Electroreductive intramolecular coupling of aromatic β- and γ-imino esters: A new synthetic method for N-alkoxycarbonyl-2-aryl-3-ones and cis-2-aryl-3-ols of pyrrolidines and piperidines

Article abstract of DOI:10.1021/jo0488917

The electroreduction of aromatic β- and γ-imino esters prepared from β-alanine and GABA in the presence of chlorotrimethylsilane and subsequent N-alkoxycarbonylation of the resulting five- and six-membered cyclized amines gave mixed ketals of N-alkoxycarb

Full text of DOI:10.1021/jo0488917

Electr or ed u ctive In tr a m olecu la r Cou p lin g of Ar om a tic â- a n d
γ-Im in o Ester s: A New Syn th etic Meth od for
N-Alk oxyca r bon yl-2-a r yl-3-on es a n d cis-2-Ar yl-3-ols of P yr r olid in es
a n d P ip er id in es
Naoki Kise,* Kengo Ohya, Kie Arimoto, Yutaka Yamashita, Yuuki Hirano, Tadahiro Ono, and
Nasuo Ueda
Department of Biotechnology, Faculty of Engineering, Tottori University, Koyama,
Tottori 680-8552, J apan
kise@bio.tottori-u.ac.jp
Received J uly 1, 2004
The electroreduction of aromatic â- and γ-imino esters prepared from â-alanine and GABA in the
presence of chlorotrimethylsilane and subsequent N-alkoxycarbonylation of the resulting five- and
six-membered cyclized amines gave mixed ketals of N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and
2-arylpiperidin-3-ones, respectively. The best result of the electroreductive intramolecular coupling
was achieved using Bu4NClO4 as a supporting electrolyte and a Pb cathode in THF. Acid hydrolysis
of the mixed ketals afforded N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones
in good yields. The reduction of these ketones with NaBH4 in methanol afforded the corresponding
N-alkoxycarbonyl-cis-2-arylpyrrolidin-3-ols and cis-2-arylpiperidin-3-ols diastereospecifically.
SCHEME 1
In tr od u ction
Pyrrolidine and piperidine skeletons are widely found
in many natural products and biologically active com-
pounds. Therefore, a number of methods for the synthesis
of these compounds have been developed.1 On the other
hand, reductive coupling of imines with carbonyl com-
pounds has been known to be useful for the synthesis of
nitrogen-containing compounds such as â-amino alco-
hols.2 In our preliminary report, we disclosed that elec-
troreduction is also an efficient tool for the reductive
coupling of aromatic imines with carbonyl compounds.3
In addition, we have recently reported that the reductive
intramolecular coupling of aromatic R-imino esters pre-
pared from chiral R-amino acids was achieved by elec-
troreduction in the presence of chlorotrimethylsilane
(CTMS) to give mixed ketals of cis-2,4-disubstituted
azetidin-3-ones stereoselectively (Scheme 1).4 At present,
electroreduction is only one method for the reductive
intramolecular coupling of imino esters. To extend the
synthetic potential of the intramolecular coupling of
imino esters, in this paper, we report the electroreduction
of aromatic â- and γ-imino acid methyl esters in the
presence of CTMS produced mixed ketals of 2-arylpyr-
SCHEME 2
rolidin-3-ones and 2-arylpiperidin-3-ones. This reaction
provides a new synthetic route to N-alkoxycarbonyl-2-
arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones from
â-alanine and γ-aminobutyric acid (GABA), respectively
(Scheme 2). In recent years, N-BOC-2-phenylpiperidin-
3-one attracts much interest as a useful synthon for the
synthesis of neurokinin receptor antagonists.5 Among
them, it has been reported that N-BOC-2-phenylpiperi-
din-3-one was reduced with L-Selectride in THF to cis-
N-BOC-2-phenylpiperidin-3-ol, a precursor of neurokinin
NK1 receptor antagonist L-733,060 (Scheme 3).5a We also
found that the reduction of N-alkoxycarbonyl-2-arylpyr-
rolidin-3-ones and 2-arylpiperidin-3-ones with NaBH4 in
methanol gave the corresponding cis-2-arylpyrrolidin-3-
(1) For recent reviews, see: (a) Bailey, P. D.; Millwood, P. A.; Smith,
P. D. Chem. Commun. 1998, 633. (b) Laschat, S.; Dickner, T. Synthesis
2000, 1781. (c) Mitchinson, A.; Nadin, A. J . Chem. Chem., Perkin
Trans. 1 2000, 2862. (d) Bates, R. W.; Sa-Ei, K. Tetrahedron 2002, 58,
5957. (e) Weintraub, P. M.; Sabol, J . S.; Kane, J . M.; Borcherding, D.
R. Tetrahedron 2003, 59, 2953.
(2) (a) Roskamp, E. J .; Pedersen, S. F. J . Am. Chem. Soc. 1987, 109,
6551. (b) Machrouhi, F.; Namy, J .-L. Tetrahedron Lett. 1999, 40, 1315.
(c) Tanaka, Y.; Taniguchi, N.; Uemura, M. Org. Lett. 2002, 4, 835.
(3) Preliminary communication: Shono, T.; Kise, N.; Kunimi, N.;
Nomura, R. Chem. Lett. 1991, 2191.
(4) Kise, N.; Ozaki, H.; Moriyama, N.; Kitagishi, Y.; Ueda, N. J . Am.
Chem. Soc. 2003, 125, 11591.
10.1021/jo0488917 CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/07/2004
7710
J . Org. Chem. 2004, 69, 7710-7719

Intramolecular Coupling of Aromatic â- and γ-Imino Esters
TABLE 1. Electr or ed u ctive Cou p lin g of 1a to 2a
SCHEME 3
yield (%)
d
run
solventa
additiveb cathode
of 2a c
2a ′/2a ′′
1
2
3
4
5
6
7
8
9
Bu4NClO4/THF CTMS/TEA
Bu4NClO4/THF none
Bu4NClO4/THF CTMS
Bu4NBF4/THF CTMS/TEA
Bu4NPF6/THF CTMS/TEA
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Pb
Pt
Au
Ag
Cu
Zn
Sn
Al
70
0
42:58
56
70
63
69
60
0
64
66
65
67
68
60
52
42:58
41:59
43:57
47:53
52:48
Bu4NBr/THF
Bu4NCl/THF
LiClO4/THF
CTMS/TEA
CTMS/TEA
CTMS/TEA
Bu4NClO4/THF CTMS/TEA
34:66
43:57
41:59
40:60
30:70
34:66
26:74
10 Bu4NClO4/THF CTMS/TEA
11 Bu4NClO4/THF CTMS/TEA
12 Bu4NClO4/THF CTMS/TEA
13 Bu4NClO4/THF CTMS/TEA
14 Bu4NClO4/THF CTMS/TEA
15 Bu4NClO4/THF CTMS/TEA
SCHEME 4
a
b
0.3 M electrolyte in solvent. 5 equiv to 1a . c Isolated yields.
Diastereomeric ratios determined by 1H NMR spectra. 2a ′ was
d
less polar than 2a ′′ in TLC analysis on silica gel (hexanes-ethyl
acetate).
ols and cis-2-arylpiperidin-3-ols diastereospecifically in
good yields (Scheme 4).
The diastereomeric mixture of the mixed ketal 2a was
easily and quickly hydrolyzed to the corresponding ketone
3a in quantitative yield by treatment with 1 M HCl/
dioxane at room temperature. Therefore, ketone 3a could
be more conveniently prepared without isolation of 2a .
A variety of N-arylmethylidene-â-alanine methyl esters
1a -j were electrochemically reduced under the same
conditions as run 1 in Table 1, the resulted pyrrolidines
were protected with a MOC (methoxycarbonyl) or BOC
group, and then the crude mixed ketals were hydrolyzed
with 1 M HCl to ketones 3 or 4. The results were
summarized in Table 2. All substrates except for 1h gave
the corresponding N-protected 2-arylpyrrolidin-3-ones 3
and 4 in moderate to good yields. These results show that
the reductive coupling was less affected by substitution
of both electron-donating and electron-withdrawing groups.
In the case of 1h (Ar ) 1-naphthyl), the yield of 3h
decreased probably due to steric hindrance. In the case
of acid-sensitive substrate 1j (Ar ) 2-furyl), the acid
hydrolysis was carried out at 0 °C.
Resu lts a n d Discu ssion
According to our study,4 we surveyed conditions for the
electroreductive intramolecular coupling of â-imino esters
using N-benzyliden-â-alanine methyl ester (1a ) as a
substrate and THF as a solvent in the presence of 5 equiv
of chlorotrimethylsilane (CTMS) and triethylamine (TEA).
The results are summarized in Table 1. The reductive
coupling product, mixed ketal of 2-phenypyrrolidin-3-one,
was isolated as methyl carbamate 2a , since free pyrrol-
idine was air-sensitive. The product 2a was obtained as
a mixture of two diastereomers 2a ′ and 2a ′′. The stereo-
chemistry of each isomer could not be determined. The
best result (70% combined yield of 2a ′ and 2a ′′) was
obtained when the electroreduction was carried out with
Bu4NClO4 as a supporting electrolyte and a Pb cathode
(Table 1, run 1). The presence of CTMS was essential
for the reductive coupling (run 2); a complex mixture was
obtained in the absence of CTMS. Although the addition
of TEA was not crucial, the absence of TEA somewhat
decreased the yield of 2a (run 3). Some other tetrabutyl-
ammonium salts also afforded comparable results to run
1 (runs 4-7), whereas the use of LiClO4 produced a
complex mixture (run 8). The yields obtained with several
other cathodes were slightly less than or nearly equal to
that in run 1 (runs 9-15).
The electroreductive method was also effective for the
construction of piperidines. The electroreduction of N-
benzylidene-GABA methyl esters (5a ) occurred under the
same conditions as run 1 in Table 1. The resulting mixed
ketal of 2-phenylpiperidin-3-one was isolated as methyl
carbamate 6a in a 72% yield (Scheme 5). The mixed ketal
6a was also obtained as a mixture of two diastereomers
(6a ′/6a ′′ ) 33:67), and the diastereomeric mixture was
easily hydrolyzed to ketone 7a with 1 M HCl/dioxane at
room temperature. Next, a variety of N-arylmethylidene-
GABA methyl esters 5a -j were electrochemically re-
duced, protected with a MOC or BOC group, and succes-
sively hydrolyzed to give the corresponding ketones 7 or
8 (Table 3). Similarly to the pyrrolidine formation
described above, aryl substitution minimally influenced
the piperidine formation except for the case of the
1-naphthyl group (5h ).
(5) (a) Calvez, O.; Langlois, N. Tetrahedron Lett. 1999, 40, 7099.
(b) Kulagowski, J . J .; Curtis, N. R.; Swain, C. J .; Williams, B. J . Org.
Lett. 2001, 3, 667. (c) Lee, J .; Hoang, T.; Lewis, S.; Weissman, S. A.;
Askin, D.; Volante, R. P.; Reider, P. J . Tetrahedron Lett. 2001, 42, 6223.
(d) Maligres, P. E.; Waters, M. M.; Lee, J .; Reamer, R. A.; Askin, D.;
Ashwood, M. S.; Cameron, M. J . Org. Chem. 2002, 67, 1093. (e)
Yamazaki, N.; Atobe, M.; Kibayashi, C. Tetrahedron Lett. 2002, 43,
7979. (f) Huang, P.-Q.; Liu, L.-X.; Wei, B.-G.; Ruan, Y.-P. Org. Lett.
2003, 5, 1927. (g) Bhaskar, G.; Rao, B. V. Tetrahedron Lett. 2003, 44,
915.
J . Org. Chem, Vol. 69, No. 22, 2004 7711

Kise et al.
TABLE 2. Electr or ed u ctive Cou p lin g of â-Im in o Ester sa
TABLE 3. Electr or ed u ctive Cou p lin g of γ-Im in o Ester sa
yieldb (%)
imine
Ar
product
yieldb (%)
imine
Ar
product
1a
C6H5
3a
4a
3b
4b
3c
4c
3d
4d
3e
4e
3f
68
70
64
65
64
60
65
64
63
62
58
56
55
62
35
60
56
56
5a
Ph
7a
8a
7b
8b
7c
8c
7d
8d
7e
8e
7f
70
69
72
65
69
65
72
66
69
70
67
67
59
52
25
63
57
51
1b
1c
1d
1e
1f
p-MeOC6H4
m-MeOC6H4
o-MeOC6H4
3,4-(MeO)2C6H3
p-FC6H4
5b
5c
5d
5e
5f
p-MeOC6H4
m-MeOC6H4
o-MeOC6H4
3,4-(MeO)2C6H3
p-FC6H4
4f
8f
1g
p-NCC6H4
3g
4g
3h
3i
4i
3j
5g
p-NCC6H4
7g
8g
7h
7i
8i
7j
1h
1i
1-naphthyl
2-naphthyl
5h
5i
1-naphthyl
2-naphthyl
1j
2-furyl
5j
2-furyl
a
a
The electroreduction was carried out in 0.3 M Bu4NClO4/THF.
Isolated yields.
The electroreduction was carried out in 0.3 M Bu4NClO4/THF.
Isolated yields.
b
b
SCHEME 5
SCHEME 6
As previously reported,4 a mixed ketal of 2-phenyl-
azetidin-3-one was formed in poor yield (20%) by the
electroreduction of N-benzylidene glycine methyl ester
(Scheme 6). The seven-membered cyclized product could
not be obtained from aromatic δ-imino ester 9 by this
methodology; simply reduced amine 10 was the only one
isolatable product. In addition, aliphatic imines 11 and
12 were not reduced under the conditions.
The speculated mechanism of the electroreductive
coupling can be illustrated in Scheme 7, similarly to the
previous report.4 The equilibrium of the formation of an
imine 1a ‚CTMS complex was also observed in the 1H
NMR analysis of 1a in the presence of CTMS (Table 4).
One-electron transfer to 1a ‚CTMS complex followed by
N-silylation and further one-electron transfer to the
resulting radical A generates the anion B. Intramolecular
attack of the carbanion to the ester group in B forms
O-anion C, which is subsequently O-silylated to D. The
pyrrolidine E is obtained by N-desilylation of D during
workup.
Red u ction of N-Alk oxyca r bon yl-2-a r yl-3-on es of
P yr r olid in es a n d P ip er id in es. It has already been
known that the reduction of N-BOC-2-phenylpiperidin-
3-one (7a ) with L-Selectride at -78 °C afforded N-BOC-
cis-2-phenylpiperidin-3-ol stereospecifically (Scheme 3).5a
We surveyed the reduction of 7a with several hydride
reagents as depicted in Table 5. It was found that all
hydride reagents employed gave only the cis-isomer of
the alcohol 16a . Therefore, other N-alkoxycarbonyl-2-
aryl-3-ones of pyrrolidines (3 and 4) and piperidines (7
and 8) were reduced with NaBH4 in methanol (Table 6),
since it is the most economical and convenient method.
Of the alcohols 13-16 obtained as single stereoisomers,
N-BOC-cis-2-phenyl-3-ols 14a and 16a were confirmed
by comparison of their spectroscopic data with reported
ones.6 The stereostructures of several N-MOC-2-aryl-3-
ols, 13a , 13f, 13g, 15a , and 15d , were established to be
2,3-cis by X-ray crystallographic analysis. These results
imply that the other alcohols 13-16 also possess 2,3-cis
configuration.
Con clu sion
This paper describes the electroreductive intramolecu-
lar coupling of aromatic â- and γ-imino esters in the
(6) Tomooka, K.; Nakazaki, A.; Nakai, T. J . Am. Chem. Soc. 2000,
122, 408.
7712 J . Org. Chem., Vol. 69, No. 22, 2004

Intramolecular Coupling of Aromatic â- and γ-Imino Esters
SCHEME 7
TABLE 4. 1H NMR Ch em ica l Sh ifts of 1a in th e
P r esen ce of CTMS
TABLE 6. Red u ction of 2-Ar yl-3-on es of P yr r olid in es
a n d P ip er id in esa
CTMS (equiv)
CHdN (δ)
NCH2 (δ)
0
8.33
8.53
8.69
8.71
8.73
8.33
3.89
4.06
4.16
4.17
4.18
3.88
0.5
1.0
2.0
3.0
3.0a
a
3 equiv of TEA was added.
ketone
Ar
n
alcohol
yieldb (%)
3a
4a
3b
4b
3c
4c
3d
4d
3e
4e
3f
C6H5
1
13a
14a
13b
14b
13c
14c
13d
14d
13e
14e
13f
14f
13g
14g
13i
84
88
71
85
71
83
74
82
75
80
62
79
64
68
74
84
86
93
90
83
79
86
66
76
78
87
74
77
52
58
84
76
TABLE 5. Red u ction of 7a to 16a
p-MeOC6H4
m-MeOC6H4
o-MeOC6H4
3,4-(MeO)2C6H3
p-FC6H4
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
reagent
solvent
T (°C)
yielda (%)
L-Selectride
NaBH4
LiBH4
THF
CH3OH
THF
-78
82
93
80
51
5
5
5
4f
3g
4g
3i
p-NCC6H4
2-naphthyl
C6H5
Bu4NBH4
CH2Cl2
a
Isolated yields.
4i
14i
7a
8a
7b
8b
7c
8c
7d
8d
7e
8e
7f
15a
16a
15b
16b
15c
16c
15d
16d
15e
16e
15f
16f
15g
16g
15i
presence of CTMS and TEA followed by N-alkoxycarbo-
nylation to produce N-alkoxycalbonyl mixed ketals of
2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones. The
addition of CTMS to the catholyte is essential to promote
the electroreductive coupling. Because the N-alkoxycal-
bonyl mixed ketals were easily hydrolyzed to ketones by
treatment with 1 M HCl, this electroreduction provides
a new method for the synthesis of N-protected 2-arylpyr-
rolidin-3-ones and 2-arylpiperidin-3-ones from â-alanine
and GABA, respectively. In addition, these N-alkoxycal-
bonyl-2-aryl-3-ones of pyrrolidines and piperidines were
stereospecifically transformed to the corresponding
N-alkoxycalbonyl-cis-2-aryl-3-ols by reduction with NaBH4
in methanol.
p-MeOC6H4
m-MeOC6H4
o-MeOC6H4
3,4-(MeO)2C6H3
p-FC6H4
8f
7g
8g
7i
p-NCC6H4
2-naphthyl
8i
16i
a
The reduction was carried out with NaBH4 in methanol at 5
b
°C. Isolated yields.
Exp er im en ta l Section
Gen er a l P r oced u r es. Column chromatography was per-
formed on silica gel 60. THF was distilled from sodium
benzophenone ketyl radical. CTMS and TEA were distilled
from CaH2. Aromatic â- or γ-imino esters were prepared by
treatment of â-alanine or GABA methyl ester with aromatic
aldehydes in dichloromethane in the presence of magnesium
sulfate at room temperature and isolated by distillation in
vacuo or by recrystallization from hexanes-ethyl acetate (1g,i
and 5g,i).
Typ ica l P r oced u r e for Electr or ed u ction of Im in o
Ester s 1 a n d 5. A 0.3 M solution of Bu4NClO4 in THF (15
mL) was placed in the cathodic chamber of a divided cell (40-
mL beaker, 3-cm diameter, 6-cm height) equipped with a lead
cathode (5 × 5 cm2), a platinum anode (2 × 1 cm2), and a
ceramic cylindrical diaphragm (1.5-cm diameter). A 0.3 M
solution of Bu4NClO4 in DMF (4 mL) was placed in the anodic
chamber (inside the diaphragm). Imino ester (1a ) (191 mg, 1
mmol), CTMS (0.64 mL, 5 mmol), and triethylamine (0.70 mL,
J . Org. Chem, Vol. 69, No. 22, 2004 7713

Kise et al.
5 mmol) were added to the cathodic chamber. After 300 C of
electricity was passed at a constant current of 100 mA at room
temperature, the catholyte was evaporated in vacuo. The
residue was diluted with Et2O (30 mL) and 1 M NaHCO3 (30
mL). To the mixture was added ClCO2Me (0.39 mL, 5 mmol)
dropwise, and then the suspended mixture was stirred at room
temperature for 1 h. Insoluble Bu4NClO4 was filtered off, and
the filtrate was extracted with Et2O three times. The crude
mixture was purified by column chromatography on silica gel
(hexanes-ethyl acetate, 50:1) to give 2a in a 70% yield as a
mixture of two diastereomers (2a ′:2a ′′ ) 42:58). These isomers
2a ′ and 2a ′′ could be separated by further column chromatog-
raphy on silica gel (hexanes-ethyl acetate, 100:1).
Hyd r olysis of Mixed Keta l 2a to Keton e 3a . To a
solution of 2a (0.5 mmol) in dioxane (2.5 mL) was added 1 M
HCl (2.5 mL). The mixture was stirred at room temperature
for 1 h, diluted with H2O (10 mL), and then extracted with
Et2O three times. The produced 3a was isolated by column
chromatography on silica gel in a 96% yield.
δ 2.58-2.79 (m, 2 H), 3.68 (brs, 3 H), 3.80 (s, 3 H), 3.84-3.96
(m, 1 H), 4.04-4.23 (m, 1 H), 4.92 (s, 1 H), 6.80-6.87 (m, 3
H), 7.23-7.31 (m, 1 H); 13C NMR (CDCl3) δ 35.1 (t), 42.2 (t),
52.7 (q), 55.1 (q), 65.3 (d), 111.5 (d), 113.0 (d), 117.6 (d), 129.6
(d), 137.7 (s), 155.4 (s), 159.7 (s), 208.4 (s). Anal. Calcd for
C
13H15NO4: C, 62.64; H, 6.07; N, 5.62. Found: C, 62.74; H,
6.12; N, 5.43.
1-BOC-2-(3-m eth oxyp h en yl)p yr r olid in -3-on e (4c): col-
orless paste; Rf 0.42 (hexanes-ethyl acetate, 2:1); IR (neat)
1761, 1699, 1601, 1585, 1491, 777, 737, 696 cm-1 1H NMR
;
(CDCl3) δ 1.27 (brs, 9 H), 2.62-2.74 (m, 2 H), 3.80 (s, 3 H),
3.85-3.92 (m, 1 H), 4.00-4.07 (m, 1 H), 4.83 (brs, 1 H), 6.76-
6.87 (m, 3 H), 7.24-7.28 (m, 1 H); 13C NMR (CDCl3) δ 27.9
(q), 35.1 (t), 41.6 (t), 55.0 (q), 65.7 (d), 80.2 (s), 111.4 (d), 112.9
(d), 117.8 (d), 129.5 (d), 138.9 (s), 154.2 (s), 159.7 (s), 209.2 (s).
Anal. Calcd for C16H21NO4: C, 65.96; H, 7.27; N, 4.81. Found:
C, 66.12; H, 7.38; N, 4.69.
1-MOC-2-(2-m eth oxyph en yl)pyr r olidin -3-on e (3d): white
solid; Rf 0.39 (hexanes-ethyl acetate, 1:1); mp 124-125 °C;
IR (KBr) 1757, 1705, 1688, 1599, 1589, 1497, 772, 762 cm-1
;
Typ ica l P r oced u r e for Syn th esis of Keton es 3, 4, 7, a n d
8 fr om Im in o Ester s 1 a n d 5 by Su ccessive Electr olysis
a n d Hyd r olysis. After electroreduction of 1a (1 mmol) was
carried out as described above, the catholyte was evaporated
in vacuo. The residue was diluted with Et2O (30 mL) and 1 M
NaHCO3 (30 mL). To the mixture was added (BOC)2O (0.44 g,
2 mmol), and then the suspended mixture was stirred at room
temperature for 1 h. Insoluble Bu4NClO4 was filtered off, and
the filtrate was extracted with Et2O three times. After the
solvent was removed, to the residue were added dioxane (2.5
mL) and 1 M HCl (2.5 mL). The mixture was stirred at room
temperature for 1 h, diluted with H2O (10 mL), and extracted
with Et2O three times. The crude mixture was purified by
column chromatography on silica gel to give 4a in a 70% yield.
1-MOC-2-p h en ylp yr r olid in -3-on e (3a ): colorless paste; Rf
0.24 (hexanes-ethyl acetate, 2:1); IR (neat) 1759, 1699, 1601,
1545, 1493, 916, 773, 741, 700 cm-1; 1H NMR (CDCl3) δ 2.48-
2.80 (m, 2 H), 3.67 (brs, 3 H), 3.85-3.98 (m, 1 H), 4.05-4.25
(m, 1 H), 4.96 (s, 1 H), 7.23-7.41 (m, 5H); 13C NMR (CDCl3) δ
35.1 (t), 42.1 (t), 52.6 (q), 65.3 (d), 125.4 (d), 127.6 (d), 128.5
(d), 136.1 (s), 155.3 (s), 208.6 (s). Anal. Calcd for C12H13NO3:
C, 65.74; H, 5.98; N, 6.39. Found: C, 65.68; H, 6.04; N, 6.31.
1-BOC-2-p h en ylp yr r olid in -3-on e (4a ): white solid; Rf
0.17 (hexanes-ethyl acetate, 5:1); mp 103-105 °C; IR (KBr)
1753, 1674, 1495, 1475, 741, 700 cm-1; 1H NMR (CDCl3) δ 1.25
(brs, 9 H), 2.63-2.76 (m, 2 H), 3.87-3.94 (m, 1 H), 4.01-4.09
(m, 1 H), 4.85 (brs, 1 H), 7.22-7.37 (m, 5 H); 13C NMR (CDCl3)
δ 27.9 (q), 35.1 (t), 41.6 (t), 67.6 (d), 80.2 (s), 125.6 (d), 127.5
(d), 128.4 (d), 137.4 (s), 154.2 (s), 209.5 (s). Anal. Calcd for
1H NMR (CDCl3) δ 2.63-2.81 (m, 2 H), 3.63 (brs, 3 H), 3.77
(s, 3 H), 3.84 (dt, 1 H, J ) 8.6, 10.8 Hz), 3.98-4.18 (m, 1 H),
4.86 (brs, 1 H), 6.85 (d, 1 H, J ) 8.4 Hz), 6.94 (d, 1 H, J ) 7.3
Hz), 7.18-7.45 (m, 2 H); 13C NMR (CDCl3) δ 36.3 (t), 42.9 (t),
52.2 (q), 55.0 (q), 63.6 (d), 110.8 (d), 120.3 (d), 126.4 (s), 129.5
(d), 132.1 (d), 154.8 (s), 155.7 (s), 210.7 (s). Anal. Calcd for
C
13H15NO4: C, 62.64; H, 6.07; N, 5.62. Found: C, 62.58; H,
6.10; N, 5.55.
1-BOC-2-(2-m eth oxyph en yl)pyr r olidin -3-on e (4d): white
solid; Rf 0.43 (hexanes-ethyl acetate, 5:1); mp 128-129 °C;
IR (KBr) 1755, 1674, 1601, 1589, 1495, 1483, 783, 758 cm-1
;
1H NMR (CDCl3) δ 1.30 (brs, 9 H), 2.66-2.77 (m, 2 H), 3.77
(s, 3 H), 3.78-3.85 (m, 1 H), 3.98-4.07 (m, 1 H), 4.81 (brs, 1
H), 6.85 (d, 1 H, J ) 8.0 Hz), 6.93 (t, 1 H, J ) 7.5 Hz), 7.17-
7.31 (m, 2 H); 13C NMR (CDCl3) δ 28.0 (q), 36.1 (t), 42.4 (t),
55.0 (q), 63.7 (d), 79.8 (s), 110.7 (d), 119.9 (d), 127.0 (s), 129.4
(d), 132.3 (d), 154.3 (s), 155.9 (s), 211.7 (s). Anal. Calcd for
C
16H21NO4: C, 65.96; H, 7.27; N, 4.81. Found: C, 65.86; H,
7.22; N, 4.70.
1-MOC-2-(3,4-d im eth oxyp h en yl)p yr r olid in -3-on e (3e):
colorless paste; Rf 0.24 (hexanes-ethyl acetate, 1:1); IR (neat)
1759, 1699, 1593, 1514, 916, 806, 772, 731 cm-1 1H NMR
;
(CDCl3) δ 2.65-2.73 (m, 2 H), 3.70 (brs, 3 H), 3.86 (s, 3 H),
3.89 (s, 3 H), 3.83-3.97 (m, 1 H), 4.07-4.21 (m, 1 H), 4.90 (s,
1 H), 6.74-6.79 (m, 1 H), 6.80-6.86 (m, 2 H); 13C NMR (CDCl3)
δ 35.1 (t), 42.1 (t), 52.7 (q), 55.8 (q), 55.8 (q), 64.9 (d), 109.1
(d), 110.1 (d), 117.2 (d), 128.6 (s), 148.6 (s), 149.1 (s), 155.4 (s),
208.8 (s). Anal. Calcd for C14H17NO5: C, 60.21; H, 6.14; N, 5.02.
Found: C, 60.04; H, 6.12; N, 4.88.
C
15H19NO3: C, 68.94; H, 7.33; N, 5.36. Found: C, 68.90; H,
1-BOC-2-(3,4-d im eth oxyp h en yl)p yr r olid in -3-on e (4e):
colorless paste; Rf 0.41 (hexanes-ethyl acetate, 1:1); IR (neat)
7.33; N, 5.41.
1-MOC-2-(4-m eth oxyp h en yl)p yr r olid in -3-on e (3b): col-
orless paste; Rf 0.21 (hexanes-ethyl acetate, 2:1); IR (neat)
1759, 1699, 1595, 1516, 862, 810, 768, 731 cm-1 1H NMR
;
(CDCl3) δ 1.31 (brs, 9 H), 2.63-2.75 (m, 2 H), 3.85-3.91 (m, 1
H), 3.87 (s, 3 H), 3.88 (s, 3 H), 4.00-4.08 (m, 1 H), 4.81 (brs,
1 H), 6.75-6.80 (m, 2 H), 6.84 (d, 1 H, J ) 8.0 Hz); 13C NMR
(CDCl3) δ 28.0 (q), 35.1 (t), 41.6 (t), 55.7 (q), 65.3 (d), 80.3 (s),
108.9 (d), 111.1 (d), 117.6 (d), 129.9 (s), 148.5 (s), 149.0 (s),
154.3 (s), 209.7 (s). Anal. Calcd for C17H23NO5: C, 63.54; H,
7.21; N, 4.36. Found: C, 63.75; H, 7.34; N, 4.19.
1-MOC-2-(4-flu or op h en yl)p yr r olid in -3-on e (3f): color-
less paste; Rf 0.23 (hexanes-ethyl acetate, 2:1); IR (neat) 1763,
1705, 1605, 1508, 862, 822, 773 cm-1; 1H NMR (CDCl3) δ 2.59-
2.82 (m, 2 H), 3.69 (brs, 3 H), 3.83-3.95 (m, 1 H), 4.06-4.22
(m, 1 H), 4.93 (s, 1 H), 7.00-7.09 (m, 2 H), 7.20-7.28 (m, 2
H); 13C NMR (CDCl3) δ 35.2 (t), 42.2 (t), 52.8 (q), 64.7 (d), 115.5
(d, J CCF ) 21.7 Hz), 127.2 (d, J CCCF ) 7.8 Hz), 132.0 (s), 155.4
1761, 1701, 1609, 1512, 773, 733 cm-1 1H NMR (CDCl3) δ
;
2.58-2.79 (m, 2 H), 3.68 (brs, 3 H), 3.79 (s, 3 H), 3.83-3.95
(m, 1 H), 4.04-4.22 (m, 1 H), 6.85-6.91 (m, 2 H), 7.14-7.21
(m, 2 H); 13C NMR (CDCl3) δ 35.1 (t), 42.1 (t), 52.6 (q), 55.1
(q), 64.7 (d), 114.0 (d), 126.6 (d), 128.3 (s), 155.3 (s), 159.0 (s),
209.1 (s). Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07; N, 5.62.
Found: C, 62.50; H, 6.06; N, 5.43.
1-BOC-2-(4-m eth oxyph en yl)pyr r olidin -3-on e (4b): white
solid; Rf 0.50 (hexanes-ethyl acetate, 1:1); mp 69-71 °C; IR
1
(KBr) 1757, 1674, 1607, 1585, 1512, 1475, 862, 822 cm-1; H
NMR (CDCl3) δ 1.28 (brs, 9 H), 2.62-2.74 (m, 2 H), 3.79 (s, 3
H), 3.84-3.92 (m, 1 H), 3.99-4.08 (m, 1 H), 4.81 (brs, 1 H),
6.86-6.90 (m, 2 H), 7.13-7.19 (m, 2 H); 13C NMR (CDCl3) δ
27.9 (q), 35.0 (t), 41.5 (t), 54.9 (q), 65.1 (d), 80.0 (s), 113.8 (d),
126.7 (d), 129.5 (s), 154.1 (s), 158.9 (s), 209.8 (s). Anal. Calcd
for C16H21NO4: C, 65.96; H, 7.27; N, 4.81. Found: C, 65.88;
H, 7.25; N, 4.74.
1-MOC-2-(3-m eth oxyp h en yl)p yr r olid in -3-on e (3c): col-
orless paste; Rf 0.22 (hexanes-ethyl acetate, 2:1); IR (neat)
1761, 1705, 1601, 1585, 1491, 773, 696 cm-1; 1H NMR (CDCl3)
(s), 162.2 (s, J CF ) 244.4 Hz), 208.6 (s). Anal. Calcd for C12H12
-
FNO3: C, 60.76; H, 5.10; N, 5.90. Found: C, 60.85; H, 5.17;
N, 5.69.
1-BOC-2-(4-flu or op h en yl)p yr r olid in -3-on e (4f): colorless
paste; Rf 0.47 (hexanes-ethyl acetate, 2:1); IR (neat) 1755,
1674, 1603, 1510, 860, 826, 791, 756 cm-1; 1H NMR (CDCl3) δ
1.12-1.60 (m, 9 H), 2.62-2.77 (m, 2 H), 3.85-3.92 (m, 1 H),
7714 J . Org. Chem., Vol. 69, No. 22, 2004

Intramolecular Coupling of Aromatic â- and γ-Imino Esters
4.01-4.08 (m, 1 H), 4.84 (brs, 1 H), 7.02-7.07 (m, 2 H), 7.19-
7.26 (m, 2 H); 13C NMR (CDCl3) δ 27.8 (q), 35.1 (t), 41.5 (t),
127.4 (d), 128.6 (d), 134.7 (s), 155.9 (s), 204.3 (s). Anal. Calcd
for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C, 66.88;
H, 6.54; N, 5.87.
65.0 (d), 80.2 (s), 115.3 (d, J CCF ) 21.0 Hz), 127.2 (d, J CCCF
)
1-BOC-2-p h en ylp ip er id in -3-on e (8a ):5 colorless paste; Rf
0.33 (hexanes-ethyl acetate, 5:1); IR (neat) 1722, 1693, 1601,
1583, 1495, 972, 897, 860, 758, 727, 700 cm-1; 1H NMR (CDCl3)
δ 1.43 (brs, 9 H), 1.86-2.02 (m, 2 H), 2.40-2.52 (m, 2 H), 3.26-
3.38 (m, 1 H), 3.95-4.20 (m, 1 H), 5.22-5.88 (m, 1 H), 7.20-
7.23 (m, 2 H), 7.27-7.31 (m, 1 H), 7.34-7.38 (m, 2 H); 13C NMR
(CDCl3) δ 22.7 (t), 28.1 (q), 37.2 (t), 39.7 (t), 66.3 (d), 80.6 (s),
125.2 (d), 127.5 (d), 128.8 (d), 135.4 (s), 154.8 (s), 205.3 (s).
Anal. Calcd for C16H21NO3: C, 69.79; H, 7.69; N, 5.09. Found:
C, 69.86; H, 7.72; N, 4.82.
1-MOC-2-(4-m eth oxyp h en yl)p ip er id in -3-on e (7b): color-
less paste; Rf 0.31 (hexanes-ethyl acetate, 2:1); IR (neat) 1699,
1611, 1510, 961, 768, 669 cm-1; 1H NMR (CDCl3) δ 1.86-2.07
(m, 2 H), 2.47 (t, 2 H, J ) 6.8 Hz), 3.29-3.42 (m, 1 H), 3.74 (s,
3 H), 3.79 (s, 3 H), 3.97-4.25 (m, 1 H), 5.66 (s, 1 H), 6.85-
6.92 (m, 2 H), 7.09-7.16 (m, 2 H); 13C NMR (CDCl3) δ 22.7 (t),
37.0 (t), 40.2 (t), 52.9 (q), 55.1 (q), 65.3 (d), 114.1 (d), 126.4 (d),
7.6 Hz), 133.3 (s), 154.0 (s), 162.0 (d, J CF ) 244.2 Hz), 209.3
(s). Anal. Calcd for C15H18FNO3: C, 64.50; H, 6.50; N, 5.01.
Found: C, 64.57; H, 6.45; N, 4.90.
1-MOC-2-(4-cya n op h en yl)p yr r olid in -3-on e (3g): color-
less paste; Rf 0.53 (hexanes-ethyl acetate, 1:2); IR (neat) 2230,
1763, 1705, 1607, 1502, 773, 733 cm-1 1H NMR (CDCl3) δ
;
2.59-2.86 (m, 2 H), 3.69 (brs, 3 H), 3.85-3.97 (m, 1 H), 4.06-
4.26 (m, 1 H), 5.00 (s, 1 H), 3.37-3.43 (m, 2 H), 7.63-7.69 (m,
2 H); 13C NMR (CDCl3) δ 35.4 (t), 42.2 (t), 52.9 (q), 65.1 (d),
111.6 (s), 118.2 (s), 126.2 (d), 132.3 (d), 141.2 (s), 155.2 (s),
207.3 (s). Anal. Calcd for C13H12N2O3: C, 63.93; H, 4.95; N,
11.47. Found: C, 63.75; H, 4.91; N, 11.29.
1-BOC-2-(4-cya n op h en yl)p yr r olid in -3-on e (4g): white
solid; Rf 0.48 (hexanes-ethyl acetate, 1:1); mp 133-134 °C;
IR (KBr) 2232, 1757, 1676, 1609, 1504, 1475, 860, 826, 791,
1
754 cm-1; H NMR (CDCl3) δ 1.26 (brs, 6 H), 1.46 (brs, 3 H),
2.63-2.71 (m, 1 H), 2.73-2.81 (m, 1 H), 3.86-3.93 (m, 1 H),
4.03-4.11 (m, 1 H), 4.91 (brs, 1 H), 7.39 (d, 2 H, J ) 8.3 Hz),
7.66 (d, 2 H, J ) 8.3 Hz); 13C NMR (CDCl3) δ 27.8 (q), 35.3 (t),
41.6 (t), 65.4 (d), 80.7 (s), 111.3 (s), 118.3 (s), 126.3 (d), 132.2
(d), 142.5 (s), 153.9 (s), 208.0 (s). Anal. Calcd for C16H18N2O3:
C, 67.12; H, 6.34; N, 9.78. Found: C, 67.15; H, 6.37; N, 9.70.
1-MOC-2-(1-n a p h th yl)p yr r olid in -3-on e (3h ): colorless
paste; Rf 0.5 (hexanes-ethyl acetate, 1:1); IR (neat) 1759, 1699,
1510, 797, 775, 731 cm-1; 1H NMR (CDCl3) δ 2.66-2.89 (m, 2
H), 3.59 (brs, 3 H), 4.01-4.28 (m, 2 H), 5.85 (s, 1 H), 7.29 (d,
1 H, J ) 7.3 Hz), 7.42 (t, 1 H, J ) 7.6 Hz), 7.48-7.64 (m, 2 H),
7.76-7.90 (m, 2 H), 8.27 (d, 1 H, J ) 8.4 Hz); 13C NMR (CDCl3)
δ 35.0 (t), 42.3 (t), 52.8 (q), 62.5 (d), 121.8 (d), 124.2 (d), 125.0
(d), 125.9 (d), 126.3 (d), 128.4 (d), 128.5 (d), 130.7 (s), 132.8
(s), 134.0 (s), 207.4 (s). Anal. Calcd for C16H15NO3: C, 71.36;
H, 5.61; N, 5.20. Found: C, 71.40; H, 5.68; N, 5.03.
126.7 (s), 156.0 (s), 158.9 (s), 204.7 (s). Anal. Calcd for C14H17
-
NO4: C, 63.87; H, 6.51; N, 5.32. Found: C, 63.79; H, 6.57; N,
5.14.
1-BOC-2-(4-m eth oxyp h en yl)p ip er id in -3-on e (8b): color-
less paste; Rf 0.44 (hexanes-ethyl acetate, 2:1); IR (neat) 1722,
1693, 1609, 1583, 1510, 972, 899, 870, 827, 770 cm-1; 1H NMR
(CDCl3) δ 1.44 (s, 9 H), 1.87-2.01 (m, 2 H), 2.41-2.51 (m, 2
H), 3.26-3.34 (m, 1 H), 3.80 (s, 3 H), 3.97-4.16 (m, 1 H), 5.59
(brs, 1 H), 6.86-6.91 (m, 2 H), 7.09-7.14 (m, 2 H); 13C NMR
(CDCl3) δ 22.6 (t), 28.0 (q), 36.9 (t), 39.6 (t), 54.9 (q), 65.5 (d),
80.3 (s), 114.0 (d), 126.4 (d), 127.2 (s), 154.7 (s), 158.8 (s), 205.3
(s). Anal. Calcd for C17H23NO4: C, 66.86; H, 7.59; N, 4.59.
Found: C, 66.91; H, 7.62; N, 4.38.
1-MOC-2-(3-m eth oxyp h en yl)p ip er id in -3-on e (7c): color-
less paste; Rf 0.4 (hexanes-ethyl acetate, 2:1); IR (neat) 1705,
1599, 1583, 1489, 961, 768, 694 cm-1; 1H NMR (CDCl3) δ 1.86-
2.03 (m, 2 H), 2.47 (t, 2 H, J ) 6.2 Hz), 3.31-3.47 (m, 1 H),
3.74 (brs, 3 H), 3.79 (s, 3 H), 3.95-4.25 (m, 1 H), 5.57-5.85
(m, 1 H), 6.75-6.86 (m, 3 H), 7.28 (t, 1 H, J ) 8.1 Hz); 13C
NMR (CDCl3) δ 22.7 (t), 37.1 (t), 40.5 (t), 53.0 (q), 55.1 (q),
65.7 (d), 111.2 (d), 112.7 (d), 117.2 (d), 129.8 (d), 136.4 (s), 156.0
(s), 159.9 (s), 204.3 (s). Anal. Calcd for C14H17NO4: C, 63.87;
H, 6.51; N, 5.32. Found: C, 63.85; H, 6.52; N, 5.24.
1-MOC-2-(2-n a p h t h yl)p yr r olid in -3-on e (3i): colorless
paste; Rf 0.25 (hexanes-ethyl acetate, 2:1); IR (neat) 1761,
1705, 1601, 1508, 816, 773, 733 cm-1; 1H NMR (CDCl3) δ 2.62-
2.84 (m, 2 H), 3.66 (brs, 3 H), 3.94-4.07 (m, 1 H), 4.11-4.28
(m, 1 H), 5.12 (s, 1 H), 7.41 (dd, 1 H, J ) 1.6, 8.6 Hz), 7.44-
7.52 (m, 2 H), 7.69 (s, 1 H), 7.78-7.87 (m, 3 H); 13C NMR
(CDCl3) δ 35.2 (t), 42.3 (t), 52.8 (q), 65.6 (d), 123.5 (d), 124.3
(d), 126.0 (d), 126.2 (d), 127.5 (d), 127.8 (d), 128.6 (d), 132.8
(s), 133.1 (s), 133.7 (s), 155.6 (s), 208.6 (s). Anal. Calcd for
1-BOC-2-(3-m eth oxyp h en yl)p ip er id in -3-on e (8c): color-
less paste; Rf 0.52 (hexanes-ethyl acetate, 2:1); IR (neat) 1699,
C
16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.48; H,
1
1601, 1585, 976, 856, 772, 694 cm-1; H NMR (CDCl3) δ 1.43
5.66; N, 5.07.
1-BOC-2-(2-n aph th yl)pyr r olidin -3-on e (4i): colorless paste;
Rf 0.64 (hexanes-ethyl acetate, 1:1); IR (neat) 1757, 1686,
1599, 1508, 1475, 866, 822, 754, 727 cm-1; 1H NMR (CDCl3) δ
1.22 (brs, 9 H), 2.67-2.80 (m, 2 H), 3.95-4.02 (m, 1 H), 4.07-
4.15 (m, 1 H), 5.04 (brs, 1 H), 7.37-7.42 (m, 1 H), 7.44-7.51
(m, 2 H), 7.68 (brs, 1 H), 7.79-7.86 (m, 3 H); 13C NMR (CDCl3)
δ 27.9 (q), 35.2 (t), 41.7 (t), 65.8 (t), 80.3 (s), 123.6 (d), 124.5
(d), 125.8 (d), 126.1 (d), 127.5 (d), 127.7 (d), 128.4 (d), 132.7
(s), 133.1 (s), 134.7 (s), 154.3 (s), 209.3 (s). Anal. Calcd for
(brs, 9 H), 1.86-2.02 (m, 2 H), 2.41-2.51 (m, 2 H), 3.26-3.40
(m, 1 H), 3.79 (S, 3 H), 3.94-4.18 (m, 1 H), 5.59 (brs, 1 H),
6.75-6.85 (m, 3 H), 7.27 (t, 1 H, J ) 7.8 Hz); 13C NMR (CDCl3)
δ 22.6 (t), 28.1 (q), 37.1 (t), 39.6 (t), 55.0 (q), 66.1 (d), 80.5 (s),
111.0 (d), 112.8 (d), 117.3 (d), 129.8 (d), 137.0 (d), 154.8 (s),
160.0 (s), 205.1 (s). Anal. Calcd for C17H23NO4: C, 66.86; H,
7.59; N, 4.59. Found: C, 67.05; H, 7.63; N, 4.40.
1-MOC-2-(2-m eth oxyp h en yl)p ip er id in -3-on e (7d ): color-
less paste; Rf 0.41 (hexanes-ethyl acetate, 1:1); IR (neat) 1701,
1601, 1587, 1493, 961, 756, 731 cm-1; 1H NMR (CDCl3) δ 2.00-
2.13 (m, 2 H), 2.51-2.71 (m, 2 H), 3.35-3.48 (m, 1 H), 3.69 (s,
3 H), 3.78 (m, 3 H), 4.07-4.22 (m, 1 H), 5.60 (s, 1 H), 6.85-
6.91 (m, 1 H), 6.91-6.99 (m, 1 H), 7.23-7.32 (m, 2 H); 13C NMR
(CDCl3) δ 23.0 (t), 36.8 (t), 40.3 (t), 52.6 (q), 55.1 (q), 64.1 (d),
111.2 (d), 120.6 (d), 126.3 (s), 129.1 (d), 130.3 (d),155.8 (s), 156.2
(s), 205.4 (s). Anal. Calcd for C14H17NO4: C, 63.87; H, 6.51; N,
5.32. Found: C, 63.65; H, 6.62; N, 5.06.
C
19H21NO3: C, 73.29; H, 6.80; N, 4.50. Found: C, 73.40; H,
6.92; N, 4.29.
1-MOC-2-(2-fu r yl)pyr r olidin -3-on e (3j): pale yellow paste;
Rf 0.32 (hexanes-ethyl acetate, 2:1); IR (neat) 1767, 1705,
1
1502, 978, 930, 773, 745 cm-1; H NMR (CDCl3) δ 2.63-2.86
(m, 2 H), 3.71 (s, 3 H), 3.80-3.92 (m, 1 H), 4.00-4.17 (m, 1
H), 5.00 (brs, 1 H), 6.32-6.35 (m, 2 H), 7.34 (t, 1 H, J ) 1.4
Hz); 13C NMR (CDCl3) δ 35.8 (t), 42.0 (t), 52.7 (q), 59.5 (d),
108.6 (d), 110.3 (d), 142.6 (d), 149.0 (s), 155.0 (s), 207.0 (s).
Anal. Calcd for C10H11NO4: C, 57.41; H, 5.30; N, 6.70. Found:
C, 57.44; H, 5.39; N, 6.51.
1-BOC-2-(2-m eth oxyp h en yl)p ip er id in -3-on e (8d ): white
solid; Rf 0.33 (hexanes-ethyl acetate, 2:1); mp 73-75 °C; IR
(KBr) 1719, 1680, 1599, 1495, 961, 907, 858, 845, 845, 773,
1
1-MOC-2-p h en ylp ip er id in -3-on e (7a ): colorless paste; Rf
0.42 (hexanes-ethyl acetate, 2:1); IR (neat) 1701, 1601, 1495,
752 cm-1; H NMR (CDCl3) δ 1.40 (s, 9 H), 2.00-2.13 (m, 2
H), 2.52-2.65 (m, 2 H), 3.33-3.40 (m, 1 H), 3.78 (s, 3 H), 4.07-
4.17 (m, 1 H), 5.61 (brs, 1 H), 6.88 (d, 1 H, J ) 8.5 Hz), 6.92-
6.96 (m, 1 H), 7.24-7.29 (m, 2 H); 13C NMR (CDCl3) δ 22.8 (t),
28.0 (q), 36.7 (t), 39.9 (t), 55.0 (d), 63.8 (d), 80.0 (s), 111.1 (d),
120.4 (d), 126.8 (s), 128.9 (d), 129.7 (d), 154.5 (s), 156.4 (s),
1
959, 770, 731, 700 cm-1; H NMR (CDCl3) δ 1.84-2.08 (m, 2
H), 2.38-2.56 (m, 2 H), 3.30-3.45 (m, 1 H), 3.74 (s, 3 H), 3.97-
4.28 (m, 1 H), 5.71 (brs, 1 H), 7.19-7.40 (m, 5 H); 13C NMR
(CDCl3) δ 22.6 (t), 37.0 (t), 40.3 (t), 52.8 (q), 65.7 (d), 125.0 (d),
J . Org. Chem, Vol. 69, No. 22, 2004 7715

Kise et al.
205.9 (s). Anal. Calcd for C17H23NO4: C, 66.86; H, 7.59; N, 4.59.
Found: C, 67.13; H, 7.60; N, 4.47.
(d), 124.7 (d), 125.9 (d), 126.5 (d), 128.5 (d), 128.9 (d), 131.3
(s), 133.4 (s), 134.0 (s), 156.1 (s), 205.1 (s). Anal. Calcd for
C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 72.12; H,
6.04; N, 4.77.
1-MOC-2-(3,4-d im et h oxyp h en yl)p ip er id in -3-on e (7e):
colorless paste; Rf 0.17 (hexanes-ethyl acetate, 2:1); IR (neat)
1697, 1591, 1514, 962, 941, 858, 812, 768 cm-1
;
1H NMR
1-MOC-2-(2-n aph th yl)piper idin -3-on e (7i): colorless paste;
Rf 0.3 (hexanes-ethyl acetate ) 5:1); IR (neat) 1701, 1632,
1599, 1508, 953, 820, 754, 733 cm-1; 1H NMR (CDCl3) δ 1.88-
2.11 (m, 2 H), 2.41-2.60 (m, 2 H), 3.41-3.52 (m, 1 H), 3.77
(brs, 3 H), 4.00-4.33 (m, 1 H), 5.86 (brs, 1 H), 7.37 (dd, 1 H,
J ) 1.6, 8.4 Hz), 7.44-7.53 (m, 2 H), 7.63 (s, 1 H), 7.77-7.87
(m, 3 H); 13C NMR (CDCl3) δ 22.7 (t), 37.2 (t), 40.6 (t), 53.0
(q), 66.0 (d), 123.0 (d), 124.0 (d), 126.0 (d), 126.2 (d), 127.3 (d),
127.7 (d), 128.7 (d), 132.3 (s), 132.5 (s), 133.0 (s), 156.1 (s),
204.5 (s). Anal. Calcd for C17H17NO3: C, 72.07; H, 6.05; N, 4.94.
Found: C, 72.18; H, 6.09; N, 4.73.
(CDCl3) δ 1.90-2.04 (m, 2 H), 2.48 (t, 2 H, J ) 6.8 Hz), 3.34-
3.46 (m, 1 H), 3.75 (s, 3 H), 3.85 (s, 3 H), 3.87 (s, 3 H), 4.00-
4.24 (m, 1 H), 5.66 (brs, 1 H), 6.69-6.77 (m, 2 H), 6.84 (d, 1 H,
J ) 8.4 Hz); 13C NMR (CDCl3) δ 22.6 (t), 37.0 (t), 40.4 (t), 52.9
(q), 55.7 (q), 65.3 (d), 108.6 (d), 111.2 (d), 117.0 (d), 127.1 (s),
148.3 (s), 149.1 (s), 156.0 (s), 204.6 (s). Anal. Calcd for C15H19
-
NO5: C, 61.42; H, 6.53; N, 4.78. Found: C, 61.30; H, 6.51; N,
4.62.
1-BOC-2-(3,4-d im et h oxyp h en yl)p ip er id in -3-on e (8e):
colorless paste; Rf 0.30 (hexanes-ethyl acetate, 2:1); IR (neat)
1720, 1693, 1591, 1516, 976, 916, 897, 858, 812, 766, 733 cm-1
;
1-BOC-2-(2-n aph th yl)piper idin -3-on e (8i): colorless paste;
Rf 0.56 (hexanes-ethyl acetate, 2:1); IR (neat) 1682, 1634,
1H NMR (CDCl3) δ 1.45 (s, 9 H), 1.87-2.02 (m, 2 H), 2.47 (t,
2 H, J ) 6.5 Hz), 3.27-3.38 (m, 2 H), 3.85 (s, 3 H), 3.87 (s, 3
H), 4.01-4.15 (m, 1 H), 5.59 (brs, 1 H), 6.69-6.76 (m, 2 H),
6.82-6.86 (m, 1 H); 13C NMR (CDCl3) δ 22.3 (t), 27.8 (q), 36.7
(t), 39.6 (t), 55.3 (q), 55.4 (q), 65.4 (d), 80.0 (s), 108.3 (d), 110.9
(d), 116.9 (d), 127.5 (s), 148.1 (s), 148.9 (s), 154.5 (s), 205.0 (s).
Anal. Calcd for C18H25NO5: C, 64.46; H, 7.51; N, 4.18. Found:
C, 64.57; H, 7.54; N, 4.05.
1
1601, 1508, 976, 955, 910, 857, 822, 754, 737 cm-1; H NMR
(CDCl3) δ 1.43 (brs, 9 H), 1.89-2.04 (m, 2 H), 2.43-2.56 (m, 2
H), 3.36-3.45 (m, 1 H), 4.00-4.25 (m, 1 H), 5.79 (brs, 1 H),
7.34-7.39 (m, 1 H), 7.46-7.52 (m, 2 H), 7.62 (s, 1 H), 7.78-
7.87 (m, 3 H); 13C NMR (CDCl3) δ 22.8 (t), 28.1 (q), 37.3 (t),
40.0 (t), 66.4 (d), 80.7 (s), 123.2 (d), 124.1 (d), 126.1 (d), 126.3
(d), 127.5 (d), 127.8 (d), 128.7 (d), 132.6 (s), 133.0 (s), 133.2
(s), 154.9 (s), 205.3 (s). Anal. Calcd for C20H23NO3: C, 73.82;
H, 7.12; N, 4.30. Found: C, 73.96; H, 7.24; N, 4.05.
1-MOC-2-(4-flu or op h en yl)p ip er id in -3-on e (7f): colorless
paste; Rf 0.41 (hexanes-ethyl acetate, 2:1); IR (neat) 1701,
1603, 1508, 961, 833, 770 cm-1; 1H NMR (CDCl3) δ 1.84-2.10
(m, 2 H), 2.38-2.58 (m, 2 H), 3.29-3.43 (m, 1 H), 3.75 (s, 3
H), 3.98-4.25 (m, 1 H), 5.68 (brs, 1 H), 7.00-7.09 (m, 2 H),
7.16-7.25 (m, 2 H); 13C NMR (CDCl3) δ 22.5 (t), 37.1 (t), 40.5
(t), 53.1 (q), 65.2 (d), 115.7 (d, J CCF ) 21.7 Hz), 127.0 (d, J CCCF
1-MOC-2-(2-fu r yl)p ip er id in -3-on e (7j): pale yellow paste;
Rf 0.35 (hexanes-ethyl acetate ) 5:1); IR (neat) 1705, 1501,
1
961, 937, 922, 885, 766, 746 cm-1; H NMR (CDCl3) δ 1.93-
2.18 (m, 2 H), 2.51-2.74 (m, 2 H), 3.32-3.50 (m, 1 H), 3.74 (s,
3 H), 3.96-4.24 (m, 1 H), 5.52-5.82 (m, 1 H), 6.27 (s, 1 H),
6.35 (dd, 1 H, J ) 1.9, 3.2 Hz), 7.37 (dd, 1 H, J ) 0.8, 1.9 Hz);
13C NMR (CDCl3) δ 22.8 (t), 37.6 (t), 40.3 (t), 53.1 (q), 60.9 (d),
108.4 (d), 110.5 (d), 142.7 (d), 149.2 (s), 155.7 (s), 202.5 (s).
Anal. Calcd for C11H13NO4: C, 59.19; H, 5.87; N, 6.27. Found:
C, 59.28; H, 5.96; N, 6.02.
) 8.3 Hz), 130.7 (s, J CCCCF ) 2.8 Hz), 156.1 (s), 162.1 (s, J CF
)
244.9 Hz), 204.4 (s). Anal. Calcd for C13H14FNO3: C, 62.14;
H, 5.62; N, 5.57. Found: C, 62.07; H, 5.58; N, 5.30.
1-BOC-2-(4-flu or op h en yl)p ip er id in -3-on e (8f): colorless
paste; Rf 0.71 (hexanes-ethyl acetate, 2:1); IR (neat) 1724,
1697, 1603, 1508, 972, 901, 833, 769 cm-1; 1H NMR (CDCl3) δ
1.43 (brs, 9 H), 1.84-2.08 (m, 2 H), 2.38-2.55 (m, 2 H), 3.24-
3.40 (m, 1 H), 3.95-4.20 (m, 1 H), 5.48-5.78 (m, 1 H), 7.02-
7.08 (m, 1 H), 7.16-7.22 (m, 1 H); 13C NMR (CDCl3) δ 22.3 (t),
Red u ction of Keton es 3, 4, 7, a n d 8 w ith Na BH4. To a
solution of a ketone (1.0 mmol) in methanol (5 mL) was added
NaBH4 (38 mg, 1.0 mmol) at 5 °C. After being stirred for 30
min at this temperature, the solvent was removed in vacuo.
The residue was column chromatographed on silica gel (hex-
anes-ethyl acetate) to give the corresponding cis-alcohol.
1-MOC-cis-2-p h en ylp yr r olid in -3-ol (13a ): white solid; Rf
0.10 (hexanes-ethyl acetate, 2:1); mp 134-136 °C; IR (KBr)
3368, 1670, 1555, 1495, 1464, 779, 756, 700, 660 cm-1; 1H NMR
(CDCl3) δ 1.16 (brs, 1 H), 1.83-2.00 (m, 1 H), 2.08-2.16 (m, 1
H), 3.51 (s, 1.5 H), 3.62-3.80 (m, 3.5 H), 4.39-4.48 (m, 1 H),
4.91 (brs, 0.5 H), 4.96 (brs, 0.5 H), 7.16-7.40 (m, 5 H); 13C
NMR (CDCl3) δ 30.8 (t), 31.8 (t), 44.6 (t), 52.3 (q), 52.3 (q),
64.2 (d), 65.1 (d), 72.1 (d), 72.7 (d), 126.9 (d), 127.5 (d), 128.3
(d), 136.9 (s), 137.4 (s), 155.5 (s), 155.9 (s). Anal. Calcd for
27.9 (q), 37.0 (t), 39.9 (t), 65.2 (t), 80.5 (s), 115.5 (d, J CCF
)
21.0 Hz), 126.9 (d, J CCCF ) 7.6 Hz), 131.3 (s), 154.6 (s), 161.9
(s, J CF ) 245.1 Hz), 205.0 (s). Anal. Calcd for C16H20FNO3: C,
65.51; H, 6.87; N, 4.78. Found: C, 65.40; H, 6.73; N, 4.63.
1-MOC-2-(4-cya n op h en yl)p ip er id in -3-on e (7g): colorless
paste; Rf 0.41 (hexanes-ethyl acetate, 1:1); IR (neat) 2230,
1705, 1607, 1502, 959, 772, 733 cm-1; 1H NMR (CDCl3) δ 1.83-
2.13 (m, 2 H), 2.36-2.61 (m, 2 H), 3.32-3.46 (m, 1 H), 3.76 (s,
3 H), 4.02-4.25 (m, 1 H), 5.74 (brs, 1 H), 7.36-7.42 (m, 2 H),
7.63-7.69 (m, 2 H); 13C NMR (CDCl3) δ 22.0 (t), 37.2 (t), 40.8
(t), 53.1 (q), 60.1 (q), 65.5 (d), 111.5 (s), 118.0 (s), 126.1 (d),
132.4 (d), 140.6 (s), 155.8 (s), 203.3 (s). Anal. Calcd for
C14H14N2O3: C, 65.11; H, 5.46; N, 10.85. Found: C, 65.22; H,
5.50; N, 10.68.
C
12H15NO3: C, 65.14; H, 6.83; N, 6.33. Found: C, 65.18; H,
6.80; N, 6.29.
1-MOC-cis-2-(4-m eth oxyp h en yl)p yr r olid in -3-ol (13b):
colorless paste; Rf 0.31 (hexanes-ethyl acetate, 1:2); IR (neat)
3437, 1684, 1600, 1589, 1491, 773, 756 cm-1; 1H NMR (CDCl3)
δ 1.17 (brs, 1 H), 1.81-2.00 (m, 1 H), 2.07-2.15 (m, 1 H), 3.53
(s, 1.5 H), 3.62-3.76 (m, 3.5 H), 3.80 (s, 3 H), 4.36-4.43 (m, 1
H), 4.86 (brs, 0.5 H), 4.91 (brs, 0.5 H), 6.89-6.93 (m, 2 H),
7.06-7.20 (m, 2 H); 13C NMR (CDCl3) δ 30.7 (t), 31.7 (t), 44.5
(t), 52.3 (q), 55.1 (q), 63.6 (d), 64.6 (d), 72.1 (d), 72.6 (d), 113.8
(d), 113.9 (d), 128.0 (d), 128.7 (s), 129.2 (s), 155.4 (s), 155.9 (s),
159.0 (s). Anal. Calcd for C13H17NO4: C, 62.14; H, 6.82; N, 5.57.
Found: C, 62.21; H, 6.85; N, 5.50.
1-BOC-2-(4-cya n op h en yl)p ip er id in -3-on e (8g): colorless
paste; Rf 0.43 (hexanes-ethyl acetate, 2:1); IR (neat) 3373,
2230, 1682, 1607, 1502, 972, 905, 878, 853, 767, 733 cm-1; 1H
NMR (CDCl3) δ 1.42 (brs, 9 H), 1.83-1.95 (m, 1 H), 1.97-2.08
(m, 1 H), 2.37-2.45 (m, 1 H), 2.49-2.57 (m, 1 H), 3.29-3.40
(m, 1 H), 3.96-4.19 (m, 1 H), 5.66 (brs, 1 H), 7.36-7.39 (m, 2
H), 7.64-7.68 (m, 2 H); 13C NMR (CDCl3) δ 22.0 (t), 28.1 (q),
37.3 (t), 40.4 (t), 65.7 (d), 81.1 (s), 111.5 (s), 118.3 (s), 126.2
(d), 132.5 (d), 141.4 (s), 154.6 (s), 204.2 (s). Anal. Calcd for
C
17H20N2O3: C, 67.98; H, 6.71; N, 9.33. Found: C, 68.11; H,
6.82; N, 9.12.
1-BOC-cis-2-(4-m eth oxyp h en yl)p yr r olid in -3-ol (14b):
white solid; Rf 0.29 (hexanes-ethyl acetate, 1:1); mp 85-87
°C; IR (KBr) 3423, 1668, 1611, 1587, 1514, 1479, 862, 808, 766
1-MOC-2-(1-n a p h th yl)p ip er id in -3-on e (7h ): white solid;
Rf 0.21 (hexanes-ethyl acetate ) 5:1); IR (KBr) 1726, 1686,
1595, 1508, 978, 945, 800, 781 cm-1; 1H NMR (CDCl3) δ 2.07-
2.26 (m, 2 H), 2.47-2.70 (m, 2 H), 3.68 (s, 3 H), 3.57-3.78 (m,
1 H), 4.04-4.23 (m, 1 H), 6.39 (brs, 1 H), 7.38-7.65 (m, 4 H),
7.77-7.89 (m, 2 H), 8.36 (d, 1 H, J ) 8.6 Hz); 13C NMR (CDCl3)
δ 22.4 (t), 37.3 (t), 41.5 (t), 53.2 (q), 64.5 (d), 123.7 (d), 124.5
1
cm-1; H NMR (CDCl3) δ 1.16 (brs, 6.3 H), 1.44 (brs, 2.7 H),
1.86-1.97 (m, 1 H), 2.05-2.13 (m, 1 H), 3.56-3.76 (m, 2 H),
3.81 (s, 3 H), 4.35-4.40 (m, 1 H), 4.78 (brs, 0.7 H), 4.89 (brs,
0.3 H), 6.88-6.92 (m, 2 H), 7.10-7.15 (m, 2 H); 13C NMR
(CDCl3) δ 27.9 (q), 28.2 (q), 31.1 (t), 31.4 (t), 44.1 (t), 44.5 (t),
7716 J . Org. Chem., Vol. 69, No. 22, 2004

Intramolecular Coupling of Aromatic â- and γ-Imino Esters
55.0 (q), 63.8 (d), 64.7 (d), 72.0 (d), 72.7 (d), 79.1 (s) 113.4 (d),
113.7 (d), 127.9 (d), 128.1 (d), 130.2 (s), 154.5 (s), 158.7 (s).
Anal. Calcd for C16H23NO4: C, 65.51; H, 7.90; N, 4.77. Found:
C, 65.45; H, 7.88; N, 4.63.
0.33 H), 6.71-6.79 (m, 2 H), 6.87 (d, 1 H, J ) 8.3 Hz); 13C
NMR (CDCl3) δ 27.8 (q), 28.2 (q), 31.2 (t), 31.5 (t), 44.2 (t),
44.6 (t), 55.6 (q), 64.2 (d), 65.0 (d), 72.0 (d), 72.8 (d), 79.1 (s),
110.1 (d), 110.67 (d), 111.1 (d), 118.7 (d), 119.1 (d), 129.5 (s),
130.7 (s), 148.0 (s), 148.6 (s), 154.5 (s). Anal. Calcd for C17H25
NO5: C, 63.14; H, 7.79; N, 4.33. Found: C, 63.25; H, 7.86; N,
4.14.
-
1-MOC-cis-2-(3-m eth oxyp h en yl)p yr r olid in -3-ol (13c):
white solid; Rf 0.16 (hexanes-ethyl acetate, 1:1); mp 125-127
°C; IR (KBr) 3396, 1674, 1612, 1585, 1487, 972, 862, 789, 775,
1
758, 704 cm-1; H NMR (CDCl3) δ 1.08-1.21 (m, 1 H), 1.83-
1-MOC-cis-2-(4-flu or oph en yl)pyr r olidin -3-ol (13f): white
solid; Rf 0.22 (hexanes-ethyl acetate, 1:1); mp 151-152 °C;
2.02 (m, 1 H), 2.07-2.16 (m, 1 H), 3.54 (brs, 1.5 H), 3.62-3.78
(m, 3.5 H), 3.81 (s, 3 H), 4.40-4.47 (m, 1 H), 4.84-4.97 (m, 1
H), 6.70-6.87 (m, 3 H), 7.30 (t, 1 H, J ) 8.3 Hz); 13C NMR
(CDCl3) δ 30.9 (t), 31.9 (t), 44.7 (t), 52.4 (q), 55.1 (q), 64.3 (d),
65.1 (d), 72.2 (d), 72.8 (d), 112.7 (d), 113.0 (d), 119.2 (d), 129.5
(d), 129.6 (d), 138.5 (s), 139.1 (s), 155.5 (s), 155.9 (s), 159.7 (s).
Anal. Calcd for C13H17NO4: C, 62.14; H, 6.82; N, 5.57. Found:
C, 62.30; H, 6.90; N, 5.38.
1
IR (KBr) 3368, 1670, 1605, 1508, 837, 820, 772, 658 cm-1; H
NMR (CDCl3) δ 1.30 (brs, 1 H), 1.80-1.99 (m, 1 H), 2.07-2.16
(m, 1 H), 3.52 (s, 1.5 H), 3.60-3.78 (m, 3.5 H), 4.37-4.66 (m,
1 H), 4.83-4.97 (m, 1 H), 7.03-7.08 (m, 2 H), 7.11-7.23 (m, 2
H); 13C NMR (CDCl3) δ 30.6 (t), 31.5 (t), 44.5 (t), 52.32 (q),
52.34 (q), 63.6 (d), 64.4 (d), 71.9 (d), 72.5 (d), 115.0 (d, J CCF
)
20.0 Hz), 128.5 (d, J CCCF ) 6.7 Hz), 132.9 (s), 133.4 (s), 155.5
(s), 155.8 (s), 162.0 (s, J CF ) 244.2 Hz). Anal. Calcd for C12H14
-
1-BOC-cis-2-(3-m et h oxyp h en yl)p yr r olid in -3-ol (14c):
colorless paste; Rf 0.16 (hexanes-ethyl acetate, 2:1); IR (neat)
FNO3: C, 62.24; H, 5.90; N, 5.85. Found: C, 60.29; H, 5.91;
N, 5.77.
3425, 1674, 1603, 1587, 783, 758, 740, 698 cm-1 1H NMR
;
(CDCl3) δ 1.16 (brs, 6 H), 1.44 (brs, 3 H), 1.86-1.97 (m, 1 H),
2.03-2.12 (m, 1 H), 3.55-3.76 (m, 2 H), 3.79 (s, 3 H), 4.36-
4.42 (m, 1 H), 4.78 (brs, 0.67 H), 4.89 (brs, 0.33 H), 6.74 (brs,
1 H), 6.76-6.84 (m, 2 H), 7.23-7.29 (m, 1 H); 13C NMR (CDCl3)
δ 27.9 (q), 28.3 (q), 31.4 (t), 31.7 (t), 44.3 (t), 44.7 (t), 55.1 (q),
64.4 (d), 65.5 (d), 72.2 (d), 73.0 (d), 79.3 (s), 112.7 (d), 112.7
(d), 119.4 (d), 119.1 (d), 129.2 (d), 129.4 (d), 140.0 (s), 154.5
(s), 159.5 (s). Anal. Calcd for C16H23NO4: C, 65.51; H, 7.90; N,
4.77. Found: C, 65.35; H, 7.81; N, 4.56.
1-BOC-cis-2-(4-flu or op h en yl)p yr r olid in -3-ol (14f): white
solid; Rf 0.42 (hexanes-ethyl acetate, 1:1); mp 155-157 °C;
1
IR (KBr) 3354, 1655, 1605, 1508, 862, 822, 773, 754 cm-1; H
NMR (CDCl3) δ 1.15 (s, 6 H), 1.44 (s, 3 H), 1.59 (brs, 1 H),
1.84-2.00 (m, 1 H), 2.06-2.15 (m, 1 H), 3.58-3.78 (m, 2 H),
4.38-4.45 (m, 1 H), 4.75-4.98 (m, 1 H), 7.03-7.09 (m, 2 H),
7.16-7.22 (m, 2 H); 13C NMR (CDCl3) δ 27.9 (q), 28.2 (q), 31.2
(t), 44.2 (t), 44.6 (t), 63.7 (d), 64.7 (d), 72.0 (d), 72.8 (d), 79.4
(s), 114.8 (d, J CCF ) 21.0 Hz), 128.6 (d), 133.2 (s), 134.3 (s),
154.4 (s), 162.0 (s, J CF ) 244.2 Hz). Anal. Calcd for C15H20
-
1-MOC-cis-2-(2-m eth oxyp h en yl)p yr r olid in -3-ol (13d ):
colorless paste; Rf 0.22 (hexanes-ethyl acetate, 1:1); IR (neat)
FNO3: C, 64.04; H, 7.17; N, 4.98. Found: C, 64.05; H, 7.22;
N, 4.92.
3423, 1678, 1610, 1585, 1512, 829, 810, 773 cm-1 1H NMR
;
(CDCl3) δ 1.84-1.98 (m, 1 H), 1.99 (brs, 1 H), 2.04-2.13 (m, 1
H), 3.53 (s, 1.5 H), 3.63-3.77 (m, 3.5 H), 3.87 (s, 3 H), 4.56
(brs, 1 H), 5.31 (brs, 0.5 H), 5.38 (brs, 0.5 H), 6.91 (d, 1 H, J )
7.8 Hz), 6.97 (t, 1 H, J ) 7.8 Hz), 7.09 (d, 1 H, J ) 7.4 Hz),
7.22-7.30 (m, 1 H); 13C NMR (CDCl3) δ 30.5 (t), 31.3 (t), 44.4
(t), 44.5 (t), 52.2 (q), 55.3 (q), 59.8 (d), 60.3 (d), 71.4 (d), 72.1
(d), 110.1 (d), 110.3 (d), 120.7 (d), 125.2 (s), 125.9 (s), 126.9
(d), 128.3 (d), 155.3 (s), 155.8 (s), 156.2 (s), 156.4 (s). Anal.
Calcd for C13H17NO4: C, 62.14; H, 6.82; N, 5.57. Found: C,
62.28; H, 6.91; N, 5.38.
1-MOC-cis-2-(4-cyan oph en yl)pyr r olidin -3-ol (13g): white
solid; Rf 0.39 (hexanes-ethyl acetate, 1:1); mp 134-135 °C;
IR (KBr) 3468, 2237, 1703, 1605, 1499, 833, 777 cm-1; 1H NMR
(CDCl3) δ 1.43 (d, 1 H, J ) 5.5 Hz), 1.82-2.03 (m, 1 H), 2.11-
2.19 (m, 1 H), 3.51 (s, 1.5 H), 3.62-3.80 (m, 3.5 H), 4.46-4.56
(m, 1 H), 4.88-4.99 (m, 1 H), 7.28-7,39 (m, 2 H), 7.63-7.67
(m, 2 H); 13C NMR (CDCl3) δ 30.9 (t), 31.8 (t), 44.6 (t), 52.5
(q), 64.2 (d), 64.9 (d), 72.0 (d), 72.6 (d), 110.6 (s), 118.5 (s), 127.8
(d), 128.0 (d), 131.7 (d), 143.6 (s), 144.0 (s), 155.5 (s). Anal.
Calcd for C13H14N2O3: C, 63.40; H, 5.73; N, 11.38. Found: C,
63.44; H, 5.73; N, 11.30.
1-BOC-cis-2-(2-m eth oxyp h en yl)p yr r olid in -3-ol (14d ):
colorless paste; Rf 0.33 (hexanes-ethyl acetate, 1:1); IR (neat)
1-BOC-cis-2-(4-cya n op h en yl)p yr r olid in -3-ol (14g): col-
orless paste; Rf 0.20 (hexanes-ethyl acetate, 1:1); IR (neat)
3439, 1693, 1603, 1589, 1493, 1479, 903, 754, 733 cm-1 1H
;
NMR (CDCl3) δ 1.15 (brs, 5.8 H), 1.45 (brs, 3.2 H), 1.85-2.12
(m, 2 H), 3.56-3.74 (m, 2 H), 3.85 (s, 3 H), 4.50-4.58 (m, 1
H), 5.25 (brs, 0.65 H), 5.36 (brs, 0.35 H), 6.90 (d, 1 H, J ) 8.5
Hz), 6.97 (t, 1 H, J ) 7.0 Hz), 7.05-7.18 (m, 1 H), 7.22-7.31
(m, 1 H); 13C NMR (CDCl3) δ 27.7 (q), 28.1 (q), 31.1 (t), 31.2
(t), 44.0 (t), 44.4 (t), 55.3 (q), 59.5 (d), 60.0 (d), 71.3 (d), 71.9
(d), 78.7 (s), 79.0 (s), 110.0 (d), 120.2 (d), 120.5 (d), 125.5 (s),
126.6 (s), 126.7 (d), 127.5 (d), 127.9 (d), 128.0(d), 154.0 (s), 154.2
(s), 156.4 (s). Anal. Calcd for C16H23NO4: C, 65.51; H, 7.90; N,
4.77. Found: C, 65.63; H, 7.97; N, 4.53.
3489, 2237, 2224, 1672, 1607, 1502, 1477, 837, 737, 725 cm-1
;
1H NMR (CDCl3) δ 1.13 (brs, 6 H), 1.43 (brs, 3 H), 1.74 (brs, 1
H), 1.85-1.98 (m, 1 H), 2.08-2.17 (m, 1 H), 3.60-3.77 (m, 2
H), 4.44-4.52 (m, 1 H), 4.83 (brs, 0.67 H), 4.92 (brs, 0.33 H),
7.34 (d, 2 H, J ) 8.2 Hz), 7.63 (d, 2 H, J ) 8.2 Hz); 13C NMR
(CDCl3) δ 27.9 (q), 28.2 (q), 31.7 (t), 44.4 (t), 44.7 (t), 64.4 (d),
65.4 (d), 72.1 (d), 72.9 (d), 79.9 (s), 110.6 (s), 118.6 (s), 126.3
(d), 128.0 (d), 131.6 (d), 132.1 (d), 144.0 (s), 145.0 (s), 154.3
(s). Anal. Calcd for C16H20N2O3: C, 66.65; H, 6.69; N, 9.72.
Found: C, 66.71; H, 7.00; N, 9.68.
1-MOC-cis-2-(3,4-dim eth oxyph en yl)pyr r olidin -3-ol (13e):
white solid; Rf 0.13 (hexanes-ethyl acetate, 1:1); mp 144-145
°C; IR (KBr) 3452, 1674, 1609, 1593, 1512, 966, 791, 773, 756
cm-1; 1H NMR (CDCl3) δ 1.05-1.20 (m, 1 H), 1.81-2.03 (m, 1
H), 2.08-2.16 (m, 1 H), 3.55 (s, 1.5 H), 3.63-3.79 (m, 3.5 H),
3.89 (s, 6 H), 4.37-4.45 (m, 1 H), 4.81-4.96 (m, 1 H), 6.67-
6.84 (m, 2 H), 6.88 (d, 1 H, J ) 8.3 Hz); 13C NMR (CDCl3) δ
30.7 (t), 31.7 (t), 44.5 (t), 52.3 (q), 55.7 (q), 63.9 (d), 64.8 (d),
72.0 (d), 72.6 (d), 110.0 (d), 110.3 (d), 110.9 (d), 111.1 (d), 118.8
(d), 129.2 (s), 129.7 (s), 148.3 (s), 148.7 (s), 155.4 (s), 155.9 (s).
Anal. Calcd for C14H19NO5: C, 59.78; H, 6.81; N, 4.98. Found:
C, 59.85; H, 6.88; N, 4.74.
1-MOC-cis-2-(2-n a p h th yl)p yr r olid in -3-ol (13i): colorless
paste; Rf 0.48 (hexanes-ethyl acetate, 1:1); IR (neat) 3418,
1682, 1634, 1601, 1508, 820, 773, 729 cm-1; 1H NMR (CDCl3)
δ 1.18 (brs, 1 H), 1.87-2.06 (m, 1 H), 2.09-2.18 (m, 1 H), 3.48
(s, 1.5 H), 3.61-3.89 (m, 3.5 H), 4.45-4.54 (m, 1 H), 5.01-
5.16 (m, 1 H), 7.28-7.38 (m, 1 H), 7.42-7.54 (m, 2 H), 7.61-
7.71 (m, 1 H), 7.77-7.88 (m, 3 H); 13C NMR (CDCl3) δ 30.5 (t),
31.5 (t), 44.5 (t), 52.2 (q), 64.1 (d), 65.1 (d), 72.1 (d), 72.6 (d),
125.2 (d), 125.4 (d), 125.6 (d), 126.0 (d), 127.4 (d), 127.6 (d),
127.7 (d), 132.6 (s), 132.7 (s), 133.0 (s), 134.7 (s), 135.3 (s), 155.4
(s), 155.8 (s), 171.0 (s). Anal. Calcd for C16H17NO3: C, 70.83;
H, 6.32; N, 5.16. Found: C, 70.96; H, 6.34; N, 5.01.
1-BOC-cis-2-(3,4-dim eth oxyph en yl)pyr r olidin -3-ol (14e):
colorless paste; Rf 0.18 (hexanes-ethyl acetate, 1:1); IR (neat)
1-BOC-cis-2-(2-n a p h th yl)p yr r olid in -3-ol (14i): colorless
paste; Rf 0.39 (hexanes-ethyl acetate, 1:1); IR (neat) 3441,
1668, 1601, 1510, 1477, 864, 822, 772, 750, 735 cm-1; 1H NMR
(CDCl3) δ 1.08 (brs, 6 H), 1.45 (brs, 3 H), 1.94-2.02 (m, 1 H),
2.09-2.18 (m, 1 H), 3.63-3.87 (m, 2 H), 4.46-4.52 (m, 1 H),
5.00 (brs, 0.67 H), 5.10 (brs, 0.33 H), 7.32-7.36 (m, 1 H), 7.42-
3435, 1693, 1609, 1595, 1518, 800, 760, 733 cm-1 1H NMR
;
(CDCl3) δ 1.17 (brs, 6 H), 1.45 (brs, 3 H), 1.89-1.98 (m, 1 H),
2.04-2.13 (m, 1 H), 3.57-3.79 (m, 2 H), 3.87 (s, 3 H), 3.89
(brs, 3 H), 4.35-4.41 (m, 1 H), 4.78 (brs, 0.67 H), 4.88 (brs,
J . Org. Chem, Vol. 69, No. 22, 2004 7717

Kise et al.
7.52 (m, 2 H), 7.66 (brs, 1 H), 7.79-7.87 (m, 3 H); 13C NMR
(CDCl3) δ 27.9 (q), 28.3 (q), 31.3 (t), 31.7 (t), 44.3 (t), 44.8 (t),
64.7 (d), 65.4 (d), 72.3 (d), 73.0 (d), 79.3 (s), 125.1 (d), 125.4
(d), 125.6 (d), 125.7 (d), 126.0(d), 127.5 (d), 127.6 (d), 132.7
(s),133.0 (s), 135.1 (s), 136.0 (s), 154.5 (s). Anal. Calcd for
1-BOC-cis-2-(2-m eth oxyph en yl)piper idin -3-ol (16d): col-
orless paste; Rf 0.26 (hexanes-ethyl acetate, 2:1); IR (neat)
3450, 1682, 1601, 1589, 1461, 962, 878, 754, 731 cm-1; 1H NMR
(CDCl3) δ 1.25 (s, 9 H), 1.64-1.89 (m, 4 H), 3.35-3.42 (m, 1
H), 3.86 (s, 3 H), 4.08-4.14 (m, 1 H), 4.15-4.20 (m, 1 H), 5.60
(d, 1 H, J ) 6.0 Hz), 6.90 (d, 1 H, J ) 8.5 Hz), 6.95 (t, 1 H, J
) 8.0 Hz), 7.22-7.28 (m, 2 H); 13C NMR (CDCl3) δ 21.1 (t),
25.5 (t), 27.9 (q), 40.1 (t), 54.4 (d), 55.3 (q), 68.2 (d), 79.1 (s),
110.2 (d), 120.6 (d), 127.4 (d), 127.9 (d), 128.3 (s), 155.2 (s),
156.6 (s). Anal. Calcd for C17H25NO4: C, 66.43; H, 8.20; N, 4.56.
Found: C, 66.48; H, 8.30; N, 4.35.
C
19H23NO3: C, 72.82; H, 7.40; N, 4.47. Found: C, 72.88; H,
7.43; N, 4.39.
1-MOC-cis-2-p h en ylp ip er id in -3-ol (15a ): White solid; Rf
0.46 (hexanes-ethyl acetate, 2:1); mp 72-75 °C; IR (KBr)
3470, 1678, 1603, 1582, 1499, 957, 858, 818, 788, 766, 735,
1
706 cm-1;. H NMR (CDCl3) δ 1.63-1.74 (m, 2 H), 1.75-1.89
(m, 3 H), 3.04 (dt, 1 H, J ) 4.2, 13.1 Hz), 3.69 (s, 3 H), 4.01-
4.13 (m, 2 H), 5.43 (d, 1 H, J ) 5.5 Hz), 7.25-7.30 (m, 1 H),
7.32-7.37 (m, 2 H), 7.46-7.51 (m, 2 H); 13C NMR (CDCl3) δ
23.6 (t), 27.4 (t), 39.3 (t), 52.7 (q), 58.4 (d), 70.0 (d), 126.8 (d),
1-MOC-cis-2-(3,4-dim eth oxyph en yl)piper idin -3-ol (15e):
colorless paste; Rf 0.16 (hexanes-ethyl acetate, 2:1); IR (neat)
3435, 1674, 1607, 1589, 1522, 974, 926, 885, 858, 812, 768,
733, 704 cm-1 1H NMR (CDCl3) δ 1.60-1.90 (m, 4 H), 1.99
;
128.1 (d), 128.4 (d), 137.5 (s), 156.5 (s). Anal. Calcd for C13H17
-
(brs, 1 H), 3.00 (dt, 1 H, J ) 1.3, 13.3 Hz), 3.70 (s, 3 H), 3.86
(s, 3 H), 3.87 (s, 3 H), 3.98-4.09 (m, 1 H), 5.39 (d, 1 H, J ) 5.5
Hz), 6.83 (d, 1 H, J ) 8.7 Hz), 7.03 (dd, 1 H, J ) 1.9, 8.7 Hz),
7.06 (d, 1 H, J ) 1.9 Hz); 13C NMR (CDCl3) δ 23.5 (t), 27.6 (t),
39.4 (t), 52.8 (q), 55.7 (q), 55.8 (q), 58.3 (d), 70.1 (d), 110.8 (d),
112.0 (d), 120.5 (d), 129.9 (s), 148.0 (s), 148.6 (s), 156.5 (s).
Anal. Calcd for C15H21NO5: C, 61.00; H, 7.17; N, 4.74. Found:
C, 60.88; H, 7.20; N, 4.50.
NO3: C, 66.36; H, 7.28; N, 5.95. Found: C, 66.39; H, 7.30; N,
5.85.
1-MOC-cis-2-(4-m eth oxyph en yl)piper idin -3-ol (15b): col-
orless paste; Rf 0.13 (hexanes-ethyl acetate, 2:1); IR (neat)
3431, 1678, 1611, 1582, 1512, 962, 862, 833, 770, 735 cm-1
;
1H NMR (CDCl3) δ 1.61-1.72 (m, 2 H), 1.74-1.90 (m, 3 H),
3.01 (dt, 1 H, J ) 3.7, 13.3 Hz), 3.69 (s, 3 H), 3.80 (s, 3 H),
3.99-4.09 (m, 2 H), 5.39 (d, 1 H, J ) 6.0 Hz), 6.86-6.89 (m, 2
H), 7.40-7.43 (m, 2 H); 13C NMR (CDCl3) δ 23.7 (t), 27.5 (t),
39.2 (t), 52.7 (q), 55.0 (q), 57.9 (d), 70.1 (d), 113.5 (d), 129.4
(s), 129.6 (d), 156.5 (s), 158.4 (s). Anal. Calcd for C14H19NO4:
C, 63.38; H, 7.22; N, 5.28. Found: C, 63.45; H, 7.26; N, 5.06.
1-BOC-cis-2-(3,4-d im eth oxyph en yl)p iper id in -3-ol (16e):
colorless paste; Rf 0.26 (hexanes-ethyl acetate, 2:1); IR (neat)
3435, 1670, 1609, 1591, 1516, 972, 876, 812, 766, 733 cm-1
;
1H NMR (CDCl3) δ 1.40 (s, 9 H), 1.62-1.72 (m, 1 H), 1.75-
1.88 (m, 3 H), 2.99 (dt, 1 H, J ) 4.0, 13.0 Hz), 3.87 (s, 3 H),
3.88 (s, 3 H), 3.96-4.02 (m, 1 H), 4.03-4.10 (m, 1 H), 5.30 (d,
1 H, J ) 5.5 Hz), 6.83 (d, 1 H, J ) 9.0 Hz), 6.98-7.04 (m, 2
H); 13C NMR (CDCl3) δ 23.5 (t), 27.3 (t), 28.0 (q), 38.9 (t), 55.3
(q), 57.6 (d), 70.0 (d), 79.5 (s), 110.4 (d), 111.7 (d), 120.2 (d),
1-BOC-cis-2-(4-m eth oxyph en yl)piper idin -3-ol (16b): col-
orless paste; Rf 0.33 (hexanes-ethyl acetate, 2:1); IR (neat)
3427, 1666, 1611, 1581, 1512, 964, 881, 827, 802, 764, 735,
1
702 cm-1; H NMR (CDCl3) δ 1.39 (s, 9 H), 1.61-1.88 (m, 4
130.4 (s), 147.4 (s), 148.1 (s), 155.0 (s). Anal. Calcd for C18H27
-
H), 3.00 (dt, 1 H, J ) 3.5, 13.0 Hz), 3.81 (s, 3 H), 3.99 (dt, 1 H,
J ) 6.0, 13.5 Hz), 4.01-4.08 (m, 1 H), 5.30 (d, 1H, J ) 6.0
Hz), 6.85-6.89 (m, 2 H), 7.36-7.40 (m, 2 H); 13C NMR (CDCl3)
δ 23.5 (t), 27.5 (t), 28.1 (q), 39.0 (t), 54.9 (q), 57.9 (d), 70.0 (d),
79.6 (s), 113.3 (d), 129.5 (d), 130.0 (s), 155.2 (s), 158.2 (s). Anal.
Calcd for C17H25NO4: C, 66.43; H, 8.20; N, 4.56. Found: C,
66.63; H, 8.34; N, 4.29.
NO5: C, 64.07; H, 8.07; N, 4.15. Found: C, 64.21; H, 8.20; N,
3.98.
1-MOC-cis-2-(4-flu or op h en yl)p ip er id in -3-ol (15f): color-
less paste; Rf 0.20 (hexanes-ethyl acetate, 2:1); IR (neat) 3431,
1678, 1605, 1508, 962, 864, 837, 772 cm-1; 1H NMR (CDCl3) δ
1.60-1.94 (m, 4 H), 2.90-2.97 (m, 1 H), 3.70 (s, 3 H), 3.97-
4.05 (m, 1 H), 4.06-4.12 (m, 1 H), 5.44 (d, 1 H, J ) 6.0 Hz),
6.99-7.05 (m, 2 H), 7.46-7.51 (m, 2 H); 13C NMR (CDCl3) δ
23.7 (t), 27.4 (t), 39.2 (t), 52.8 (q), 57.7 (d), 70.1 (d), 114.8 (d,
1-MOC-cis-2-(3-m eth oxyph en yl)piper idin -3-ol (15c): col-
orless paste; Rf 0.10 (hexanes-ethyl acetate, 2:1); IR (neat)
3431, 1678, 1600, 1583, 1491, 970, 789, 770, 735, 700 cm-1
;
1H NMR (CDCl3) δ 1.62-1.88 (m, 5 H), 3.07 (dt, 1 H, J ) 4.2,
13.3 Hz), 3.69 (s, 3 H), 3.80 (s, 3 H), 4.01-4.11 (m, 2 H), 5.38
(d, 1 H, J ) 5.5 Hz), 6.80-6.84 (m, 1 H), 7.04-7.07 (m, 2 H),
7.24-7.29 (m, 1 H); 13C NMR (CDCl3) δ 23.4 (t), 27.5 (t), 39.5
(t), 52.7 (q), 55.0 (q), 58.6 (d), 70.0 (d), 112.0 (d), 114.6 (d), 120.6
(d), 129.2 (d), 139.2 (s), 156.5 (s), 159.4 (s). Anal. Calcd for
J CCF ) 21.0 Hz), 130.1 (d, J CCCF ) 7.6 Hz), 133.2 (s, J CCCCF
3.8 Hz), 156.5 (s), 161.6 (s, J CF ) 244.2 Hz). Anal. Calcd for
13H16FNO3: C, 61.65; H, 6.37; N, 5.53. Found: C, 61.70; H,
)
C
6.39; N, 5.48.
1-BOC-cis-2-(4-flu or op h en yl)p ip er id in -3-ol (16f): color-
less paste; Rf 0.50 (hexanes-ethyl acetate, 2:1); IR (neat) 3431,
1
C
14H19NO4: C, 63.38; H, 7.22; N, 5.28. Found: C, 63.27; H,
1666, 1605, 1508, 966, 881, 864, 833, 814, 764, 733 cm-1; H
7.20; N, 5.11.
NMR (CDCl3) δ 1.39 (S, 9 H), 1.60-1.88 (m, 4 H), 2.90-2.98
(m, 1 H), 3.95-4.01 (m, 1 H), 4.05-4.11 (m, 1 H), 5.34 (d, 1 H,
J ) 5.5 Hz), 6.99-7.05 (m, 2 H), 7.42-7.47 (m, 2 H); 13C NMR
(CDCl3) δ 23.6 (t), 27.4 (t), 28.2 (q), 39.2 (t), 57.8 (d), 70.1 (d),
80.0 (s), 114.8 (d, J CCF ) 21.0 Hz), 130.0 (d, J CCCF ) 7.6 Hz),
133.9 (s, J CCCCF ) 2.9 Hz), 155.3 (s), 161.5 (s, J CF ) 244.2 Hz).
Anal. Calcd for C16H22FNO3: C, 65.07; H, 7.51; N, 4.74.
Found: C, 65.24; H, 7.46; N, 4.51.
1-MOC-cis-2-(4-cya n op h en yl)p ip er id in -3-ol (15g): color-
less paste; Rf 0.20 (hexanes-ethyl acetate, 2:1); IR (neat) 3443,
2230, 1686, 1609, 1504, 959, 868, 841, 772, 737, 702 cm-1; 1H
NMR (CDCl3) δ 1.61-1.92 (m, 4 H), 2.25 (brs, 1 H), 2.80-2.88
(m, 1 H), 3.72 (s, 3 H), 3.97-4.07 (m, 1 H), 4.10-4.18 (m, 1
H), 5.51 (d, 1 H, J ) 5.1 Hz), 7.60-7.63 (m, 2 H), 7.65-7.69
(m, 2 H); 13C NMR (CDCl3) δ 23.6 (t), 27.6 (t), 39.6 (t), 53.0
(q), 58.2 (d), 70.1 (d), 110.6 (s), 118.7 (s), 129.2 (d), 131.8 (d),
143.6 (s), 156.5 (s). Anal. Calcd for C14H16N2O3: C, 64.60; H,
6.20; N, 10.76. Found: C, 64.52; H, 6.29; N, 10.53.
1-BOC-cis-2-(3-m eth oxyp h en yl)p ip er id in -3-ol (16c): col-
orless paste; Rf 0.30 (hexanes-ethyl acetate, 2:1); IR (neat)
3435, 1666, 1601, 1583, 970, 868, 787, 754, 731, 696 cm-1; 1H
NMR (CDCl3) δ 1.38 (s, 9 H), 1.63-1.73 (m, 1 H), 1.75-1.86
(m, 3 H), 3.04 (dt, 1 H, J ) 4.2, 12.8 Hz), 4.05-4.11 (m, 1 H),
5.29 (d, 1 H, J ) 5.5 Hz), 6.80-6.83 (m, 1 H), 7.01-7.05 (m, 2
H), 7.26 (t, 1 H, J ) 7.8 Hz); 13C NMR (CDCl3) δ 23.3 (t), 27.5
(t), 28.2 (q), 39.2 (t), 54.9 (q), 59.0 (d), 70.0 (d), 79.8 (s), 112.0
(d), 114.2 (d), 120.5 (d), 129.0 (d), 139.9 (s), 155.2 (s), 159.3
(s). Anal. Calcd for C17H25NO4: C, 66.43; H, 8.20; N, 4.56.
Found: C, 66.55; H, 8.31; N, 4.38.
1-MOC-cis-2-(2-m et h oxyp h en yl)p ip er id in -3-ol (15d ):
white solid; Rf 0.13 (hexanes-ethyl acetate, 2:1); mp 144-146
°C; IR (KBr) 3456, 1672, 1599, 1493, 955, 903, 847, 775, 660
1
cm-1; H NMR (CDCl3) δ 1.70-1.87 (m, 4 H), 2.41 (brs, 1 H),
3.38-3.47 (m, 1 H), 3.61 (s, 3 H), 3.87 (s, 3 H), 4.15-4.24 (m,
2 H), 5.66 (d, 1 H, J ) 6.0 Hz), 6.91 (d, 1 H, J ) 7.8 Hz), 6.94-
6.99 (m, 1 H), 7.23-7.29 (m, 2 H); 13C NMR (CDCl3) δ 21.2 (t),
25.5 (t), 40.3 (t), 52.5 (q), 54.7 (d), 55.5 (q), 68.2 (d), 110.7 (d),
120.7 (d), 127.2 (s), 127.5 (d), 128.2 (d), 156.4 (s), 156.7 (s).
Anal. Calcd for C14H19NO4: C, 63.38; H, 7.22; N, 5.28. Found:
C, 63.39; H, 7.24; N, 5.20.
1-BOC-cis-2-(4-cya n op h en yl)p ip er id in -3-ol (16g): color-
less paste; Rf 0.31 (hexanes-ethyl acetate, 2:1); IR (neat) 3437,
2230, 1674, 1609, 1504, 1477, 966, 883, 862, 829, 771, 737,
1
704 cm-1; H NMR (CDCl3) δ 1.40 (s, 9 H), 1.59-1.78 (m, 3
H), 1.82-1.90 (m, 1 H), 2.77-2.85 (m, 1 H), 3.93-4.01 (m, 1
7718 J . Org. Chem., Vol. 69, No. 22, 2004

Intramolecular Coupling of Aromatic â- and γ-Imino Esters
H), 4.09-4.16 (m, 1 H), 5.43 (d, 1 H, J ) 5.1 Hz), 7.58-7.65
(m, 4 H); 13C NMR (CDCl3) δ 23.5 (t), 27.8 (t), 28.2 (q), 39.6
(t), 58.2 (d), 70.2 (d), 80.5 (s), 110.6 (s), 118.8 (s), 129.1 (d),
131.8 (d), 144.4 (s), 155.2 (s). Anal. Calcd for C17H22N2O3: C,
67.53; H, 7.33; N, 9.26. Found: C, 67.72; H, 7.40; N, 9.09.
1-MOC-cis-2-(2-n a p h th yl)p ip er id in -3-ol (15i): colorless
paste; Rf 0.53 (hexanes-ethyl acetate, 1:1); IR (neat) 3460,
parameters and converged with unweighted and weighted
agreement factors of R ) 0.040 and Rw ) 0.049.
Cr ysta l d a ta for 13f: C13H14O3N2, FW ) 246.27, mono-
clinic, P21/a (no. 14), colorless block, a ) 9.9726(6) Å, b )
12.5133(6) Å, c ) 10.5966(7) Å, â ) 110.642(2)°, V ) 1237.5-
(1) Å3, T ) 298 K, Z ) 4, Dcalcd ) 1.322 g/cm3, µ ) 0.95 cm-1
,
GOF ) 0.995. The final cycle of full-matrix least-squares
refinement on F was based on 2317 observed reflections and
220 variable parameters and converged with unweighted and
weighted agreement factors of R ) 0.038 and Rw ) 0.063.
Cr ysta l d a ta for 13g: C12H14O3NF, FW ) 239.25, mono-
clinic, P21/c (no. 14), colorless block, a ) 13.994(3) Å, b ) 8.865-
(3) Å, c ) 13.764(4) Å, â ) 42.472(6)°, V ) 1153.0(5) Å3, T )
298 K, Z ) 4, Dcalcd ) 1.378 g/cm3, µ ) 1.09 cm-1, GOF ) 1.002.
The final cycle of full-matrix least-squares refinement on F
was based on 1850 observed reflections and 211 variable
parameters and converged with unweighted and weighted
agreement factors of R ) 0.037 and Rw ) 0.050.
1678, 1601, 1506, 972, 947, 820, 758, 735 cm-1 1H NMR
;
(CDCl3) δ 1.66-1.99 (m, 4 H), 2.05 (s, 1 H), 3.10 (dt, 1 H, J )
4.2, 13.1 Hz), 3.70 (s, 3 H), 4.05-4.13 (m, 1 H), 4.16-4.22 (m,
1 H), 5.59 (d, 1 H, J ) 5.5 Hz), 7.44-7.50 (m, 2 H), 7.56 (m, 1
H, J ) 1.9, 8.7 Hz), 7.79-7.85 (m, 3 H), 7.99 (s, 1 H); 13C NMR
(CDCl3) δ 23.6 (t), 27.5 (t), 39.5 (t), 52.8 (q), 70.2 (d), 125.8 (d),
125.9 (d), 126.4 (d), 127.3 (d), 127.8 (d), 128.0 (d), 132.3 (s),
133.0 (s), 135.1 (s), 156.6 (s). Anal. Calcd for C17H19NO3: C,
71.56; H, 6.71; N, 4.91. Found: C, 71.65; H, 6.75; N, 4.77.
1-BOC-cis-2-(2-n a p h th yl)p ip er id in -3-ol (16i): colorless
paste; Rf 0.32 (hexanes-ethyl acetate, 2:1); IR (neat) 3425,
1666, 1601, 1506, 970, 951, 889, 858, 820, 758, 737, 702 cm-1
;
Cr ysta l d a ta for 15a : C13H15O7N, FW ) 235.28, mono-
clinic, P21/a (no. 14), colorless block, a ) 15.495(4) Å, b )
10.946(3) Å, c ) 15.325(3) Å, â ) 27.877(5)°, V ) 1215.3(5) Å3,
T ) 298 K, Z ) 4, Dcalcd ) 1.286 g/cm3, µ ) 0.91 cm-1, GOF )
0.998. The final cycle of full-matrix least-squares refinement
on F was based on 1609 observed reflections and 171 variable
parameters and converged with unweighted and weighted
agreement factors of R ) 0.041 and Rw ) 0.042.
Cr ysta l d a ta for 15d : C14H19O4N, FW ) 265.31, mono-
clinic, P21/c (no. 14), colorless block, a ) 9.717(2) Å, b ) 9.665-
(2) Å, c ) 14.758(3) Å, â ) 105.305(8)°, V ) 1336.8(4) Å3, T )
298 K, Z ) 4, Dcalcd ) 1.318 g/cm3, µ ) 0.96 cm-1, GOF ) 1.000.
The final cycle of full-matrix least-squares refinement on F
was based on 2031 observed reflections and 249 variable
parameters and converged with unweighted and weighted
agreement factors of R ) 0.031 and Rw ) 0.036.
1H NMR (CDCl3) δ 1.38 (s, 9 H), 1.64-1.83 (m, 2 H), 1.83-
1.95 (m, 2 H), 3.05 (dt, 1 H, J ) 3.7, 12.9 Hz), 4.03 (dd, 1 H,
J ) 3.7, 13.8 Hz), 4.13-4.20 (m, 1 H), 5.51 (d, 1H, J ) 5.5
Hz), 7.44-7.49 (m, 2 H), 7.54 (dd, 1 H, J ) 1.9, 8.7 Hz), 7.78-
7.84 (m, 3 H), 7.97 (s, 1 H); 13C NMR (CDCl3) δ 23.4 (t), 27.6
(t), 28.3 (q), 39.5 (t), 58.9 (d), 70.2 (d), 80.0 (s), 125.7 (d), 125.9
(d), 126.5 (d), 127.2 (d), 127.4 (d), 127.8 (d), 128.0 (d), 132.4
(s), 133.1 (s), 135.8 (s), 155.4 (s). Anal. Calcd for C20H25NO3:
C, 73.37; H, 7.70; N, 4.28. Found: C, 73.52; H, 7.76; N, 4.21.
X-r a y Cr ysta llogr a p h ic An a lysis. All measurements were
made on a Rigaku RAXIS imaging plate area detector with
graphite monochromated Mo KR radiation. The structure was
solved by direct methods with SIR92 and expanded by using
Fourier techniques with DIRDIF99. The non-hydrogen atoms
were refined anisotropically. Hydrogen atoms were refined
isotropically. All calculations were performed with the Crys-
talStructure crystallographic software package.
Su p p or t in g In for m a t ion Ava ila b le: A drawing of the
1
electrolysis cell, H and 13C NMR spectra of 2a ′, 2a ′′, 6a ′, and
Cr ysta l d a ta for 13a : C12H15O3N, FW ) 221.26, mono-
clinic, P21/c (no. 14), colorless block, a ) 13.831(2) Å, b ) 8.845-
(1) Å, c ) 13.595(2) Å, â ) 42.811(4)°, V ) 1130.2(2) Å3, T )
298 K, Z ) 4, Dcalcd ) 1.300 g/cm3, µ ) 0.93 cm-1, GOF ) 1.003.
The final cycle of full-matrix least-squares refinement on F
was based on 1494 observed reflections and 160 variable
6a ′′, and X-ray crystallographic structures (ORTEP) of 13a ,f,g
and 15a ,d , as well as crystallographic files (CIF). This material
is available free of charge via the Internet at http://pubs.acs.org.
J O0488917
J . Org. Chem, Vol. 69, No. 22, 2004 7719