the cleavage of the silyl enol ether to the ketone.3b For an
interesting study in this field, see: Vorndam, P. E. J. Org.
Chem. 1990, 55, 3693.
References and Notes
(11) Conversion of the carboxylic Diels–Alder adducts of
Danishefsky’s diene to cyclohexenones has been recently
reported using acid catalysts such as Yb(OTf)3, although
upon some substrates amounts of the corresponding
methoxylated derivatives were also obtained: Inokuchi, T.;
Okano, M.; Miyamoto, T.; Madon, H. B.; Takagi, M. Synlett
2000, 1549.
(1) Quirante, J.; Escolano, C.; Massot, M.; Bonjoch, J.
Tetrahedron 1997, 53, 1391.
(2) For recent Diels–Alder approaches to functionalized
aminocyclohexenes, see: (a) Huang, Y.; Iwama, T.; Rawal,
V. H. J. Am. Chem. Soc. 2000, 122, 7843, and references
cited therein. (b) Wipf, P.; Wang, X. Tetrahedron Lett.
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(12) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.;
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(13) McGill, J. M.; Labell, E. S.; Williams, M. Tetrahedron Lett.
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(3) (a) Danishefsky, S.; Kitahara, T. J. Org. Chem. 1975, 40,
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Chem. 1977, 42, 2277. (b) Lemmens, J. M.; Thijs, L.;
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(7) (a) Carter, M. J.; Fleming, I.; Percival, A. J. Chem. Soc.,
Perkin Trans. 1 1981, 2415. (b) Kosugi, H.; Hoshino, K.;
Uda, H. Chem. Lett. 1991, 1577.
(14) 1H NMR (CDCl3, 300 MHz): = 1.09–1.28 (m, 2 H, H-2ax,
H-6ax), 1.46 (qd, 2 H, J = 13, 3.5 Hz, H-3ax, H-5ax), 2.02 (m,
4 H, H-3, H-5), 2.28 (tt, 1 H, J = 12, 3.5 Hz, H-1), 2.51 (tt, 1
H, J = 11, 3.5 Hz, H-4), 3.66 (s, 3 H, OCH3), 3.82 (s, 2 H,
CH2Ar), 7.20–7.40 (m, 5 H, Ar-H); 13C NMR (CDCl3, 75
MHz): = 27.7 (C-6, C-2), 32.3 (C-5, C-3), 42.9 (C-1), 51.0
(CH2Ar), 51.6 (OCH3), 55.5 (C-4), 126.9, 128.1, 128.4,
140.2 (Ar), 176.2 (CO).
(15) Compounds of this type have recently been used to
synthesise 2-iodoanilines: Hegde, S. G.; Kassim, A. M.;
Kennedy, A. I. Tetrahedron 2001, 57, 1689.
(16) Danishefsky, D.; Kitahara, T.; Schuda, P. F. Org. Synth.
1983, 61, 147.
Synthesis 2001, No. 13, 1971–1974 ISSN 0039-7881 © Thieme Stuttgart · New York