Synthesis of medium and large cyclic amines in rhodium-catalysed reactions of aminoalkenes with H2/CO1

Article abstract of DOI:10.1071/CH00112

Rhodium-catalysed reactions of N-benzyl- or N-alkyl-aminoalkenes (6) with H₂/CO can give cyclic amines (7) (7-13 ring size) in good to excellent yields when BIPHEPHOS is used as a ligand. Hydrogenation of the aminoalkene becomes a competing reaction for the smaller rings but can be overcome by using a H₂/CO gas ratio of 1:5. Reactions of 2-alkenyloxybenzylamines (13) gave 9-, 12- and 17-membered rings (14) in 30-40% yield, but dimer formation (16) and/or hydrogenation were competing reactions. Similar reactions of alkenylamides and ortho-alkenylanilines gave only non-cyclized amino aldehydes as products in low isolated yields.

Full text of DOI:10.1071/CH00112

C S I R O P U B L I S H I N G
Australian Journal
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Volume 53, 2000
© CSIRO 2000
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Aust. J. Chem., 2000, 53, 835–844
Synthesis of Medium and Large Cyclic Amines in Rhodium-Catalysed
Reactions of Aminoalkenes with H2/CO1
David J. Bergmann,A Eva M. Campi,A W. Roy Jackson,A,B Antonio F. PattiA,C and Dilek SaylikA
A Department of Chemistry, P.O. Box 23, Monash University, Vic. 3800.
B Author to whom correspondence should be addressed (e-mail: W.R.Jackson@sci.monash.edu.au).
C School of Applied Sciences, Monash University, Vic. 3800.
Rhodium-catalysed reactions of N-benzyl- or N-alkyl-aminoalkenes (6) with H /CO can give cyclic amines (7)
2
(7–13 ring size) in good to excellent yields when BIPHEPHOS is used as a ligand. Hydrogenation of the aminoalkene
becomes a competing reaction for the smaller rings but can be overcome by using a H /CO gas ratio of 1 : 5.
2
Reactions of 2-alkenyloxybenzylamines (13) gave 9-, 12- and 17-membered rings (14) in 30–40% yield, but dimer
formation (16) and/or hydrogenation were competing reactions. Similar reactions of alkenylamides and
ortho-alkenylanilines gave only non-cyclized amino aldehydes as products in low isolated yields.
C
0
1
D
J
e
a
Marg.CaCmeycpi, licW. AmRoinyJaesckson,AtnonioF. PatiandDi lekSayli
k
Keywords: Cyclic amines; rhodium catalysts; Biphepos.
17
Introduction
It has been shown
reactions of unsaturated amines with H /CO can give 5- and
6-membered lactams in good yields. Carbonylation reactions
were found to be favoured over hydroformylation reactions
by using gas mixtures with a high CO content (typically H /
species is reduced either with sodium borohydride or by
hydrogen over a palladium catalyst.
18
2–5
that metal-catalysed carbonylation
It was thus decided to study the rhodium-catalysed
reactions of unsaturated amines with H /CO and either first
2
2
isolate but then immediately reduce the initially formed
cyclic species or establish reaction conditions which would
lead to their ‘in situ’ reduction. In this paper we describe
such reactions which have been shown to be successful for
the synthesis of a range of cyclic amines.
2
CO, 1 : 9) and bulky phosphine ligands, e.g. tris(o-tolyl)
6
phosphine. Products arising from hydroformylation rather
than carbonylation have been obtained, usually where the
imine, iminium salt or enamine, arising from cyclization of
Results and Discussion
the first formed amino aldehyde is either reduced to a cyclic
4,5,7,8
Reactions of 10-Undecenamine
amine
or trapped by intramolecular reaction with a
9
6,10,11
10,12
pendant hydroxy group, amine,
or amide.
In
10-Undecenamine (1) was reacted with H /CO (1 : 1 or
2
several of these publications initial coordination of the amine
nitrogen to the rhodium metal has been suggested, and studies
involving stoichiometric reactions of unsaturated amines
1 : 9), [Rh(OAc) ] and PPh as ligand (Scheme 1). No
2 2 3
evidence for carbonylation products was obtained but the
initial product showed peaks consistent with an imine N=CH
1
with rhodium compounds have shown that such coordination
group in both the H and 13C n.m.r. spectra. These peaks
13,14
is facile.
The catalytic systems referred to in most cases
disappeared on standing, leading to only polymeric material.
Immediate reduction of the product, presumably containing
the cyclic imines (2) and (3) with sodium borohydride,
followed by acetylation, led to isolation of a mixture of the
N-acetyl-1-azacyclotridecane (4; R = Ac) and the N-acetyl-
3-methyl-1-azacyclododecane (5; R = Ac) in modest yield
(38%). The regioisomers (4) and (5) were in a ratio c. 2 : 1,
use very low ratios of rhodium to substrate, typically 1 : 200,
and thus it appeared to us that only the newly created
aldehyde would be in close proximity to the intramolecular
coordinated nitrogen atom. Thus ‘disguised high dilution’
15
conditions
would be effectively established and the
possibility of obtaining medium and large heterocycles from
these reactions was investigated. Initial attempts involving
rhodium-catalysed reactions of some alkenyloxybenzyl-
reflecting
an
expected
linear-to-branched
initial
hydroformylation ratio which had not been perturbed by
amine coordination. The possibility that the imines (2) and
(3) were arising via an initial carbonylation followed by
reduction and elimination of water was excluded, as the
13-membered cyclic lactam (laurolactam) was shown to be
inert under the reaction conditions.
amines with H /CO, in all cases, gave only polymeric
2
16
material. It thus appears that either polymerization is
preferred to cyclization or that the initially formed cyclic
imine, or iminium salt, is prone to polymerization under the
reaction conditions. Support for the latter possibility comes
from the reported successful syntheses of cyclic amines from
amino aldehydes only when the initially formed cyclic
Attempts to achieve ‘in situ’ reduction by increasing the
hydrogen partial pressure (H /CO, 9 : 1, 1200 psi) gave
2
Manuscript received 25 August 2000
© CSIRO 2000
10.1071/CH00112
0004-9425/00/100835

836
D. J. Bergmann et al.
Cyclization of the secondary amine with an intermediate
aldehyde must give an iminium salt or enamine and recent
work has shown that enamines hydrogenate more rapidly
21
than imines. Use of BIPHEPHOS as ligand led to the expected
6,22,23
improvement in regioselectivity
and only N-ben-
zylazacyclotridecine (7a; R = Bn) was isolated (entries 2 and
3). The BIPHEPHOS/Rh system proved to be a more efficient
hydrogenation system for iminium salts or enamines than the
polymeric material together with some evidence for the
formation of cyclic imines, while adding sodium
borohydride or sodium cyanoborohydride to the reaction
mixture gave only recovered starting material. Only
polymeric material was obtained when the zwitterionic
5
PPh /Rh system. A reaction using H /CO in the ratio 1 : 1
3
2
(entry 2) gave the cyclic amine (7a; R = Bn) in 47% isolated
yield, and this was further improved to 85% when H /CO
2
catalyst, Rh(1,5-COD)BPh , which can function as a catalyst
4
was used in the ratio 9 : 1 (entry 3). Very similar results were
obtained for reactions of the N-butyl compound (6a; R=Bu)
5,19
for both hydroformylation
used.
and imine reduction, was
20
(entries 6–8), with
a
high yield (82%) of the
azacyclotridecine (7a; R = Bu) being obtained when BIPHEPHOS
Reactions of N-Substituted 10-Undecenamines (6a)
was used as ligand together with a H /CO ratio of 9 : 1.
2
A reaction of N-benzyl-10-undecenamine (6a; R = Bn) with
A reaction of N-phenylundec-10-enamine (6a; R = Ph),
containing a weakly nucleophilic nitrogen atom, gave no
cyclic material, and a mixture of amino aldehydes was
isolated in low yield (24%) after chromatography.
Surprisingly, the ratio of linear to branched compounds was
c. 1 : 3, both in the crude product and in the isolated material,
PPh as ligand and a 1 : 1 ratio of H /CO directly gave the
3
2
cyclic amines (7 and 8; R = Bn) in a ratio c. 2 : 1 in c. 25%
isolated yield, together with polymeric material (Scheme 2,
Table 1, entry 1) and a similar result was obtained for the
o-tolylmethyl compound (6a; R = (o-Tol)CH ) (entry 4).
2
24
in contrast to the normal preference for linear product.
Table 1. Rhodium-catalysed reactions of N-substituted
undecenamines (6a) with H2/CO
Reactions of (6a) were carried out for 20 h at 80° with an initial gas
pressure (H2 + CO) of 2.76 MPa (400 psi) with [Rh(OAc)2]2 and ligand
in molar ratio 200 : 1 : 4
Reactions of N-Substituted Aminoalkenes (6b–d)
The reaction conditions which led to high yields of the
13-membered cyclic amine (7a), i.e. use of BIPHEPHOS and a
ratio of 9 : 1 H /CO, were applied to reactions for the shorter
2
chain aminoalkenes (6b) and (6d) (Scheme 2; Table 2). Only
modest yields (20–25%) of the 10- and 7-membered cyclic
amines (7b) and (7d) were isolated, together with the
aminoalkanes (9b,d) derived from hydrogenation of the
starting alkene (35–40%) (Table 2, entries 10 and 12). The
Entry Reactant (6a) Ratio Ligand Product ratioA Isolated yield
R
H2/CO
(7a) (8a) (%)B of (7a)
1
2
3
4
5
6
7
8
Bn
Bn
Bn
1 : 1
PPh3
70
30
–
–
15
–
25
47
85
22
28
22C
40
82
1 : 1 BIPHEPHOS 100
9 : 1 BIPHEPHOS 100
1 : 1
1 : 5 BIPHEPHOS 100
1 : 1
partial pressure of hydrogen in the H /CO was decreased to
2
(o-Tol)CH2
(o-Tol)CH2
Bu
PPh3
85
1 : 1 and 1 : 5, in attempts to overcome the problem of alkene
hydrogenation. No improvement was observed when a 1 : 1
PPh3
gas ratio of H /CO was used for a reaction of (6b; R = Bn)
Bu
Bu
1 : 1 BIPHEPHOS 100
9 : 1 BIPHEPHOS 100
–
–
2
(entry 9), but reaction of N-benzyl-5-hexenamine (6c;
R = Bn) gave the 8-membered azocane (7c) in 43% yield
(entry 11). A recent publication has recommended the use of
even lower partial pressures of hydrogen to overcome this
A Estimated from 1H and 13C n.m.r. spectra of the total product.
B Material purified by selective extraction and/or chromatography.
C Isolated from complex mixture of products.

Synthesis of Medium and Large Cyclic Amines
837
Table 2. Rhodium-catalysed reactions of N-substituted
aminoalkenes (6b–d) with H2/CO and BIPHEPHOS as ligand
Reaction conditions and yields as for Table 1
Entry
Reactant
R
Ratio
Isolated yields (%)
H2/CO
(7)
(9)
9
(6b)
(6b)
(6c)
(6d)
(6d)
Bn
Bn
Bn
1 : 1
9 : 1
1 : 1
9 : 1
1 : 5
25
25
43
20
60
35
35
–
40
–
10
11
12
13
PhCH(Me)
PhCH(Me)
Related studies were also carried out with a range of
related 2-alkenyloxybenzylamines (13). Reactions of the
primary amine (13a; Bn = H) under the usual conditions with
1 : 1 or 1 : 9 H /CO, or with Rh (CO) , were similar to those
25
problem. When a gas ratio of 1 : 5 H /CO was used for a
2
2
4
12
reaction of (6d), the cyclic amine (7d) was obtained in 60%
yield with no evidence for substrate hydrogenation (entry
13). A reaction of the substituted undecenamine (6a;
of undec-10-enamine (1), in that only polymeric material
was obtained unless reaction products were immediately
reduced as described above (Scheme 4). The cyclic amines
were isolated as their N-acetyl derivatives (14a; Bn = Ac) and
(15a; Bn = Ac) in 36% yield and c. equimolar ratio.
R = (o-Tol)CH ) under these conditions gave only a modest
2
yield of the cyclic amine (7a; R = (o-Tol)CH ) (Table 1,
2
entry 5), lower than that obtained with the benzyl analogue
(6a; R = Bn) by using a 1 : 1 gas ratio (Table 1, entry 2).
Polymeric material was the only other product. It thus seems
that the problem of olefin hydrogenation versus
hydroformylation becomes more acute as the chain length of
the aminoalkene decreases. Such an observation makes it
even more difficult to predict the optimum pressure ratio of
Reactions of the N-benzyl derivative (13a) gave a low
isolated yield of cyclic product (14a) when PPh was used as
3
ligand (Table 3; entry 14) and this increased to 34% when
BIPHEPHOS was used as ligand but, surprisingly, together with a
significant yield of the dimer (16a) (entry 15). An increase
in the hydrogen partial pressure gave a comparable yield of
monomer (14a) but also increased the yield of the dimer
(16a) (to 44%) together with some hydrogenated starting
material (17a) (16%) (entry 16). A reaction using a gas
H and CO to achieve high yields of cyclic amines with a
2
minimum of polymerization and double bond hydrogenation.
mixture with a high CO partial pressure (1 : 5 H /CO) gave
2
Reactions of Some Amidoalkenes
a similar ratio of products to the reaction with a H /CO ratio
2
Hydroformylation of some pent-4- and but-3-enamides has
been shown to give 5- and 6-membered heterocycles in the
presence of rhodium catalysts with or without added ligands
of 1 : 1, but in reduced yield (entry 17).
Reactions of the hexenyloxy homologue (13b) with either
1 : 1 or 9 : 1 H /CO gas ratios gave complex mixtures of
2
at temperatures of 80–100° and with H /CO gas pressures of
c. 8.2 MPa (1200 psi). The reactions of some undec-10-
products from which only small amounts (c. 20%) of the
hydrogenated starting material (17b) could be isolated
(Scheme 4; Table 3, entries 18 and 19). Use of the CO-rich
gas mixture led to the isolation of the cyclic amines (14b)
and (15b) in 30 and 10% yields, respectively. No
hydrogenation product or dimer was detected (entry 20).
2
8b
enamides were attempted under similar conditions to see if
medium ring compounds would be formed. Reactions of
undec-10-enamide with H /CO, 1 : 1, and PPh as ligand, at
2
3
80° gave polymeric material. Reactions of the N-benzyl,
N-butyl and N-aryl derivatives either with PPh as ligand at
A reaction of the allyloxybenzylamine (13c) with 1:1 H /
3
2
80° or by using Rh (CO) with no added ligand at 100° with
CO and BIPHEPHOS gave the cyclic benzoxazonine (14c) in 33%
yield, together with the dimer (16c) (19%) and some
deallylated starting materials (18%) (Scheme 4; Table 3,
4
12
decreased pressures, 5.52 MPa (800 psi), of a mixture of H /
2
CO, 1 : 3, gave no evidence for cyclic products. Starting
amidoalkene was recovered from reactions of the N-phenyl
compound, and in the other cases, linear and branched
aldehydes resulting from hydroformylation were formed.
entry 21). A similar reaction but using PPh was more
3
complex, giving rise only to the phenol arising from
deallylation (25%) and a benzoxazine (19%) arising from a
16
previously noted rearrangement.
Reactions of Some Alkenyloxyamines
The unpredictable formation of dimeric compounds in
some cases mirrors other recent syntheses of medium and
large heterocycles involving heterogeneous metal-catalysed
The possibility of introducing a second heteroatom into the
heterocycles was briefly investigated. Reaction of N-benzyl-
3-(but-3-enyloxy)propenamine (10) with BIPHEPHOS and a 9 : 1
26
hydrogenation cyclization of some nitroaldehydes.
H /CO gas ratio gave mainly the hydrogenated material (12)
(46% isolated) together with a complex mixture of products
(Scheme 3). Reduction of the hydrogen partial pressure to
2
Experimental
All operations involving ligands, catalysts and hydride reagents were
carried out under an atmosphere of dry nitrogen with dry solvents that
were distilled prior to use. Flash chromatography was performed on
E. Merck 230–400 mesh silica gel or alumina (basic, activity 1).
1H n.m.r. spectra were measured at 200, 300 or 400 MHz, 13C at 50 or
100 MHz. Mass spectra including accurate mass measurements were
1 : 1 H /CO, and use of PPh as a ligand, gave the cyclic
2
3
amine (11) in low yield (14%). The yield of amine thus
paralleled that from the aminoalkene (6b; R = Bn) of the
same chain length (Table 2, entries 9 and 10).

838
D. J. Bergmann et al.
obtained by electrospray mass spectroscopy (ESI) with a cone voltage
of 25 V and with methanol as the mobile phase. Analytical gas–liquid
chromatography was carried out by using a 1.8 m × 0.5 mm stainless
steel column of 10% S.E. 30 on acid-washed DMCS chromosorb W 80/
100.
Table 3. Rhodium-catalysed reactions of N-benzyloxyben-
zylamines (13) with H2/CO
Reaction conditions and yields as for Table 1
Entry
Reactant Ratio Ligand
H2/CO
Product yields (%)
(14) (15) (16) (17)
1
Generally, combustion analysis gave errors > 0.4% even though H
13
and C n.m.r. spectra suggested analytically pure material.
14
15
16
17
18
19
20
21
(13a)
(13a)
(13a)
(13a)
(13b)
(13b)
(13b)
(13c)
1 : 1
1 : 1
9 : 1
1 : 5
1 : 1
9 : 1
1 : 5
1 : 1
PPh3
10
34
38
20
–
–
30
33
–
–
–
–
–
–
20
44
10
–
–
–
19
–
–
16
–
BIPHEPHOS
BIPHEPHOS
BIPHEPHOS
BIPHEPHOS
BIPHEPHOS
BIPHEPHOS
BIPHEPHOS
Materials
Rhodium(III) trichloride trihydrate (RhCl .nH O, n ≈ 3) was supplied by
3
2
Johnson Matthey Pty Ltd and converted into tetrakis
28
(acetato)dirhodium(II), [Rh(OAc) ] ,27 Rh (CO)
and 1,5-cyclo-
20
20
–
4
12
2 2
octadienetetraphenylboratorhodium, Rh(1,5-COD)(BPh ).29 BIPHEPHOS
4
was prepared according to a literature procedure.22 Light petroleum
refers to the fraction of petroleum, b.p. 60–80°.
10
–
A
–
Alkenylamides were prepared by reactions of undec-10-enoyl
chloride with the appropriate amine.
A 2-Benzylaminomethylphenol (18%) was also isolated.
Undec-10-enamide was prepared as a cream solid (4.27 g, 86%),
. 13
m.p. 84.5–86° (lit.30 88.5–89°) C n.m.r. δ (50 MHz) 25.48, 28.82,
29.00, 29.15, 29.23 (C 3,4,5,6,7,8); 33.72 (C 9); 35.92 (C 2); 114.08
(C 11); 139.11 (C 10); 176.09 (CO).
Primary Alkenylamines
Primary amines were prepared by reduction of the appropriate azide,33
N-Benzylundec-10-enamide was prepared as a cream solid (1.32 g,
amide34 or nitrile.34
31
. 13
36%), m.p. 57.5–59° (lit. 60–61°) C n.m.r. δ (50 MHz) 25.78,
Undec-10-enamine (1) was prepared as a clear oil (72–88%), b.p.
28.90, 29.07, 29.30 (C 3,4,5,6,7,8); 33.80 (C 9); 36.78 (C 2); 43.63
13
(oven) 85°/0.1 mm (lit.30,35 b.p. 80–82°/0.06 mm). C n.m.r. δ (50
(PhCH N); 114.17 (C 11); 127.54 (C 4′); 127.85 (C 3′,5′); 128.73
2
MHz) 26.78, 28.81, 29.01, 29.34, 29.38, 29.47 (C 3,4,5,6,7,8); 33.70,
33.77 (C 2,9); 42.16 (C 1); 113.98 (C 11); 139.04 (C 10).
(C 2′,6′); 138.36 (C 1′); 139.20 (C 10); 173.10 (C 1).
N-Butylundec-10-enamide was prepared as a low-melting solid
(5.23 g, 81%), m.p. 35° (lit.32 b.p. 195°/1.5 mm) (Found: m/z 240.2316.
3-(But-3-enyloxy)propanamine. Reaction of 3-(but-3-enyloxy)
propanenitrile36 (5.00 g, 40.0 mmol) with LiAlH (2.28 g, 60.0 mmol)
+
13
4
(C
H NO+H) requires m/z 240.2327). C n.m.r. δ (50 MHz) 13.71
15 29
in ether (50 ml) at reflux for 2 h gave the corresponding amine37 as a
(C 4′); 20.03 (C 3′); 25.81, 26.47, 28.83, 29.01, 29.27 (C 3,4,5,6,7,8);
31.70 (C 2′); 33.73 (C 9); 36.82 (C 2); 39.12 (C 1′); 114.08 (C 11);
139.10 (C 10); 173.10 (C 1).
clear oil (4.07 g, 79%) (Found: m/z 128.1067. C
H NO requires m/z
17 15
13
128.1075). C n.m.r. δ (50 MHz) 32.75 (C 2); 33.61 (C 2′); 39.07 (C 1);
68.41 (C 3); 69.57 (C 1′); 115.64 (C 4′); 134.70 (C 3′).
N-Phenylundec-10-enamide was prepared as a cream solid (1.77 g,
. 13
50%), m.p. 56–58° (lit.31 54–55°) C n.m.r. δ (50 MHz) 25.80, 28.84,
Synthesis of Compounds (13a) and (13b)
29.03, 29.29 (C 3,4,5,6,7,8); 33.74 (C 9); 37.46 (C 2); 114.14 (C 11);
120.20 (C 3′,5′); 124.39 (C 4′); 128.87 (C 2′,6′); 137.76 (C 1′); 139.11
(C 10); 172.40 (C 1).
The 2-substituted benzylamines were prepared from the corresponding
2-substituted benzonitriles as described below.
N-(3,5-Dimethoxyphenyl)undec-10-enamide was prepared as a
+
2-(Undec-10-enyloxy)benzonitrile
brown solid (1.48 g, 43%) (Found: m/z 320.2224. (C
H NO +H)
19 29 3
–1
1
requires m/z 320.2226). ν
(neat) 1660s cm . H n.m.r. δ (200 MHz)
Reaction of 2-hydroxybenzonitrile (1.11 g, 9.3 mmol), undec-10-enyl
mesylate (2.30 g, 9.3 mmol) and K CO (1.92 g, 13.9 mmol) in dry
acetone (50 ml) at reflux for 16
max
1.29, br s, 10H, H 4,5,6,7,8; 1.69, m, 2H, H 3; 1.98–2.07, m, 2H, H 9;
2
3
2.33, t, 2H, J 7.5 Hz, H 2; 3.75, s, 6H, OCH ; 4.89–5.04, m, 2H, H 10;
h
gave 2-(undec-10-
3
5.80, ddt, 1H, J 16.8, 10.1, 6.6 Hz, H 11; 6.21, t, 1H, J 2.1 Hz, H 4′;
enyloxy)benzonitrile after chromatography (silica, 20% EtOAc/light
petroleum) as a clear oil (1.91 g, 73%) (Found: m/z 271.194.
13
6.79, d, 2H, J 1.9 Hz, H 2′,6′; 7.56, br s, 1H, NH. C n.m.r. δ (50 MHz)
+
–1 1
25.52, 28.85, 29.04, 29.22, 29.29 (C 3,4,5,6,7,8); 33.74 (C 9); 37.81
(C
H
NO+H) requires m/z 271.194). ν
(neat) 2228s cm . H
18 25
max
(C 2); 55.30 (OCH ); 96.51 (C 4′); 97.91 (C 2′6′); 114.12 (C 11);
n.m.r. δ (200 MHz) 1.19–1.52, m, 12H, H 3,4,5,6,7,8; 1.77–1.91, m,
2H, H 2′; 1.99-2.08, m, 2H, H 9′; 4.05, t, 2H, J 6.5 Hz, H 1′; 4.89-5.05,
m, 2H, H 11′; 5.81, ddt, 1H, J 16.9, 10.1, 6.6 Hz, H 10′; 6.92–7.00, m,
3
139.13 (C 10); 139.82 (C 1′); 160.96 (C 3′,5′); 171.74 (C 1). Mass
+
+
spectrum (ESI ): m/z 320.3 (M+H) .

Synthesis of Medium and Large Cyclic Amines
839
13
2H, H 4,5; 7.46–7.56, m, 2H, H 3,6. C n.m.r. δ (50 MHz) 25.78,
amine (6a; R = (o-Tol)CH ) as a clear oil (1.44 g, 89%) (Found: m/z
2
+
1
28.82, 29.02, 29.20, 29.32, 29.38 (C 2′,3′,4′,5′,6′,7′,8′); 33.72 (C 9′);
68.93 (C 1′); 101.92 (C 2); 112.11 (C 4); 114.03 (C 11′); 116.42 (CN);
120.41 (C 5); 133.64, 134.17 (C 3,6); 136.09 (C 10′); 160.74 (C 1).
274.2536. (C H N+H) requires m/z 274.2535). H n.m.r. δ (200
19 31
MHz) 1.20–1.42, m, 12H, H 3,4,5,6; 1.45–1.54, m, 2H, H 2; 1.98–2.08,
m, 2H, H 9; 2.33, s, 3H, CH ; 2.65, t, 2H, J 7.0 Hz, H 1; 3.74, s, 2H,
3
+
+
Mass spectrum (ESI ): m/z 272.1 (M+H) .
PhCH N; 4.88–5.04, m, 2H, H 11; 5.80, ddt, 1H, J 16.8, 10.1, 6.6 Hz,
2
13
H 10; 7.13–7.18, m, 3H and 7.25–7.30, m, 1H, ArH. C n.m.r. δ (50
MHz) 18.87 (CH ); 27.32, 28.87, 29.07, 29.39, 29.51, 30.07
2-(Undec-10-enyloxy)benzylamine (13a; Bn = H)
3
(C 2,3,4,5,6,7,8); 33.76 (C 9); 49.82 (C 1); 51.58 (PhCH N); 114.06
Reaction of the above nitrile (1.46 g, 5.4 mmol) with LiAlH (0.25 g,
6.5 mmol) in ether (20 ml) at reflux for 2 h gave the amine (13a; Bn=H)
2
4
(C 11); 125.80, 126.77 (C 4′,5′); 128.19, 130.13 (C 3′,6′); 136.07 (C 2′);
+
138.40 (C 1′); 140.00 (C 10). Mass spectrum (ESI ): m/z 274.3
as a clear oil (1.41 g, 95%) (Found: C, 78.7; H, 10.8; N, 5.0. C
H NO
18 29
+
1
(M+H) .
requires C, 78.5; H, 10.6; N, 5.1%). H n.m.r. δ (200 MHz) 1.31–1.50,
m, 12H, H 3′,4′,5′,6′,7′,8′; 1.71–1.86, m, 2H, H 2′; 1.98–2.08, m, 2H,
H 9′; 2.15, br s, 2H, NH ; 3.80, s, 2H, ArCH N; 3.97, t, 2H, J 6.3 Hz,
N-Benzyloct-7-enamine (6b; R = Bn)
2
2
H 1′; 4.89–5.04, m, 2H, H 11′; 5.80, ddt, 1H, J 16.9, 10.1, 6.7 Hz, H 10′;
Reaction of benzylamine (2.74 g, 25.5 mmol) with 8-bromooctene
13
6.81–6.92, m, 2H, and 7.17–7.26, m, 2H, ArH. C n.m.r. δ (50 MHz)
(2.44 g, 12.8 mmol) and K CO (3.53 g, 25.6 mmol) in dry acetone (50
2 3
26.11, 28.81, 29.02, 29.24, 29.34, 29.43 (C 2′,3′,4′,5′,6′,7′.8′); 33.71
ml) at reflux for 18 h gave a mixture of the mono- and di-alkylated
products. Purification by flash chromatography (silica, 20% EtOAc/
(C 9′); 42.64 (ArCH N); 67.61 (C 1′); 110.88 (C 4); 114.05 (C 11′);
2
120.21 (C 5); 127.98 (C 3,6); 131.41 (C 1); 139.05 (C 10′); 156.82
light petroleum) gave the amine (6b; R = Bn) as a beige oil (0.60 g,
+
+
+
(C 2). Mass spectrum (ESI ): m/z 276.2 (M+H) .
22%) (Found: m/z 218.1903. (C
H
N+H) requires m/z 218.1909).
15 23
1
H n.m.r. δ (200 MHz) 1.24–1.56, m, 8H, H 2,3,4,5; 1.98–2.08, m, 2H,
H 6; 2.61, t, 2H, J 7.0 Hz, H 1; 3.77, s, 2H, PhCH N; 4.88–5.04, m, 2H,
2-(Hex-5-enyloxy)benzonitrile
2
H 8; 5.80, ddt, 1H, J 16.9, 10.1, 6.6 Hz, H 7; 7.18–7.32, m, 5H, PhH.
Reaction of 2-hydroxybenzonitrile (1.67 g, 14.0 mmol) and hex-5-enyl
mesylate (2.50 g, 14.0 mmol) as described above gave 2-(hex-5-
enyloxy)benzonitrile as a clear oil (2.03 g, 72%) (Found: m/z 224.2037.
13
C n.m.r. δ (50 MHz, CDCl ) 27.15, 28.80, 28.98, 30.01 (C 2,3,4,5);
3
33.68 (C 6); 49.43 (PhCH N); 54.05 (C 1); 114.15 (C 8); 126.78 (C 4′);
2
+
–1 1
128.04, 128.29 (C 2′,3′,5′,6′); 139.00 (C 7); 140.51 (C 1′). Mass
(C
H
NO+Na) requires m/z 224.1051). ν
(neat) 2228s cm . H
13 15
max
+
+
spectrum (ESI ): m/z 218 (M+H) .
n.m.r. δ (200 MHz) 1.53–1.69, m, 2H, H 3′; 1.79–1.93, m, 2H, H 2′;
2.08–2.19, m, 2H, H 4′; 4.03, t, 2H, J 6.5Hz, H 1’; 4.94–5.09, m, 2H,
H 6′; 5.82, ddt, 1H, J 16.8, 10.1, 6.6 Hz, H 5′; 6.93–7.02, m, 2H and
A similar reaction in CH CN gave the title amine in 72% yield.
3
N-Benzylhex-5-enamine (6c; R = Bn)
13
7.47–7.55, m, 2H, ArH. C n.m.r. δ (50 MHz) 24.96 (C 3′); 28.15
(C 2′); 33.16 (C 4′); 68.67 (C 1′); 101.78 (C 1); 112.08 (C 3); 114.77
(C 6′); 116.16 (CN); 120.45 (C 5); 133.58, 134.21 (C 4,6); 138.17
Reaction of benzylamine (0.44 g, 4.1 mmol) with hex-5-enyl mesylate
(0.50 g, 3.4 mmol) at 60° for 18 h gave the amine (6c; R = Bn)39 after
chromatography (silica, 30% EtOAc/light petroleum) as a clear,
+
+
(C 5′); 160.63 (C 2). Mass spectrum (ESI ): m/z 201.6 (M+H) .
13
colourless oil (0.35 g, 54%). C n.m.r. δ (50 MHz) 26.56, 29.51
2-(Hex-5-enyloxy)benzylamine (13b; Bn = H)
(C 2,3); 33.58 (C 4); 49.22 (PhCH N); 54.01 (C 1); 114.39 (C 6);
2
126.77 (C 4′); 128.01, 128.29 (C 2′,3′,5′,6′); 138.69 (C 5); 140.47
(C 1′).
Reaction of the above nitrile (1.95 g, 9.7 mmol) with LiAlH (0.74 g,
19.4 mmol) as described above gave the benzylamine (13b; Bn = H) as
4
+
a clear oil (1.61 g, 81%) (Found: m/z 206.1545. (C
H NO+H)
13 19
N-Butylundec-10-enamine (6a; R = Bu)
1
requires m/z 206.1545). H n.m.r. δ (200 MHz) 1.50–1.66, m, 2H, H 3′;
1.68, s, 2H, NH ; 1.73-1.90, m, 2H, H 2′; 2.06–2.19, m, 2H, H 4′; 3.81,
Reaction of N-butylundec-10-enamide (2.0 g, 8.4 mmol) with LiAlH
2
4
s, 2H, ArCH N; 3.98, t, 2H, J 6.2 Hz, H 1′; 4.94–5.09, m, 2H, H 6′;
(0.48 g, 12.6 mmol) in ether at reflux for 2 h gave the amine as a pale
2
5.82, ddt, 1H, J 16.9, 10.1, 6.6 Hz, H 5′; 6.81–6.93, m, 2H and 7.15–
yellow oil (1.67 g, 89%), b.p. (oven) 85°/0.7 mm (lit.32 107–109°/0.8
13
-
13
7.26, m, 2H, ArH. C n.m.r. δ (50 MHz) 25.35 (C 3′); 28.65 (C 2′);
mm) (Found: m/z 224.2358. C
H
N requires m/z 224.2378).
C
15 31
33.28 (C 4′); 42.69 (ArCH N); 67.37 (C 1′); 110.84 (C 3); 114.71
n.m.r. δ (50 MHz) 14.02 (C 4′); 20.52 (C 3′); 27.40, 28.90, 29.10, 29.28,
29.42, 29.53, 30.21 (C 2,3,4,5,6,7,8); 32.35 (C 2′); 33.78 (C 9); 49.84,
50.18 (C 1,1′); 114.06 (C 11); 139.18 (C 10).
2
(C 6′); 120.24 (C 5); 127.87, 128.30 (C 4,6); 131.80 (C 1); 138.30
+
+
(C 5′); 156.73 (C 2). Mass spectrum (ESI ): m/z 206 (M+H) .
Secondary Alkenylamines
N-Phenylundec-10-enamine (6a; R = Ph)
Secondary amines were generally prepared by reductive amination of
the appropriate aromatic aldehyde and an alkenylamine,38 by reductive
amination of the appropriate alkenyl aldehyde and benzylamine, by
Reduction of the corresponding amide (0.65 g, 2.5 mmol) with
LiAlH (0.19 g, 5.0 mmol) gave the amine31 as a pale yellow oil
4
13
(0.53 g, 86%). C n.m.r. δ (50 MHz) 27.09, 28.84, 29.04, 29.36,
LiAlH reduction of the appropriate amide34 or by alkylation of
29.46 (C 2,3,4,5,6,7,8); 33.73 (C 9); 43.85 (C 1); 112.54 (C 2′,6′);
114.07 (C 11); 116.90 (C 4′); 129.06 (C 3′,5′); 139.01 (C 10); 148.41
(C 1′).
4
benzylamine with the appropriate alkenyl bromide or mesylate.
N-Benzylundec-10-enamine (6a; R = Bn)
N-Benzyl-3-(but-3-enyloxy)propanamine (10)
Reaction of benzaldehyde (0.63 g, 5.9 mmol) with undec-10-enamine
(1) (1.00 g, 5.9 mmol) in dry methanol (20 ml), followed by reduction
Reaction of benzaldehyde (1.65 g, 15.5 mmol) and 3-(but-3-
enyloxy)propanamine (2.00 g, 15.5 mmol) in methanol (15 ml),
with NaBH (0.34 g, 8.9 mmol), gave the amine (6a; R = Bn)31 as a
4
13
clear, colourless oil (1.42 g, 93%). C n.m.r. δ (50 MHz) 27.26, 28.83,
29.03, 29.35, 29.45, 30.02, 33.71 (C 2,3,4,5,6,7,8,9); 49.42 (C 1); 54.01
followed by reduction with NaBH (1.17 g, 31.0 mmol), gave the
4
amine (10) as a clear oil (2.12 g, 62%) (Found: m/z 220.1696.
+
1
(PhCH N); 114.02 (C 11); 126.70 (C 4′); 127.97, 128.22 (C 2′,6′,3′,5′);
(C
H NO+H) requires m/z 220.1701). H n.m.r. δ (200 MHz)
2
14 21
139.03 (C 10); 140.47 (C 1′).
1.80, p, 2H, J 6.5 Hz, H 2; 2.33, q, 2H, J 6.7 Hz, H 2′; 2.73, t, 2H,
J 6.8 Hz, H 1; 3.47, t, 2H, J 6.7 Hz and 3.51, t, 2H, J 6.2 Hz, H 1′,3;
The amine was also prepared in 80% yield by the reaction of
benzylamine (0.64 g, 5.9 mmol) and undec-10-enal (1.00 g, 5.9 mmol),
3.78, br s, 2H, PhCH N; 5.01–5.14, m, 2H, H 4′; 5.82, ddt, 1H,
2
13
followed by NaBH reduction.
4
J 17.0, 10.2, 6.7 Hz, H 3′; 7.22–7.34, m, 5H, PhH. C n.m.r. δ (50
MHz) 29.79 (C 2); 34.09 (C 2′); 46.81 (C 1); 53.90 (PhCH N); 69.39
2
N-(2-Methylbenzyl)undec-10-enamine (6a; R = (o-Tol)CH )
2
(C 3); 70.05 (C 1′); 116.18 (C 4′); 126.75 (C 4′′); 128.00, 128.24
+
Reaction of 2-methylbenzaldehyde (0.71 g, 5.9 mmol) with undec-10-
(C 2′′,3′′,5′′,6′′); 135.20 (C 3′); 140.27 (C 1′′). Mass spectrum (ESI ):
+
enamine (1.00 g, 5.9 mmol), followed by NaBH reduction, gave the
m/z 219.8 (M+H) .
4

840
D. J. Bergmann et al.
N-Benzyl-2-(undec-10-enyloxy)benzylamine (13a)
Unless otherwise stated, all reactions involved the use of
[Rh(OAc) ] and were carried out in benzene at 80° for 20 h. Reactions
2 2
Reaction of benzaldehyde (0.39 g, 3.6 mmol) and 2-(undec-10-
enyloxy)benzylamine (1.00 g, 3.6 mmol), followed by reduction with
involving the use of [Rh(OAc) ] and PPh as the catalyst system at 80°
2 2
3
with an initial pressure of 1 : 1 H /CO (400 psi, 2.76 MPa) are referred
2
NaBH (0.21 g, 5.5 mmol), gave the amine (13a) as a clear oil (1.13 g,
4
to as ‘the usual conditions’.
85%) (Found: C, 82.2; H, 9.8; N, 3.5. C
H NO requires C, 82.1; H,
25 35
Reactions leading to cyclized products were repeated at least once
and gave product ratios with 5% reproducibility.
1
9.7; N, 3.8%). H n.m.r. δ (200 MHz) 1.28, br s, 12H, H 3′,4′,5′,6′,7′,8′;
1.69–1.83, m, 2H, H 2′; 1.99–2.09, m, 2H, H 9′; 2.27, br s, 1H, NH;
3.76, s, 2H, PhCH N; 3.81, s, 2H, ArCH N; 4.90–5.05, m, 2H, H 11′;
2
2
1-Acetyl-3-methylazacyclododecane (5; R = Ac) and 1-Acetylazacyclo-
tridecane (4; R = Ac)
5.81, ddt, 1H, J 19.9, 10.1, 6.6 Hz, H 10′; 6.87, m, 2H, 7.17–7.27, m,
13
3H and 7.29–7.35, m, 4H, ArH. C n.m.r. δ (50 MHz) 26.19, 28.89,
29.09, 29.32, 29.42, 29.50 (C 2′,3′,4′,5′,6′,7′,8′); 33.78 (C 9′); 49.06
(ArCH N); 53.00 (PhCH N); 67.74 (C 1′); 111.00 (C 3); 114.12
Undec-10-enamine (1) (0.30 g, 1.8 mmol), [Rh(OAc) ] (3.9 mg,
2 2
8.9 µmol) and PPh (9.3 mg, 35.5 µmol) were reacted under the usual
2
2
3
(C 11′); 120.13 (C 5); 126.71 (C 1); 126.76, 127.23, 128.16, 128.27,
128.34, 130.02 (C 4,6, PhCH); 139.14 (C 10′); 140.44 (C 1′′); 157.22
conditions. Polymeric material lined the reaction vessel. Evaporation
of the benzene solution gave a viscous oil (0.25 g) (1H n.m.r. δ 5.76,
t, J 7.2 Hz; 13C n.m.r. δ 164.5, 167.7) which polymerized on
standing.
+
+
(C 2). Mass spectrum (ESI ): m/z 366.3 (M+H) .
N-Benzyl-2-(hex-5-enyloxy)benzylamine (13b)
An identical result was obtained when using a H /CO gas mixture
2
of 1 : 9. The benzene-soluble products from a repeat reaction were
Reaction of benzaldehyde (0.78 g, 7.3 mmol) and 2-(hex-5-
immediately added dropwise to a cooled suspension of LiAlH
enyloxy)benzylamine (1.50 g, 7.3 mmol), followed by NaBH
4
4
(76 mg, 2.0 mmol) in dry benzene (10ml) and heated at reflux for 2 h.
reduction as described above, gave the benzylamine (13b) as a clear oil
+
The reaction was quenched at 5° with Na SO .10H O, filtered, and
(1.78 g, 82%) (Found: m/z 296.1998. (C
H
NO+H) requires m/z
2
4
2
20 25
1
the filtrate was reacted with acetic anhydride (36 g, 3.6 mmol) at
reflux for 1 h. Water (1 ml) was added and reflux continued for a
296.2014). H n.m.r. δ (200 MHz) 1.46–1.65, m, 2H, H 3′; 1.72–1.85,
m, 2H, H 2′; 1.98, br s, 1H, NH; 2.05–2.15, m, 2H, H 4′; 3.76, s, 2H,
and 3.82, s, 2H, ArCH N and PhCH N; 3.96, t, 2H, J 6.2 Hz, H 1′;
further
1 h. Concentration under reduced pressure gave an
2
2
1
approximate 2 : 1 mixture ( H n.m.r.) of linear and branched products
as a brown oil (0.55 g). Column chromatography (basic alumina,
EtOAc) gave a mixture of 1-acetyl-3-methylazacyclododecane (5;
R = Ac) and 1-acetyl-azacyclotridecane (4; R = Ac) (0.15 g, 38%).
4.94–5.06, m, 2H, H 5′; 5.79, ddt, 1H, J 16.8, 10.2, 6.5 Hz, H 5′; 6.81–
13
6.93, m, 2H and 7.16–7.33, m, 7H, ArH. C n.m.r. δ (50 MHz) 25.41
(C 3′); 28.73 (C 2′); 33.35 (C 4′); 48.96 (ArCH N); 53.03 (PhCH N);
2
2
67.53 (C 1′); 110.99 (C 3); 114.76 (C 6′); 120.18 (C 5); 126.74, 128.03,
128.14, 128.26, (128.31(C 1)), 128.45, 129.96 (PhCH); 138.38 (C 5′);
– .
1
+
+
ν
(neat) 1654 cm Mass spectrum (ESI ): m/z 226.1 (M+H) . For
(5; R = Ac). H n.m.r. δ (200 MHz) 1.09, d, 3H, J 7.0 Hz, CH ; 1.28,
max
1
+
140.50 (C 1′′); 157.13 (C 2). Mass spectrum (ESI ): m/z 296.2
3
+
m, 14H, H 4,5,6,7,8,9,10; 1.40–1.73, m, 4H, H 3,11; 1.97, s, 3H,
(M+H) .
13
COCH ; 2.32–2.48, m, 1H, H 2; 3.16–3.26, m, 2H, H 12. C n.m.r. δ
(50 MHz) 13.15 (CH ); 21.86 (COCH ); 26.74, 28.94, 29.18, 29.27,
3
N-Benzyl-2-(prop-2-enyloxy)benzylamine (13c)
3
3
30.36, 30.30 (C 3,4,5,6,7,8,9,10,11); 39.48 (C 12); 46.13 (C 2); 170.18
Reaction of 2-hydroxybenzaldehyde and 3-bromopropene gave 2-
1
13
(prop-2-enyloxy)benzaldehyde40 as a clear oil (48%). C n.m.r. δ (50
(CO). For (4; R = Ac). H n.m.r. δ (200 MHz) 1.38, m, 16H,
H 3,4,5,6,7,8,9,10; 1.66, m, 4H, H 11,2; 2.11, s, 3H, CH ; 3.29, t, 2H,
3
MHz) 68.98 (C 1′), 112.72 (C 3); 117.86 (C 3′); 120.69 (C 4); 124.92
(C 1); 128.20 (C 5); 132.27 (C 2′); 135.72 (C 6); 160.79 (C 2); 189.50
(CHO).
13
J 7.5 Hz and 3.35, t, 2H, J 7.5 Hz, H 2 and H 13. C n.m.r. δ (50
MHz) 21.28 (COCH ); 24.10, 24.67, 25.04, 25.12, 25.20, 25.54,
3
25.66, 26.72, 29.29 (C 4,5,6,7,8,9,10,11,12); 47.16, 49.96 (C 2,13);
170.97 (CO).
Reaction of the aldehyde (1.00 g, 6.2 mmol) with benzylamine (0.66
g, 6.2 mmol), followed by NaBH reduction, gave the amine (13c) as a
4
+
An authentic sample of (4; R = Ac) was prepared by reduction of
clear oil (1.43 g, 92%) (Found: m/z 254.1543. (C
H NO+H)
17 19
1
laurolactam with LiAlH followed by acetylation to give a light brown
4
requires m/z 254.1545). H n.m.r. δ (200 MHz) 3.77, s, 2H, PhCH N;
2
oil which on distillation (b.p. (oven) 95° /0.5 mm) gave a white solid,
m.p. 40–42°.
3.84, s, 2H, ArCH N; 4.53, dt, 2H, J 5.0, 1.5 Hz, H 1′; 5.22–5.43, m,
2
2H, H 3′; 6.03, ddt, 1H, J 17.3, 10.3, 5.1 Hz, H 2′; 6.84, d, 1H, J 8.2 Hz,
13
H 3; 6.91, t, 1H, J 7.4 Hz, H 5; 7.16–7.36, m, 7H, ArH. C n.m.r. δ (50
1-Benzylazacyclotridecane (7a; R = Bn)
MHz) 48.78 (ArCH N); 53.02 (PhCH N); 68.58 (C 1′); 111.46 (C 3);
2
2
117.15 (C 3′); 120.55 (C 5); 126.77, 128.11, 128.17, 128.27, 128.51
(C 1), 130.03, 133.25 (ArCH); 140.43 (C 1′′); 156.64 (C 2). Mass
Reaction of N-benzylundec-10-enamine (6a; R = Bn) (0.2 g, 0.8 mmol),
[Rh(OAc) ] (1.7 mg, 3.8 µmol) and BIPHEPHOS (12.1 mg, 15.4 µmol)
2 2
+
+
spectrum (ESI ): m/z 254 (M+H) .
with 9 : 1 H /CO (400 psi) gave a brown oil (0.23 g), which on
2
extraction with light petroleum gave 1-benzylazacyclotridecane (7a;
General Conditions for Reaction with H /CO
1
R = Bn)41 as a semisolid (0.18g, 85%). H n.m.r. δ (200 MHz) 1.28, m,
2
Reactions were carried out in a 100 ml Parr autoclave with a glass
sleeve containing a stirrer bead. The substrate (0.1–0.3 g, c. 1 mmol),
the rhodium catalyst precursor and the ligand (in the ratio 200 : 1 : 4)
16H, H 3,4,5,6,7,8,9,10; 1.38–1.45, m, 4H, H 2,11; 2.37, t, 4H, J 6.3 Hz,
H 1,12; 3.52, s, 2H, PhCH N; 7.21–7.27, m, 1H, H 4′; 7.29–7.35, m,
2
13
4H, H 2′,3′,5′,6′. C n.m.r. δ (50 MHz) 26.95, 29.32, 29.50, 29.56
were placed in the autoclave under N followed by deoxygenated
(C 2,3,4,5,6,7,8,9,10,11); 53.08 (C 1,12); 59.02 (PhCH N); 126.59
2
2
solvent (10 ml).
(C 4′); 128.04 (C 3′,5′); 128.89 (C 2′,6′); 140.24(C 1′). Mass spectrum
+
+
The vessel was flushed and evacuated three times with 200 psi
(ESI ): m/z 274.2 (M+H) .
(1.38 MPa) of H /CO (1 : 1 molar mixture) and pressurized to 400 psi
(2.76 MPa). Alternatively, it was flushed with H and then pressurized
2
An authentic sample was prepared by reaction of azacyclotridecane
with benzyl chloride, b.p. 120°/0.1 mm (Found: C, 83.43; H, 11.50; N,
2
to an initial pressure of 400, 800 or 1200 psi (2.76, 5.52 or 8.28 MPa)
with the appropriate gas mixture. The reaction was kept at temperature
for 20 h, the autoclave cooled, the gases released and the contents
analysed as reported. In general, ratios of products including
regioisomers were determined by relative peak areas of appropriate
hydrogens in 1H n.m.r. spectra and/or relative signal intensities of
comparable carbons in 13C n.m.r. spectra. Selective extraction of the
total product with light petroleum gave in most cases n.m.r.-pure
material in higher yields than chromatography on silica or alumina.
5.18. C
H N requires C, 83.45; H, 11.43; N, 5.12%).
19 31
Reactions using BIPHEPHOS or PPh but with 1 : 1 H /CO at 80° led to
3
2
isolation of the cyclic amine (7a; R = Bn) (47% and 25%, respectively)
together with polymeric material. The n.m.r. spectra of the total
non-polymeric product showed only the cyclic amine (7a; R = Bn) in the
former case but suggested a ratio of 70 : 30 ((7a) : (8a)) in the latter case
based on the benzyl signals at c. 3.5 and the CH signal at c. 0.8 ppm in
3
the 1H n.m.r. spectra and the benzyl carbons in the 57–59 ppm region in
the 13C n.m.r. spectra.

Synthesis of Medium and Large Cyclic Amines
841
1-(2′-Methylbenzyl)azacyclotridecane (7a; R = (o-Tol)CH )
column chromatography (alumina, 2–10% EtOAc/light petroleum)
gave 1-benzylazecane (7b; R = Bn) clear oil (0.05 g, 25%) (Found: m/z
2
Reaction of N-(2-methylbenzyl)undec-10-enamine (6a; R
= (o-
+
1
232.2065. (C
H N+H) requires 232.2065). H n.m.r. δ (200 MHz)
16 25
Tol)CH ) (0.30 g, 1.1 mmol) under the usual conditions gave an 85 : 15
2
1.26–1.63, m, 14H, H 3,4,5,6,7,8,9; 2.37, t, 4H, J 6.2 Hz, H 2,10; 3.52,
s, 2H, PhCH N; 7.21–7.36, 5H, ArH. C n.m.r. δ (50 MHz) 26.82,
27.01, 29.14 (C 3,4,5,6,7,8,9); 52.88 (C 2,10); 59.38 (PhCH N); 126.57
mixture (n.m.r.) of linear and branched products as a brown oil (0.31 g).
Column chromatography (silica; 5% EtOAc/light petroleum) gave only
13
2
2
1-(2′-methylbenzyl)azacyclotridecane (7a; R = (o-Tol)CH ) as a white
2
(C 4′); 128.03, 128.86 (C 2′,3′,5′,6′); 140.41 (C 1′). Mass spectrum
solid (0.07 g, 22%). A portion of the solid was dissolved in CH Cl .
2
2
+
+
(ESI ): m/z 231.9 (M+H) .
Slow evaporation of solvent gave crystals, m.p. 97–99° (Found: C
83.60, H 11.71, N 4.62. C N requires C 83.55, H 11.58, N 4.87%).
Further elution gave N-benzyloctylamine as a yellow oil (0.07 g,
H
20 33
+
35%) (Found: m/z 232.2056. (C
H
N+H) requires m/z 232.2065).
1
16 25
H n.m.r. δ (200 MHz) 1.27, m, 16H, H 3,4,5,6,7,8,9,10; 1.37–1.43, m,
4H, H 2,11; 2.35–2.37, m, 7H, H 1,12, PhCH ; 3.48, s, 2H, PhCH N;
7.12–7.17, m, 3H and 7.33, m, 1H, ArH. C n.m.r. δ (50 MHz) 19.27
(PhCH ); 26.82, 27.48, 29.55, 29.64 (C 2,3,4,5,6,7,8,9,10,11); 53.85
1
H n.m.r. δ (200 MHz) 0.88, t, 3H, J 6.1 Hz, H 8; 1.26–1.51, m, 12H,
H 2,3,4,5,6,7; 2.38, t, 2H, J 7.5 Hz, H 1; 3.53, s, 2H, PhCH N; 7.29–
7.31, m, 5H, ArH. C n.m.r. δ (50 MHz) 14.14 (C 8); 22.71, 26.98,
27.48, 29.56, 29.69 (C 2,3,4,5,6); 31.95 (C 7); 49.48 (PhCH N); 53.82
2
3
13
2
13
3
2
(C 1,12); 57.06 (PhCH N); 125.36, 126.54 (C 4′,5′); 129.60, 130.00
2
(C 1); 126.59 (C 4′); 128.04, 128.85 (C 2′,3′,5′,6′); 140.19 (C 1′). Mass
+
(C 3′,6′); 137.04, 138.02 (C 1′,2′). Mass spectrum (ESI ): m/z 288.3
+
+
spectrum (ESI ): m/z 219.9 (M+H) .
+
(M+H) .
A reaction using PPh under otherwise identical conditions gave an
3
A reaction using BIPHEPHOS and a H /CO ratio of 1 : 5 (400 psi) at 80°
2
almost identical result.
gave only (7a; R = o-(Tol)CH ), which was isolated in 28% yield.
2
1-Benzylazocane (7c; R = Bn)
1-Butylazacyclotridecane (7a; R = Bu)
Reaction of N-benzylhex-5-enamine (6c; R = Bn) (0.15 g, 0.8 mmol),
Reaction of N-butylundec-10-enamine (6a; R = Bu) (0.15 g, 0.7 mmol),
[Rh(OAc) ] (1.8 mg, 4.0 µmol) and BIPHEPHOS (16.6 mg, 15.9 µmol)
2 2
[Rh(OAc) ] (1.5 mg, 3.3 µmol) and BIPHEPHOS (10.4 mg, 13.3 µmol)
2 2
under the usual conditions gave a brown oil (0.20 g). Column
with 9 : 1 H /CO (400 psi) gave a brown oil (0.15 g) whose light
2
chromatography (alumina: 10% EtOAc/CH Cl ) gave 1-benzylazocane
2
2
petroleum extract gave 1-butylazacyclotridecane (7a; R = Bu) as a
1
+
(7c; R = Bn) as a clear oil (0.07 g, 43%). H n.m.r. δ (200 MHz) 1.47–
waxy solid (0.13 g, 82%) (Found: m/z 240.2681. (C
H N+H)
16 33
1
1.72, m, 10H, H 3,4,5,6,7; 2.55, t, 4H, J 6.0 Hz, H 2,8; 3.60, s, 2H,
requires m/z 240.2691). H n.m.r. δ (200 MHz) 0.84, t, 3H, J 6.8 Hz,
H 4′; 1.19–1.38, m, 26H, H 3,4,5,6,7,8,9,10,11,12,2′,3′; 2.31, t, 4H, J
6.6 Hz, H 2,13,1′. C n.m.r. δ (50 MHz) 14.04 (C 4′); 20.72 (C 3′);
26.76, 27.60, 29.18, 29.29, 29.58 (C 3,4,5,6,7,8,9,10,11,12,2′); 54.04
). 13
PhCH N; 7.22–7.40, m, 5H, ArH (in agreement with literature42
C
2
13
n.m.r. δ (50 MHz) 26.16, 27.82, 29.73 (C 3,4,5,6,7); 54.08 (C 2,8);
63.59 (PhCH N); 126.65 (C 4′); 128.04, 128.95 (ArCH); C 1′ not
2
+
+
+
+
observed. Mass spectrum (ESI ): m/z 204.0 (M+H) .
(C 2,13,1′). Mass spectrum (ESI ): m/z 240.1 (M+H) .
An authentic sample, prepared from reaction of azatricyclodecane
and butyl bromide had identical spectra, b.p. 100°/0.1 mm (Found: C,
N-(1-Phenylethyl)azepane (7d; R = PhCH(Me))
80.08; H, 13.61; N, 6.14. C
5.85%).
H
N requires C, 80.26; H, 13.89; N,
Reaction of N-(1-phenylethyl)pent-4-enamine (6d; R = PhCH(Me))
16 33
(0.25 g, 1.3 mmol), [Rh(OAc) ] (3.0 mg, 6.6 µmol) and BIPHEPHOS (10.0
2 2
Reaction with 1 : 1 H /CO by using BIPHEPHOS or PPh as ligands gave
mg, 13.2 µmol) by using 1 : 5 H /CO (400 psi) gave an oil (0.27 g)
3
2
2
(7a; R = Bu) in 40 and 22% yield, respectively. The total product of the
latter reaction was very complex and showed some evidence for lactam
formation (13C n.m.r. δ 172.9).
which on distillation gave the azepane (7d) as a clear oil (0.16 g, 60%),
b.p. (oven) 130°/0.5 mm (lit.43 b.p. (oven) 130°/0.4 mm) with identical
spectral data to those described previously.
An identical reaction but using 9 : 1 H /CO gave an oil (0.3 g).
2
2-Methyl-11-phenylaminoundecanal and 12-Phenylaminoundecanal
Distillation gave a mixture of (7d) and hydrogenated starting material
(9d) (0.15 g) in a 1 : 2 ratio. Chromtography (silica, 30% EtOAc/light
Reaction of N-phenylundec-10-enamine (0.30 g, 1.2 mmol),
[Rh(OAc) ] (2.7 mg, 6.1 µmol) and PPh (6.4 mg, 24.5 µmol) under
1
petroleum) gave a sample of (9d). H n.m.r. δ (200 MHz) 0.86, t, 3H, J
2 2
3
6.6 Hz, H 5: 1.17–1.57, m, 6H, H 2,3,4; 1.35, d, 3H, J 6.6 Hz, CH
the usual conditions gave the linear and branched aldehyde isomers in
the ratio 25 : 75 as a brown oil (0.37 g). Column chromatography (silica,
3
CH; 2.33–2.55, m, 2H, H 1; 3.75, q, 1H, J 6.6 Hz,CH; 7.18–7.37, m,
5H, PhH. 13C n.m.r. δ (50 MHz) 14.00 (C 5); 22.57 (C 4); 24.33
10% EtOAc/light petroleum) gave 2-methyl-11-phenylaminoundecanal
+
(CH CH); 29.53, 29.95 (C 2,3); 47.86 (C 1); 58.37 (CH); 126.50,
(0.06 g, 18%) (Found: m/z 551.4586. (2(C
H
NO)+H) requires m/z
3
18 29
)
126.75, 128.34 (PhCH); 145.87 (C 1′). Mass spectrum (ESI+ m/z
–1
1
551.4576). ν
(neat) 1714s cm . H n.m.r. δ (400 MHz) 1.08, d, 3H,
J 7.0 Hz, CH ; 1.29–1.37, m, 14H, H 3,4,5,6,7,8,9; 1.60, m, 2H, H 2;
max
+
192.2 (M+H) .
3
An authentic sample of the alkane (9d) was prepared by
hydrogenation of the alkene (6d; R = PhCH(Me)), b.p. (oven) 105°/
0.5 mm.
2.29–2.33, m, 1H, H 2; 3.09, t, 2H, J 7.1 Hz, H 11; 6.59, dd, 1H, J 8.6,
1.1 Hz, H 4′; 7.16, dd, 2H, J 8.5, 7.3 Hz, H 3′,5′; 9.60, d, 1H, J 2.0 Hz,
13
H 1. C n.m.r. δ (100 MHz) 13.35 (CH ); 26.92, 27.15, 29.38, 29.40,
3
29.48, 29.53, 30.54 (C 3,4,5,6,7,8,9,10); 43.99 (C 11); 46.31 (C 2);
N-Benzyl-11-formylundecanamide and N-Benzyl-10-formylundecana-
mide
112.69 (C 2′,6′); 117.07 (C 4′); 129.20 (C 3′,5′); 148.56 (C 1′); 205.29
+
+
(C 1). Mass spectrum (ESI ): m/z 276.2 (M+H) .
Further elution gave 12-phenylaminoundecanal (0.02 g, 6%). ν
Reaction of N-benzylundec-10-enamide (0.30 g, 1.1 mmol) and
Rh (CO) (2.1 mg, 2.7 µmol) with 1 : 3 H /CO, (800 psi) at 100° gave
an approximately 55 : 45 mixture of the linear and branched aldehydes
as a brown solid (0.37 g). Recrystallization from ether/light petroleum
max
–1
1
(neat) 1713s cm
.
H n.m.r. δ (400 MHz) 1.23–1.39, m, 16H,
4
12
2
H 3,4,5,6,7,8,9,10; 1.61, m, 2H, H 11; 2.41, td, 2H, J 7.3, 1.9 Hz, H 2;
3.10, t, 2H, J 7.1 Hz, H 12; 6.59, d, 2H, J 7.7 Hz, H 2′,6′; 6.68, t, 1H, J
7.3 Hz, H 4′; 7.16, dd, 2H, J 8.3, 7.4 Hz, H 3′,5′; 9.76, t, 1H, J 1.9 Hz,
gave N-benzyl-11-formylundecanamide as a cream solid (0.13 g, 39%)
13
+
H 1. C n.m.r. δ (100 MHz) 24.07, 28.73, 28.79, 28.96, 29.18, 29.68
(Found: m/z 304.2277. (C
H
NO +H) requires m/z 304.2276). ν
19 29
2
max
–1
1
(C 2,3,4,5,6,7,8,9,10,11); 44.03 (C 12); 112.72 (C 2′,6′); 117.11 (C 4′);
(Nujol) 1709w cm
.
H n.m.r. δ (400 MHz) 1.28, br s, 12H,
H 4,5,6,7,8,9; 1.63, m, 4H, H 3,10; 2.20, t, 2H, J 7.5 Hz, H 2; 2.41, dt,
+
129.23 (C 3′,5′); 148.59 (C 1′); 202.87 (C 1). Mass spectrum (ESI ): m/
+
z 276.2 (M+H) .
2H, J 1.9, 7.3 Hz, H 11; 4.43, d, 2H, J Hz, PhCH N; 5.75, br s, 1H, NH;
2
13
7.25–7.37, m, 5H, ArH; 9.75, t, 1H, J 1.9 Hz, CHO. C n.m.r. δ (100
1-Benzylazecane (7b; R = Bn)
MHz) 22.08, 25.74, 29.13, 29.22, 29.28, 29.31, 29.35
Reaction of N-benzyloct-7-enamine (6b; R = Bn) (0.20 g, 9.2 mmol),
(C 3,4,5,6,7,8,9,10); 36.80 (C 2); 43.62 (PhCH N); 43.90 (C 11);
2
[Rh(OAc) ] (2.0 mg, 4.6 µmol) and BIPHEPHOS (14.4 mg, 18.4 µmol)
127.50, 127.84, 128.71 (ArCH); 138.47 (C 1′); 172.98 (C 1); 202.89
2 2
+
+
with 9 : 1 H /CO (400 psi) gave a brown oil (0.20 g). Gradient elution
(CHO). Mass spectrum (ESI ): m/z 304.2 (M+H) .
2

842
D. J. Bergmann et al.
1
Concentration of the filtrate gave N-benzyl-10-formyl-
undecanamide as a clear oil (0.12 g, 36%). ν (neat) 1712s, 1648s
cm . H n.m.r. δ (200 MHz) 1.06, d, 3H, J 7.0 Hz, H 11; 1.27, br s,
10H, H 4,5,6,7,8; 1.57–1.71, m, 2H, H 3; 1.96–2.01, m, 2H, H 9; 2.18,
t, 2H, J 7.5 Hz, H 2; 2.24–2.39, m, 1H, H 10; 4.36, d, 2H, J 5.7 Hz,
requires m/z 234.1858). H n.m.r. δ (400 MHz) 1.49–1.60, m, 4H and
1.62–1.74, m, 4H, H 3,7,8,9; 2.41, t, 2H, J 5.4 Hz, H 6; 2.52, t, 2H, J 6.1
max
–1
1
Hz, H 4; 3.49, s, 2H, PhCH N; 3.63-3.66, m, 4H, H 2,10; 7.21–7.25, m,
1H and 7.26–7.37, m, 4H, ArH. C n.m.r. δ (100 MHz) 26.12 (C 7);
27.17 (C 3,8,9); 48.46 (C 4); 55.05 (C 6); 61.09 (PhCH N); 66.45 (C 2);
2
13
2
PhCH N; 6.53, br s, 1H, NH; 7.21–7.34, m, 5H, ArH; 9.55, d, 1H, J 2.1
72.61 (C 10); 126.71 (C 4′); 128.06, 129.33 (C 2′,3′,5′,6′); 140.31
2
13
+
+
Hz, CHO. C n.m.r. δ (50 MHz) 13.15 (C 11); 25.61, 26.72, 28.96,
(C 1′). Mass spectrum (ESI ): m/z 234.1 (M+H) .
29.09, 29.37, 30.29 (C 3,4,5,6,7,8,9); 36.41 (C 2); 43.25 (PhCH N);
A reaction using BIPHEPHOS under standard conditions gave a mixture
of products. Chromatography (alumina, 50% EtOAc/light petroleum)
gave only hydrogenated starting material, N-benzyl-3-butyl-
oxypropanamine (12) (0.14 g, 46%) (Found: m/z 222.1846.
2
46.11 (C 10); 127.14, 127.52, 128.40 (ArCH); 138.39 (C 1′); 173.25
+
+
(C 1); 205.36 (CHO). Mass spectrum (ESI ): m/z 304.3 (M+H) .
+
1
N-Butyl-11-formylundecanamide and N-Butyl-10-formylundecana-
mide
(C
H NO+H) requires m/z 222.1858). H n.m.r. δ (400 MHz) 0.82,
14 23
t, 3H, J 7.3 Hz, H 4′; 1.23–1.29, m, 2H, H ′; 1.41–1.48, m, 2H, H 2′;
1.68, t, 2H, J 6.7 Hz, H 2; 2.62, t, 2H, J 6.9 Hz, H 1; 3.30, t, 2H, J 6.6
3
Reaction of N-butylundec-10-enamide (0.30 g, 1.3 mmol) and
Rh (CO) (2.3 mg, 3.1 µmol) with 1 : 3 H /CO (800 psi) in
Hz, H 3; 3.38, t, 2H, J 6.3 Hz, H 1′; 3.66, s, 2H, PhCH N; 7.19–7.26,
2
4
12
2
13
m, 5H, PhH. C n.m.r. δ (100 MHz) 13.84 (C 4′); 19.29 (C 3′); 29.92
tetrahydrofuran gave a 55 : 45 mixture of linear and branched aldehydes
as a brown solid (0.33 g). Recrystallization from ether/light petroleum
(C 2); 31.75 (C 2′); 46.87 (C 1); 53.93 (PhCH N); 69.35, 70.66 (C 1′,3);
2
126.78 (C 4′′); 128.02, 128.31 (C 2′′,3′′,5′′,6′′); 140.33 (C 1′′). Mass
gave N-butyl-11-formylundecanamide as a cream solid (0.11 g, 33%)
+
+
+
spectrum (ESI ): m/z 221.9 (M+H) .
(Found: m/z 270.2422. (C
H
NO +H) requires m/z 270.2433). ν
16 31
–1
2
max
1
(Nujol) 1708m, 1639m cm . H n.m.r. δ (200 MHz) 0.92, t, 3H, J 7.0
Hz, H 4′; 1.28, br s, 12H, H 4,5,6,7,8,3′; 1.36-1.52, m, 2H, H 2′; 1.55–
1.66, m, 4H, H 3,10; 2.15, t, 2H, J 7.5 Hz, H 2; 2.42, dt, 2H, J 7.3, 1.8
Hz, H 11; 3.25, q, 2H, J6.8 Hz, H 1′; 5.43, br s, 1H, NH; 9.76, t, 1H, J
14-Acetyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1,14-
benzoxazacycloheptadecine (14a; Bn = Ac) and 13-Acetyl-11-methyl-
3,4,5,6,7,8,9,10,11,12,13,14-dodecahydro-2H-1,13-benzoxazacyclo-
hexadecine (15a; Bn = Ac)
13
1.8 Hz, CHO. C n.m.r. δ (50 MHz) 13.77 (C 4′); 20.08 (C 3′); 24.69,
25.78, 28.90, 29.03, 29.16 (C 3,4,5,6,7,8,9); 31.73 (C 2′); 33.98 (C 10);
36.92 (C 2); 39.29 (C 1′); 173.06 (C 1); 202.70 (CHO). Mass spectrum
The product from a reaction of 2-(undec-10-enyloxy)benzylamine
(13a; Bn = H). (0.30 g, 1.1 mmol) under the usual conditions was
+
+
13
(ESI ): m/z 270.1 (M+H) .
reduced with NaBH and acetylated as described above. The 1H and
C
4
Concentration of the filtrate gave N-butyl-10-formylundecanamide
n.m.r. spectra indicated an equimolar mixture of linear and branched
products (14a; Bn = Ac) and (15a; Bn = Ac). Chromatography
(alumina, EtOAc) gave the mixture of N-acetyl compounds as a clear oil
–1 1
as a yellow oil (0.16 g, 47%). ν
(neat) 1710s, 1644m cm . H n.m.r.
max
δ (400 MHz) 0.92, t, 3H, J 7.3 Hz, H 4′; 1.09, d, 3H, J 7.0 Hz, H 11;
1.29–1.39, m, 12H, H 4,5,6,7,8,3′; 1.43–1.52, m, 2H, H 2′; 1.58–1.65,
m, 4H, H 3,9; 2.17, t, 2H, J 7.5 Hz, H 2; 2.32, m, 1H, H 10; 3.23, q, 2H,
(0.13 g 36%) (Found: m/z 332.2586. (C
H NO +H)+ requires m/z
21 33 2
332.2589). Further chromatography (20% EtOAc/light petroleum)
allowed partial separation for spectral assignment. 14-Acetyl-
2,3,4,5,6,7,8,9,10, 11, 12, 13, 14, 15-tetradecahydro-1, 14-benzoxaza-
13
J 7.1 Hz, H 1′; 6.23, br s, 1H, NH; 9.61, d, 1H, 2.0 Hz, CHO. C n.m.r.
δ (50 MHz) 13.61 (C 4′); 16.87 (C 11); 19.92 (C 3′); 25.71, 29.05
(C 3,4,5,6,7,8,9); 31.46 (C 2′); 36.53 (C 2); 39.17 (C 1′); 39.31 (C 10);
1
cycloheptadecine (14a; Bn = Ac): H n.m.r. δ (200 MHz) 0.81, m, 2H
+
+
181.06 (CHO). Mass spectrum (ESI ): m/z 270.3 (M+H) .
A reaction under the usual conditions gave the linear and branched
aldehydes in a 70 : 30 ratio.
and 1.15–1.5, m, 18H, H 3,4,5,6,7,8,9,10,11,12; 1.74–1.87, m, 2H,
H 13; 1.97, s, 3H, COCH ; 3.86–3.96, m, 2H, H 2; 4.38–4.57, m, 2H,
3
H 15; 6.74-6.93, m, 3H and 7.13–7.21, m, 1H, H 16,17,18,19. 13-
Acetyl-11-methyl-3,4,5,6,7,8,9,10,11,12,13,14-dodecahydro-2H-1,13-
1
N-(3,5-Dimethoxyphenyl)-11-formylundecanamide and N-(3,5-
Dimethoxyphenyl)-10-formylundecanamide
benzoxa-zacyclohexadecine (15a; Bn = Ac): H n.m.r. δ (200 MHz)
0.86, d, 3H, J 6.6 Hz, CH ; 1.16–1.51, m, 14H and 1.54–1.65, m, 2H,
3
H 3,4,5,6,7,8,9,10; 1.74–1.84, m, 2H, H 2; 3.22–3.37, m, 1H, H 11;
3.97–4.67, 2H, H 2; 4.55–4.68, m, 2H, H 14; 6.82–7.02, m, 3H and
7.11–7.28, m, 1H, H 15,16,17,18.
Reaction of N-(3,5-dimethoxyphenyl)undec-10-enamide (0.30 g, 0.9
mmol), under the usual conditions, gave a 2 : 1 mixture (1H n.m.r.) of
linear and branched aldehydes as a brown solid (0.33 g). Trituration
with ether gave N-(3,5-dimethoxyphenyl)-11-formylundecanamide as a
–1
1
14-Benzyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1,14-ben-
zoxazacycloheptadecine (14a) and 6,25-Dibenzyl-5,6,7,8,9,10,11,12,
13,14,15,16,17,18,24,25,26,27,28,29,30,31,32,33,34,35,36,37-octa-
icosahydrodibenzo[b,s][1,18,5,22]dioxadiazacyclotetratriacontine
(16a)
brown solid (0.15 g, 48%). ν
(Nujol) 1721s, 1665s cm . H n.m.r.
max
δ (200 MHz) 1.28, br s, 12H, H 4,5,6,7,8,9; 1.59–1.71, m, 4H, H 3,10;
2.34, t, 2H, J 7.6 Hz, H 2; 2.42, dt, 2H, J 7.2, 1.9 Hz, H 11; 3.77, 6H,
OCH ; 6.22, s, 1H, H 4′; 6.79, s, 2H, H 2′,6′; 7.31, br s, 1H, NH; 9.76,
3
13
br s, 1H, CHO. C n.m.r. δ (50 MHz) 22.05, 25.47, 29.10, 29.19, 29.29
(C 3,4,5,6,7,8,9,19); 37.87 (C 2); 43.92 (C 11); 55.38 (OCH ); 96.56
A reaction of N-benzyl-2-(undec-10-enyloxy)benzylamine (13a) (0.30
g, 0.8 mmol) under the usual conditions gave a brown oil (0.30 g) whose
1H n.m.r. spectrum indicated only a small amount of branched chain
product (15a) (δ 0.96, d, J 6.8 Hz). Column chromatography (silica,
10% EtOAc/light petroleum) gave 14-benzyl-2,3,4,5,6,7,8,9,10,11,12,
13,14,15-tetradecahydro-1,14-benzoxazacycloheptadecine (14a) as a
3
(C 4′); 97.84 (C 2′,6′); 139.84 (C 1′); 161.03 (C 3′,5′); 171.55 (C 1);
203.11 (CHO).
Concentration of the filtrate gave N-(3,5-dimethoxyphenyl)-10-
formylundecanamide as a yellow oil (0.05 g, 16%). ν
1665s cm . H n.m.r. δ (200 MHz) 1.08, d, 3H, J 7.0 Hz, H 11; 1.28,
br s, 10H, H 4,5,6,7,8; 1.58–1.71, m, 4H, H 3,9; 2.28–2.37, m, 3H,
(neat) 1721s,
max
–1
1
clear oil (0.03 g, 10%) (Found: C, 82.1; H, 10.1; N, 4.0. C
H NO
26 37
H 2,10; 3.74, s, 6H, OCH , 6.21, t, 1H, J 2.2 Hz, H 4′; 6.81, d, 2H, J 2.2
3
requires C, 82.3; H, 9.8; N, 3.7%) (Found: m/z 380.2921.
13
+
1
Hz, H 2′,6′; 8.09, br s, 1H, NH; 9.60, d, 1H, J 2.0 Hz, CHO. C n.m.r.
(C
H NO+H) requires m/z 380.2953). H n.m.r. δ (200 MHz) 1.15–
26 37
δ (50 MHz) 13.19 (C 11); 25.42, 26.74, 28.96, 29.13, 29.18, 29.39,
1.35, m, 14H, H 5,6,7,8,9,10,11; 1.40–1.50, m, 4H, H 4,12; 1.66–1.75,
m, 2H, H 3; 2.43, t, 2H, J 7.5 Hz, H 13; 3.57, s, 2H and 3.63, s, 2H, H 15
29.56, 30.31 (C 3,4,5,6,7,8,9); 37.54 (C 2); 46.18 (C 10); 55.17
(OCH ); 96.32 (C 4′); 97.95 (C 2′,6′); 139.86 (C 1′); 160.80 (C 3′,5′);
and PhCH N; 3.91, t, 2H, J 5.5 Hz, H 2; 6.72–6.86, m, 2H, H 17,19;
3
2
13
172.03 (C 1); 205.68 (CHO).
7.05–7.39, m, 7H, H 16,18, PhH. C n.m.r. δ (50 MHz) 24.74, 25.51,
25.86,
26.27,
26.65,
26.94,
27.27,
27.47,
29.16
5-Benzyl-1,5-oxazecane (11)
(C 3,4,5,6,7,8,9,10,11,12); 51.72, 53.40, 58.04 (C 13, PhCH N, C 15);
2
Reaction of N-benzyl-3-(but-3-enyloxy)propanamine (10) (0.20 g, 0.9
mmol) under the usual conditions gave a yellow oil which on
67.59 (C 2); 110.93 (C 19); 119.97 (C 17); 126.56 (C 4′); 127.42,
128.11, 128.62, 129.88 (C 16,18,2′,3′,5′,6′); 140.52 (C 1′); 157.25
+
chromatography (alumina, 5% EtOAc/CH Cl ) gave 5-benzyl-1,5-
(C 19a) (C 15a not observed). Mass spectrum (ESI ): m/z 380.3
2
2
+
+
oxazecane (11) (0.03 g, 14%) (Found: m/z 234.1853. (C
H
NO+H)
(M+H) .
15 23

Synthesis of Medium and Large Cyclic Amines
843
A reaction of the amine (0.2 g, 0.6 mmol) under the usual
conditions but with BIPHEPHOS gave a brown oil (0.24 g). The light
petroleum extract of the oil was chromatographed (silica, 10% EtOAc/
light petroleum) to give (14a) as a semisolid (0.07 g, 34%). The light
petroleum insoluble material was the dimeric compound 6,25-
dibenzyl-5,6,7,8,9,10,11,12,13,14,15,16,17,18, 24, 25, 26, 27, 28,29,
30, 31, 32, 33, 34, 35, 36,37-octaicosahydrodibenzo[b,s][1,18,5,22]di-
oxadiazacyclotetratriacontine (16a) (0.04 g, 20%), m.p. 111–113°
H 6′; 1.18–1.43, m, 6H, H 3′,4′,5′; 1.62–1.72, m, 2H, H 2′; 3.68, s, 2H
and 3.73, s, 2H, ArCH N, PhCH N; 3.88, t, 2H, J 6.4 Hz, H 1′; 6.74–
2
2
13
6.85, m, 2H, H 3,5; 7.10–7.25, m, 7H, H 4,6, PhH. C n.m.r. δ (50
MHz) 14.02 (C 6′); 22.56, 25.87, 29.12 (C 3′,4′,5′); 31.52 (C 2′); 49.02
(ArCH N); 53.00 (PhCH N); 67.77 (C 1′); 111.01 (C 3); 120.12 (C 5);
2
2
126.76, 128.17, 128.27, 130.00 (C 4,6, PhCH); 140.45 (C 1′′); 157.23
+
+
(C 2). Mass spectrum (ESI ): m/z 298.1 (M+H) .
+
1
6-Benzyl-2,3,4,5,6,7-hexahydro-1,6-benzoxazonine (14c), 6,17-Diben-
zyl-5,6,7,8,9,10,16,17,18,19,20,21-dodecahydrodibenzo[b,k]
[1,10,5,14]dioxadiazacyclooctadecine (16c) and 3-Benzyl-2-(1'-
methylethyl)-3,4-dihydro-2H-1,3-benzoxazine
(Found: m/z 759.5794. (C
H N O +H) requires m/z 759.5828). H
52 74 2 2
n.m.r. δ (200 MHz) 1.22–1.50, m, 28H, H 9,10,11,12,13,14,15,28,29,
30,31,32,33,34; 1.75–1.79, m, 8H, H 8,16,25,27; 2.44, t, 4H, J 7.2 Hz,
H 7,26; 3.61, s, 4H and 3.68, s, 4H, H 5,24, PhCH N; 3.95, t, 4H, J 5.8
2
Hz, H 18,37; 6.80–6.93, m, 4H, H 1,3,20,22; 7.14–7.51, m, 14H,
H 2,4,21,23, PhH. C n.m.r. δ (50 MHz) 26.52, 27.42, 29.54, 29.78
(C 8 9,10,11,12,13,14,15,16,17,27,28,29,30,31,32,33,34,35, 36 );
Reaction of N-benzyl-2-(propenyloxy)benzylamine (13c) (0.2 g, 0.7
mmol) by using BIPHEPHOS under standard conditions gave a yellow oil
(0.22 g). Column chromatography (silica, 10% EtOAc/light petroleum)
13
51.50,53.63, 58.63 (PhCH N, C 5,7,24,26); 68.01 (C 18,37); 111.17
2
first gave 6-benzyl-2,3,4,5,6,7-hexahydro-1,6-benzoxazonine (14c) as a
+
(C 1,20); 120.08 (C 3,22); 126.70 (C 4′); 128.11, 128.84, 130.80
(C 2,4,21,23, PhCH); 157.44 (C 19a,38a) (C 4a,23a, C 1′ not observed).
yellow oil (0.07 g, 33%) (Found: m/z 268.1695. (C
H NO+H)
18 21
1
requires m/z 268.1701). H n.m.r. δ (200 MHz) 1.59–1.82, m, 4H,
H 3,4; 2.93, t, 2H, J 6.0 Hz, H 5; 3.70, s, 2H and 3.75, s, 2H, H 7,
+
+
Mass spectrum (ESI ): m/z 759.6 ((M+H) .
A reaction of the amine (0.10 g, 0.3mmol) by using BIPHEPHOS as
PhCH N; 4.35, t, 2H, J 5.6 Hz, H 2; 6.78–7.36, m, 9H, H–8,9,10,11,
2
13
above with 1 : 5 H /CO gave, after chromatography (silica, 5–10%
PhH. C n.m.r. δ (50 MHz) 24.31 (C 3); 26.97 (C 4); 54.17, 54.65 (C 7,
2
EtOAc/light petroleum), the cyclic amine (14a) (0.02 g, 20%) followed
by the dimer (16a) (0.01 g, 10%).
PhCH N); 58.97 (C 5); 74.45 (C 2); 119.45 (C 7a); 121.23, 123.01,
2
126.70, 128.06, 128.30, 128.89, 130.08 (C 8,9,10,11, PhCH); 138.97
+
+
A reaction of the amine (0.11 g, 0.3 mmol) by using BIPHEPHOS with
(C 1′) 159.05 (C 11a). Mass spectrum (ESI ): m/z 268 (M+H) .
The second fraction was the dimer 6,17-dibenzyl-5,6,7,8,
9,10,16,17,18,19,20,21-dodecahydrodibenzo[b,k][1,10,5,14] dioxadi-
azacyclooctadecine (16c) as a yellow oil (0.04 g, 19%). Trituration of
the oil with ether gave a beige solid, m.p. 85–90° (Found: m/z
9 : 1 H /CO gave a brown oil (0.14 g). Column chromatography (silica,
2
10% EtOAc/light petroleum) of the light petroleum extract gave the
cyclic amine (14a) (0.04 g, 38%), followed by impure (17a) (0.02 g,
+
16%). Mass spectrum (ESI ): m/z 368.3 (M+H)+. The light petroleum
+
1
insoluble material was the dimer (16a) (0.05 g, 44%).
535.3330. (C
H N O +H) requires m/z 535.3324). H n.m.r. δ (200
36 42 2 2
MHz) 1.78, m, 8H, H 8,9,19,20; 2.56, t, 4H, J 7.3 Hz, H 7,18; 3.64, s,
8-Benzyl-6-methyl-2,3,4,5,6,7,8,9-octahydro-1,8-benzoxazacyclounde-
cine (15b) and 9-Benzyl-3,4,5,6,7,8,9,10-octahydro-2H-1,9-benzoxa-
zacyclododecine (14b)
4H and 3.76, s, 4H, H 5,16, PhCH N; 3.91, t, 4H, J 5.0 Hz, H 10,21;
2
6.76, d, 2H, J 8.2 Hz, H 1,12; 6.90, dt, 2H, J 7.4, 0.9 Hz, H 3,14; 7.13–
13
7.43, m, 14H, H 2,4,13,15, PhH. C n.m.r. δ (50 MHz) 22.41 (C 9,20);
Reaction of N-benzyl-2-(hex-5-enyloxy)benzylamine (13b) (0.1 g,
27.07 (C 8,19); 51.52, 52.63 (C 5,16, PhCH N); 58.08 (C 7,18); 67.70
2
0.3 mmol) with BIPHEPHOS and 1 : 5 H /CO gave a brown oil (0.11 g),
(C 10,21); 110.99 (C 1,12); 119.45 (C 4a,15a); 119.98 (C 3,14); 126.66,
2
showing (14b) and (15b) in a ratio of 70 : 30. Column chromatography
(silica, 1% ether/light petroleum) gave 8-benzyl-6-methyl-
127.80, 128.16, 128.68, 130.47 (C 2,4,13,15, PhCH); 138.95 (C 1′);
+
+
157.38 (C 11a,22a). Mass spectrum (ESI ): m/z 535.2 (M+H) .
2,3,4,5,6,7,8,9-octahydro-1,8-benzoxazacycloundecine (15b) as a clear
The third fraction was 2-(N-benzylaminomethyl)phenol44 (0.03 g,
+
+
oil (0.01 g, 10%) (Found: m/z 310.2169. (C
H
NO+H) requires m/z
18%) (Found: m/z 214.1222. (C
214.1232).
H
NO+H) requires m/z
21 27
14 15
1
13
310.2171). H n.m.r. δ (400 MHz) 0.66, m, 1H, H 5 ; 0.77, d, 3H, J 6.4
C n.m.r. δ (50 MHz) 51.78 (ArCH N); 52.49
A
2
Hz, CH ; 1.45–1.54, m, 1H, H 4 ; 1.70–1.83, m, 2H, H 4 ,3 ; 1.99, m,
(PhCH N); 116.36 (C 6); 119.05 (C 4); 122.18 (C 2); 127.53 (C 4′);
3
A
B
A
2
1H, H 3 ; 2.09–2.17, m, 2H, H 5 ,7A; 2.23, dd, 1H, J 12.0, 4.6 Hz,
128.33, 128.47, 128.64, 128.76 (C 3,5,2′,3′,5′,6′); 138.29 (C 1′);
B
B
H 7 ; 2.32–2.40, m, 1H, H 6; 3.02, d, 1H, J 13.1 Hz, H 9 ; 3.40, d, 1H,
158.15 (C 1).
B
A
J 13.6 Hz and 3.77, d, 1H, J 13.6 Hz, PhCH N; 3.78–3.83, m, 1H, H 2 ;
A reaction of the amine (0.3 g, 0.8 mmol) under the usual conditions
gave a yellow oil (0.32 g). Column chromatography (silica, 2% EtOAc/
light petroleum) gave 3-benzyl-2-(1'-methylethyl)-3,4-dihydro-2H-1,3-
benzoxazine as a clear oil (0.06 g, 19%) (Found: m/z 268.1695.
2
A
4.09, d, 1H, J 13.1 Hz, H 9 ; 4.24–4.27, m, 1H, H 2 ; 6.81, d, 1H, J 8.4
B
B
Hz, H 13; 6.82, dt, 1H, J 8.6, 1.0 Hz, H 11; 7.09, dd, 1H, J 7.1, 1.7 Hz,
13
H 10; 7.14–7.25, m, 6H, H 12, PhH. C n.m.r. δ (100 MHz) 17.80
+
1
(CH ); 24.58 (C 4); 25.42 (C 3); 26.80 (C 6); 31.67 (C 5); 52.59 (C 9);
(C H NO+H) requires m/z 268.1701). H n.m.r. δ (400 MHz) 1.05,
3
18 21
59.29 (PhCH N); 60.44 (C 7); 68.00 (C 2); 110.16 (C 13); 119.20
d, 3H, J 6.7 Hz, CH ; 1.09, d, 3H, J 6.5 Hz, CH ; 2.10–2.18, m, 1H,
3 3
2
(C 11); 126.43 (C 5′); 127.79, 128.27 (C 12); 128.40 (C 9a); 129.06
(PhCH); 130.73 (C 10); 140.23 (C 1′); 157.68 (C 13a). Mass spectrum
H 1′; 3.74, d, 1H, J 18.1 Hz, H 4 ; 3.75, d, 1H, J 13.8 Hz and 3.91, d,
A
1H, J 14.0 Hz, PhCH N; 3.93, d, 1H, J 18.0 Hz, H 4 ; 4.36, d, 1H, J 9.7
2
B
+
+
(ESI ): m/z 310.3 (M+H) .
Hz, H 2; 6.81–6.90, m, 3H, H 5,6,8; 7.11-7.15, m, 1H, H 7; 7.25–7.27,
13
Further elution (silica, 1% EtOAc/light petroleum) gave 9-benzyl-
m, 1H and 7.31–7.37, m, 4H, PhH. C n.m.r. δ (100 MHz) 18.29, 19.51
3,4,5,6,7,8,9,10-octahydro-2H-1,9-benzoxazacyclododecine (14b) as a
(CH ); 29.90 (C 1′); 46.55 (C 4); 54.03 (PhCH N); 96.62 (C 2); 116.53
3
2
+
clear oil (0.03 g, 30%) (Found: m/z 310.2164. (C
H
NO+H)
(C 8); 119.56 (C 4a); 120.14 (C 6); 127.05 (C 4′); 127.62, 127.66
(C 5.7); 128.36, 128.52 (PhCH); 139.06 (C 1′); 153.64 (C 8a). Mass
21 27
1
requires m/z 310.2171). H n.m.r. δ (400 MHz) 1.43, m, 4H, H 5,6;
1.60, m, 2H, H 7; 1.67, p, 2H, J 6.1 Hz, H 4; 1.89, p, 2H, J 5.6 Hz, H 3;
+
+
spectrum (ESI ): m/z 267 (M+H) .
2.39, m, 2H, H 8; 3.57, s, 2H, and 3.64, s, 2H, H 10, PhCH N; 4.09, t,
2
2H, J 5.5 Hz, H 2; 6.87, t, 1H, J 7.4 Hz, H 14; 6.91, d, 1H, J 8.1 Hz,
H 12; 7.18–7.31, m, 7H, H 11,13, PhH. C n.m.r. δ (100 MHz) 22.73
(C 4,7); 24.47 (C 5 or 6); 27.02 (C 3); 29.40 (C 5 or 6); 51.84, 52.54,
Acknowledgments
13
We thank the Australian Research Council for support and
for provision of an Australian postgraduate award (to DJB)
and Johnson Matthey Pty Ltd for a loan of rhodium.
58.60 (C 8,10, PhCH N); 67.34 (C 2); 112.10 (C 14); 119.96 (C 12);
2
126.58, 127.99, 128.37, 129.05, 132.47 (C 11,13, PhCH); 158.12
+
(C 14a) (C 10a and C 1′ not observed). Mass spectrum (ESI ): m/z
+
310.3 (M+H) .
References
Reactions of the amine (0.3 g, 1.0 mmol) with BIPHEPHOS and 1 : 1 or
1
9 : 1 H /CO gave in each case a mixture of products. Only N-benzyl-
Bergmann, D. J., Campi, E. M., Jackson, W. R., Patti, A. F., and
2
2-(hexyloxy)benzylamine (17b) was isolated from the light petroleum
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Anastasiou, D., and Jackson, W. R., J. Organomet. Chem., 1991,
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2
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H
NO+H)
27
20
1
requires m/z 298.2171). H n.m.r. δ (200 MHz) 0.81, t, 3H, J 6.8 Hz,

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