Palladium-catalyzed coupling of vinyl phosphates with aryl or heteroaryl boronic acids. Application to the synthesis of substituted nitrogen containing heterocycles

Article abstract of DOI:10.1016/S0040-4020(01)00651-2

Substituted nitrogen-containing heterocycles were prepared in three steps from commercially available derivatives via an extension of the Suzuki reaction involving the palladium-catalyzed coupling of vinyl phosphates with aryl or heteroaryl boronic acids.

Full text of DOI:10.1016/S0040-4020(01)00651-2

TETRAHEDRON
Pergamon
Tetrahedron 57 ;2001) 6969±6975
Palladium-catalyzed coupling of vinyl phosphates with aryl or
heteroaryl boronic acids. Application to the synthesis of
substituted nitrogen containing heterocycles
p
Â
Franck Lepifre, Sylvain Clavier, Pascal Bouyssou and Gerard Coudert
   Â
Institut de Chimie Organique et Analytique associe au CNRS, Universite d'Orleans, BP 6759, 45067 Orleans Cedex 02, France
Received 28 March 2001; revised 31 May 2001; accepted 18 June 2001
AbstractÐSubstituted nitrogen-containing heterocycles were prepared in three steps from commercially available derivatives via an
extension of the Suzuki reaction involving the palladium-catalyzed coupling of vinyl phosphates with aryl or heteroaryl boronic acids.
q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
vinyl phosphates could constitute an interesting alternative
to their tri¯ate counterparts. Recently, we also used these
reactive intermediates for the synthesis of substituted
benzoxazines, pyridoxazines and benzothiazines.5 These
unusual heterocyclic systems were prepared via the ®rst
reported extension of the Suzuki6 reaction involving
palladium-catalyzed coupling of vinyl phosphates with aryl
or heteroaryl boronic acids. The present paper concerns the
application of our methodology to the synthesis of medium-
sized and large N-heterocycles. We focused our interest on the
preparation of six-, seven- and thirteen-membered rings
ene-carbamates substituted or not on position C2.
The synthesis of N-heterocycles of various sizes constitutes
a most important theme within organic chemistry owing to
their presence in a wide range of natural and synthetic
products. Access to substituted N-heterocycles through a
process involving the functionalization of lactams via
their vinyl tri¯ates was ®rst reported by Isobe a few years
ago.1 Ever since, the tri¯ate-based methodology has been
widely used for the elaboration of substituted nitrogen
containing heterocycles.2
However, in spite of their important potential these vinyl
tri¯ates present such drawbacks as a relative lack of stability
and the necessity to use expensive tri¯ating agents.
The synthesis of vinyl phosphates was realized from the six-
membered N-COOPh protected lactam and the seven- and
thirteen-membered N-Boc protected lactams via their
corresponding lithium enolates ;Scheme 1).
It was reported, ®rst by Nicolaou3 and next by Jiang,4 that
Scheme 1.
Keywords: coupling reactions; palladium and compounds; boronic acids; vinyl phosphates; N-heterocycles.
Corresponding author. Tel.: 12-38-49-45-89; fax: 12-38-41-72-81; e-mail: gerard.coudert@univ-orleans.fr
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020;01)00 651-2

6970
F. Lepifre et al. / Tetrahedron 57 12001) 6969±6975
2. Results and discussions
phosphate 4 was then engaged in palladium-catalyzed
coupling reactions involving aryl or heteroaryl boronic
acids according to a procedure we previously described5,8
;Table 1).
2.1. Synthesis,hydrogenolysis and Suzuki coupling of the
six-membered ketene aminal diphenyl phosphate 4
The N-Boc protected valerolactam was ®rst prepared
according to Murai.2b Unfortunately, in spite of numerous
experiments, we were unable to isolate the corresponding
vinyl phosphate in good yield. Consequently we changed
the N-protecting group and moved to the preparation of
N-COOPh protected valerolactam 1 which was obtained
in 73% yield according to Comins.2a The corresponding
lithium enolate obtained at 2788C in dry tetrahydrofuran
with LDA ;1.2 equiv.) and TMEDA ;1.2 equiv.) was then
reacted with freshly distilled diphenyl chlorophosphate
;1.2 equiv.). Vinyl phosphate 4, puri®ed by ¯ash chromato-
graphy on silica gel was eventually obtained in 82% yield.
Compound 10a was previously reported by Comins2a
whereas derivatives 10b±e were unknown.
2.2. Synthesis,hydrogenolysis and Suzuki coupling of the
seven- and thirteen-membered ketene aminal diphenyl
phosphates 5 and 6
N-Boc lactams 2 and 3 were prepared in 88 and 73% yields,
respectively, from the corresponding commercially
available lactams by treatment with di-tert-butyldicarbonate
in tetrahydrofuran, at room temperature in the presence of
DMAP. The lithium enolates, obtained from 2 and 3 at
2788C with LDA ;1.2 equiv.) in dry tetrahydrofuran in
the presence of TMEDA ;1.2 equiv.), were quenched with
diphenyl chlorophosphate ;1.2 equiv.) leading to vinyl
phosphates 5 and 6 in good yields ;83 and 96%,
respectively).
The reduction of 4 was ®rst performed by adapting a pro-
cedure previously described by Cacchi et al.7 Treatment of 4
with triethylammonium formate, palladium acetate
;0.04 equiv.) and triphenylphosphine ;0.08 equiv.) in re¯ux-
ing tetrahydrofuran led to unsaturated carbamate 7 in 79%
yield ;Scheme 2).
Hydrogenolysis of 5 and 6 according to the procedure
previously described led to the corresponding unsaturated
In order to obtain 2-substituted heterocyclic systems, vinyl
Scheme 2.
Table 1.
a
10Ar
A
Yield ;%)
89
95
B
C
90
D
90
77
E
a
Isolated yields.

F. Lepifre et al. / Tetrahedron 57 12001) 6969±6975
6971
Scheme 3.
Table 2.
Ar
n
11
Yield ;%)a
n
12
Yield ;%)a
2
a
808
a
94
2
2
b
c
79
96
8
8
b
c
83
93
2
2
d
e
74
91
8
8
d
e
94
90
a
Isolated yields.
carbamates 8 and 9 in 90and 83% yields, respectively
;Scheme 3).
melting point apparatus and were uncorrected. IR spectra
were recorded on a Perkin±Elmer FT PARAGON 1000 PC.
1H- and 13C NMR were recorded on a Bruker Avance
DPX250spectrometer ;250.13 MHz, 1H, 62.89 MHz, 13C),
multiplicities were determined by the DEPT 135 sequence.
MS were recorded on a Perkin±Elmer SCIEX API 3000
spectrometer. All reactions were carried out in a ¯ame-
dried glassware under an argon atmosphere. Thin-layer
chromatography ;TLC) was carried out on Merck silica
gel 60F254 precoated plates. `Usual workup' means extrac-
tion with EtOAc, drying with MgSO4, ®ltration and
evaporation.
Vinyl phosphates 5 and 6 were also used in Suzuki type
reactions with some typical aryl or heteroaryl boronic
acids to obtain medium-sized and large 2-substituted hetero-
cyclic systems 11 and 12. Table 2 summarizes the results of
the palladium-catalyzed coupling reactions.8
In conclusion we have shown that an extension of the
Suzuki reaction involving the coupling of boronic acids
and lactam-derived vinyl phosphates allows, under mild
conditions, an easy access to cyclic six-, seven- and thirteen-
membered ene-carbamates, substituted on C2 with aryl or
heteroaryl groups. These derivatives constitute ideal pre-
cursors for the construction of complex heterocyclic
systems likely to be of interest in medicinal chemistry.
Studies are currently in progress in this area.
3.1.1. Phenyl 2-oxopiperidine-1-carboxylate .1). To a
cold ;2788C) solution of d-valerolactam ;1 g, 10mmol)
in dry THF ;50mL) was added a solution of n-BuLi,
1.6 M in hexane ;7.5 mL, 12 mmol). The reaction mixture
was stirred for 2 h at 2788C and a solution of phenyl chloro-
formate freshly distilled ;2.5 mL, 20mmol) in dry THF
;5 mL) was added dropwise. The mixture was stirred for
2 h at 2788C, allowed to warm to room temperature and
treated with water ;30mL). After the usual workup and
recrystallization in pentane ;60mL), 1 was obtained as a
3. Experimental
3.1. General
white solid ;1.6 g, 73%). Mp: 1178C. IR ;KBr): n ;cm21
2944 ;C±H); 1777 and 1676 ;CvO); 1589, 1485 and 1454
)
Melting points were determined with a BuÈchi SMP-20

6972
F. Lepifre et al. / Tetrahedron 57 12001) 6969±6975
1
;CvC). H NMR ;CDCl3): d ;ppm) 1.90±1.93 ;m, 4H, H4
and H5); 2.62 ;t, 2H, H3, J3,4ˆ6.5 Hz); 3.86 ;t, 2H, H6,
J5,6ˆ6 Hz); 7.16±7.27 ;m, 3H); 7.35±7.41 ;m, 2H). 13C
NMR ;CDCl3): d ;ppm) 20.65 and 22.80 ;2CH2, C4 and
C5); 35.15 ;CH2, C3); 47.10;CH 2, C6); 121.60;2CH);
126.15 ;CH); 129.55 ;2CH); 150.80 and 153.15 ;2C);
171.40;C, C2). MS: m/z 220;M 11).
3.74 ;t, 2H, H6, J5,6ˆ6 Hz); 5.24 ;td, 1H, H3, J3,4ˆ4 Hz
and JH,Pˆ3 Hz); 7.02±7.34 ;m, 15H). 13C NMR ;CDCl3):
d ;ppm) 21.75 ;CH2, C4); 22.75 ;CH2, C5); 46.15 ;CH2, C6);
101.20 ;CH, C3); 120.25, 121.55, 125.60, 129.30 and 129.85
;15CH); 124.95, 139.65, 150.45, 150.95 and 152.55 ;5C).
MS: m/z 452 ;M11).
3.1.5. tert-Butyl 7-[.diphenoxyphosphoryl)oxo]-2,3,4,5-
tetrahydro-1h-azepine-1-carboxylate .5). The reaction
was carried out as described above for the synthesis of
compound 4 with 2 ;0.97 g, 4.56 mmol). Flash chromato-
graphy with petroleum ether/EtOAc ;80/20) gave 5 as a
colorless oil ;1.69 g, 83%). IR ;NaCl ®lm): n ;cm21) 2979
and 2930;C±H); 1713 ;C vO); 1690, 1590, 1491 and 1453
3.1.2. tert-Butyl 2-oxoazepane-1-carboxylate .2). To a
solution of e-caprolactam ;5.49 g, 48 mmol) in THF
;120mL) was added 4-dimethylaminopyridine ;6.45 g,
52.8 mmol)
and
di-tert-butyldicarbonate
;11.52 g,
52.8 mmol). The resulting mixture was stirred at room
temperature for 25 h. After concentration and hydrolysis,
the reaction mixture was extracted with EtOAc. The
combined organic phases were washed with hydrochloric
acid solution ;5%), brine, dried over MgSO4 and concen-
trated to give 2 as colorless oil ;9.05 g, 88%). IR ;NaCl
®lm): n ;cm21) 2979 and 2933 ;C±H); 1768 and 1715
;CvO). 1H NMR ;CDCl3): d ;ppm) 1.52 ;s, 9H,
;CH3)3C); 1.73 ;m, 6H, H4, H5 and H6); 2.65 ;m, 2H, H3);
3.76 ;m, 2H, H7). 13C NMR ;CDCl3): d ;ppm) 28.15 ;3CH3,
1
;CvC); 1303 ;PvO). H NMR ;CDCl3): d ;ppm) 1.47±
1.56 ;m, 11H, ;CH3)3C and H5); 1.67±1.80;m, 2H, H6);
2.09±2.14 ;m, 2H, H4); 3.55 ;m, 2H, H7); 5.45 ;td, 1H,
H3, J3,4ˆ7 Hz and JH,Pˆ3 Hz); 7.19±7.40;m, 10H). 13C
NMR ;CDCl3): d ;ppm) 24.05 ;CH2, C5); 24.50;CH
,
2
C4); 28.25 ;3CH3, ;CH3)3C); 29.45 ;CH2, C6); 46.70;CH ,
2
C7); 81.30;C, ;CH 3)3C); 109.65 ;CH, C3); 120.15 and
120.25 ;4CH); 125.55 ;2CH); 129.90 ;4CH); 145.25 ;C,
C2); 150.60 and 150.70 ;2C); 153.15 ;C, CvO). MS: m/z
446 ;M11).
;CH3)3C); 23.65, 28.80and 29.35 ;3CH , C4, C5 and C6);
2
39.65 ;CH2, C3); 46.25 ;CH2, C7); 82.85 ;C, ;CH3)3C);
153.05 ;C, O±CvO); 175.85 ;C, C2). MS: m/z 214 ;M11).
3.1.6. tert-Butyl 2-[.diphenoxyphosphoryl)oxo]aza-2-
cyclotridecene-1-carboxylate .6). The reaction was carried
out as described above for the synthesis of compound 4 with
3 ;1.356 g, 4.56 mmol). Flash chromatography with petro-
leum ether/EtOAc ;80/20) gave 6 as a colorless oil ;2.32 g,
96%). IR ;NaCl ®lm): n ;cm21) 2931 and 2859 ;C±H); 1715
3.1.3. tert-Butyl 2-oxoazacyclotridecane-1-carboxylate
.3). To a solution of 2-azacyclotridecanone ;4.03 g,
20mmol) in THF ;40mL) was added triethylamine
;2.8 mL, 20mmol), 4-dimethylaminopyridine ;1.22 g,
20mmol) and di- tert-butyldicarbonate ;9 g, 40mmol).
The resulting mixture was stirred at room temperature for
25 h. After concentration and hydrolysis, the reaction
mixture was extracted with EtOAc. The combined organic
phases were washed with hydrochloric acid solution ;5%),
brine, dried over MgSO4 and concentrated to give 3 as
colorless oil ;4.34 g, 73%). IR ;NaCl ®lm): n ;cm21) 2923
and 2861 ;C±H); 1733 and 1693 ;CvO). 1H NMR ;CDCl3):
d ;ppm) 1.27 ;m, 14H, 7CH2); 1.53 ;m, 11H, ;CH3)3C and
H4); 1.69±1.74 ;m, 2H, H12); 2.89±2.93 ;m, 2H, H13); 3.80±
3.84 ;m, 2H, H3). 13C NMR ;CDCl3): d ;ppm) 24.30, 25.05,
25.20, 25.35, 25.90, 26.65, 27.10, 27.75 and 28.05 ;9CH2);
28.20;3CH 3, ;CH3)3C); 38.05 ;CH2, C13); 44.05 ;CH2, C3);
1
;CvO); 1592, 1493 and 1457 ;CvC); 1318 ;PvO). H
NMR ;CDCl3): d ;ppm) 1.26±1.34 ;m, 12H, 6CH2); 1.40
;m, 11H, ;CH3)3C and CH2); 1.60±1.65 ;m, 2H, H12); 2.13
;m, 2H, H4); 3.33±3.38 ;m, 2H, H13); 5.08 ;m, 1H, H3);
7.18±7.36 ;m, 10H). 13C NMR ;CDCl3): d ;ppm) 23.70,
24.40, 24.85, 25.10, 25.60, 26.30, 27.35 ;9CH2); 28.25
;3CH3, ;CH3)3C); 44.95 ;CH2, C13); 80.90 ;C, ;CH3)3C);
117.90;CH, C3); 12.030;4CH); 125.50;2CH); 129.90
;4CH); 139.30;C, C2); 150.60 ;2C); 154.20 ;C, CvO).
MS: m/z 530;M 11).
3.1.7. Phenyl 3,4-dihydro-1.2H)-pyridinecarboxylate .7).
To a solution of 4 ;316 mg, 0.7 mmol), triphenylphosphine
;15 mg, 0.056 mmol) and palladium;II) acetate ;6 mg,
0.028 mmol) in DME ;1.4 mL) was added a solution of
triethylamine ;300 mL, 2.1 mmol) and formic acid ;55 mL,
1.4 mmol) in DME ;1.4 mL). The reaction mixture was
re¯uxed for 40min, allowed to cool to room temperature
and hydrolyzed with distilled water ;20mL). After the usual
workup and ¯ash chromatography on silica gel with petro-
leum ether/EtOAc ;90/10), 7 was obtained as a white solid
;112 mg, 79%). Mp: 618C. IR ;KBr): n ;cm21) 2925 ;C±H);
1713 ;CvO); 1651, 1596, 1487 and 1456 ;CvC). 1H NMR
;CDCl3): d ;ppm) 1.86±1.93 ;m, 2H, H5); 2.03±2.10 ;m,
2H, H4); 3.66±3.81 ;m, 2H, H6); 4.96±5.07 ;m, 1H, H3);
6.91±6.97 ;m, 1H, H2); 7.10±7.24 ;m, 3H); 7.32±7.38 ;m,
82.70;C, ;CH ) C); 153.90;C, O±CvO); 177.10;C, C2).
3 3
MS: m/z 298 ;M11).
3.1.4. Phenyl 6-[.diphenoxyphosphoryl)oxo]-3,4-dihydro-
1.2H)-pyridinecarboxylate .4). To a cold ;2788C) solu-
tion of 1 ;1 g, 4.56 mmol) in dry THF ;40mL) and
N,N,N0,N0-tetramethylenediamine ;0.85 mL, 5.47 mmol)
was added a solution of LDA 2 M in heptane/THF
;2.8 mL, 5.47 mmol). The reaction mixture was stirred at
2788C for 2 h and a solution of freshly distilled diphenyl
chlorophosphate ;1.15 mL, 5.47 mmol) was added dropwise
into dry THF ;5 mL). The mixture was stirred for 3 h at
2788C, allowed to warm to room temperature and treated
with 5% ammonium hydroxide solution ;30mL). After the
usual workup and ¯ash chromatography on silica gel with
petroleum ether/EtOAc/ triethylamine ;80/15/5), 4 was
obtained as a pale brown oil ;1.68 g, 82%). IR ;NaCl
®lm): n ;cm21) 2936 ;C±H); 1736 ;CvO); 1591, 1493
and 1457 ;CvC); 1380;P vO). 1H NMR ;CDCl3): d
;ppm) 1.82±1.87 ;m, 2H, H5); 2.22±2.26 ;m, 2H, H4);
2H). 13C NMR ;CDCl3): d ;ppm) 21.50;CH , C4); 21.65
2
;CH2, C5); 42.55 ;CH2, C6); 107.60 ;CH, C3); 121.75 ;2CH);
124.90;CH, C2); 125.25 ;C); 125.55 ;CH); 129.40;2CH);
151.25 ;C, CvO). MS: m/z 204 ;M11). Anal. Calcd for
C12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.85; H,
6.47; N, 6.96.

F. Lepifre et al. / Tetrahedron 57 12001) 6969±6975
6973
1
3.1.8. tert-Butyl 2,3,4,5-tetrahydro-1H-azepine-1-car-
boxylate .8). The reaction was carried out as described
above for the synthesis of compound 7 with 5 ;312 mg,
0.7 mmol). Flash chromatography with petroleum ether/
EtOAc ;80/20) gave 8 as a colorless oil ;124 mg, 90%).
IR ;NaCl ®lm): n ;cm21) 2982 and 2930;C±H); 1730
and 1456 ;C vC); 1201 ;C±O±C). H NMR ;CDCl3): d
;ppm) 1.92±2.00 ;m, 2H, H5); 2.27±2.34 ;m, 2H, H4); 3.75
;s, 3H, OCH3); 3.79±3.84 ;m, 2H, H6); 5.39 ;t, 1H, H3,
J3,4ˆ4 Hz); 6.74±6.85 ;m, 4H); 6.81±6.85 ;m, 1H); 7.05±
7.21 ;m, 2H); 7.27±7.30;m, 2H). 13C NMR ;CDCl3): d
;ppm) 23.60;CH , C4); 23.80;CH , C5); 45.60;CH , C6);
2
2
2
1
;CvO); 1654 ;CvC). H NMR ;CDCl3): d ;ppm) 1.48 ;s,
55.40;CH 3, OCH3); 113.70;2CH); 115.60;CH, C3); 121.40
;2CH); 125.30;CH); 126.40;2CH); 129.15 ;2CH); 132.50,
139.35, 151.15, 153.45 and 159.05 ;5C). MS: m/z 310
;M11). Anal. Calcd for C19H19NO3: C, 73.77; H, 6.19; N,
4.53. Found: C, 73.85; H, 6.13; N, 4.57.
9H, ;CH3)3C); 1.70±1.80;m, 4H, H5 and H6); 2.14±2.20;m,
2H, H4); 3.62±3.66 ;m, 2H, H7); 4.95 ;m, 1H, H3); 6.47 ;m,
1H, H2). 13C NMR ;CDCl3): d ;ppm) 25.30;CH 2, C5); 26.30
;CH2, C4); 28.45 ;3CH3, ;CH3)3C); 28.15 ;CH2, C6); 47.00
;CH2, C7); 80.35 ;C, ;CH3)3C); 114.20;CH, C3); 130.70
;CH, C2); 153.80;C, C vO). MS: m/z 198 ;M11). Anal.
Calcd for C11H19NO2: C, 66.97; H, 9.71; N, 7.10. Found: C,
66.84; H, 9.80; N, 7.18.
3.1.12. Phenyl 6-.1-naphtyl)-3,4-dihydro-1.2H)-pyridine-
carboxylate .10c). The reaction was carried out as
described above for the synthesis of compound 10a with
1-naphtylboronic acid ;130mg, 0.75 mmol). Flash chroma-
tography with petroleum ether/EtOAc ;95/5) gave 10c as a
white solid ;148 mg, 90%) recrystallized in pentane. Mp:
1128C. IR ;KBr): n ;cm21) 3060, 2931 ;C±H); 1705
3.1.9. tert-Butyl aza-2-cyclotridecene-1-carboxylate .9).
The reaction was carried out as described above for the
synthesis of compound 7 with 6 ;371 mg, 0.7 mmol).
Flash chromatography with petroleum ether gave 9 as a
1
;CvO); 1639, 1591 and 1484 ;CvC). H NMR ;CDCl3):
colorless oil ;164 mg, 83%). IR ;NaCl ®lm): n ;cm21
)
d ;ppm) 2.12 ;m, 2H, H5); 2.43 ;m, 2H, H4); 4.05 ;m, 2H,
H6); 5.45 ;t, 1H, H3, J3,4ˆ4 Hz); 6.27 ;m, 2H); 6.90±7.08
;m, 3H); 7.35±7.45 ;m, 4H); 7.71±7.74 ;m, 1H); 7.80±7.84
;m, 1H); 7.99±8.03 ;m, 1H). 13C NMR ;CDCl3): d ;ppm)
23.45 ;CH2, C4); 23.60;CH , C5); 44.90;CH , C6); 117.15
;CH, C3); 120.95 ;2CH); 124.80, 125.00, 125.45, 125.55,
125.65, 126.15, 127.75 and 128.50;8CH); 128.85 ;2CH);
131.15, 133.50, 137.95, 138.05, 150.65 and 152.75 ;6C).
MS: m/z 330;M 11). Anal. Calcd for C22H19NO2: C,
80.22; H, 5.81; N, 4.25. Found: C, 80.32; H, 5.88; N, 4.26.
1
2928 and 2859 ;C±H); 1707 ;CvO); 1659 ;CvC). H
NMR ;CDCl3): d ;ppm) 1.33±1.48 ;m, 23H, ;CH3)3C and
7CH2); 1.58±1.65 ;m, 2H, H12); 2.03±2.07 ;m, 2H, H4);
3.45 ;m, 2H, H13); 4.94±5.01 ;m, 1H, H3); 6.57±6.81 ;m,
1H, H2). 13C NMR ;CDCl3): d ;ppm) 24.05, 24.20, 25.60,
26.20, 26.35, 26.50, 26.75 and 27.40 ;8CH2); 28.45 ;3CH3,
2
2
;CH3)3C); 30.05 ;CH2, C4); 43.20;CH , C13); 80.35 ;C,
2
;CH3)3C); 111.55 ;CH, C3); 128.30;CH, C2); 153.85 ;C,
CvO). MS: m/z 282 ;M11). Anal. Calcd for C17H31NO2:
C, 72.55; H, 11.10; N, 4.98. Found: C, 72.70; H, 11.20; N,
4.82.
3.1.13. Phenyl 6-.2-furyl)-3,4-dihydro-1.2H)-pyridine-
carboxylate .10d). The reaction was carried out as
described above for the synthesis of compound 10a with
2-furylboronic acid ;84 mg, 0.75 mmol). Flash chromato-
graphy with petroleum ether/EtOAc ;95/5) gave 10d as a
colorless oil ;121 mg, 90%). IR ;NaCl ®lm): n ;cm21) 2937
;C±H); 1731 ;CvO); 1594, 1493 and 1457 ;CvC), 1164
3.1.10. Phenyl 6-phenyl-3,4-dihydro-1.2H)-pyridine-
carboxylate .10a). To a suspension of Pd;PPh3)4 ;30mg,
0.025 mmol) in DME ;0.5 mL), 4 ;226 mg, 0.5 mmol) was
added and the mixture was stirred for 10min at room
temperature. Benzeneboronic acid ;94 mg, 0.75 mmol) in
a minimum of ethanol and aqueous Na2CO3 ;2 M solution,
0.5 mL, 1 mmol) were then added. The reaction mixture
was re¯uxed for 0.5 h and allowed to cool to room tempera-
ture. After the usual workup and ¯ash chromatography on
silica gel with petroleum ether/EtOAc ;95/5), 10a was
obtained as a colorless oil ;140mg, 89%). IR ;NaCl ®lm):
n ;cm21) 3058 and 2934 ;C±H); 1735 ;CvO); 1645, 1593,
1
;C±O±C). H NMR ;CDCl3): d ;ppm) 1.89±1.99 ;m, 2H,
H5); 2.28±2.35 ;m, 2H, H4); 3.79 ;t, 2H, H6, J5,6ˆ5.5 Hz);
0
0
5.69 ;t, 1H, H3, J3,4ˆ4 Hz); 6.31±6.34 ;m, 2H, H3 and H4 );
6.96±6.99 ;m, 2H); 7.08±7.17 ;m, 1H); 7.21±7.32 ;m, 3H,
0
2Harom and H5 ). 13C NMR ;CDCl3): d ;ppm) 23.05 ;CH2,
0
C4); 23.55 ;CH2, C5); 45.05 ;CH2, C6); 105.50 ;CH, C4 );
0
111.05 ;CH, C3 ); 115.95 ;CH, C3); 121.35 ;2CH); 125.35
0
;CH); 129.20;2CH); 130.90;C); 141.05 ;CH, C5 ); 151.15,
1
1494 and 1455 ;CvC). H NMR ;CDCl3): d ;ppm) 1.92±
2.03 ;m, 2H, H5); 2.30±2.37 ;m, 2H, H4); 3.83±3.88 ;m, 2H,
H6); 5.49 ;t, 1H, H3, J3,4ˆ4 Hz); 6.66±6.74 ;m, 2H); 7.05±
7.41 ;m, 8H). 13C NMR ;CDCl3): d ;ppm) 23.65 and 23.70
151.80and 156.30;3C). MS: m/z 270;M 11). Anal. Calcd
for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.28;
H, 5.62; N, 5.26.
;2CH2, C4 and C5); 45.50;CH , C6); 116.90;CH, C3);
2
121.30, 125.25, 125.30, 127.40, 128.30 and 129.10
;10CH); 120.15, 129.50 and 139.70 ;3C); 151.00 ;C,
CvO). MS: m/z 280;M 11). Anal. Calcd for C18H17NO2:
C, 77.40; H, 6.13; N, 5.01. Found: C, 77.35; H, 6.16; N,
4.95.
3.1.14. Phenyl 6-.2-benzo[b]thiophenyl)-3,4-dihydro-
1.2H)-pyridinecarboxylate .10e). The reaction was carried
out as described above for the synthesis of compound
10a with 2-benzo[b]thiophenylboronic acid ;136 mg,
0.75 mmol). Flash chromatography with petroleum ether/
EtOAc ;95/5) gave 10e as a white solid ;129 mg, 77%)
3.1.11. Phenyl 6-.p-methoxyphenyl)-3,4-dihydro-1.2H)-
pyridinecarboxylate .10b). The reaction was carried out
as described above for the synthesis of compound 10a
with p-methoxybenzeneboronic acid ;114 mg, 0.75 mmol).
Flash chromatography with petroleum ether/EtOAc ;80/20)
gave 10b as a colorless oil ;147 mg, 95%). IR ;NaCl ®lm): n
;cm21) 2935 ;C±H); 1709 ;CvO); 1642, 1609, 1593, 1512
recrystallized in pentane. Mp: 1298C. IR ;KBr): n ;cm21
)
2935 ;C±H); 1727 ;CvO); 1641, 1589, 1494 and 1454
;CvC). H NMR ;CDCl3): d ;ppm) 1.92±2.01 ;m, 2H,
1
H5); 2.33±2.40;m, 2H, H4); 3.81±3.86 ;m, 2H, H6); 5.79
;t, 1H, H3, J3,4ˆ4 Hz); 6.87±6.91 ;m, 2H); 7.06±7.28 ;m,
6H); 7.65±7.75 ;m, 2H). 13C NMR ;CDCl3): d ;ppm) 23.55
;CH2, C4); 23.65 ;CH2, C5); 45.65 ;CH2, C6); 119.10;CH,

6974
F. Lepifre et al. / Tetrahedron 57 12001) 6969±6975
C3); 119.30, 121.45, 122.30, 123.55, 124.30, 124.45 and
125.45 ;7CH); 129.20 ;2CH); 134.50, 138.80, 139.90,
142.95, 151.10and 153.65 ;6C). MS: m/z 336 ;M11).
Anal. Calcd for C20H17NO2S: C, 71.62; H, 5.11; N, 4.18.
Found: C, 71.58; H, 5.15; N, 4.20.
324 ;M11). Anal. Calcd for C21H25NO2: C, 77.99; H, 7.79;
N, 4.33. Found: C, 78.13; H, 7.88; N, 4.30.
3.1.18. tert-Butyl 7-.2-furyl)-2,3,4,5-tetrahydro-1H-
azepine-1-carboxylate .11d). The reaction was carried
out as described above for the synthesis of compound 10a
with 5 ;223 mg, 0.5 mmol) and 2-furylboronic acid ;84 mg,
0.75 mmol). Flash chromatography with petroleum ether/
EtOAc ;95/5) gave 11d as a pale yellow solid ;97 mg,
74%). Mp: 878C. IR ;KBr): n ;cm21) 2981 and 2933
;C±H); 1697 ;CvO); 1648, 1491 and 1449 ;CvC); 1158
;C±O±C). 1H NMR ;CDCl3): d ;ppm) 1.27 ;s, 9H,
;CH3)3C); 1.45±1.50;m, 4H, H5 and H6); 1.80;m, 2H,
H7); 2.26 ;m, 2H, H4); 6.04 ;t, 1H, H3, J3,4ˆ7 Hz); 6.17
3.1.15.
tert-Butyl
7-phenyl-2,3,4,5-tetrahydro-1H-
azepine-1-carboxylate .11a). The reaction was carried
out as described above for the synthesis of compound 10a
with 5 ;223 mg, 0.5 mmol). Flash chromatography with
petroleum ether/EtOAc ;95/5) gave 11a as a white solid
;109 mg, 80%). Mp: 838C. IR ;KBr): n ;cm21) 2976 and
2934 ;C±H); 1697 ;CvO); 1636, 1493 and 1447 ;CvC).
1H NMR ;CDCl3): d ;ppm) 1.09 ;s, 9H, ;CH3)3C); 1.47±
1.56 ;m, 4H, H5 and H6); 1.85 ;m, 2H, H7); 2.30;m, 2H, H4);
5.87 ;t, 1H, H3, J3,4ˆ6.5 Hz); 7.23±7.30;m, 5H). 13C NMR
;m, 1H, H4 ); 6.35 ;m, 1H, H3 ); 7.31 ;m, 1H, H5 ). 13C
NMR ;CDCl3): d ;ppm) 24.40;CH 2, C5); 27.05 ;CH2,
C4); 28.20;3CH , ;CH3)3C); 29.90;CH , C6); 47.45 ;CH2,
0
0
0
;CDCl3): d ;ppm) 24.30;CH , C5); 27.65 ;CH2, C4); 28.05
2
3
2
0
C7); 79.95 ;C, ;CH3)3C); 105.15 ;CH, C4 ); 111.20;CH,
;3CH3, ;CH3)3C); 29.80;CH , C6); 48.05 ;CH2, C7); 79.85
2
0
0
;C, ;CH3)3C); 122.55 ;CH, C3); 125.10;2CH); 127.35 ;CH);
128.20;2CH); 139.85 ;C); 144.55 ;C, C2); 154.20;C,
CvO). MS: m/z 274 ;M11). Anal. Calcd for C17H23NO2:
C, 74.69; H, 8.48; N, 5.12. Found: C, 74.69; H, 8.56; N,
4.99.
C3 ); 121.50;CH, C3); 135.95 ;C); 141.40;CH, C5 );
153.00and 154.10;2C). MS: m/z 264 ;M11). Anal.
Calcd for C15H21NO3: C, 68.42; H, 8.04; N, 5.32. Found:
C, 68.42; H, 7.98; N, 5.21.
3.1.19. tert-Butyl 7-.benzo[b]thiophenyl)-2,3,4,5-tetra-
hydro-1H-azepine-1-carboxylate .11e). The reaction
was carried out as described above for the synthesis of
3.1.16. tert-Butyl 7-.p-methoxyphenyl)-2,3,4,5-tetrahydro-
1H-azepine-1-carboxylate .11b). The reaction was carried
out as described above for the synthesis of compound 10a
with 5 ;223 mg, 0.5 mmol) and p-methoxybenzeneboronic
acid ;114 mg, 0.75 mmol). Flash chromatography with
petroleum ether/EtOAc ;95/5) gave 11b as a white solid
;112 mg, 74%). Mp: 798C. IR ;KBr): n ;cm21) 2969 and
2927 ;C±H); 1701 ;CvO); 1643, 1608, 1511 and 1444
compound 10a with
5
;223 mg, 0.5 mmol) and
2-benzo[b]thiophenylboronic acid ;136 mg, 0.75 mmol).
Flash chromatography with petroleum ether/EtOAc ;95/5)
gave 11e as a white solid ;150mg, 91%). Mp: 153 8C. IR
;KBr): n ;cm21) 2972 and 2918 ;C±H); 1695 ;CvO); 1636,
1
1519, 1457 and 1439 ;CvC). H NMR ;CDCl3): d ;ppm)
1.22 ;s, 9H, ;CH3)3C); 1.51 ;m, 2H, H5); 1.82±1.87 ;m, 2H,
1
;CvC); 1249 ;C±O±C). H NMR ;CDCl3): d ;ppm) 1.09
;s, 9H, ;CH3)3C); 1.44 ;m, 4H, H5 and H6); 1.81 ;m, 2H, H7);
2.24 ;m, 2H, H4); 3.78 ;s, 3H, OCH3); 5.74 ;t, 1H, H3,
²
H6); 2.28±2.32 ;m, 2H, H4); 3.43±3.59 ;m, 2H, H7); 6.09 ;t,
0
1H, H3, J3,4ˆ6.5 Hz); 7.11 ;s, 1H, H2 ); 7.25±7.30;m, 2H);
0
0
J3,4ˆ6.5 Hz); 6.80;d, 2H, H3 and H5 , Jorthoˆ9 Hz); 7.21
7.63±7.75 ;m, 2H). 13C NMR ;CDCl3): d ;ppm) 24.25 ;CH2,
C5); 27.55 ;CH2, C4); 28.15 ;3CH3, ;CH3)3C); 29.75 ;CH2,
;d, 2H, H2 and H6 , Jorthoˆ9 Hz). 13C NMR ;CDCl3): d
0
0
0
C6); 47.40;CH 2, C7); 80.15 ;C, ;CH3)3C); 119.10;CH, C2 );
;ppm) 24.40;CH , C5); 27.55 ;CH2, C4); 28.10;3CH ,
3
2
;CH3)3C); 29.85 ;CH2, C6); 48.00 ;CH2, C7); 55.45 ;CH3,
0
122.20, 123.40, 124.30 and 124.40 ;4CH); 125.25 ;CH, C3);
139.00, 139.50, 140.15 and 143.60 ;4C); 154.00 ;C, CvO).
MS: m/z 330;M 11). Anal. Calcd for C19H23NO2S: C,
69.27; H, 7.04; N, 4.25. Found: C, 69.30; H, 7.10; N, 4.24.
OCH3); 79.70;C, ;CH ) C); 113.50and 114.00;2CH, C3
3 3
0
and C5 ); 120.95 ;CH, C3); 126.00and 126.20;2CH, C2 and
0
0
C6 ); 132.55 ;C, C1 ); 144.20;C, C2); 154.25 ;C, CvO);
0
0
159.15 ;C, C4 ). MS: m/z 304 ;M11). Anal. Calcd for
C18H25NO3: C, 71.26; H, 8.31; N, 4.62. Found: C, 71.22;
H, 8.40; N, 4.73.
3.1.20. tert-Butyl 2-phenylaza-2-cyclotridecene-1-car-
boxylate .12a). The reaction was carried out as described
above for the synthesis of compound 10a with 6 ;265 mg,
0.5 mmol). Flash chromatography with petroleum ether/
EtOAc ;95/5) gave 12a as a colorless oil ;169 mg, 94%).
IR ;NaCl ®lm): n ;cm21) 2938 and 2859 ;C±H); 1698
3.1.17. tert-Butyl 7-.1-naphtyl)-2,3,4,5-tetrahydro-1H-
azepine-1-carboxylate .11c). The reaction was carried
out as described above for the synthesis of compound 10a
with 5 ;223 mg, 0.5 mmol) and 1-naphtylboronic acid
;130mg, 0.75 mmol). Flash chromatography with petro-
leum ether/EtOAc ;95/5) gave 11c as a white solid
;155 mg, 96%). Mp: 1168C. IR ;KBr): n ;cm21) 2930;C±
1
;CvO); 1638, 1601, 1494 and 1460 ;CvC). H NMR
;CDCl3): d ;ppm) 1.37±1.42 ;m, 23H, ;CH3)3C and
7CH2); 1.76±1.78 ;m, 2H, H12); 2.25±2.32 ;m, 2H, H4);
3.57 ;m, 2H, H13); 5.55 ;m, 1H, H3); 7.27±7.32 ;m, 5H).
13C NMR ;CDCl3): d ;ppm) 23.90, 25.05, 26.75 and 28.10
;9CH2); 28.05 ;3CH3, ;CH3)3C); 48.35 ;CH2, C13); 79.70;C,
;CH3)3C); 127.35 ;2CH); 127.90;CH); 128.45 ;2CH);
128.80;CH, C3); 138.50and 139.75 ;2C); 155.50 ;C,
CvO). MS: m/z 359 ;M11). Anal. Calcd for C23H35NO2:
C, 77.27; H, 9.87; N, 3.92. Found: C, 77.11; H, 9.99; N,
4.10.
1
H); 1690;C vO); 1643, 1508 and 1441 ;CvC). H NMR
;CDCl3): d ;ppm) 0.76 ;s, 9H, ;CH3)3C); 1.63±1.72 ;m, 2H,
H5); 1.87±1.94 ;m, 2H, H6); 2.39±2.46 ;m, 2H, H4); 3.89±
3.93 ;m, 2H, H7); 5.66 ;t, 1H, H3, J3,4ˆ6 Hz); 7.36±7.44 ;m,
4H); 7.51±7.83 ;m, 2H); 8.23±8.26 ;m, 1H). 13C NMR
;CDCl3): d ;ppm) 24.10;CH 2, C5); 27.80;3CH
;CH3)3C); 27.95 ;CH2, C4); 29.25 ;CH2, C6); 49.30;CH ,
,
3
2
C7); 79.90;C, ;CH ) C); 125.20;CH, C3); 124.45, 125.05,
3 3
125.55, 125.75, 125.85, 127.55 and 128.30;7CH); 131.50,
133.95, 138.80and 141.75 ;4C); 154.25 ;C, CvO). MS: m/z
²
Obtained from CH correlation.

F. Lepifre et al. / Tetrahedron 57 12001) 6969±6975
6975
3.1.21. tert-Butyl 2-.p-methoxyphenyl)aza-2-cyclotride-
cene-1-carboxylate .12b). The reaction was carried out as
described above for the synthesis of compound 10a with 6
;265 mg, 0.5 mmol) and p-methoxybenzylboronic acid
;114 mg, 0.75 mmol). Flash chromatography with petro-
leum ether/EtOAc ;95/5) gave 12b as a white solid
;167 mg, 86%). IR ;KBr): n ;cm21) 2975 and 2935
;C±H); 1692 ;CvO); 1636, 1610, 1513 and 1452 ;CvC);
1249 ;C±O±C). 1H NMR ;CDCl3): d ;ppm) 1.18±1.41 ;m,
23H, ;CH3)3C and 7CH2); 1.76±1.79 ;m, 2H, H12); 2.26 ;m,
2H, H4); 3.52 ;m, 2H, H13); 3.81 ;s, 3H, OCH3): 5.48 ;m,
3.1.24. tert-Butyl 2-.benzo[b]thiophenyl)aza-2-cyclotri-
decene-1-carboxylate .12e). The reaction was carried out
as described above for the synthesis of compound 10a with
6 ;265 mg, 0.5 mmol) and 2-benzo[b]thiophenylboronic
acid ;136 mg, 0.75 mmol). Flash chromatography with
petroleum ether/EtOAc ;95/5) gave 12e as a white solid
;187 mg, 90%). Mp: 1168C. IR ;KBr): n ;cm21) 2929 and
2859 ;C±H); 1694 ;CvO); 1633, 1458 and 1391 ;CvC).
1H NMR ;CDCl3): d ;ppm) 1.25±1.56 ;m, 23H, ;CH3)3C
and 7CH2); 1.77 ;m, 2H, H12); 2.53 ;m, 2H, H4); 3.52 ;m,
2H, H13); 5.74 ;m, 1H, H3); 7.22±7.32 ;m, 3H); 7.71±7.80
;m, 2H). 13C NMR ;CDCl3): d ;ppm) 23.90, 24.15, 25.05,
0
0
1H, H3); 6.86 ;d, 2H, H3 and H5 , Jorthoˆ8.5 Hz); 7.23 ;d,
2H, H2 and H6 , Jorthoˆ8.5 Hz). 13C NMR ;CDCl3): d ;ppm)
26.35 and 27.55 ;8CH2); 28.30;CH , C4); 28.45 ;3CH3,
2
;CH3)3C); 48.10;CH , C13); 80.05 ;C, ;CH3)3C); 121.65
2
0
0
23.90, 25.10, 26.75 and 28.05 ;9CH2); 28.20;3CH
;CH3)3C); 48.25 ;CH2, C13); 55.35 ;CH3, OCH3); 79.55
,
3
;C); 122.20, 123.30and 123.60;3CH); 124.40;CH,
C3);
0
;C, ;CH3)3C); 113.30;2CH, C3 and C5 ); 127.80;CH,
0
124.45 ;2CH); 132.20, 133.75 and 139.60 ;3C); 155.00
;C, CvO). MS: m/z 415 ;M11). Anal. Calcd for
C25H35NO2S: C, 72.60; H, 8.53; N, 3.39. Found: C, 72.56;
H, 8.52; N, 3.44.
0
C3); 129.65 ;2CH, C2 and C6 ); 133.55 ;C, C1 ); 139.30
0
0
0
;C, C2); 155.15 ;C, CvO); 158.80;C, C4 ). MS: m/z 389
;M11). Anal. Calcd for C24H37NO3: C, 74.38; H, 9.62; N,
3.61. Found: C, 74.32; H, 9.70; N, 3.55.
References
3.1.22. tert-Butyl 2-.1-naphtyl)aza-2-cyclotridecene-1-
carboxylate .12c). The reaction was carried out as
described above for the synthesis of compound 10a with 6
;265 mg, 0.5 mmol) and 1-naphtylboronic acid ;130 mg,
0.75 mmol). Flash chromatography with petroleum ether/
EtOAc ;95/5) gave 12c as a colorless oil ;190mg, 93%).
IR ;NaCl ®lm): n ;cm21) 2929 and 2856 ;C±H); 1699
1. ;a) Okita, T.; Isobe, M. Tetrahedron 1995, 51, 3737±3744.
;b) Okita, T.; Isobe, M. Synlett 1994, 589±590.
2. ;a) Foti, C. J.; Comins, D. L. J. Org. Chem. 1995, 60, 2656±
2657. ;b) Tsushima, K.; Hirade, T.; Hasegawa, H.; Murai, A.
Chem. Lett. 1995, 9, 801±802. ;c) Beccalli, E. M.; Marchesini,
A. Tetrahedron 1995, 51, 2353±2362. ;d) Luker, T.; Hiemstra,
H.; Speckamp, W. N. J. Org. Chem. 1997, 62, 3592±3596.
;e) Luker, T.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem.
1997, 62, 8131±8140. ;f) Luker, T.; Hiemstra, H.; Speckamp,
1
;CvO); 1640, 1591 and 1460 ;CvC). H NMR ;CDCl3):
d ;ppm) 0.87 ;m, 8H, 4CH2); 1.18±1.58 ;m, 17H, ;CH3)3C
and 4CH2); 1.91 ;m, 2H, H4); 3.65 ;m, 2H, H13); 5.75 ;m,
1H, H3); 7.41±7.48 ;m, 4H); 7.76±7.85 ;m, 2H); 8.12 ;m,
1H). 13C NMR ;CDCl3): d ;ppm) 24.00, 24.95, 25.20, 25.85,
25.90, 27.10, 27.85, 28.20 and 28.70 ;9CH2); 27.95 ;3CH3,
;CH3)3C); 44.05 ;CH2, C13); 79.95 ;C, ;CH3)3C); 125.20
;2CH); 125.75, 125.85 and 127.05 ;3CH); 127.95 ;CH,
C3); 128.20;2CH); 128.4,0 132.45, 133.60and 136.65
;4C); 154.90;C, CvO). MS: m/z 409 ;M11). Anal.
Calcd for C27H37NO2: C, 79.56; H, 9.15; N, 3.44. Found:
C, 79.32; H, 9.30; N, 3.26.
Â
W. N. Tetrahedron Lett. 1996, 37, 8257±8260. ;g) Bernabe, P.;
Rutjes, F. P. J. T.; Hiemstra, H.; Speckamp, W. N. Tetrahedron
Lett. 1996, 37, 3561±3564. ;h) Ha, J. D.; Kang, C. H.; Belmore,
K. A.; Cha, J. K. J. Org. Chem. 1998, 63, 3810±3811. ;i) Ha,
J. D.; Lee, D.; Cha, J. K. J. Org. Chem. 1997, 62, 4550±4551.
;j) Brosius, A. D.; Overman, L. E.; Schwink, L. J. Am. Chem.
Soc. 1999, 121, 700±709. ;k) Occhiato, E. G.; Trabocchi, A.;
Guarna, A. Org. Lett. 2000, 2, 1241±1242.
3. ;a) Nicolaou, K. C.; Shi, G.-Q.; Namoto, K.; Bernal, F. Chem.
Commun. 1998, 1757±1758. ;b) Nicolaou, K. C.; Shi, G.-Q.;
3.1.23. tert-Butyl 2-.2-furyl)aza-2-cyclotridecene-1-
carboxylate .12d). The reaction was carried out as
described above for the synthesis of compound 10a with 6
;265 mg, 0.5 mmol) and 2-furylboronic acid ;84 mg,
0.75 mmol). Flash chromatography with petroleum ether/
EtOAc ;95/5) gave 12d as a colorless oil ;164 mg, 94%).
IR ;NaCl ®lm): n ;cm21) 2931 and 2858 ;C±H); 1701
È
Gartner, G. P.; Yang, Z. J. Am. Chem. Soc. 1997, 119, 5467±
5468.
4. Jiang, J.; De Vita, R. J.; Doss, G. A.; Goulet, M. T.; Wyvratt,
M. J. J. Am. Chem. Soc. 1999, 121, 593±594.
5. ;a) Lepifre, F.; Buon, C.; Rabot, R.; Bouyssou, P.; Coudert, G.
Tetrahedron Lett. 1999, 40, 6373±6376. ;b) Lepifre, F.; Buon,
C.; Bouyssou, P.; Coudert, G. Heterocycl. Commun. 2000, 6,
397±402. ;c) Buon, C.; Chacun-Lefevre, L.; Rabot, R.;
Bouyssou, P.; Coudert, G. Tetrahedron 2000, 56, 605±614.
6. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457±2483.
7. Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1984, 25,
4821±4824.
1
;CvO); 1464 ;CvC); 1156 ;C±O±C). H NMR ;CDCl3):
d ;ppm) 1.26±1.62 ;m, 23H, ;CH3)3C and 7CH2); 1.70;m,
2H, H12); 2.49 ;m, 2H, H4); 3.49 ;m, 2H, H13); 5.54 ;m, 1H,
0
0
0
H3); 6.24 ;m, 1H, H4 ); 6.40;m, 1H, H3 ); 7.39 ;m, 1H, H5 ).
13C NMR ;CDCl3): d ;ppm) 23.90, 25.20, 25.55, 25.90,
26.05, 26.15, 27.20 and 28.40 ;8CH2); 27.55 ;CH2, C4);
28.20;3CH 3, ;CH3)3C); 48.45 ;CH2, C13); 79.60;C,
8. Palladium-catalysed coupling reactions were also performed in
high yields with ;Ph3P)2PdCl2 according to the conditions
reported in Ref. 2k.
0
;CH3)3C); 108.90 ;CH, C4 ); 110.95 ;CH, C3 ); 129.75 ;C);
0
0
130.60 ;CH, C3); 131.00;C); 141.70;CH, C5 ); 152.20and
155.35 ;2C). MS: m/z 349 ;M11). Anal. Calcd for
C21H33NO3: C, 72.58; H, 9.57; N, 4.03. Found: C, 72.31;
H, 9.70; N, 4.20.