Palladium-catalyzed cyclization of N-n-butyl, N-(o-iodobenzyl)-3-butenamides: Six- versus seven- and eight-membered ring formation

Article abstract of DOI:10.1055/s-2002-34875

The regiochemistry of the palladium-catalyzed annulation of N-n-butyl, N-(o-iodobenzyl)-3-butenamides 1 can be dramatically varied by addition of water to the reaction mixture. In anhydrous DMF 1 lead to 6-membered ring formation, while in aqueous DMF 7/8

Full text of DOI:10.1055/s-2002-34875

1860
LETTER
Palladium-Catalyzed Cyclization of N-n-Butyl, N-(o-Iodobenzyl)-3-buten-
amides: Six- versus Seven- and Eight-membered Ring Formation
Cyclizationof
N
-
a
n
-
Butyl,
N
-
(
o
-Iodob
f
enzyl)-3
a
-butenamid
e
es lla Ferraccioli,*a Davide Carenzi,a Marta Catellanib
a
CNR-Istituto di Scienze e Tecnologie Molecolari (ISTM), Via C. Golgi 19, 20133 Milano, Italy
Fax +39(2)50314139; E-mail: rferra@icil64.cilea.it
b
Dipartimento di Chimica Organica e Industriale, Parco Area delle Scienze 17/A, 43100 Parma, Italy
Received 1 August 2002
catalytically hydrogenated to 34 in the presence of Pd/C
(Scheme 1).
Abstract: The regiochemistry of the palladium-catalyzed annula-
tion of N-n-butyl, N-(o-iodobenzyl)-3-butenamides 1 can be dra-
matically varied by addition of water to the reaction mixture. In
anhydrous DMF 1 lead to 6-membered ring formation, while in
aqueous DMF 7/8-membered rings were formed. The water effect
was also observed in MeCN and THF.
Surprisingly, the regioselectivity of annulation changed
dramatically if water was present in the reaction mixture.
With a DMF–water mixture (10/1, v/v) the reaction pro-
ceeded through exo and endo insertion of the terminal car-
bon-carbon double bond leading to 7- and 8-membered
ring formation (Scheme 2). In particular, compounds 1
(R1 = H, Me) led to the isomeric 1H-2-benzazepin-3-one
derivatives 4, 4a and dihydro-2H-2-benzazocin-3-ones 5
and 5a (Table 1, entries 2, 4). With 1 (R1 = Me) 2-benza-
zepine derivative 4b bearing a vinyl substituent on C-5
carbon atom was also obtained. Compound 1 (R1 = Ph)
transformed regioselectively into 4, 4a (entry 6). Particu-
larly in the cases of R1 = H, Me the mixture of isomeric
Heck products turned out to be difficult to separate by
flash chromatography. Base treatment of the crude ob-
tained from 1 (t-BuOK, DMF, 80 °C, 18 h) allowed the
transformation into the thermodynamically more stable
compounds 4a and 5a (Scheme 2), which could be sepa-
rated and characterized.5
Key words: palladium catalysis, cyclization, medium-sized rings,
regioselectivity, water
Palladium-catalyzed intramolecular arylation of a carbon-
carbon double bond has become an important and general
tool in the synthesis of carbo- and heterocycles.1 Being in-
terested into benzazepine and benzodiazepine synthesis
by metal-catalysed seven-membered ring formation from
properly o-substituted iodoarenes,2 we carried out a study
on palladium-catalyzed intramolecular cyclisation of N-n-
butyl, N-(o-iodophenylmethyl)amides (1) of organic acid
(3-butenoic, 3-pentenoic, 4-phenyl-3-butenoic acid) chlo-
rides, respectively. In the presence of Pd(OAc)2/Ph3P as a
catalyst, n-Bu4NOAc as a base in dry DMF3 at 85 °C com-
pounds 1 underwent 6-membered ring cyclization leading
to (E)-(Z)-1,4-dihydro-2H-isoquinolin-3-one derivatives
2 (1/1, molar ratio). In the case of R1 = Ph, the isomer (E)-
2a was also obtained in addition to 2 E and Z (1/1/1, molar
ratio) (Scheme 1 and Table 1, entries 1, 3, 5).4 They were
Remarkably, the yields of endo cyclization products
steadily decrease with more sterically hindered R1 groups,
as shown by comparing exo/endo (4/5) product ratios ob-
tained with R1 = H (62/38), R1 = Me (87/13) and R1 = Ph
(100/0).
Scheme 1 6-Membered ring cyclization products obtained in anhydrous DMF
Synlett 2002, No. 11, Print: 29 10 2002.
Art Id.1437-2096,E;2002,0,11,1860,1864,ftx,en;G21202ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Cyclization of N-n-Butyl, N-(o-Iodobenzyl)-3-butenamides
1861
Table 1 Palladium-Catalyzed Cyclization of 1a
Substrate
1
Solvent
Time
(h)
Yieldb
(%)
Product ratioc
2–2a/4–4a/5–5a
1
2
R1 = H
R1 = H
R1 = Me
R1 = Me
R1 = Ph
R1 = Ph
R1 = H
R1 = H
R1 = Ph
R1 = Ph
R1 = H
R1 = H
R1 = H
R1 = Ph
R1 = Ph
R1 = H
R1 = H
DMF
2
2
60
100/–/–
–/62/38
96/4/–
DMF/H2Od
DMF
87e
49f
76e
50
3
20
2.5
2
4
DMF/H2Od
DMF
–/87/13g
100/–/–
–/100/–
90/4/6
5
6
DMF/H2Od
MeCN
2.5
2.5
3
62e
55
7
8
MeCN/H2Od
MeCN
85
–/72/28
100/–/–
–/100/–
100/–/–
100/–/–i
9/68/23
100/–/–
–/100/–
30/30/40
–/35/65
9
3
52
10
11
12
13
14
15
16
17
MeCN/H2Od
THF
2.5
20h
5h
5h
3h
4h
2
73
62
THF
n.d.
72
THF/H2Od
THF
58
THF/H2Od
DMF
66
62j
53k
DMF
1
a Reactions were run with 10% mol Pd(OAc)2, 20% mol Ph3P, 2.5 equiv n-Bu4NOAc, [1] = 0.05 M, at 85 °C (unless otherwise indicated) for
the time required for complete conversion of 1.
b Isolated yield.
c Determined by 1H NMR analysis of the crude.
d 10/1, v/v.
e Isolated yield after t-BuOK treatment of the crude, in DMF at 80 °C for 18 h.
f 6% of the starting material was recovered.
g Determined by 1H NMR analysis of the crude, after t-BuOK treatment.
h At reflux.
i 1H NMR analysis of the reaction mixture after 5h showed the presence of (E)-(Z)-2 (15%), and iso-1 (85%).
j Reaction was run with 2.5 mol% of Herrmann catalyst.9
k Reaction was run with 2.5 mol% of Pd2(dba)3 CHCl3 and 10 mol% of (o-Tol)3P, at 65 °C.
Independently of the substituents (R1 = H, Me, Ph) sub- tion of 1 occurs the reaction proceeds through the well es-
strates 1 show a similar behaviour in DMF, both under tablished pathway of oxidative addition to palladium(0)
anhydrous and aqueous conditions. The palladium-catal- followed by ring closure and H-elimination to afford sev-
yzed annulations of the model compounds 1 (R1 = H, Ph), en and eight-membered rings 4–4b and 5–5a. If 1 first
were also carried out in other solvents such as MeCN and isomerizes to iso-1, six-membered rings 2 and 2a are
THF. Under anhydrous conditions 6-membered ring cy- formed (Scheme 3).
clization was largely or completely favoured (entries 7, 9,
11, 14), whereas the addition of water caused highly or
completely selective 7-/8-membered ring formation (en-
To prove this point iso-1 (R1 = H) was synthesized and
treated with Pd(OAc)2/Ph3P as catalyst, n-Bu4NOAc as a
base in anhydrous DMF. The reaction gave 2, isolated in
tries 8, 10, 13, 15). Under dry conditions the reactions pro-
56% yield. This implies an intramolecular reaction of the
ceeded with lower yields due to alteration of the first
Pd-C bond with the double bond carbon to the carbonyl
products formed.
group. Apparently, the intramolecular 6-ring formation
A reasonable hypothesis to account for these results is that makes up for the unfavorable electronic situation1
the reaction of 1 proceeded through different pathways (Scheme 3).
depending on double bond isomerization. If no isomeriza-
Synlett 2002, No. 11, 1860–1864 ISSN 0936-5214 © Thieme Stuttgart · New York

1862
R. Ferraccioli et al.
LETTER
5 hours 2 (15%) was present together with iso-1 (85%).
Apparently, the addition of water caused a decreased me-
dium basicity thus preventing the isomerization process.8
Replacing n-Bu4NOAc with other bases such as MgO and
Na2CO3 in anhydrous DMF, led to 6-membered rings 2
(R1 = H), deriving from isomerization to iso-1 (less than
20%) to a low extent. Again, their formation could be
completely suppressed by water addition.
Interestingly, the water effect was curtailed in the pres-
ence of a more active catalyst. With Herrmann
palladacycle9 or Pd2(dba)3/(o-Tol)3P CHCl3 as catalyst,
the reaction of 1 (R1 = H) in anhydrous DMF led to 7-/8-
membered rings with high or complete regioselectivity
(entries 16, 17). The substrate ability to undergo base-cat-
alyzed isomerization being unaltered, we argue that 1
(R1 = H) must undergo palladium-catalyzed annulation at
higher rate than isomerization to iso-1. If performed in
aqueous DMF under the same conditions the last two re-
actions again led to 4, 4a and 5, 5a with complete regiose-
lectivity and improved yields (90%, 81%).
Scheme 2 7-, 8-Membered ring cyclization products obtained in
aqueous DMF. With R1 = Me a 2-benzazepine derivative bearing a
vinyl substituent on the C-5 carbon atom (4b) also formed
The question now arises whether the isomerization of 1 is
base-catalyzed or proceeds at the level of the palladium
complex resulting from oxidative addition, probably
through an 3-allylpalladium complex.6 Our experiments
support the first hypothesis. Compounds 1 (R1 = H, Me)
treated with n-Bu4NOAc at 85 °C under anhydrous condi-
tions and in the absence of palladium catalyst, isomerized
into the thermodynamically more stable compounds iso-1.
No evidence of iso-1 (R1 = Ph) was observed under the
same conditions. This is due to the stabilizing effect of the
phenyl group on the , position of the side chain double
bond.7 In this case base-catalyzed formation of the less
stable isomer iso-1 (R1 = Ph) must occur under kinetic
control to allow formation of the 6-membered ring. By
contrast, in aqueous DMF compounds 1 treated with n-
Bu4NOAc at 85 °C turned out to be stable.
In summary, we have shown that with Pd(OAc)2/Ph3P as
a catalyst the regiochemistry of the cyclization of 1 can be
determined by the presence or absence of water. The -,
-, and -carbon atoms of the 3-butenamide chain of 1 can
be selectively involved in the palladium-catalyzed in-
tramolecular carbon-carbon coupling, giving rise to 6-
membered rings (isoquinoline) in the absence of water, or
seven-membered (2-benzazepine) and 8-membered (2-
benzazocine) rings in its presence. These nuclei are relat-
ed to pharmacologically interesting compounds.10
Since the Pd(OAc)2 system in the presence of n-Bu4NOAc
is largely used in organic synthesis our results may have
implications in all cases where medium basicity affects
substrate reactivity.
The intermediacy of iso-1 in the palladium-catalyzed re-
actions was proved in the case of 1 (R1 = H). As shown
in Table 1 (entries 11 and 12), under anhydrous conditions
in THF 1 (R1 = H) was converted into 2 in 20 hours. After
Acknowledgement
We thank the National Research Council (CNR) and the Ministero
Università e Ricerca Scientifica for financial support.
Scheme 3 Proposed isomerization pathways of 1
Synlett 2002, No. 11, 1860–1864 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Cyclization of N-n-Butyl, N-(o-Iodobenzyl)-3-butenamides
1863
J = 15.8 Hz), 4.67 (d, 1 H, J = 15.8 Hz), 7.14–7.31 (m, 9
H);13C NMR (75 MHz, CDCl3): = 13.9 (Me), 20.1, 28.9,
32.9, 35.3, 46.9 (CH2), 47.5 (CH), 50.4 (CH2), 125.3, 125.9,
126.5, 127.4, 127.5, 128.3, 128.4 (CH), 131.3, 136.7, 141.4,
171.3 (Cquat); MS (EI): m/z (%) = 306(75) [M – 1], 214(90),
203(100), 158(25), 91(90). Anal. Calcd for C21H25NO: C,
82.04; H, 8.20; N, 4.56. Found: C, 82.32; H, 8.19; N, 4.61.
(5) Palladium-catalyzed Cyclization of 1 in Aqueous DMF:
Synthesis of 2,3-Dihydro-1H-2-benzazepin-3-ones (4a)
and 1,4-Dihydro-2H-2-benzazocin-3-ones (5a). In a
Schlenk-type flask nBu4NOAc (173 mg, 0.575 mmol),
Pd(OAc)2 (5.2 mg, 0.023 mmol), Ph3P (12.1 mg, 0.046
mmol), a solution of 1 (0.23 mmol) in degassed DMF (4.2
mL), degassed water (0.42 mL) were added under nitrogen.
The mixture was heated at 85 °C under stirring until the
conversion was complete (TLC), then worked-up as
described in ref.3 The crude obtained was dissolved in dry
DMF (3.0 mL) and added with t-BuOK (28 mg, 0.25 mmol).
The resulting mixture was heated under stirring at 80 °C for
18 h. After cooling it was poured into water (7 mL) and
extracted with ether (3 4 mL). The combined organic layer
was dried (Na2SO4) and evaporated under vacuo. The crude
was purified by flash chromatography on silica gel (EtOAc/
petroleum ether) to give in order of elution 5a (R1 = H, Me)
and 4a (R1 = H, Me, Ph).
References
(1) For recent review, see: Beletskaya, I. P.; Cheprakov, A. V.
Chem. Rev. 2000, 100, 3009; and references therein.
(2) (a) Bocelli, G.; Catellani, M.; Chiusoli, G. P.; Cugini, F.;
Lasagni, B.; Neri Mari, M. Inorg. Chim. Acta 1998, 270,
123. (b) Tietze, L. F.; Ferraccioli, R. Synlett 1998, 145.
(c) Bocelli, G.; Catellani, M.; Cugini, F.; Ferraccioli, R.
Tetrahedron Lett. 1999, 40, 2623. (d) Catellani, M.;
Catucci, C.; Celentano, G.; Ferraccioli, R. Synlett 2001, 803.
(3) The use of quaternary ammonium salts in the Heck reaction
in dry and aqueous solvents was thoroughly studied by
Jeffery: (a) Jeffery, T. Tetrahedron 1996, 52, 10113; and
references therein. (b) Jeffery, T.; David, M. Tetrahedron
Lett. 1998, 39, 5751. (c) For a recent report on water effect
on Heck reaction see ref.1
(4) Palladium-catalyzed Cyclization of 1 in Dry DMF:
Synthesis of 1,4-Dihydro-2H-isoquinolin-3-ones (3): n-
Bu4NOAc (173 mg, 0.575 mmol) was placed in a Schlenk-
type flask and stirred under vacuo at 110 °C for 2 h in order
to remove water. After cooling to r.t. 1 (0.23 mmol),
Pd(OAc)2 (5.2 mg, 0.023 mmol), Ph3P (12 mg, 0.046 mmol)
and dry and degassed DMF (the content of water was
0.005%) (4.6 mL, 0.05 M) were added under nitrogen. The
mixture was heated at 85 °C under stirring until the
conversion was complete (monitored by TLC). The reaction
mixture was cooled, diluted with water (10 mL) and
extracted with diethyl ether (3 5 mL). After drying
(Na2SO4) and removal of the solvent the residue was purified
by flash chromatography on silica gel (eluent: EtOAc/
petroleum ether) leading to (E), (Z)-2 (R1 = H, 1/1, 60%
yield), (R1 = Me, 1/1, 49% yield), (E), (Z)-2 and (E)-2a
(R1 = Ph, 1/1/1, 50% yield), respectively (Table 1, entries 1,
3, 5; the configuration of 2 was determined by NOESY
experiments). Due to their instability 2 and 2a, were
submitted to catalytic reduction with 10% Pd/C (25–30%
mol) under 1 atm of hydrogen in EtOAc for 24 h. After usual
work-up and purification of the crude by flash
5a (R1 = H): Mp 41–42 °C (n-hexane/EtOAc); IR (nujol):
1737, 1646 cm–1; 1H NMR (300 MHz, CDCl3): = 0.92 (t, 3
H, J = 7.3 Hz), 1.3 (sextet, 2 H, J = 7.4 Hz), 1.49–1.59 (m, 2
H), 3.33–3.40 (m, 4 H), 4.45 (s, 2 H), 5.8 (ddd, 1 H, J = 12.6,
6.4, 6.4 Hz), 6.55 (d, 1 H, J = 12.6 Hz), 7.16–7.32 (m, 4 H);
13C NMR (75 MHz, CDCl3): = 13.9 (Me), 20.1, 29.5, 38.9,
45.1, 51.9 (CH2), 125.7, 127.6, 128.4, 130.1, 131.6, 131.8
(CH), 135.0, 136.5, 168.7 (Cquat); MS (EI): m/z
(%) = 229(60) [M+], 186(30), 129(100), 115(40). Anal.
Calcd for C15H19NO: C, 78.56; H, 8.35; N, 6.11. Found: C,
78.48; H, 8.41; N, 6.15.
4a (R1 = H): Oil; IR (neat): 2931, 2872, 1737, 1636, 1595
cm–1; 1H NMR (300 MHz, CDCl3): = 0.85 (t, 3 H, J = 7.3
Hz), 1.20–1.27 (m, 2 H), 1.47–1.57 (m, 2 H), 2.29 (s, 3 H),
3.44–3.49 (m, 2 H), 3.7–4.5 (br s, 2 H), 6.4 (s, 1 H), 7.25–
7.48 (m, 4 H); 13C NMR (75 MHz, CDCl3): = 13.7 (Me),
19.9 (CH2), 23.9 (Me), 30.5, 47.1, 51.6 (CH2), 125.5, 126.9,
127.2, 128.2, 128.8 (CH), 137.1, 137.7, 143.0, 166.4 (Cquat);
MS (EI): m/z (%) = 229(80) [M+], 187(90), 173(100),
159(60), 129(85), 115(55). Anal. Calcd for C15H19NO: C,
78.56; H, 8.35; N, 6.11. Found: C, 78.75; H, 8.15; N, 5.99.
5a (R1 = Me): Oil; IR(neat): 2958, 2927, 2871, 1728, 1635
cm–1; 1H NMR (300 MHz, CDCl3): = 0.91 (t, 3 H, J = 7.3
Hz), 1.25–1.37 (m, 2 H), 1.50–1.63 (m, 2 H), 2.06 (s, 3 H),
2.64 (d, 2 H, J = 8.0 Hz), 3.49 (pst, 2 H, J = 7.49 Hz), 4.16
chromatography on silica gel (EtOAc/petroleum ether)
compounds 3 were obtained.
3 (R1 = H): Oil, yield: 72%; IR (neat): 2961, 2931, 2872,
1651 cm–1; 1H NMR (300 MHz, CDCl3): = 0.82 (t, 3 H,
J = 7.53 Hz), 0.87 (t, 3 H, J = 7.6 Hz), 1.22–1.34 (m, 2 H),
1.47–1.57 (m, 2 H), 1.71–1.86 (m, 2 H), 3.24–3.34 (m, 1 H),
3.39 (t, 1 H, J = 6.86 Hz), 3.55–3.65 (m, 1 H), 4.17 (d, 1 H,
J = 15.8 Hz), 4.59 (d, 1 H, J = 15.8 Hz), 7.05–7.20 (m, 4 H);
13C NMR (75 MHz, CDCl3): = 11.1, 13.8 (Me), 20.1, 27.1,
29.4, 46.9 (CH2), 49.0 (CH), 50.4 (CH2), 125.1, 126.4,
127.3, 127.6 (CH), 131.2, 136.6, 171.6 (Cquat); Ms (EI): m/z
(%) = 231(12) [M+], 202(100), 160(50), 146(25), 132(60),
117(55), 91(20). Anal. Calcd for C15H21NO: C, 77.88; H,
9.15; N 6.05. Found: C, 78.02; H, 9.14; N, 6.12.
(s, 2 H), 5.62 (br t, 1 H, J = 8.0 Hz), 7.17–7.30 (m, 4 H); 13
C
NMR (75 MHz, CDCl3): = 13.9, 20.1, 22.1, 30.3, 39.3,
3 (R1 = Me): Oil, yield 68%; IR(neat): 2959, 2929, 2871,
1647 cm–1; 1H NMR (300 MHz, DMSO-d6): = 0.76 (t, 3 H,
J = 7.3 Hz), 0.80 (t, 3 H, J = 7.3 Hz), 1.13–1.2 (m, 4 H),
1.40–1.6 (m, 4 H), 3.17–3.20 (m, 1 H), 3.30 (t, 1 H, J = 7.0
Hz), 3.43–3.52 (m, 1 H), 4.26 (d, 1 H, J = 16.1 Hz), 4.56 (d,
1 H, J = 16.1 Hz), 7.10–7.20 (m, 4 H); 13C NMR (75 MHz,
DMSO-d6): = 14.0 (2 C), 19.8 (2 C), 29.2, 35.2, 45.9, 47.3,
49.5, 125.7, 126.6, 127.4 (2 C), 132.3, 137.1, 170.6; Ms (EI):
m/z (%) = 245(15) [M+], 203 (100), 174 (30), 146 (15), 131
(30), 117 (15), 91 (10). Anal Calcd for C16H23NO: C, 78.32;
H, 9.45; N 5.71. Found: C, 78.14; H, 9.59; N, 5.78.
3 (R1 = Ph): Oil, yield: 70%; IR(neat): 2957, 2928, 2860,
1651 cm–1; 1H NMR (300 MHz, CDCl3): = 0.94 (t, 3 H,
J = 7.3 Hz), 1.35 (sextet, 2 H, J = 7.4 Hz), 1.59 (quintet, 2
H, J = 7.5 Hz), 1.96–2.20 (m, 2 H), 2.65 (t, 2 H, J = 8.3 Hz),
3.32–3.42 (m, 1 H), 3.60–3.72 (m, 2 H), 4.26 (d, 1 H,
50.5, 52.4, 119.2, 125.6, 128.0, 128.4, 130.3, 133.8, 140.4,
142.3, 168.4; MS (EI): m/z (%) = 243 (15) [M+], 200 (40),
187 (25), 144 (25), 129 (100), 115 (20); HRMS (EI): Calcd
for C16H21NO: 243.1623. Found: 243.1654.
4a (R1 = Me): Mp 52–53 °C (n-hexane); IR(nujol): 1733,
1641, 1596 cm–1; 1H NMR (300 MHz, CDCl3): = 0.86 (t, 3
H, J = 7.2 Hz), 1.11 (t, 3 H, J = 7.0 Hz), 1.20–1.29 (m, 2 H),
1.45–1.60 (m, 2 H), 2.69–2.73 (br q, 2 H, J = 8.0 Hz), 3.46
(pst, 2 H, J = 7.3 Hz), 4.0 (br s, 1 H), 4.35 (br s, 1 H), 6.26
(br s, 1 H), 7.27–7.50 (m, 4 H);13C NMR (75 MHz, CDCl3):
= 13.2, 13.7, 19.9, 29.8, 30.5, 46.9, 51.6, 123.9, 126.6,
127.2, 128.1, 128.5, 137.0, 137.6, 148.6, 166.5; MS (EI): m/
z (%) = 243 (65) [M+], 201 (72), 187 (100), 173 (45), 144
(30), 128 (43), 115 (20). Anal Calcd for C16H21NO: C, 78.97;
H, 8.70; N, 5.76. Found: C, 78.93; H, 8.41; N, 5.71.
Synlett 2002, No. 11, 1860–1864 ISSN 0936-5214 © Thieme Stuttgart · New York

1864
R. Ferraccioli et al.
LETTER
(6) Tsuji, J. Palladium Reagents and Catalysts; Wiley:
4a (R1 = Ph): Mp 92–93 °C (n-hexane); IR(nujol): 1746,
1636, 1597 cm–1; 1H NMR (300 MHz, CDCl3): = 0.8 (t, 3
H, J = 7.3 Hz), 1.16 (sextet, 2 H, J = 7.6 Hz), 1.46 (quintet,
2 H, J = 7.5 Hz), 3.40 (t, 2 H, J = 7.3 Hz), 3.90 (br s, 3 H),
4.25 (br s, 1 H), 6.20 (s, 1 H), 7.10–7.30 (m, 8 H), 7.40–7.45
(m, 1 H); 13C NMR (75 MHz, CDCl3): = 14.2 (Me), 20.4,
30.9, 43.5, 47.4, 52.1 (CH2), 126.9, 127.4, 127.7, 128.6,
129.0, 129.2, 129.3 (CH), 137.3, 138.0, 138.8, 146.0, 166.7
(Cquat); MS (EI): m/z (%) = 305(100) [M+], 263(87),
249(50), 206(33), 115(25), 91(67) Anal Calcd for
C21H23NO: C, 82.59; H, 7.59; N, 4.59. Found: C, 82.76; H,
7.46; N, 4.71.
Chichester, 1995.
(7) Linstead, R. P.; Williams, L. T. L. J. Chem. Soc. 1926, 2735.
(8) Although the water effect is felt even in the presence of
traces of water we preferred to carry out experiments with
10% water for reasons of reproducibility.
(9) Herrmann, W. A.; Brossmer, C.; Reisinger, C. P.; Riermeier,
T. H.; Oefele, K.; Beller, M. Chem.–Eur. J. 1997, 3, 1357.
(10) (a) Chem. Abstr. 1978, 88, 152456. (b) Knobloch, K.;
Eberbach, W. Org. Lett. 2000, 2, 1117. (c) Lindman, S.;
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Synlett 2002, No. 11, 1860–1864 ISSN 0936-5214 © Thieme Stuttgart · New York