Hydrogenation of nitroarenes bearing aldehyde containing side chains over palladium and platinum catalysts: A new route to medium and large heterocyclic compounds

Article abstract of DOI:10.1016/S0040-4020(01)00716-5

A wide range of nitroarenes bearing aldehyde containing side chains, readily available by hydroformylation of the corresponding alkenes have been hydrogenated over heterogeneous palladium or platinum catalysts to give medium and large heterocycles either resulting from direct cyclisation or by the formation of dimers. The yields of monomers and dimers are discussed as a function of ring size and the pattern of heteroatom substitution in the substrates; in general the greater the number of heteroatoms in the chain, the greater the yield of cyclic compounds.

Full text of DOI:10.1016/S0040-4020(01)00716-5

TETRAHEDRON
Pergamon
Tetrahedron 57 /2001) 7557±7574
Hydrogenation of nitroarenes bearing aldehyde containing side
chains over palladium and platinum catalysts: a new route to
medium and large heterocyclic compoundsq
Tina Ventrice,a Eva M. Campi,a W. Roy Jacksona,b,p and Antonio F. Pattic
aSchool of Chemistry, Monash University, P.O. Box 23, Melbourne, Vic. 3800, Australia
bCentre for Green Chemistry, Monash University, Melbourne, Vic. 3800, Australia
cSchool of Applied Sciences, Monash University, Gippsland Campus, Churchill, Vic. 3841, Australia
Received 28 March2001; revised 11 June 2001; accepted 5 July 2001
AbstractÐA wide range of nitroarenes bearing aldehyde containing side chains, readily available by hydroformylation of the corresponding
alkenes have been hydrogenated over heterogeneous palladium or platinum catalysts to give medium and large heterocycles either resulting
from direct cyclisation or by the formation of dimers. The yields of monomers and dimers are discussed as a function of ring size and the
pattern of heteroatom substitution in the substrates; in general the greater the number of heteroatoms in the chain, the greater the yield of
cyclic compounds. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
of the substrate. Some support for this proposal came from a
recent report of the synthesis of a 17-membered cyclic
amine in good yield /66%) by hydrogenolysis of a Cbz-
protected aminoaldehyde.11 Presumably, the ®rst step of
this preparation involves formation of an aminoaldehyde
which subsequently cyclises to form an iminium salt or
enamine which is hydrogenated to form the amine. In a
related sequence, a Boc-protected aminoaldehyde was
converted into a 14-ring macrocycle, in modest yield, by
Hydrogenation of nitroarenes bearing aldehyde or ketone
containing side chains /hereafter referred to as nitro-
aldehydes or nitroketones) over platinum metal catalysts
has long been established as a route to 5- and 6-membered
cyclic amines.2 Indoles have been prepared in high yields by
hydrogenation of nitroketones over Pd/C3 or of nitro-
aldehydes over Rh-catalysts.4 Pyrrolidines have been
prepared by hydrogenation of g-nitroketones over Raney
Ni5 and a phenanthridine resulted from a related Zn/acetic
acid reduction of a nitroaldehyde.6 The method has also
been applied to the synthesis of benzodiazepines,7 azepine
imines8 /7 ring) and a diazecinone /8 ring).9 In some cases,
e.g. in the hydrogenation of aliphatic a-nitroketones, a
piperazine, a dimeric product, is produced.10
treatment withtri¯uoroacetic acid, trieythlamine and
subsequent reduction withcyanoboroyhdride.
12
Ojima
has also shown that N-protected diallylamines react
under hydroformylation/cyclisation conditions to form
N-protected enamines witha pendant aldyedhe.
13
Although all of this evidence points to the involvement
of aminoaldehydes, it should be noted that on one
occasion in our work an aminoaldehyde was isolated
from hydroformylation of an aminoalkene without
cyclisation /see below). Aminoaldehydes are again
possible intermediates in the hydrogenation of nitro-
aldehydes and thus this reaction may lead to similar good
yields of large and possibly medium heterocycles. Nitro-
arenes bearing aldehyde containing side chains are readily
available by hydroformylation of alkenyl substituted
nitroarenes.14,15
The high yields of cyclic compounds formed in these
reactions prompted us to examine this method as a general
route to the preparation of medium and large heterocycles.
As the reactions occur on a metal catalyst that is present in
relatively low concentrations, it appeared possible that
cyclisation could be preferred over oligomerisation or poly-
merisation without the need to have very low concentrations
Further support for the proposed method comes from
the reported formation of large ring amines from
hydroformylation of aminoalkenes under conditions
whereby an intermediate enamine is hydrogenated16 or
trapped by reaction withan appropriately substituted
nucleophile.17
q See Ref. 1.
Keywords: hydrogenation; catalysis; medium-ring heterocycles; macro-
cycles.
p
Corresponding author. Tel.: 161-3-9905-4552; fax: 161-3-9905-4597;
e-mail: w.r.jackson@sci.monash.edu.au
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020/01)00716-5

7558
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
2. Results and discussion
similar yield of dimeric product /75%, entry 7) could be
obtained by the use of a Pt catalyst at 1 atm of H2, it was
felt that the use of high pressure equipment was not justi®ed
and subsequent reactions only involved the use of 1 atm H2.
2.1. Preparation of nitroaldehydes
The nitroaldehydes were all prepared by rhodium-catalysed
hydroformylation of nitrobenzenes substituted with alkene
containing side chains /Scheme 1). A variety of such
alkenes with o, m, and p-substituted nitro groups, with
side chains containing only C, with one or more O atoms,
withS, withN, or withN and O atoms were prepared by
standard methods as described in Section 3. Hydroformyl-
ation of the nitroalkenes 1 was carried out using PPh3 as
ligand to give linear and branched aldehydes, 2 and 3 in a
ratio of ca. 70:30. In general, the aldehydes were readily
separated by column chromatography on silica. Use of the
bulky bisphosphite ligand, BIPHEPHOS18 led to a much
greater proportion /$90:10) of the linear aldehydes.
Hydrogenations of 4f were carried out over Pd using
alternative solvents to methanol. Use of either benzene or
ethyl acetate led to reductions in yields of dimer /34 and
33%, respectively) withconcomitant increases in polymer
formation.
A reaction of compound 4p over Pd at a higher concentra-
tion /£3.3) gave a reduced yield of bothmonomeric /75 to
34%) and dimeric /6 to 0%) products /cf. entries 19 and 21).
Again, more polymeric products were formed. The lower
concentration /4.8£1023 M), comparable to that used by
Japanese workers in the hydrogenation of the Cbz-protected
amino aldehyde11 was thus adopted.
Aldehydes which were b to an oxygen atom in the chain
were prepared by hydroformylation of vinyl ethers which
gave linear to branched ratios of ca. 30:70 with either PPh3
or BIPHEPHOS as ligand.
2.4. Effect of ring size on product distribution
The effect of chain length on product distribution for
compounds with only one or no heteroatoms in the chain
was examined. Highyields of 7-membered monomeric
products were obtained and no 14-membered dimers were
formed /entries 1 and 2). No clear pattern was observed for
the formation of 8- and 16-membered compounds /entries
3±5) and polymer formation was .50% in eachcase. Reac-
tions leading to medium size rings /9- and 10-membered)
were as expected unfavourable relative to dimer formation
/18- and 20-membered) /entries 6±9 and 11±14) withone
substrate 4f giving up to 75% of the 18-membered ring
dimer. Surprisingly, introduction of a NCOPhgroup into
the chain led to formation of the monomeric 9-ring
compound in modest yield /22%) withno dimer /entry
10). Larger /15- and 16-membered ring) monomers formed
more easily than their corresponding dimers /30- and 32-
membered rings) /entries 22±24). In eachof these cases
overall yields were ca. 50% withmonomer to dimer ratios
between 1.5 and 3:1.
Some dif®culties were encountered in hydroformylation
of compounds containing allyloxy substituents, where
signi®cant amounts /10±20%) of alcohols arising from
hydrogenolysis reactions were formed.
2.2. Hydrogenations of nitroaldehydes
Reaction conditions. The nitroaldehydes 4 were hydro-
genated over PtO2 or 10% Pd/C catalysts at ambient
temperature with1 atm of H . A greater quantity /2.6£
2
1024 mol) of PtO2 was used than palladium /5.6£
1025 mol) as reactions using a smaller amount of Pt
/5.6£1025 mol) did not go to completion.
2.3. Reduction of ortho-nitroaldehydes 4
Bothmonomeric 5 and dimeric 6 products were formed in
these reactions together with varying amounts of polymers
/Scheme 2, Table 1). The ratios of monomers to dimers were
estimated either by HPLC or from the mass of products
isolated by chromatography on silica. Concordant results
were obtained for the two methods demonstrating product
stability on silica chromatography. The yields quoted in
Table 1 are yields of isolated products which in all cases
were shown to be pure by a range of analytical techniques.
Thus, in general, the results re¯ected the well established
ease of formation of smaller /7-membered) rings, the dif®-
cult formation of medium /9- and 10-membered) rings and
the ease of formation of large rings /.15-membered).19
2.5. Effect of increased heteroatom substitution on
product distribution
The effect of hydrogen pressure was evaluated by a hydro-
genation of compound 4f over Pd at ca. 80 atm H2 which
gave the dimeric product in higher yield /74%) than the
Reactions of a range of nitroaldehydes containing two or
three heteroatoms in the side chain were examined. No
general improvement in total yields of cyclic products was
observed but the introduction of two ethyleneoxy groups led
reaction with1 atm of H /64%, entry 6). However, as a
2
Scheme 1.

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7559
Scheme 2.
Table 1. Isolated yields of heterocycles from hydrogenation of o-nitroaldehydes
Product yield /%)a
Entry
Reactant
/ )CHO 4
Catalyst
Monomer 5
Dimer 6
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
2-/CH2)2CH/CH3)CHO
2-CH2OCH/CH3)CHO
2-O/CH2)2CH/CH3)CHO
2-CH2SCH2CH/CH3)CHO
2-O/CH2)3CHO
Pd
Pd
Pd
Pt
Pd
Pd
Pt
67/7)
56/7)
14/8)
20/8)
33/8)
±/9)
±
±/14)
±/14)
30/16)
±/16)
8/16)
64/18)
75
2-O/CH2)4CHO
2-O/CH2)4CHO
4f
8
9
4g
4h
4i
4j
4j
2-O/CH2)3CH/CH3)CHO
2-CH2O/CH2)3CHO
2-N/COPh)/CH2)4CHO
2-O/CH2)2OCH/CH3)CHO
2-O/CH2)2OCH/CH3)CHO
2-O/CH2)5CHO
2-O/CH2)2OCH2CH/CH3)CHO
2-O/CH2)2O/CH2)3CHO
2-O/CH2)2O/CH2)3CHO
2-O/CH2)2N/SO2Me)/CH2)3CHO
2-O[/CH2)2O]2CH2CH/CH3)CHO
2-O[/CH2)2O]2/CH2)3CHO
2-O[/CH2)2O]2/CH2)3CHO
2-O[/CH2)2O]2/CH2)3CHO
2-O/CH2)9CH/CH3)CHO
2-O/CH2)11CHO
Pd
Pd
Pd
Pd
Pt
Pd
Pd
Pd
Pt
±
62/18)
23/18)
±/18)
58/18)
47/18)
20/20)
37/20)
36/22)
18
±/22)
±/26)
6/28)
±
±/9)
22/9)
±/9)
±/9)
7/10)
±/10)
19/11)
22
36/11)
56/13)
75/14)
58
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4k
4l
4m
4m
4n
4o
4p
4p
4p
4q
4r
4r
Pt
Pd
Pd
Pt
Pdb
Pt
34
±
29/15)
27/16)
36
18/30)
19/32)
11
Pd
Pt
2-O/CH2)11CHO
Reactions at ambient temperature withH 2 /1 atm) using a substrate concentration of 4.76£1023 M in methanol /typically using 100 mg of substrate) with Pd
/5.6£1025 mol) as 10% Pd/C and Pt /3£1024 mol) as PtO2.
a
Ring size in parentheses.
Reaction at higher concentration /£5).
b
to a high preference for monomer formation. Thus signi®-
cant yields /56±75%) of 13- and 14-membered ring
compounds were formed at the expense of dimers /entries
18±20). This selectivity is greater than that noted above
for the formation of 15- versus 30- and 16- versus
32-membered rings when only one oxygen atom is present
in the side chain /entries 22±24). Increased heteroatom
substitution led to signi®cant amounts of 11-membered
ring formation /entries 15 and 16) and once again
introduction of a N-atom in the chain as a sulfonamide
gave only 11-ring monomer albeit in modest yield /entry
17). In contrast, the substitution of a further oxygen atom as
in compound 4l led to only dimer formation /20-membered
ring) /entry 14) whereas some monomer /7%) was obtained
from reaction of the pentamethylene compound 4k
/entry 13).
Table 2. Isolated yields of heterocycles from hydrogenation of m- and p-nitroaldehydes
Product yield /%)
Entry
Reactant
/ )CHO 4
Catalyst
Monomer 5
Dimer 6
25
26
27
28
29
4s
4t
4u
4v
4w
3-O/CH2)2CH/CH3)CHO
3-O/CH2)4CHO
4-O/CH2)5CHO
4-O/CH2)2O/CH2)3CHO
4-O[/CH2)2O]2/CH2)3CHO
Pd
Pd
Pd
Pt
6/9)
10/10)
±/12)a
7/13)
39/18)
17/20)
11/24)
22/26)
26/32)
Pt
±/16)
Conditions as in Table 1.
Amino alcohol from reduction of CHO and NO2 groups also formed /45%).
a

7560
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
2.6. Reaction of meta- and para-substituted compounds
Insight II program20 for the potential interactions of one
Ag1 ion withthe monomer 5m and for two Ag1 ions with
the dimer 6m. The minimum energy conformation of the
A limited number of meta- and para-substituted nitro-
aldehydes were hydrogenated. In general, overall recoveries
of cyclic products were only modest /Scheme 2 and Table 2).
Perhaps surprisingly, small amounts of 9- and 10-membered
cyclic compounds were isolated in spite of the additional
constraint imposed upon the ring system by the increased
number of sp2 carbon atoms /entries 25 and 26). Reaction of
the para-substituted compound 4u was unique in that the
major product was the aminoalcohol resulting from reduc-
tion of both the nitro and aldehyde groups /entry 27).
1
monomer 5m withone Ag ion had the Ag1 ion sitting
above the three donor atoms with minimal conformational
change in the calculated structure. In contrast, the minimum
energy conformation of the dimer with two Ag1 ions sitting
above the plane of the ring required more extensive confor-
mational changes from the free dimer structure.
Compound 6j was prepared in which the two O and one N
atoms in eachside of an 18-membered ring were all
separated by two carbon atoms in an attempt to increase
the potential for chelation. Studies were carried out by
2.7. Potential template effects
Professor Lindoy's group who evaluated the stability
1
constant data for the complexation of 6j withCu
and
A series of potential templating agents was added to hydro-
genations of nitroaldehyde 4m. The resulting monomeric
and dimeric products had two oxygen and one nitrogen or
four oxygen and two nitrogen atoms as potential chelating
sites. Addition of Ag/OTf)2 /1 or 2 equiv.), Ba/NO3)2
/1 equiv.) or La/OTf)3 /1 equiv.) all led to the exclusive
formation of monomer in greater yields than when no
additive was present /Table 3). Addition of Ba/OTf)2
surprisingly gave only polymeric material withno
recoverable cyclic products.
Ag1 ions. The measured values of log K of ca. 3 were
signi®cantly less than those recorded for 14- and 16-
membered rings containing four heteroatoms /N2O2, N2S2,
or N4) where log K values of 8±15 were obtained.21 It was
concluded that the geometry of 6j was not conducive to
complex formation and no further studies were carried out.
2.8. Mechanistic considerations
The exclusive formation of monomers, dimers and polymers
and the absence of trimers and other oligomers was noted in
all cases. Other studies have shown that under acid catalysis,
facile equilibration between monomers, dimers and
oligomers results.22 It is possible that the imines remain
close to the catalyst surface in our reactions and that hydro-
genation competes witholigomerisation leading to stable
products. It is dif®cult to see why such high yields of
dimer can be obtained, e.g. 75% of dimer 6f /entry 7,
Table 1).
Energy minimisation calculations were carried out using the
Table 3. Effects of potential templating agents on the hydrogenations of the
nitroaldehyde 4m /glycine, dissolved in the minimum amount of water, and
added to the methanol solution)
Additive
Product yield /%)a
5m
6m
±
19
30
33
30
±
36
±
±
±
±
Ag/OTf) 1 equiv.
Ag/OTf) 2 equiv.
Ba/NO3)2 1 equiv.
Ba/OTf) 2 1 equiv.
La/OTf)3 1 equiv.
Glycine 1 equiv.
When a further degree of conformational restriction was
imposed on the nitroaldehyde in 7, only the 17-membered
cyclic compound 8 was obtained in moderate to good yields
/47%, Pt and 65%, Pd) withno trace of any dimeric
compounds /Scheme 3).
45
21
±
33
Reaction over Pd/C in methanol.
Isolated yields.
a
The possible direct involvement of the Pt or Pd catalysts in
the cyclisation step was explored by preparation of the
Scheme 3.
Scheme 4.

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7561
aminoaldehyde 10. Reaction of the aminoalkene 9 with
H2/CO in the presence of Rh/BIPHEPHOS at 808C gave
the aminoaldehyde 10 in moderate yield /40%)
/Scheme 4). This result was surprising as both 16- and
32-membered heterocycles form easily /entries 23 and 24,
Table 1). In addition, hydroformylation of a related
aminoalkene, N-benzyl-2-/undec-10-enyloxy)benzylamine
gave a 17-membered heterocycle /34%) together with the
34-membered heterocycle /20%).16
under standard conditions gave the alkene as a viscous
yellow oil after ¯ashchromatography /silica, 20% EtOAc/
light petroleum) /1.3 g, 84%). /Found: m/z 319.1047.
/C17H16N2O31Na)1 requires m/z 319.1059). nmax /®lm)
3450, 1657, 1603, 1579, 1529, 1389, 1369, 1348, 1317,
1
785, 735, 704 cm21. H NMR d /400 MHz) 2.33, m, 2H,
H20; 3.42, m, 1H and 4.15±4.20, m, 1H, H10; 4.89±4.95, m,
2H, H40; 5.59, m, 1H, H30; 6.48±6.50, m, 1H, H5; 6.71±
6.74, m, 2H and 6.84, m, 3H, PhH; 7.25, m, 1H, H4; 7.31±
13
7.32, m, 2H, H3,6. C NMR d /100 MHz) 32.59 /C20);
50.77 /C10); 116.68 /C40); 125.39 /C3,5,6); 127.25,
129.76, 132.87 /C4, PhCH);137.38 /C30). Mass spectrum
/ESI1): m/z 297.2 /M1H)1.
3. Experimental
Operations involving ligands and catalysts were carried out
under an atmosphere of dry N2 using dry solvents that were
distilled prior to use.
3.1.2. 2-21,4-Dioxahex-5-enyl)nitrobenzene 2precursor to
4j). Reaction of 2-/2-hydroxyethoxy)nitrobenzene /1.0 g,
5.46 mmol) with ethyl vinyl ether /20 ml) and mercuric/II)
25
Flash chromatography was performed using E.Merck 230±
acetate /0.1 g) at re¯ux for 24 has described previously
1
400 meshsilica gel. H NMR spectra were measured at 200,
gave the alkene as a yellow oil after ¯ash chromatography
/silica, 10% EtOAc/light petroleum) /400 mg, 26%).
/Found: C, 57.4; H, 5.4; N, 6.4. C10H11NO4 requires C,
57.4; H, 5.3; N, 6.7%). nmax /®lm) 2934, 1608, 1584,
1526, 1488, 1453, 1354, 1323, 1279, 1256, 1199, 1167,
300 or 400 MHz and 13C were recorded at 50 or 100 MHz.
Mass spectra including accurate mass measurements /EI)
were obtained at 70 eV or by Electrospray Mass Spectro-
scopy /ESI) witha cone voltage of 25 V and withmethanol
as the mobile phase. High Performance Liquid Chromato-
graphy /HPLC) was performed on a Waters Model 6000A
1
1092, 1048, 982, 927, 853, 773, 745 cm21. H NMR d
/300 MHz) 4.06±4.11, m, 3H, H30 and H60Z; 4.26, dd,
Jˆ14.3, 2.3 Hz, 1H, H60E; 4.33±4.36, m, 2H, H20; 6.5, dd,
Jˆ14.3, 6.7 Hz, 1H, H50; 7.03±7.13, m, 2H, H3,5; 7.49±
7.55, m, 1H, H4; 7.82, dd, Jˆ8.1, 1.6 Hz, 1H, H6. 13C NMR
d /100 MHz) 66.29 /C30); 68.61 /C20); 87.52 /C60); 115.35
/C3); 121.03 /C5); 125.65 /C6); 134.03 /C4); 140.47 /C1);
151.59 /C50); 152.10 /C2). Mass spectrum /ESI1): m/z
210.0 //M1H)1, 8%); 232.1 //M1Na)1, 100).
Ê
/Column: Deltapak C18 Ð 100 A, 3.9 mm£30 cm, 10 m),
Waters gradient programme Model 660 and Waters Model
481 Detector. Unless otherwise stated, the gradient elution
involved an initial composition of 20:80% CH3CN/water,
increased to 100% CH3CN within 40 min with a ¯ow rate of
1 ml/min. Product distributions were obtained from peak
areas from a peak printout using HP Chemstation 3365
Series II software.
3.1.3.
2-[2N-Methylsulfonyl)-1-oxa-4-azahept-6-enyl]-
Rhodium/III) trichloride trihydrate /RhCl3´nH2O, nˆ
approx. 3) was supplied by Johnson Matthey Pty Ltd and
converted into tetrakis/acetato)dirhodium/II), [Rh/OAc)2]2.23
[6,60-{[3,30-bis/1,1-dimethylethyl)-5,50-dimethoxy-1,10-bi-
phenyl]-2,20-diyl}bis/oxy)]bis-dibenzo[d,f][1,3,2]dioxa-
phosphepin], BIPHEPHOS, was prepared by a literature
procedure.18 Platinum oxide /PtO2) was obtained from
Johnson Matthey Pty Ltd and 10% Pd/C was obtained
from Aldrich. Light petroleum refers to the fraction of
petroleum bp 60±808C.
nitrobenzene 2precursor to 4n). Reaction of 2-/1-oxa-4-
azahept-6-enyl)nitrobenzene /0.5 g, 2.25 mmol) with
methanesulfonyl chloride /1.29 g, 11 mmol) using standard
conditions gave the alkene as a viscous yellow oil which
solidi®ed on standing /0.52 g, 76%) mp 59.7±60.38C.
/Found: C, 48.0; H, 5.4; N, 9.5. C12H14N2O5S requires C,
48.0; H, 5.4; N, 9.3%). nmax /®lm) 2935, 1607, 1584, 1525,
1488, 1454, 1329, 1277, 1256, 1148, 1048, 1010m, 776,
1
746 cm21. H NMR d /300 MHz) 2.90, s, 3H, CH3; 3.64,
t, Jˆ5.4 Hz, 2H, H30; 4.03, apparent doublet, Jˆ6.3 Hz, 2H,
H50; 4.27, t, Jˆ5.4 Hz, 2H, H20; 5.26±5.38, m, 2H, H70;
5.84, ddt, Jˆ16.6, 10.1, 6.4 Hz, 1H, H60; 7.03±7.09, m, 2H,
H3,5; 7.50±7.56, m, 1H, H4; 7.83, dd, Jˆ8.0, 1.7 Hz, 1H,
H6. 13C NMR d /100 MHz) 39.52 /CH3); 45.78 /C30); 51.44
/C50); 68.92 /C20); 114.49 /C3); 119.77 /C70); 120.99 /C5);
125.72 /C6); 132.59 /C4); 134.34 /C60); 139.91 /C1);
151.69 /C2). Mass spectrum /ESI1): m/z 301.2 /M1H)1.
3.1. Alkenylnitrobenzenes and related compounds
The following were prepared by known literature
methods: 2-/but-3-enyloxy)nitrobenzene /precursor to
4a);24 2-/2-oxabut-3-enyl)nitrobenzene /precursor to 4b);25
2-/but-3-enyloxy)nitrobenzene /precursor to 4c and 4f);26
2-/2-thiapent-4-enyl)nitrobenzene /precursor to 4d);15,27
2-/prop-2-enyloxy)nitrobenzene /precursor to 4e);28 2-/2-
oxapent-4-enyl)nitrobenzene /precursor to 4h);29 2-/1,4-
dioxahept-6-enyl)nitrobenzene /precursor to 4l and 4m);30
2-/1,4,7-trioxadec-9-enyl)nitrobenzene /precursor to 4o and
4p);30 2-/undec-10-enyloxy)nitrobenzene /precursor to 4q
and 4r)31 and 4-/but-3-enyloxy)nitrobenzene /precursor to
4u).32
3.1.4. 2-[2N-Benzyl)undec-10-enyloxy]aniline 29). Reac-
tion of 2-/undec-10-enyloxy)aniline /0.2 g, 0.76 mmol)
and benzaldehyde /0.16 g, 1.53 mmol) in MeOH /10 ml)
at 1008C for 3 hfollowed by reduction using NaBH
4
/86 mg, 2.28 mmol) as described previously34 gave the
alkene as a yellow oil after ¯ash chromatography /silica,
5% EtOAc/light petroleum) /0.13 g, 48%). /Found: m/z
352.2634. /C24H33NO1H)1 requires m/z 352.2640). nmax
/®lm) 2926, 2854, 1602, 1519, 1453, 1246, 1214, 1048,
3.1.1. 2-[2N-Benzoyl)but-3-enylamino]nitrobenzene 2pre-
cursor to 4i). Reaction of 2-/but-3-enylamino)nitro-
benzene33 /1.0 g, 5.2 mmol) withbenzoyl chloride /2 ml)
1
1028, 909, 734, 698 cm21. H NMR d /200 MHz) 1.21±
1.44, bs, 12H, H30,40,50,60,70,80; 1.79, pentet, Jˆ6.5 Hz,

7562
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
2H, H20; 1.98±2.08, m, 2H, H90; 3.99, t, Jˆ6.5 Hz, 2H, H10;
4.36, s, 2H, PhCH2; 4.89±5.04, m, 2H, H110; 5.81, ddt,
Jˆ17.1, 10.2, 6.6 Hz, 1H, H100; 6.54±6.68, m, 2H, H4,6;
6.75- 6.84, m, 2H, H3, 5; 7.21- 7.50, m, 5H, PhH. 13C NMR
d /75 MHz) 25.17, 27.94, 28.12, 28.37, 28.39, 28.42, 28.53
/C20,30,40,50,60,70,80); 32.80 /C90); 47.01 /CH2Ph); 67.40
/C10); 109.19, 109.59 /C3,6); 113.13 /C110); 115.59,
120.17 /C4,5); 125.82, 126.32, 126.58 /PhCH); 127.48
/C1); 138.21 /C2); 138.20 /C100); 145.23 /PhC). Mass
spectrum: /ESI1): m/z 352.2 /M1H)1. Mass spectrum
/EI): m/z 351 /M1, 23%), 198 /20), 108 /23), 91 /100), 55 /47).
1469, 1390, 1348, 1287, 1246, 1096, 1036, 991, 921, 863,
796, 737, 672 cm21. 1H NMR d /200 MHz) 2.56, qt, Jˆ6.7,
1.3 Hz, 2H, H20; 4.06, t, Jˆ6.6 Hz, 2H, H10; 5.08±5.23, m,
2H, H40; 5.89, ddt, Jˆ17.0, 10.2, 6.7 Hz, 1H, H30; 7.21±
7.22, m, 1H, H4; 7.39, t, Jˆ8.2 Hz, 1H, H5; 7.67±7.69, m,
1H, H2; 7.74±7.80, m, 1H, H6. 13C NMR d /50 MHz) 33.25
/C20); 67.78 /C10); 108.72 /C2); 115.58 /C6); 117.40 /C40);
121.54 /C4); 129.83 /C5); 133.77 /C30); 149.01 /C1);
159.33 /C2). Mass spectrum /ESI1): m/z 216.1 /M1Na)1.
3.2.3. 2-21-Oxa-4-azahept-6-enyl)nitrobenzene. This com-
pound was prepared from 2-/2-bromoethoxy)nitrobenzene
/1.0 g, 4.08 mmol) and prop-2-enylamine /2.33 g, 41 mmol)
in CH3CN as an orange oil /0.85 g, 94%). /Found: m/z
223.1081. /C11H14N2O31H)1 requires m/z 223.1083). nmax
/®lm) 3424, 2884, 1604, 1567, 1520, 1348, 1295, 1046,
3.1.5. 2-2Undec-10-enyloxy)aniline. Reaction of 2-/undec-
10-enyloxy)nitrobenzene /0.5 g, 1.72 mmol) and SnCl2´
2H2O /2.48 g, 10.9 mmol) in absolute EtOH /10 ml) at
35
708C for 2 has described prevoiusly gave the alkene as
1
a pale red liquid after ¯ash chromatography /silica, 50%
CH2Cl2/light petroleum) /0.42 g, 93%). /Found: m/z
262.2165. /C17H27NO1H)1 requires m/z 262.2171). nmax
/®lm) 3376, 3381, 3075, 2627, 2854, 1614, 1506, 1460,
746 cm21. H NMR d /300 MHz) 2.62, t, Jˆ6.1 Hz, 1H,
NH; 3.38, t, Jˆ5.3 Hz, 2H, H30; 3.62±3.67, m, 4H, H
20,50; 5.13±5.20, m, 2H, H70; 5.76, ddt, Jˆ17.5, 9.9,
6.5 Hz, 1H, H60; 7.05±7.25, m, 1H, H5; 7.27, dd, Jˆ8.3,
1.1 Hz, 1H, H3; 7.44±7.49, m, 1H, H4; 7.69, dd, Jˆ8.1,
1276, 1221, 1142, 1043, 909, 737 cm21 1H NMR d
.
13
/300 MHz) 1.30±1.46, bs, 12H, H30,40,50,60,70,80; 1.81,
pentet, Jˆ6.7 Hz, 2H, H20; 2.04, q, Jˆ6.7 Hz, 2H, H90;
3.58, bs, 2H, NH2; 3.98, t, Jˆ6.5 Hz, 2H, H10; 4.90±5.03,
m, 2H, H110; 5.81, ddt, Jˆ17.5, 10.3, 6.6 Hz, 1H, H100;
6.73±6.80, m, 4H, ArH. 13C NMR d /75 MHz) 26.20,
28.98, 29.17, 29.26, 29.39, 29.46, 29.57, /C20,30,40,
50,60,70,80); 33.84 /C90); 68.33 /C10); 111.59 /C110);
114.18, 115.09 /C3,6); 118.49 /C4); 120.99 /C5); 136.39
/C1); 139.25 /C100); 146.84 /C2). Mass spectrum /EI): m/
z 261 /M1, 22%), 145 /21), 143 /90), 109 /100), 80 /36), 55
/55).
1.6 Hz, 1H, H6. C NMR d /100 MHz) 53.39 /C30);
57.78 /C50); 59.26 /C20); 118.94 /C70); 122.63 /C3);
124.47 /C5); 125.51 /C6); 132.97 /C4); 133.43 /C60);
134.21 /C1); 144.27 /C2). Mass spectrum /ESI1): m/z
223.1 /M1H)1.
3.2.4. 2-{1,4,7-Trioxa-7-[2-2prop-2-enyloxy)phenyl]hep-
tyl}nitrobenzene 2precursor to 7). This compound was
prepared from 2-/prop-20-enyloxy)phenol36 and 2-/6-
chloro-1,4-dioxahexyl)nitrobenzene37 as a pale yellow oil
after ¯ash chromatography /silica, 30% EtOAc/light
petroleum) /71%). /Found: C, 63.7; H, 5.9; N, 3.9.
C19H21NO6 requires C 63.5, H 5.9, N 3.9%). nmax /®lm)
2932, 2873, 1608, 1526, 1503, 1452, 1355, 1278, 1255,
3.2. Preparation of alkenes by a standard alkylation
procedure26
1215, 1166, 1127, 1047, 928, 852, 772, 744 cm21 1H
.
NMR d /300 MHz) 3.92±3.98, m, 4H, H30,50; 4.15±4.19,
m, 2H and 4.23±4.26, m, 2H, H20,60; 4.55, dt, Jˆ5.2,
1.6 Hz, 2H, H1000; 5.22, apparent dq, Jˆ10.5, 1.5 Hz, 1H,
H3000E; 5.38, apparent dq, Jˆ17.3, 1.7 Hz, 1H, H3000Z; 6.04,
ddt, Jˆ17.3, 10.5, 5.3 Hz, 1H, H2000; 6.85±7.10, m, 6H,
H3,5, ArCH; 7.43±7.49, m, 1H, H4; 7.78, dd, Jˆ8.1,
1.7 Hz, 1H, H6. 13C NMR d /100 MHz) 68.89, 69.54,
69.78, 70.12, 70.71 /C20,30,50,60,1000); 114.40, 114.75,
114.99 /C3,7,ArCH); 117.58 /C3000); 120.46 /C5); 121.31,
121.48 /C6,ArCH); 125.37 /ArCH); 133.48, 133.98
/C2000,4); 139.95 /C1); 148.66, 148.69 /ArC); 152.14 /C2).
Mass spectrum /ESI1): m/z 360.3 //M1H)1, 50%); 382.3
//M1Na)1, 100).
3.2.1. 2-2Pent-4-enyloxy)nitrobenzene 2precursor to 4g
and 4k). A stirred mixture of 2-nitrophenol /2.8 g,
20 mmol), 5-bromopent-1-ene /2.0 g, 13 mmol) and
K2CO3 /2.8 g, 20 mmol) in DMSO was heated to 1108C
for three days. Distillation gave the alkene as a pale yellow
oil /2.36 g, 85%), bp /oven) 1308C /0.04 mm. /Found: C,
64.1; H, 6.7; N, 6.9. C11H13NO3 requires C, 63.8; H, 6.3; N,
6.8%). nmax /®lm) 3078, 2976, 2944, 2882, 1641, 1609,
1583, 1522, 1488, 1451, 1392, 1355, 1280, 1257, 1165,
1150, 1089, 1044, 1005, 917, 855, 772, 745, 670, cm21
.
1H NMR d /200 MHz) 1.96, pentet, Jˆ6.4 Hz, 2H, H20;
2.27, q, Jˆ6.5 Hz, 2H, H30; 4.10, t, Jˆ6.3 Hz, 2H, H10;
4.95±5.11, m, 2H, H50; 5.83, ddt, Jˆ16.9, 10.2, 6.7 Hz,
1H, H40; 6.95±7.09, m, 2H, H3,5; 7.50, m, 1H, H4; 7.80,
dd, Jˆ8.0, 1.7 Hz, 1H, H6. 13C NMR d /50 MHz) 27.88,
29.69 /C20,30); 68.46 /C10), 114.30 /C3); 115.32 /C50);
119.04 /C5); 125.26 /C6); 133.96 /C4); 137.27 /C40);
139.71 /C1); 152.18 /C2). Mass spectrum /EI): m/z 207
/M1, 1%), 161 /7), 139 /11), 123 /10), 122 /9), 109 /10),
107 /9), 92 /5), 69 /51), 68 /100), 67 /55), 65 /15).
3.3. Preparation of alkenes using phase transfer
catalysis30
3.3.1. 4-21,4-Dioxahept-6-enyl)nitrobenzene 2precursor
to 4v). Reaction of 4-¯uoronitrobenzene /1.06 g, 7.48
mmol) and 3-oxahex-5-en-1-ol /1.62 g, 11.2 mmol) in
anhydrous benzene /10 ml) with 50% aqueous NaOH
/4.5 g) and benzyltriethylammonium chloride /0.09 g,
0.39 mmol) at re¯ux withvigorous stirring for 4 hgave
the alkene as a yellow oil after ¯ash chromatography /silica,
20% EtOAc/light petroleum) /1.90 g, 95%). /Found: C,
59.5; H, 5.8; N, 6.3. C11H14NO4 requires C, 59.2; H, 5.9;
N, 6.3.). nmax /®lm) 3084, 2930, 2864, 1594, 1514, 1453,
3.2.2. 3-2But-3-enyloxy)nitrobenzene 2precursor to 4s
and 4t). This compound was prepared from 3-nitrophenol
and 4-bromobut-1-ene as a pale yellow liquid /57%), bp
/oven) 708C /0.02 mm. /Found: C, 62.0; H, 5.9; N, 7.0.
C10H11NO3 requires C, 62.2; H, 5.7; N, 7.2%.) nmax /®lm)
3081, 2981, 2936, 2878, 1643, 1618, 1581, 1540, 1484,

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7563
1422, 1379, 1342, 1299, 1263, 1174, 1111, 1036, 996, 924,
846, 753, 691, 658 cm21. 1H NMR d /300 MHz) 3.80±3.83,
m, 2H, H30; 4.08, dt Jˆ5.6, 1.3 Hz, 2H, H50; 4.20±4.23, m,
2H, H20; 5.18±5.33, m, 2H, H70; 5.86±5.98, m, 1H, H60;
6.97, dd, Jˆ9.3, 2.2 Hz, 1H, H3,5; 8.17, dd, Jˆ9.2, 2.2 Hz,
72.42 /C50); 114.61 /C70); 117.52 /C3); 125.83 /C2);
134.29 /C60); 141.63 /C1); 163.87 /C4). Mass spectrum
/ESI1): m/z 246.1 /M1Na)1.
involved reaction of 2-/but-3-enyloxy)nitrobenzene /1.0 g,
5.2 mmol), [Rh/OAc)2]2 /11 mg, 24.8 mmol) and PPh3
/27 mg, 103 mmol) in EtOAc /20 ml) withH /CO /1:1,
2
400 psi) at 708C for 20 h. Evaporation of the solvent
under reduced pressure gave a brown residue /1.17 g).
13
1
The H NMR spectrum indicated a 60:40 mixture of the
2H, H2,6. C NMR d /75 MHz) 68.10, 68.26 /C10,30);
linear and branched aldehydes /4f) and /4c), respectively.
Flash chromatography /silica, 10% EtOAc/light petroleum)
gave 2-/30-formylbutyloxy)nitrobenzene /4c) as a yellow
liquid /395 mg, 34%) /Found: C, 58.9; H, 5.8; N, 6.1.
C11H13NO4 requires C, 59.2; H, 5.9; N, 6.3%). nmax /®lm)
2965, 2938, 1725, 1608, 1583, 1526, 1489, 1472, 1353,
1309, 1280, 1256, 1166, 1090, 1046, 848, 773, 746,
3.3.2. 4-21,4,7-Trioxadec-9-enyl)nitrobenzene 2precursor
to 4w). Reaction of 4-¯uoronitrobenzene and 3,6-dioxanon-
8-en-1-ol as described above gave the alkene as a yellow oil
after distillation, bp /oven) 558C/0.04 mm /66%). /Found:
C, 58.3; H, 6.3; N, 5.3. C13H17NO5 requires C, 58.4; H, 6.4;
N, 5.2%). nmax /®lm) 3082, 2870 m, 1608, 1594, 1513,
1498, 1342, 1299, 1264, 1174, 1111, 1055, 926, 848, 753,
658 cm21. 1H NMR d /300 MHz) 3.61±3.69, m, 2H, 3.72±
3.75, m, 2H, and 3.89±3.92, m, 2H, H30,50,60; 4.03, dt,
Jˆ5.7, 1.4 Hz, 2H, H80; 4.22±4.25, m, 2H, H20; 5.18,
1
670 cm21. H NMR d /200 MHz) 1.21, d, Jˆ7.3 Hz, 3H,
H40; 1.88, ddt, Jˆ14.5, 6.3, 1.9 Hz, 1H and 2.21±2.38, m,
1H, H20; 2.77, sextet, Jˆ7.2 Hz, 1H, H30; 4.18, m, 2H, H10;
6.99±7.09, m, 2H, H3,5; 7.52, dd, Jˆ8.5, 1.7 Hz, 1H, H4;
7.84, dd, Jˆ8.0, 1.7 Hz, 1H, H6; 9.71,d, Jˆ1.2 Hz, 1H,
13
CHO. C NMR d /100 MHz) 13.43 /C40); 29.61 /C20);
43.08 /C30); 66.90 /C10); 114.49 /C3); 120.50 /C5);
125.58 /C6); 134.09 /C4); 133.4 /C1); 152.01 /C2);
204.01 /CHO). Mass spectrum /EI): m/z 222 /M121,
,1%), 178/1), 139/10), 113/19), 109/15), 99/14), 92/10),
85/100), 81/16), 78/16), 65/28), 64/20), 63/30), 57/32),
56/20), 55/45).
apparent dq, Jˆ10.4, 1.3 Hz, 1H, H100 ; 5.27, apparent
E
dq, Jˆ17.2, 1.6 Hz, 1H, H100 ; 5.91, ddt, Jˆ17.3, 10.4,
Z
5.6 Hz, 1H, H90; 6.98, dd, Jˆ9.3, 2.2 Hz, 2H, H3,5; 8.18,
dd, Jˆ9.3, 2.2 Hz, 2H, H2,6. 13C NMR d /50 MHz) 68.19,
69.41, 70.96 /C 30,50,60); 72.28 /C 20,80); 114.58 /C 3,5);
117.23 /C100); 125.84 /C 2,6); 134.58 /C90); 141.56 /C1);
163.86 /C4). Mass spectrum /ESI1): m/z 268.1 /M1H)1,
7%); 290.2 /M1Na)1, 100).
Further elution gave 2-/4-formylbutyloxy)nitrobenzene /4f)
as a yellow liquid /406 mg, 35%) /Found: C, 59.2; H, 5.8; N,
6.3. C11H13NO4 requires C, 59.2; H, 5.9; N, 6.3%). nmax
/®lm) 2941, 1710, 1607, 1579, 1526, 1485, 1377, 1352,
3.4. General conditions for reaction with H2/CO
1
1281, 1254, 1167, 1007, 858, 745, 665 cm21. H NMR d
/400 MHz) 1.82±1.89, m, 4H, H20,30; 2.55, td, Jˆ6.8,
1.5 Hz, 2H, H40; 4.12, t, Jˆ5.7 Hz, 2H, H10; 6.90±7.01,
m, 1H, H5; 7.08, dd, Jˆ8.4, 0.8 Hz, 1H, H3; 7.52, m, 1H,
H4; 7.80, dd, Jˆ8.1, 1.7 Hz, 1H, H6; 9.78, t, Jˆ1.5 Hz, 1H,
43.11 /C40); 68.96 /C10); 114.32 /C3); 120.13 /C5);
125.31/C6); 133.98 /C4); 134.10 /C1); 152.07 /C2);
202.03 /CHO). Mass spectrum /EI): m/z 224 /M111,
,1%), 222 /M121,,1), 193/49), 175/100), 174 /35), 146
/52), 85 /100).
Reactions were carried out in a l00 ml Parr autoclave witha
glass sleeve containing a stirrer bead. The substrate /0.3±
1 g, ca. 1±5 mmol), rhodium catalyst precursor and ligand
/in ratio 200:1:4) were placed in the autoclave under N2
followed by deoxygenated benzene or EtOAc /10±20 ml).
The vessel was ¯ushed and evacuated three times with
200 psi /1.38 mPa) of H2/CO /1:1 M mixture) and pres-
surised to 400 psi /2.76 mPa). The vessel was kept at the
reaction temperature for 20 h, the autoclave cooled, the
gases released and the solvent removed under reduced pres-
sure. In general, ratios of products including regioisomers
were determined by relative peak areas of appropriate
13
CHO. C NMR d /100 MHz) 18.50 /C30); 28.17 /C20);
A similar reaction of the alkene /0.3 g, 1.55 mmol)
[Rh/OAc)2]2 /3.4 mg, 7.4 mmol) and BIPHEPHOS
/24 mg, 30.5 mmol) gave the linear and branched aldehydes
in the ratio of 90:10 with ca. 10% of 2-nitrophenol.
1
hydrogens in the H NMR spectra.
Unless otherwise stated, reactions involved the use of
[Rh/OAc)2]2 and BIPHEPHOS as the catalyst system at
808C for 20 hwithH 2/CO, 1:1 at 400 psi.
3.4.2. 2-23-Formylbutyl)nitrobenzene 24a). Reaction of
2-/but-3-enyl)nitrobenzene /260 mg, 1.46 mmol) gave the
linear and branched aldehydes /ratio 96:4) as an orange
oil /300 mg). Puri®cation gave /4a) /10 mg, 3%) and 2-/4-
formylbutyl)nitrobenzene /150 mg, 50%).
All aldehyde products were isolated by ¯ash chromato-
graphy on silica using EtOAc/light petroleum as eluent
/generally 5, 10 or 20%) with the branched isomer having
the higher Rf value. In general, it was dif®cult to obtain
analytically pure samples of the aldehydes and thus they
were used immediately after spectroscopic characterisation.
A similar reaction of the alkene /1.0 g, 5.65 mmol)
using PPh3 as ligand gave the linear and branched
aldehydes in a 55:45 ratio. The aldehyde /4a) was isolated
as a yellow oil /455 mg, 39%). /Found: m/z 162.0554^
0.002. /C11H13NO3±C2H5O)1 requires m/z 162.0553).
nmax /®lm) 2935, 2865, 1708, 1681, 1524, 1462, 1349,
3.4.1. 2-24-Formylbutyloxy)nitrobenzene 24f) and 2-23-
formylbutyloxy)nitrobenzene 24c). A typical procedure
²
911, 786, 733 cm21 1H NMR d /400 MHz) 1.20, d,
.
²
Aldehydes have been named as formyl substituted nitrobenzenes for
Jˆ7.1 Hz, 3H, H40; 1.69±1.78, m, 1H, and 2.03±2.12, m,
1H, H20; 2.45, td, Jˆ6.9, 1.7 Hz, 1H, H30; 2.90±2.95, m,
2H, H10; 7.34±7.39, m, 2H, H 3,5; 7.51±7.55, m, 1H, H4;
consistency with the naming of the precursor alkenes; IUPAC nomencla-
ture would name them, e.g. as 5-/2-nitrophenoxy)pentanal /4f) and
2-methyl-4-/2-nitrophenoxy)butanal /4c).

7564
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7.92, dd, Jˆ8.6, 1.5 Hz, 1H, H6; 9.67, d, Jˆ1.7 Hz, 1H,
31.41 /C10); 46.09 /C30); 124.87 /C6); 127.35 /C5);
132.02 /C3); 133.11 /C4); 136.66 /C2); 149.26 /C1);
204.26 /CHO).
121 /41), 120 /59), 108 /38), 96 /28), 92 /93), 78 /100), 77
/60), 65 /98). The spectral data was consistent with
literature data.15
13
CHO. C NMR d /75 MHz) 13.38 /C40); 30.59 /C20);
2-/5-Formyl-2-thiapentyl)nitrobenzene was isolated as a
yellow oil /91 mg, 20%). nmax /®lm) 2934, 2822, 2726,
1
2-/4-Formylbutyl)nitrobenzene was isolated as a yellow
liquid /506 mg, 43%) /Found: m/z 162.0553^0.002.
/C11H13NO3±C2H5O)1 requires m/z 162.0553). nmax /®lm)
2935, 2866, 1711, 1682, 1524, 1461, 1348, 912, 787,
1720, 1697, 1577, 1526, 1444, 1349, 788, 710 cm21. H
NMR d /200 MHz) 1.88, m, 2H, H40; 2.48, t, Jˆ7.1 Hz,
2H, H30; 2.56, td, Jˆ7.1, 1.2 Hz, H50; 4.05, s, 2H, H10;
7.39±7.58, m, 3H, H3,4,5; 7.97, dd, Jˆ7.8, 1.3 Hz, 1H,
H6; 9.76, t, Jˆ1.2 Hz, 1H, CHO. 13C NMR d /50 MHz)
21.41 /C40); 31.25 /C10); 33.17 /C30); 42.37 /C50); 125.29
/C6); 128.17 /C5); 131.87 /C3); 132.95 /C4); 134.01 /C1);
148.68 /C2); 201.39 /CHO). Mass spectrum /EI): m/z 239
/M1, 3%), 168 /3), 136 /25), 135 /51), 121 /32), 120 /53),
108 /28), 92 /95), 89 /41), 79 /38), 78 /80), 77 /48), 65
/100).
1
735 cm21. H NMR d /300 MHz) 1.69±1.74, m, 4H, H20,
30; 2.49, td, Jˆ6.9, 1.6 Hz, 2H, H40; 2.91, t, Jˆ7.3 Hz, 2H,
H10; 7.32±7.39, m, 2H, H 3,5; 7.49±7.54, m, 1H, H4; 7.89,
dd, Jˆ8.6, 1.6 Hz, 1H, H6; 9.78, t, Jˆ1.6 Hz, 1H, CHO. 13C
NMR d /50 MHz) 21.84 /C30); 30.10 /C20); 32.77 /C10);
43.50 /C40); 124.72 /C6); 127.09 /C5); 131.87 /C3); 132.94
/C4); 136.89 /C2); 149.27 /C1); 202.24 /CHO).
3.4.3. 2-23-Formyl-2-oxabutyl)nitrobenzene 24b). Reac-
tion of 2-/2-oxabut-3-enyl)nitrobenzene /230 mg, 1.28
mmol) gave the linear and branched aldehydes /ratio
30:70) as a viscous, orange oil /280 mg). The aldehyde
/4b) was isolated as a yellow oil /176 mg, 66%). /Found:
m/z 123.0317. /C10H11NO4±C4H6O2 requires m/z 123.0321).
A similar reaction using PPh3 as ligand gave the linear and
branched aldehydes in a ratio of 30:70. Puri®cation gave
/4d) /126 mg, 37%).
3.4.5. 2-23-Formylpropyloxy)nitrobenzene 24e). Reaction
of 2-/prop-2-enyloxy)nitrobenzene /800 mg, 4.47 mmol) at
708C gave an orange oil /800 mg) whose 1H NMR spectrum
indicated a mixture of the linear and branched aldehydes
/ratio ca. 1:1) withca. 5% of 2-nitrophenol.
n
max /®lm) 2878, 1728, 1613, 1578, 1520, 1448, 1344, 1306,
1108, 859, 792, 730 cm21. H NMR d /400 MHz) 1.4, d,
Jˆ6.9 Hz, 3H, H40; 4.02, qd, Jˆ6.9, 1.4 Hz, 1H, H30; 4.96±
4.99, m, 2H, H10; 7.61±7.67, m, 2H, H3,5; 7.82±7.84, m,
1H, H4; 8.06, dd, Jˆ8.2, 1.3 Hz, 1H, H6. 13C NMR d
/75 MHz) 15.11 /C40); 68.60 /C10); 80.64 /C30); 124.79
/C6); 128.39, 128.98 /C3,5); 133.72 /C4); 134.12 /C2);
147.36 /C1); 202.28 /CHO).
1
A similar reaction of the alkene /3.0 g, 16.8 mmol) using
PPh3 gave 2-nitrophenol and the linear and branched alde-
hydes in a ratio of 2:1:1 respectively. The aldehyde /4e) was
isolated as a yellow oil /780 mg, 22%). nmax /®lm) 1721,
1608, 1583, 1522, 1488, 1490, 1352, 1279, 1256, 1166, 774,
746, 667 cm21. 1H NMR d /200 MHz) 2.18, approx. pentet,
Jˆ6.0 Hz, 2H, H20; 2.75, t, Jˆ6.9 Hz, 2H, H30; 4.16, t,
Jˆ6.0 Hz, 2H, H10; 7.01±7.11, m, 2H, H3,5; 7.53, td,
Jˆ7.4, 1.7 Hz, 1H, H4; 7.81, dd, Jˆ8.1, 1.7 Hz, 1H, H6;
9.83, t, Jˆ1.0 Hz, 1H, CHO. 13C NMR d /50 MHz) 21.34,
39.91 /C20, 30); 67.93 /C10); 114.22 /C3); 120.15 /C5);
125.25 /C6), 134.05 /C4); 141.78 /C1); 153.27 /C2);
201.51 /CHO). Mass spectrum /EI): m/z 209 /M1, 1%),
179 /2), 162 /3), 139 /12), 123 /9), 106 /25), 92 /25), 81
/52), 72 /70), 71 /100), 65 /13), 63 /45), 52 /28).
2-/4-Formyl-2-oxabutyl)nitrobenzene was isolated as a
yellow oil /30 mg, 11%) /Found: m/z 123.0320.
/C10H11NO4±C4H6O2)1 requires m/z 123.0321). nmax
/®lm) 2872, 1730, 1613, 1578, 1525, 1448, 1343, 1306,
1
1106, 858, 792, 730 cm21. H NMR d /400 MHz) 2.77,
td, Jˆ6.0, 1.8 Hz, 2H, H40; 3.93, t, Jˆ6.0 Hz, 2H, H30;
4.91, bs, 2H, H10; 7.40±7.48, m, 2H, H3,5; 7.72±7.75, m,
1H, H4; 8.07, dd, Jˆ8.2, 1.2 Hz, 1H, H6. 13C NMR d
/75 MHz) 43.79 /C40); 64.85 /C30); 69.77 /C10); 124.68
/C6); 128.12, 128.69 /C3,5); 133.68 /C4); 134.58 /C2);
147.36 /C1); 200.62/CHO).
3.4.6. 2-24-Formylpentyloxy)nitrobenzene 24g) and 2-25-
formylpentyloxy)nitrobenzene 24k). Reaction of 2-/pent-
4-enyloxy)nitrobenzene /600 mg, 2.9 mmol) using PPh3
gave the linear and branched aldehydes /ratio 70:30) as an
orange oil /670 mg). The aldehyde /4g) was isolated as a
pale, yellow oil /158 mg, 23%). nmax /®lm) 2960, 2877,
1723, 1608, 1583, 1525, 1488, 1469, 1353, 1281, 1256,
A similar reaction using PPh3 as ligand gave the linear and
branched aldehydes in a 30:70 ratio.
3.4.4. 2-24-Formyl-2-thiapentyl)nitrobenzene 24d). Reac-
tion of 2-/2-thiapent-4-enyl)nitrobenzene /400 mg, 1.91
mmol) withH /CO /1:1) /1000 psi) at 808C for 72 hgave
2
1
the linear and branched aldehydes /ratio 70:30) as a viscous,
light brown oil /513 mg). The aldehyde /4d) was isolated as
a yellow oil /20 mg, 4%). nmax /®lm) 2932, 2828, 2726,
1723, 1608, 1577, 1525, 1446, 1421, 1348, 1307, 860,
1165, 1150, 1089, 1044, 1006, 854, 745 cm21. H NMR d
/300 MHz) 1.35, d, Jˆ7.1 Hz, 3H, H50; 2.43, sextetd,
Jˆ6.9, 1.8 Hz, 2H, H40; 4.11, t, Jˆ5.9 Hz, 2H, H10; 6.98±
7.06, m, 2H, H3,5; 7.5, td, Jˆ8.5, 1.7 Hz, 1H, H4; 7.81, dd,
Jˆ8.1, 1.7 Hz, 1H, H6. 13C NMR d /100 MHz) 13.44 /C50);
26.40, 26.79 /C20,30); 45.83 /C40); 69.17 /C10); 114.44
/C3);120.32 /C5); 125.57 /C6); 134.04 /C4); 140.02 /C1);
152.24 /C2); 204.70 /CHO).
1
787, 709 cm21. H NMR d /200 MHz) 1.08, d, Jˆ7.0 Hz,
3H, H50; 2.37±2.50, m, 2H, and 2.73, m, 1H, H30,40; 4.01, s,
2H, H10; 7.32±7.50, m, 3H, H3,4,5; 7.90, dd, Jˆ8.1, 1.2 Hz,
1H, H6; 9.54, d, Jˆ1.2 Hz, 1H, CHO. 13C NMR d /50 MHz)
13.34 /C50); 32.38, 33.91 /C10,30); 45.95 /C40); 125.25
/C6); 128.27 /C5); 131.82 /C3); 133.02 /C4); 133.64
/C1); 148.57 /C2); 202.86 /CHO). Mass spectrum /EI):
m/z 239 /M1, 1%), 169 /4), 151/30), 136 /32), 135 /50),
The aldehyde /4k) was isolated as a pale, yellow oil
/445 mg, 65%). /Found: C, 60.7; H, 6.7; N, 6.2.
C12H15NO4 requires C, 60.8; H, 6.4; N, 5.9%) nmax /®lm)

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7565
2943, 2868, 1719, 1608, 1582, 1523, 1490, 1467, 1390,
1353, 1281, 1256, 1166, 1150, 1089, 1043, 1003, 857,
m, 2H, H30; 3.93, t, Jˆ6.0 Hz, 2H, H50; 4.23±4.26, m,
2H, H20; 7.02±7.11, m, 2H, H3,5; 7.51±7.54, m, 1H, H4;
7.84, dd, Jˆ8.1, 1.6 Hz, 1H, H6; 9.78, t, Jˆ1.8 Hz, 1H,
69.29, 69.63 /C20,30); 115.13 /C3); 120.80 /C5); 125.61
/C6); 134.06 /C4); 140.39 /C1); 152.25 /C2); 201.05
/CHO).
1
773, 746 cm21. H NMR d /200 MHz) 1.46±1.64, m, 2H,
13
H30; 1.67±1.75, m, 2H, H40; 1.85, approx. pentet, Jˆ6.7 Hz,
2H, H20; 2.49, td, Jˆ6.9, 1.5 Hz, 2H, H50; 4.11, t, 2H,
Jˆ6.2 Hz, 2H, H10; 6.97±7.09, m, 2H, H3,5; 7.48±7.56,
m, 1H, H4; 7.80, dd. Jˆ8.1, 1.7 Hz, 1H, H6; 9.78, t,
Jˆ1.6 Hz, 1H, CHO. 13C NMR d /50 MHz) 21.42, 25.29,
28.52 /C20,30,40); 43.56 /C50); 68.98 /C10); 114.26 /C3);
119.99 /C5); 125.31 /C6); 133.98 /C4); 139.68 /C1);
152.15 /C2); 202.42 /CHO).
CHO. C NMR d /100 MHz) 43.93 /C60); 65.41 /C50);
A similar ratio of aldehydes was obtained using BIPHE-
PHOS as ligand
3.4.10. 2-26-Formyl-1,4-dioxaheptyl)nitrobenzene 24l)
and 2-27-formyl-1,4-dioxaheptyl)nitrobenzene 24m).
Reaction of 2-/1,4-dioxahept-6-enyl)nitrobenzene /500 mg,
2.24 mmol) gave the linear and branched aldehydes /ratio
70:30) as a yellow oil /550 mg). The aldehyde /4l) was
isolated as a yellow oil /101 mg, 18%) /Found: m/z
183.0525^0.002. /C12H15NO5±C4H6O)1 requires m/z
183.0532). nmax /®lm) 2935, 2877, 1724, 1608, 1584,
1526, 1488, 1452, 1355, 1279, 1256, 1167, 1132, 1096,
A similar reaction under the standard conditions gave /4k)
and /4g) in the ratio 93:7.
3.4.7. 2-25-Formyl-2-oxapentyl)nitrobenzene 24h). Reac-
tion of 2-/2-oxapent-4-enyl)nitrobenzene /1.0 g, 5.2 mmol)
gave the linear and branched aldehydes /ratio 80:20) as a
yellow oil /1.10 g). The aldehyde /4h) was isolated as an
orange oil /324 mg, 28%). nmax /®lm) 2929, 2871, 2727,
1724, 1613, 1578, 1526, 1479, 1446, 1411, 1341, 1305,
1
1046, 852, 773, 746, 671 cm21. H NMR d /400 MHz)
1146, 1114, 1078, 1042, 961, 859, 791, 730 cm21
.
1H
1.09, d, Jˆ7.1 Hz, 3H, H70; 2.57±2.66, m, 1H, H60; 3.73±
3.78, m, 2H, H50; 3.81±3.85, m, 2H, H30; 4.20±4.23, m, 2H,
H20; 6.98±7.04, m, 1H, H5; 7.07±7.09, m, 1H, H3; 7.48±
7.52, m, 1H, H4; 7.81, dd, Jˆ8.1, 1.7 Hz, 1H, H6; 9.70, d,
NMR d /200 MHz) 2.01, pentet, Jˆ6.0, 2H, H20; 2.60, td,
Jˆ6.1, 1.5 Hz, 2H, H30; 3.62, t, Jˆ6.0 Hz, 2H, H10; 4.86, s,
2H, PhCH2; 7.44, m, 2H, H3,5; 7.61±7.75, m, 1H, H4; 8.05,
dd, Jˆ8.1, 1.1 Hz, 1H, H6; 9.92, t, Jˆ1.5 Hz, 1H, CHO. 13C
NMR d /50 MHz) 22.41 /C20); 40.81 /C30); 69.46, 70.08
/PhCH2, C10); 124.59 /C6); 127.98, 128.60 /C3,5); 133.58
/C4); 134.84 /C2); 202.08 /CHO).
13
Jˆ1.5 Hz, 1H, CHO. C NMR d /100 MHz) 10.46 /C70);
46.79 /C60); 69.41, 69.49 /C30,40); 71.64 /C20); 115.03
/C3); 120.67 /C5); 125.45 /C6); 134.00 /C4); 140.18
/C1); 152.14 /C2); 203.72 /CHO). Mass spectrum /ESI)1:
m/z 276.0 /M1Na)1.
3.4.8. 2-[2N-benzoyl)-4-formylbutylamino]nitrobenzene
24i). Reaction of 2-[/N-benzoyl)but-3-enylamino]nitro-
benzene /400 mg, 1.35 mmol) gave the linear and branched
aldehydes /ratio 90:10) with ca. 17% recovered alkene as a
thick, yellow oil /430 mg). The aldehyde /4i) was isolated as
a yellow, viscous oil /302 mg, 69%). 13C NMR d /50 MHz):
19.29 /C30); 27.10 /C20); 43.28 /C40); 50.22 /C10); 125.73,
127.94, 128.30, 128.37, 130.00, 133.89 /C3,4,5,6, PhCH);
202.04 /CHO).
The aldehyde /4m) was isolated as a yellow oil /348 mg,
61%). /Found: m/z 210.0767. /C12H15NO5±C2H3O)1
requires m/z 210.0766). nmax /®lm) 2934, 2875, 1722,
1608, 1583, 1526, 1488, 1451, 1356, 1279, 1257, 1166,
1
1129, 1090, 1046, 852, 774, 746, 670 cm21. H NMR d
/400 MHz) 1.89, apparent pentet, Jˆ6.6 Hz, 2H, H60;
2.51, td, Jˆ7.1, 1.5 Hz, 2H, H70; 3.57, t, Jˆ6.1 Hz, 2H,
H50; 3.78±3.80, m, 2H, H30; 4.20±4.23, m, 2H, H20;
6.99±7.04, m, 1H, H5; 7.09, dd, Jˆ8.5, 1.0 Hz, 1H, H3;
7.48±7.52, m, 1H, H4; 7.79, dd, Jˆ8.1, 1.6 Hz, 1H, H6;
9.75, t, Jˆ1.4 Hz, 1H, CHO. 13C NMR d /100 MHz)
22.43 /C60); 40.69 /C70); 68.82, 69.43 /C30,50); 70.51
/C20); 115.02 /C3); 120.63 /C5); 125.48 /C6); 133.98
/C4); 140.24 /C1); 152.22 /C2); 204.00 /CHO). Mass
spectrum /ESI1): m/z 276.0 /M1Na)1.
3.4.9. 2-25-Formyl-1,4-dioxahexyl)nitrobenzene 24j).
Reaction of 2-/1,4-dioxahex-5-enyl)nitrobenzene /180 mg,
0.86 mmol) using PPh3 as ligand gave the linear and
branched aldehydes /ratio 30:70) as a viscous, orange oil
/225 mg). The aldehyde /4j) was isolated as a yellow oil.
/145 mg, 73%) /Found: m/z 210.0763. /C11H13NO5±CHO)1
requires m/z 210.0766). nmax /®lm) 2933, 1729, 1608, 1583,
1525, 1487, 1451, 1353, 1278, 1256, 1166, 1127, 1046, 924,
3.4.11. 2-[2N-Methylsulfonyl)-4-aza-7-formyl-1-oxahep-
tyl]nitrobenzene 24n). Reaction of 2-[/N-methylsulfonyl)-
1-oxa-3-azahept-6-enyl]nitrobenzene /400 mg, 1.33 mmol)
gave the linear and branched aldehydes /ratio 70:30) as a
viscous, yellow oil /448 mg). 2-[/N-methylsulfonyl)-4-aza-
6-formyl-1-oxaheptyl]nitrobenzene was isolated as a yellow
oil which solidi®ed on standing /95 mg, 22%). nmax
/CH2Cl2) 3054, 2986, 2934, 1725, 1608, 1586, 1527,
1
852, 745 cm21. H NMR d /400 MHz) 1.33, d, Jˆ7.0 Hz,
3H, H60; 3.97, t, Jˆ4.3 Hz, 2H, H30; 4.06, qd, Jˆ7.0,
1.2 Hz, 1H, H50; 4.29, t, Jˆ4.8 Hz, 2H, H20; 7.01±7.13,
m, 2H, H3,5; 7.50±7.55, m, 1H, H4; 7.82, dd, Jˆ7.1,
1.7 Hz, 1H, H6; 9.66, d, Jˆ1.2 Hz, 1H, CHO. 13C NMR d
/100 MHz) 15.21 /C60); 68.29, 69.64 /C20,30); 81.17 /C50);
114.98 /C3); 120.88 /C5); 125.71 /C6); 134.13 /C4); 140.39
/C1); 152.18 /C2); 202.74 /CHO).
1
1488, 1459, 1422, 1337, 1267, 1149, 1092, 1001 cm21. H
NMR d /300 MHz) 1.18, d, Jˆ7.2 Hz, 3H, H70; 2.87±3.02,
bs, 4H, SO2CH3, H60; 3.42, dd, Jˆ14.7, 6.0 Hz, 1H and
3.65±3.75, m, 3H, H30,50; 4.27±4.33, m, 2H, H20; 7.05±
7.11, m, 2H, H3,5; 7.53±7.58, m, 1H, H4; 7.86, dd,
Jˆ8.1, 1.7 Hz, 1H, H6; 9.70, d, Jˆ2.0 Hz, 1H, CHO. 13C
NMR d /75 MHz) 11.91 /C70); 38.43 /SO2CH3); 46.03,
47.90, 49.65 /C30,50,60); 68.88 /C20); 114.52 /C3); 121.19
2-/6-Formyl-1,4-dioxahex-5-enyl)nitrobenzene was isolated
as a yellow oil /35 mg, 18%) /Found: m/z 210.0763.
/C11H13NO5±CHO)1 requires m/z 210.0766). nmax /®lm)
2933, 1729, 1608, 1583, 1525, 1487, 1451, 1353, 1278,
1256, 1166, 1128, 1046, 852, 746 cm21 1H NMR d
.
/400 MHz) 2.68, td, Jˆ6.0, 1.8 Hz, 2H, H60; 3.86±3.88,

7566
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
/C5); 125.79 /C6); 134.44 /C4); 139.88 /C1); 151.54 /C2);
203.39 /CHO).
m, 1H, H5; 7.06, dd, Jˆ8.5, 0.9 Hz, 1H, H3; 7.47±7.52, m,
1H, H4; 7.80, dd, Jˆ8.1, 1.7 Hz, 1H, H6; 9.61, d, Jˆ2.0 Hz,
26.94, 28.88 /C30,80,90); 29.17, 29.27, 29.44, 29.59 /C
20,40,60,70); 30.55 /C20); 46.34 /C100); 69.67 /C10); 114.48
/C3); 120.03 /C5); 125.51 /C6); 133.92 /C4); 140.13 /C1);
152.51 /C2); 205.38 /CHO).
13
1H, CHO. C NMR d /100 MHz): 13.35 /C110); 25.85,
The aldehyde /4n) was isolated as a yellow oil which
solidi®ed on standing /290 mg, 66%). /Found: m/z
273.0576^0.002. /C13H18N2O6S±C3H5O)1 requires m/z
273.0545). nmax /CH2Cl2) 3061, 2932, 2877, 1725, 1608,
1585, 1528, 1488, 1459, 1337, 1270, 1260, 1149,
1001 cm21
.
1H NMR
d
/300 MHz) 1.97, pentet,
The aldehyde /4r) was isolated as a yellow oil /225 mg,
70%) /Found: m/z 344.1839. /C18H27NO41Na)1 requires
m/z 344.1838). nmax /®lm) 2927, 2854, 1724, 1608, 1583,
1526, 1489, 1467, 1353, 1281, 1256, 746 cm21. 1H NMR d
/200 MHz) 1.29, bs, 14H, H30,40,50,60,70,80,90; 1.62±1.65,
m, 2H, H100; 1.75±1.85, m, 2H, H20; 2.42, td, Jˆ7.2,
1.7 Hz, 2H, H110; 4.09, t, Jˆ6.4 Hz, 2H, H10; 6.95±7.10,
m, 2H, H3,5; 7.51, td, Jˆ7.5, 1.7 Hz, 1H, H4; 7.79, dd,
Jˆ8.1, 1.6 Hz, 1H, H6; 9.76, t, Jˆ1.7 Hz, 1H, CHO. 13C
NMR d /50 MHz) 21.87, 25.63, 28.74, 28.94, 29.03, 29.15,
29.18, 29.25, 30.21 /C20,30,40,50,60,70,80,90,100); 43.70
/C110); 69.37 /C10); 114.25 /C3); 119.78 /C5); 125.23
/C6); 133.88 /C4); 139.69 /C1); 152.27 /C2); 202.78
/CHO).
Jˆ7.0 Hz, 2H, H60; 2.57, td, Jˆ6.9, 0.9 Hz, 2H, H70;
2.89, s, 3H, CH3; 3.36±3.41, m, 2H, H50; 3.67, t,
Jˆ5.2 Hz, 2H, H30; 4.31, t, Jˆ5.2 Hz, 2H, H20; 7.05±
7.12, m, 2H, H3,5; 7.53±7.58, m, 1H, H4; 7.85, dd,
Jˆ8.0, 1.7 Hz, 1H, H6; 9.79, t, Jˆ1.0 Hz, 1H, CHO. 13C
NMR d /75 MHz) 20.92 /C60); 38.56 /CH3); 40.48 /C70);
46.94, 48.30 /C30,50); 68.85 /C20); 114.48 /C3); 121.16
/C5); 125.78 /C6); 134.39 /C4); 139.96 /C1); 151.58
/C2); 201.27 /CHO).
3.4.12. 2-29-Formyl-1,4,7-trioxadecyl)nitrobenzene 24o)
and 2-210-formyl-1,4,7-trioxadecyl)nitrobenzene 24p).
Reaction of 2-/1,4,7-trioxadec-9-enyl)nitrobenzene /500 mg,
1.87 mmol) gave the linear and branched aldehydes /ratio
83:17) as a viscous yellow oil /590 mg). The aldehyde /4o)
was isolated as a yellow oil /93 mg, 17%).1H NMR d
/200 MHz) 1.11, d, Jˆ7.1 Hz, 3H, H100; 2.61±2.75, m,
1H, H90; 3.61±3.69, m, 2H and 3.72±3.76, m, 2H and
3.88±3.92, m, 2H, H30,50,60; 4.24±4.28, m, 2H, H20;
6.99±7.13, m, 2H, H3,5; 7.49±7.57, m, 1H, H4; 7.83, dd,
Jˆ8.1, 1.7 Hz, 1H, H6; 9.72, d Jˆ1.5 Hz, 1H, CHO. 13C
NMR d /50 MHz) 10.58 /C100); 46.72 /C90); 69.30, 69.43,
69.61, 70.79, 70.95, 71.24 /C20,30,50,60,80); 114.93 /C3);
120.57 /C5); 125.51 /C6); 134.04 /C4); 140.11 /C1);
152.22 /C2); 203.99 /CHO).
A similar reaction using PPh3 as ligand gave the linear and
branched aldehydes /4q) and /4r) in the ratio 70:30.
3.4.14. 3-23-Formylbutyloxy)nitrobenzene 24s) and 3-24-
formylbutyloxy)nitrobenzene 24t). Reaction of 3-/but-3-
enyloxy)nitrobenzene /300 mg, 1.55 mmol) gave the linear
and branched aldehydes /ratio 90:10) as an orange oil
/364 mg). The aldehyde /4s) was isolated as a pale,
yellow oil /17 mg, 5%). /Found: m/z 223.0846^0.003.
/C11H13NO4)1 m/z 223.0845). nmax /®lm) 2943, 2866,
1721, 1608, 1582, 1524, 1489, 1469, 1353, 1281, 1256,
1
1166, 1150, 1089, 1044, 1003, 857, 773, 745 cm21. H
The aldehyde /4p) was isolated as a yellow oil /435 mg,
78%). /Found: C, 56.4; H, 6.6, N, 4.8. C14H19NO6 requires
C, 56.6; H, 6.4; N, 4.7%). nmax /®lm) 2931, 2877, 1723,
1608, 1584, 1526, 1488, 1453, 1357, 1279, 1256, 1166,
NMR d /200 MHz) 1.21, d, Jˆ7.2 Hz, 3H, H40; 1.75±
1.94, m, 1H and 2.11±2.28, m, 1H, H20; 2.50±2.65, m,
1H, H30; 4.03, t, Jˆ6.1 Hz, 2H, H10; 7.08±7.14, m, 1H,
H4; 7.33, t, Jˆ8.1 Hz, 1H, H5; 7.56±7.58, m, 1H, H6;
7.66±7.71, m, 1H, H2; 9.64, d, Jˆ1.4 Hz, 1H, CHO. 13C
NMR d /50 MHz) 13.06 /C40); 29.48 /C20); 43.17 /C30);
65.72 /C10); 108.50 /C3); 115.51 /C5); 121.21 /C6); 129.77
/C4); 148.82/C1); 158.89 /C2); 203.77 /CHO).
1
1132, 1046, 1001, 926, 852, 774, 746 cm21. H NMR d
/200 MHz) 1.92, pentet, Jˆ6.2 Hz, 2H, H90; 2.53, td,
Jˆ6.1, 1.6 Hz, 2H, H100; 3.51, t, Jˆ6.1 Hz, 2H, H80;
3.56±3.63, m, 2H and 3.69±3.75, m, 2H, and 3.88±3.93,
m, 2H, H30,50,60; 4.27, m, 2H, H20; 6.99±7.14, m, 2H, H
3,5; 7.48±7.57, m, 1H, H4; 7.83, dd, Jˆ8.07, 1.7 Hz, 1H,
H6; 9.77, t, Jˆ1.6 Hz, 1H, CHO. 13C NMR d /50 MHz)
22.42 /C90); 40.83 /C100); 69.27, 69.60, 70.10, 70.18,
71.06 /C20,30,50,60,80); 114.89 /C3); 120.57 /C5); 125.54
/C6); 134.06 /C4); 140.09 /C1); 152.24 /C2); 202.42
/CHO).
The aldehyde /4t) was isolated as a yellow oil /280 mg,
81%). /Found: m/z 223.0843^0.003. /C11H13NO4)1 m/z
223.0845). nmax /®lm) 2944, 2867, 1722, 1608, 1582,
1525, 1489, 1466, 1352, 1281, 1256, 1166, 1150, 1089,
1
1044, 1002, 857, 773, 746 cm21. H NMR d /200 MHz)
1.72±1.82, m, 4H, H20, 30; 2.45±2.52, m, 2H, H40; 3.93±
3.99, m, 2H, H10: 7.09±7.15, m, 1H, H4; 7.33, t, Jˆ8.1 Hz,
1H, H5; 7.58±7.60, m, 1H, H6; 7.67- 7.72, m, 1H, H2; 9.72,
t, Jˆ1.4 Hz, 1H, CHO. 13C NMR d /50 MHz) 18.52, 28.23
/C20,30); 43.24 /C40); 67.98 /C10); 108.54 /C3); 115.49
/C5); 121.39 /C6); 129.82 /C4); 148.97 /C1); 159.28
/C2); 201.97 /CHO).
3.4.13. 2-210-Formylundecyloxy)nitrobenzene 24q) and
2-211-formylundecyloxy)nitrobenzene 24r). Reaction of
2-/undec-10-enyloxy)nitrobenzene /300 mg, 1.0 mmol)
gave the linear and branched aldehydes /ratio 90:10) as a
yellow oil /354 mg). The aldehyde /4q) was isolated as a
yellow oil /32 mg, 10%) /Found: m/z 344.1835.
/C18H27NO41Na)1 requires m/z 344.1838). nmax /®lm)
2930, 2856, 1724, 1608, 1583, 1526, 1489, 1466, 1353,
A similar reaction using PPh3 as ligand gave the linear and
branched aldehydes /4s) and /4t) in the ratio 55:45.
1
1281, 1256, 1165, 746 cm21. H NMR d /400 MHz) 1.08,
d, Jˆ7.0 Hz, 3H, H110; 1.30, bs, 12H, H30,40,50,60,70,80;
1.44±1.49, m, 2H, H90; 1.79±1.86, m, 2H, H20; 2.29±
2.30, m, 1H, H100; 4.09, t, Jˆ6.4 Hz, 2H, H10; 6.97±7.01,
3.4.15. 4-24-Formylbutyloxy)nitrobenzene 24u). Reaction
of 4-/but-3-enyloxy)nitrobenzene /500 mg, 2.59 mmol)
gave the linear and branched aldehydes /ratio 94:6) as a

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7567
viscous, yellow oil /574 mg). 4-/3-Formylbutyloxy)nitro-
benzene was isolated as a yellow liquid /23 mg, 4%).
/Found: m/z 209.0698^0.002. /C11H13NO4±CH2)1 requires
m/z 209.0688). nmax /®lm) 2936, 1725, 1594, 1514, 1341,
decyl)nitrobenzene was isolated as a yellow oil. /90 mg,
16%) /Found: C, 56.9; H, 6.1; N, 5.2. C14H19NO6 requires
C, 56.6; H, 6.4; N, 4.7%). /Found: m/z 227.0791^0.002.
/M2C4H6O)1 requires m/z 227.0794). nmax /®lm) 2876,
1723, 1608, 1540, 1514, 1342, 1264, 1111, 848, 753 cm21.
1H NMR d /400 MHz) 1.12, d, Jˆ7.1 Hz, 3H, H100; 2.61±
2.68, m, 1H, H90; 3.63±3.74, m, 6H and 3.86±3.89, m, 2H, H
30,50,60,80; 4.21±4.22, m, 2H, H20; 6.99, dd, Jˆ9.3, 2.2 Hz,
2H, H3,5; 8.46, dd, Jˆ9.3, 2.2 Hz, 2H, H 2,6; 9.72, d,
1299, 1263, 1174, 1111, 847, 753 cm21 1H NMR d
.
/400 MHz) 1.20, d, Jˆ7.2 Hz, 3H, H40; 1.86±1.94, m, 1H
and 2.22±2.30, m, 1H, H20; 2.62±2.67, m, 1H, H30; 3.60, t,
Jˆ6.2 Hz, 2H, H10; 6.92, dd, Jˆ9.3, 2.2 Hz, 2H, H3,5; 8.16,
dd, Jˆ9.3, 2.2 Hz, 2H, H2,6; 9.69, d, Jˆ1.4 Hz, 1H, CHO.
13C NMR d /100 MHz) 13.41 /C40); 29.69 /C30); 43.32
/C20); 66.10 /C10); 114.42 /C3,5); 125.88 /C2,6); 141.63
/C1); 163.61 /C4); 203.67 /CHO).
13
Jˆ1.6 Hz, 1H, CHO. C NMR d /100 MHz) 10.57 /C100);
46.69 /C90); 68.13, 69.38 /C50,60,80); 71.07, 71.26 /C20,30);
114.57 /C3,5); 125.78 /C2,6); 141.57 /C1); 163.84 /C4);
203.70 /CHO).
The aldehyde /4u) was isolated as a yellow oil /461 mg,
80%). nmax /®lm) 2944, 1722, 1593, 1514, 1471, 1338,
The aldehyde /4w) was isolated as a yellow oil /352 mg,
62%). /Found: C, 56.8; H, 6.2; N, 4.9%. C14H19NO6 requires
C, 56.6; H, 6.4; N, 4.7%). nmax /®lm) 2877, 1720, 1594,
1517, 1458, 1343, 1300, 1264, 1175, 1111, 1054, 849,
1
1299, 1263, 1174, 1111, 846, 753, 654 cm21. H NMR d
/400 MHz) 1.78±1.88, m, 4H, H20,30; 2.53, td, Jˆ7.0,
1.4 Hz, 2H, H40; 4.05, t, Jˆ5.9 Hz, 2H, H10; 6.91, d,
Jˆ9.3, 2.2 Hz, 2H, H3,5; 8.14, d, Jˆ9.3, 2.2 Hz, 2H, H
2,6; 9.78, t, Jˆ1.5 Hz, 1H, CHO. 13C NMR d /100 MHz)
18.56 /C30); 28.31 /C20); 43.28 /C40); 68.25 /C10); 114.35
/C3,5); 125.82 /C2,6); 141.40 /C1); 163.93 /C4); 201.81
/CHO).
1
753 cm21. H NMR d /200 MHz) 1.92, pentet, Jˆ6.1 Hz,
2H, H90; 2.52, td, Jˆ6.0, 1.5 Hz, 2H, H100; 3.51, t,
Jˆ6.1 Hz, 2H, H80; 3.57±3.61, m, 2H and 3.67±3.72, m,
2H and 3.88±3.90, m, 2H, H30,50,60; 4.22±4.24, m, 2H, H20;
6.98, dd, Jˆ9.3, 2.1 Hz, 2H, H3,5; 8.19, dd, Jˆ9.3, 2.1 Hz,
2H, H 2,6; 9.77, t, Jˆ1.6 Hz, 1H, CHO. 13C NMR d
/75 MHz) 22.50 /C90); 40.83 /C100); 68.24, 69.39 70.17,
70.21, 70.89 /C20,30,50,60,80); 114.61 /C3,5); 125.84
/C2,6); 141.65 /C1); 163.88 /C4); 202.14 /CHO).
A similar reaction using PPh3 as ligand gave the linear and
branched aldehydes in the ratio 55:45.
3.4.16. 4-27-Formyl-1,4-dioxaheptyl)nitrobenzene 24v).
Reaction of 4-/1,4-dioxahept-6-enyl)nitrobenzene /500 mg,
0.23 mmol) gave the linear and branched aldehydes /ratio
70:30) as an orange oil /300 mg). 4-/6-Formyl-1,4-dioxa-
heptyl)nitrobenzene was isolated as a yellow oil /100 mg,
18%) /Found: m/z 183.0532^0.002. /C12H15NO5±C4H6O)1
requires m/z 183.0532). nmax /®lm) 2934, 2878, 1723, 1608,
1594, 1514, 1455, 1342, 1300, 1264, 1175, 1111, 1053, 847,
3.4.18. N-Benzyl-2-211-formylundecyloxy)aniline 210).
Reaction of N-benzyl-2-/undec-10-enyl-oxy)aniline /80 mg,
0.23 mmol) gave the linear aldehyde as a viscous, yellow oil
/93 mg). Puri®cation gave /10) as a viscous, yellow oil
1
/50 mg, 58%). H NMR d /200 MHz) 1.30, bs, 14H, H
30,40,50,60,70,80,90; 1.50±1.68, m, 2H, H 100; 1.75±1.86,
m, 2H, H20; 2.43, td, Jˆ7.3, 1.8 Hz, 2H, H110; 4.02, t,
Jˆ6.5 Hz, 2H, H10; 4.39, s, 2H, PhCH2; 4.70, bs, 1H, NH;
6.58±6.71, m, 2H, H4,6; 6.70±6.87, m, 2H, H3,5; 7.27±
7.43, m, 5H, PhH; 9.77, t, Jˆ1.8 Hz, 1H, CHO. 13C NMR
d /50 MHz) 22.04, 26.13, 28.68, 29.13, 29.31, 29.47, 29.51
/C 20, 30, 40, 50, 60, 70, 80, 90, 100); 43.88 /C110); 47.98
/PhCH2); 110.24, 110.45, 116.63, 121.09 /C3,4,5,6);
127.01, 127.29, 128.30, 128.53 /PhCH); 138.13, 139.67
/C2 and PhC); 146.19 /C1); 202.92 /CHO). Mass spectrum
/ESI1): m/z 382.2 /M1H)1.
1
752, 658 cm21. H NMR d /300 MHz) 1.14, d, Jˆ7.2 Hz,
3H, H80; 2.65±2.71, m, 1H, H60; 3.83±3.86, m, 2H, H30;
4.19±4.22, m, 2H, H20; 6.97, dd, Jˆ9.3, 2.2 Hz, 2H, H3,5;
8.19, dd, Jˆ9.3, 2.2 Hz, 2H, H2,6; 9.72, d, Jˆ1.5 Hz, 1H,
13
CHO. C NMR d /75 MHz) 10.70 /C70); 46.75 /C60);
68.09, 69.53 /C30,50); 71.52 /C20); 114.63 /C3,5); 125.91
/C2,6); 141.76 /C1); 163.81 /C2); 203.42 /CHO).
The aldehyde /4v) was isolated as a yellow oil /340 mg,
60%). /Found: m/z 210.0769^0.002. /C12H15NO5±
C2H3O)1 requires m/z 210.0766). nmax /®lm) 2929, 2872,
1721, 1608, 1594, 1513, 1341, 1299, 1264, 1175, 1111,
3.4.19.
2-{7-[2-23-Formylpropyloxy)phenyl]-1,4,7-tri-
oxaheptyl}nitrobenzene 27). Reaction of 2-{1,4,7-trioxa-
7-[2-prop-2-enyloxy)phenyl]heptyl}nitrobenzene /550 mg,
1.5 mmol) gave the linear aldehyde /7) and 2-[7-/2-hydro-
xyphenyl)-1,4,7-trioxaheptyl]nitrobenzene /ratio 1:1) as a
viscous, orange oil /575 mg). The aldehyde /7) was isolated
as a yellow oil /235 mg, 40%). /Found: m/z 412.1372.
/C20H23NO71Na)1 requires m/z 412.1372). nmax /®lm)
2928, 1720, 1608, 1525, 1503, 1452, 1353, 1277, 1255,
1125, 1048, 744 cm21. 1H NMR d /400 MHz) 2.14, pentet,
Jˆ6.0 Hz, 2H, H2000; 2.68, td, Jˆ7.0, 1.5 Hz, 2H, H3000;
3.97±4.02, m, 4H, H30,50; 4.05, t, Jˆ6.0 Hz, 2H, H1000;
4.17±4.19, m, 2H and 4.29±4.31, m, 2H, H20,60; 6.88±
6.95, m, 4H, ArCH; 7.02±7.06, m, 1H, H5; 7.14, dd,
Jˆ8.5, 1.1 Hz, 1H, H3; 7.49±7.54, m, 1H, H4; 7.83, dd,
Jˆ8.1, 1.7 Hz, 1H, H6; 9.86, t, Jˆ1.5 Hz, 1H, CHO. 13C
NMR d /100 MHz) 22.33 /C2000); 40.67 /C3000); 68.21, 68.94,
69.54, 69.76, 70.36 /C20,30,50,60,1000); 114.49, 114.75,
1
1052, 847, 753, 657 cm21. H NMR d /300 MHz) 1.90±
1.99, m, 2H, H60; 2.55, td, Jˆ7.0, 1.5 Hz, 2H, H70; 3.58,
t, Jˆ6.1 Hz, 2H, H50; 3.78±3.81, m, 2H, H30; 4.16±4.21, m,
2H, H20; 6.98, dd, Jˆ9.3, 2.2 Hz, 2H, H3,5; 8.20, dd, Jˆ9.4,
2.3 Hz, 2H, H2,6; 9.78, t, Jˆ1.5 Hz, 1H, CHO. 13C NMR d
/75 MHz) 22.44 /C60); 40.77 /C70); 68.17, 68.92 /C30,50);
70.48 /C20); 114.62 /C3,5); 125.90 /C2,6); 141.74 /C1);
163.86 /C4); 201.94 /CHO).
A similar reaction using PPh3 as ligand gave the linear and
branched aldehydes in the ratio 30:70.
3.4.17. 4-210-Formyl-1,4,7-trioxadecyl)nitrobenzene 24w).
Reaction of 4-/1,4,7-trioxadec-9-enyl)nitrobenzene /500 mg,
1.9 mmol) gave to the linear and branched aldehydes /ratio
70:30) as an orange oil /570 mg). 4-/9-Formyl-1,4,7-trioxa-

7568
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
115.09 /C3,ArCH); 120.65, 121.58, 121.65 /C5,ArCH);
125.52 /C6); 134.03 /C1); 148.92, 148.94 /ArC); 152.28
/C2); 202.23 /CHO).
C20H26N2O2 requires C, 73.8; H, 7.7; N, 8.6%). nmax
/Nujol) 3052, 2933, 2874, 1603, 1513, 1260, 1250, 1221,
1
1134, 1140, 761, 744, 738, 711, 698 cm21. H NMR d
/300 MHz) 1.90±2.10, m, 8H, H7,8,17,18; 3.18, t,
Jˆ5.5 Hz, 4H, H9,19, 4.03, t, Jˆ5.1 Hz, 4H, H6,16; 6.59,
dd, Jˆ7.7, 1.5 Hz, H1,11; 6.64, td, Jˆ7.6, 1.4 Hz, 2H,
H3,13; 6.75, dd, Jˆ7.8, 1.3 Hz, 2H, H4,14; 6.87, td,
Jˆ7.6, 1.4 Hz, 2H, H2,12. 13C NMR d /100 MHz) 26.27,
27.15 /C7,8,17,18); 43.57 /C9,19); 67.39 /C6,16); 107.83,
109.94 /C1,4,11,14); 114.16, 116.46 /C3,13); 121.21
/C2,12); 137.99 /C10a,20a); 145.99 /C4a,14a). Mass spec-
trum /EI): m/z 326 /M1, 19%), 253/5), 218/5), 210/8),
198/5), 176/5), 165/12), 164/100), 163/80), 162/55),
134/12), 122/28), 121/10), 120/55), 109/18), 93/13),
80/12), 77/19), 65/19), 55/28).
Further elution gave 2-[7-/2-hydroxyphenyl)-1,4,7-trioxa-
heptyl]nitrobenzene as a yellow oil. /269 mg, 45%). nmax
/®lm) 3356, 2935, 2876, 1608, 1584, 1528, 1486, 1450,
1352, 1278, 1256, 1166, 1132, 1092, 1044, 852, 746,
1
670 cm21. H NMR d /400 MHz) 3.65, t, Jˆ5.8 Hz, 2H
and 3.86, t, Jˆ5.3 Hz, 2H, H30,50; 3.92±3.96, m, 2H and
4.26±4.29, m, 2H, H20,60; 6.86±6.94, m, 2H, ArCH; 7.00±
7.06, m, 2H, H5, ArCH; 7.11, d, Jˆ8.5 Hz, 2H, H3, ArCH;
7.49±7.54, m, 1H, H4; 7.83, dd, Jˆ8.0, 1.6 Hz, 1H, H6. 13C
NMR d /100 MHz) 43.01 /C50); 69.41, 69.78; 71.89
/C20,30,60); 115.11, 115.45 /C3,ArCH); 120.63, 121.53
/C5,ArCH) 125.52, 125.56 /C6,ArCH); 134.01 /C4);
149.58 /ArC,C1); 152.23 /C2).
3.5.2. 3-Methyl-2,3,4,5-tetrahydro-1H-benzazepine 25a).
Reaction of 2-/3-formylbutyl)nitrobenzene /4a) /100 mg,
0.48 mmol) and 10% Pd/C in MeOH /101 ml) gave a yellow
oil /86 mg). Puri®cation gave the benzazepine /5a) as a
yellow oil /52 mg, 67%). /Found: C, 81.7, H, 9.6, N, 8.7.
3.5. Hydrogenation reactions using 10% Pd/C or PtO2
Reactions were carried out using standard apparatus for
atmospheric pressure hydrogenation /1 atm,15 psi,
0.1 mPa) at ambient temperature /15±208C) for 24 hin
MeOH /50±100 ml) withusually 100 mg substrate and
60 mg PtO2 or 10% Pd/C /ratio of substrate:catalyst 0.83:1
to 20:1). The catalyst was removed by ®ltration through a
Celite pad and the ®lter pad washed with MeOH /20 ml) and
CH2Cl2 /20 ml). The crude product obtained after removal
of the solvent under vacuum was puri®ed by ¯ash chromato-
graphy on silica /eluent: 5% EtOAc/light petroleum) with
monomeric products having a higher Rf value than the
corresponding dimers.
1
C11H15N requires C, 81.9, H, 9.4, N, 8.7%). H NMR d
/400 MHz) 0.92, d, Jˆ6.6 Hz, 3H, CH3; 1.10±1.20, m,
1H, H3; 1.82±1.93, m, 2H, H4; 2.49, dd, Jˆ12.7, 9.5 Hz,
1H and 3.20, dd, Jˆ12.7, 3.3 Hz, 1H, H2; 2.70±2.82, m, 2H,
H5; 3.50, bs, 1H, NH; 6.70, dd, Jˆ7.8, 1.0 Hz, 1H, H9; 6.81,
td, Jˆ7.4, 1.2 Hz, 1H, H7; 7.02, td, Jˆ7.4, 1.5 Hz, 1H, H8;
7.08, dd, 7.4, 1.3 Hz, 1H, H6; 13C NMR d /100 MHz) 19.75
/CH3); 33.96, 34.93, 36.59 /C3,4,5); 55.41 /C2); 119.16,
120.89 /C7,9); 126.59 /C8); 130.62 /C6); 133.53 /C5a);
150.24 /C9a). Mass spectrum /ESI1): m/z 161.7 /M1H)1.
3.5.3. 3-Methyl-1,2,3,5-tetrahydro-4,1-benzoxazepine 25b).
Reaction of 2-/3-formyl-2-oxabutyl)nitrobenzene /4b)
/86 mg, 0.41 mmol) and 10% Pd/C /52 mg) in MeOH
/86 ml) gave a white solid /68 mg). Puri®cation gave the
benzoxazepine as /5b) as a yellow crystalline solid
/37 mg, 56%) mp 62.3±64.78C. /Found: C, 73.5; H, 8.2;
N, 8.6. C10H12NO requires C, 73.6; H, 8.0; N, 8.6%). nmax
/CH2Cl2): 3380, 3053, 2975, 2949, 2884, 2840, 1606, 1590,
Reactions leading to cyclised products were repeated at
least once and gave product ratios with ^5% reproduc-
ibility.
3.5.1. 3,4,5,6-Tetrahydro-2H-1,6-benzoxazocine 25e) and
7,8,9,10,17,18,19,20-octahydro-6H,16H-dibenzo[b, j][1,
9,4,12]dioxadiazacyclohexadecine 26e). A typical pro-
cedure involved reaction of a mixture of 2-/3-formylpropyl-
oxy)nitrobenzene /4e) /100 mg, 0.48 mmol) and 10% Pd/C
1
1503, 1483, 1442, 1371, 1314, 1280, 1260, 1096 cm21. H
NMR d /300 MHz) 1.20, d, Jˆ6.4 Hz, 3H, CH3; 2.76, dd,
Jˆ13.3, 9.1 Hz, 1H and 3.22, dd, Jˆ13.2, 1.8 Hz, 1H, H2,
3.71±3.78, m, 1H, H3; 3.94, bs, 1H, NH; 4.55, d,
Jˆ13.4 Hz, 1H and 4.71, d, Jˆ13.4 Hz, 1H, H5; 6.76±
6.78, m, 1H and 6.83±6.87, m, 1H, H7,9; 7.10±7.15, m,
2H, H6,8. 13C NMR d /100 MHz) 19.36 /CH3); 55.52
/C2); 73.12 /C5); 78.08 /C3); 118.41 /C9); 120.61 /C7);
128.46, 129.43 /C6,8); 130.31 /C5a); 149.79 /C9a). Mass
spectrum /ESI1): m/z 164.0 /M1H)1.
/60 mg) in MeOH /100 ml) withH /1 atm) at ambient
2
temperature for 24 h. Following ®ltration to remove the
catalyst, the solvent was removed under reduced pressure
to give a yellow residue /70 mg). Flash chromatography
/silica, 5% EtOAc/light petroleum) gave the benzoxazocine
/5e) as a yellow oil /26 mg, 33%). /Found: m/z
163.100^0.002. C10H13NO requires m/z 163.099). nmax
/Nujol) 3052, 2929, 1602, 1513, 1445, 1279, 1260, 1258,
1
1105, 1048, 762 cm21. H NMR d /200 MHz) 1.80±2.05,
3.5.4. 4-Methyl-3,4,5,6-tetrahydro-2H-1,6-benzoxazo-
cine 25c) and 8,18-dimethyl-7,8,9,10,17,18,19,20-octa-
hydro-6H,16H-dibenzo[b, j][1,9,4,12]dioxadiazacyclo-
hexadecine 26c). Reaction of 2-/3-formylbutyl-
oxy)nitrobenzene /4c) /150 mg, 0.67 mmol) and 10% Pd/
C in MeOH /150 ml) gave a pink solid /132 mg). HPLC
analysis indicated that the cyclohexadecine /6c) and the
benzoxazocine /5c) were present in a ratio of 5:3, respec-
tively. The benzoxazocine /5c) was isolated as a colourless
®lm /16 mg, 14%) mp /HCl salt) 162.3±166.18C. /Found:
C, 74.4; H, 8.5; N, 7.9. C11H15NO requires C, 74.6; H, 8.5;
N, 7.9%). HPLC 46.79 min /40±100% CH3CN/H2O). nmax
m, 4H, H3,4; 3.20, t, Jˆ6.6 Hz, 2H, H5; 4.04, t, Jˆ5.4 Hz,
2H, H2; 6.60±6.77, m, 3H, H7,9,10; 6.85, td, Jˆ7.5, 1.6 Hz,
1H, H8. 13C NMR d /100 MHz) 26.43, 26.55 /C3,4); 42.54
/C5); 67.54 /C2); 109.48, 109.83 /C7,10); 116.02 /C9);
121.26 /C8); 138.63 /C6a); 146.22 /C10a). Mass spectrum
/EI): m/z 163 /M1, 60%), 162/53), 149/11), 148/17),
134/31), 133/12), 132/14), 122/21), 121/16), 120/100),
106/15), 92/21), 91/20), 77/22), 65/30), 55/30). Spectral
data was in accordance with that described in the literature.38
Further elution gave the dimer /6e) as a yellow solid /7 mg,
8%) mp 162.9±163.88C. /Found: C, 73.5; H 7.7; N, 8.6.

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7569
/®lm) 3416, 2854, 2869, 1602, 1502, 1456, 1382, 1354,
0.45 mmol) and PtO2 /60 mg) in MeOH /100 ml) gave a
white solid /89 mg). Puri®cation gave the dimer /6f) as a
white solid /53 mg, 75%) mp 198.5±200.78C. /Found: C,
74.5; H, 8.4; N, 7.8. C22H30N2O2 requires C, 74.6; H, 8.5; N,
7.9%). HPLC 26.7 min. nmax /Nujol) 3425, 3062, 2923,
1602, 1519, 1458, 1377, 1365, 1249, 1214, 1142, 1051,
1
1248, 1193, 1112, 1048, 1017, 975, 753, 736 cm21. H
NMR d /200 MHz) 0.99, d, Jˆ6.9 Hz, 3H, CH3; 1.44±
1.69, m, 1H and 1.71±1.83, m, 1H, H3; 1.95±2.06, m, 1H,
H4; 3.25, dd, Jˆ14.3, 6.5 Hz, 1H and 3.74, dd, Jˆ14.3,
4.6 Hz, 1H, H5; 4.07, ddd. Jˆ11.4, 8.3, 3.3 Hz, 1H and
4.20, ddd, Jˆ11.4, 6.5, 3.7 Hz, 1H, H2; 6.54±6.63, 2H, H
7,9; 6.87, td, Jˆ6.5, 1.5 Hz, 2H, H8,10. 13C NMR d
/50 MHz) 19.11 /CH3); 31.16 /C3); 35.72 /C4); 49.78
/C5); 73.37 /C2); 116.33, 117.60 /C7,10); 124.59, 124.79
/C8,9); 138.54 /C6a); 146.02 /C10a). Mass spectrum /EI):
m/z 177 /M1, 68%), 176 /M121, 28), 162/3), 149/13),
148/12), 134/30), 133/10), 132/20), 122/28), 121/15),
120/100), 106/10), 93/12), 77/13), 65/31), 55/33).
1
728, 717 cm21. H NMR d /400 MHz) 1.70±1.90,m, 12H,
H7,8,9,18,19,20; 3.20, t, Jˆ5.1 Hz, 4H, H10,21; 4.04, t,
Jˆ5.6 Hz, 4H, H6,17; 4.2, bs, 2H, NH; 6.57±6.63, m, 3H,
H1,12,14; 6.67±6.75, apparent td, Jˆ7.7, 1.5 Hz, 3H,
H3,4,15; 6.81±6.90, td, Jˆ7.5, 1.6 Hz, 2H, H2,13. 13C
NMR d /100 MHz) 24.66, 28.74, 29.51 /C7,8,9,18,19,20);
42.87 /C10,21); 67.06 /C6,17); 109.16, 109.30,
/C1,4,12,15); 116.12 /C3,14), 120.95 /C2,13), 138.20
/C11a,22a); 145.66 /C4a,15a). Mass spectrum /EI): m/z
354 /M1, 38%), 179/12), 178/100), 177/50), 176/58),
148/13), 122/38), 120/57), 109/10), 93/10), 77/15), 65/12).
The dimer /6c) was isolated as a white solid /42 mg, 36%)
mp 183.9±186.88C. /Found: C, 74.2; H, 8.4; N, 7.9.
C22H30N2O2 requires C, 74.6; H, 8.5; N, 7.9%). HPLC
43.2 and 43.8 min /40±100% CH3CN/H2O). nmax /Nujol)
3054, 1604, 1513, 1265, 1248, 1217, 1114, 1047, 994,
Reactions of /4f) in benzene and EtOAc gave /6f) in 34 and
33% yields, respectively.
896, 738, 705 cm21 1H NMR d /400 MHz) 1.07, d,
.
Jˆ7.0 Hz, 3H and 1.08, d, Jˆ7.1 Hz, 3H, 2£CH3; 1.50±
1.57, m, 1H 1.62±1.74, m, 1H, 2.21±2.27, m, 1H and
2.34±2.39, m, 1H, H7,17; 2.06±2.09, m, 2H, H8,18;
2.84±2.96, m, 2H and 3.03±3.06, m, 2H, H9,19; 3.96±
4.02, m, 2H, 4.04±4.06, m, 1H and 4.07±4.11, m, 1H,
H6,16; 4.22, bs, 1H and 4.41, bs, 1H, NH; 6.55±6.66, m,
4H, 6.73±6.81, m, 2H and 6.85±6.89, m, 2H,
H1,2,3,4,11,12,13,14. 13C NMR d /100 MHz) 19.01,19.07
/CH3); 31.32, 31.33 /C8,18); 34.44, 34.85 /C7,17); 49.81
/C9,19); 65.23, 65.78 /C6,16); 109.06, 109.18, 109.69,
109.90, 115.90, 116.03, 121.11, 121.27 /C1,2,3,4,11,12,
13,14); 138.33, 138.64 /C10a,20a); 145.92, 146.33
/C4a,14a). Mass spectrum /EI): m/z 354 /M1, 12%),
179/15), 178 /100), 177/90), 176/50), 134/15), 122/35),
120/50), 93/10), 60/10), 77/18), 65/18), 55/18).
A similar reaction using 10% Pd/C withH /1200 psi) at
2
ambient temperature for 24 husing a stainless steel Parr
autoclave gave a solid residue /85 mg) which was puri®ed
to give /6f) /59 mg, 74%).
A reaction of /4f) /105 mg, 0.47 mmol) and 10% Pd/C
/60 mg) in MeOH /105 ml) gave a white solid /72 mg).
Puri®cation gave /6f) as a white solid /53 mg, 64%).
3.5.7. 9,20-Dimethyl-6,7,8,9,10,11,17,18,19,20,21,22-dodeca-
hydrodibenzo[b,k][1,10,4,13]dioxadiazacyclooctadecine
26g). Reaction of 2-/4-formylpentyloxy)nitrobenzene /4g)
/50 mg, 0.22 mmol) and 10% Pd/C /30 mg) in MeOH
/49 ml) gave the dimer /6g) as a white solid /26 mg, 62%)
mp 138.5±140.58C. /Found: C, 75.6; H, 8.9; N 7.2.
C24H34N2O2 requires C 75.4; H 8.9; N 7.2%). nmax
/CH2Cl2) 3429, 2931, 2875, 1602, 1514, 1476, 1444,
A similar reaction of /4c) /163 mg, 0.73 mmol) and 10% Pd/
C /17 mg) in MeOH /35 ml) gave a white solid /99 mg).
HPLC analysis of the crude indicated the cyclohexadecine
/6c) and the benzoxazocine /5c) were present in a ratio of
4:1 withthe dimeric compound / 6c) being present as a
mixture of two isomers, possibly meso and racemic. Puri®-
cation of the crude gave /5c) as a yellow liquid /31 mg,
26%) followed by /6c) as a white solid /48 mg, 37%). The
HCl salt of the monomer /5c) was prepared from ether/HCl
/1.3 M).
1
1269, 1247, 1216, 1139, 1049, 1003 cm21. H NMR d
/300 MHz) 1.08, d, Jˆ6.7 Hz, 6H, 2£CH3; 1.20±1.32, m,
1H, 1.35±1.46, m, 1H, 1.74±1.87, m, 2H, 1.88±2.07, m, 5H
and 2.10±2.21, m, 1H, H7,8,9,18,19,20; 2.84±2.92, m, 2H
and 3.19, dt, Jˆ11.5, 3.1 Hz, 2H, H10,21; 3.99, dq, Jˆ8.7,
2.8 Hz, 2H and 4.06±4.14, m, 2H, H6,17; 4.27, bs, 2H, NH;
6.58±6.67, m, 4H, H1,3,12,14; 6.74, d, Jˆ7.8 Hz, 2H,
H4,15; 6.87, td, Jˆ7.6, 1.4 Hz, 2H, H2,13. 13C NMR d
/75 MHz) 17.87, 17.97 /CH3); 26.50, 26.70 /C8,19);
30.92, 31.16 /C7,18); 32.16, 32.26 /C9,20); 49.57, 49.96
/C10,21); 67.29, 67.46 /C6,17); 109.21, 109.34 /C1,12);
115.94, 115.97 /C3,4,14,15); 120.98, 121.02 /C2,13);
138.21, 138.29 /C11a,22a); 146.07, 146.10 /C4a,15a).
Mass spectrum /ESI1): m/z 382 /M1H)1.
3.5.5. 3-Methyl-1,3,4,6-tetrahydro-2H-5,1-benzothiazo-
cine 25d). Reaction of 2-/4-formyl-2-thiapentyl)nitro-
benzene /4d) /50 mg, 0.21 mmol) and PtO2 /30 mg) in
MeOH /47 ml) gave a dark brown residue /40 mg). Puri®-
cation gave the thiazocine /5d) as a yellow oil /6 mg, 20%).
n
max /®lm) 3082, 3046, 3016, 2927, 2854, 1672, 1634, 1608,
1584, 1489, 1452, 1404, 1281, 1252, 1165, 1090, 1047,
1007, 924, 860 cm21 13C NMR d /50 MHz) 18.56 /CH3);
3.5.8. 5,6,7,8,9,11,16,17,18,19,20,22-Dodecahydrodiben-
zo[c, l][1,10,5,14]dioxadiazacyclooctadecine 26h). Reac-
tion of 2-/5-formyl-2-oxapentyl)nitrobenzene /4h) /150
mg, 0.57 mmol) and 10% Pd/C in MeOH /140 ml) gave a
white solid /100 mg). Puri®cation gave the dimer /6h) as a
®ne, crystalline solid /28 mg, 23%). /Found: C, 74.6; H, 8.5;
N 7.7. C22H30N2O2 requires C, 74.6; H, 8.5; N, 7.9%). nmax
.
33.62, 34.73 /C3,4); 40.08 /C2); 51.59 /C6); 118.28, 119.89,
128.21, 132.33 /C7,8,9,10); 122.30 /C6a); 148.10 /C10a).
Mass spectrum /ESI1): m/z 161.8 /M1H)1.
3.5.6. 6,7,8,9,10,11,17,18,19,20,21,22-Dodecahydrodiben-
zo[b,k][1,10,4,13]dioxadiazacyclooctadecine 26f). Reac-
tion of 2-/4-formylbutyloxy)nitrobenzene /4f) /100 mg,
/CH2Cl2) 3421, 2987, 2954, 1601, 1524, 1268, 1256 cm21
.
1H NMR d /300 MHz) 1.68±1.85, m, H7,8,18,19; 3.08±
3.13, m, 4H, H6,17; 3.50, t, Jˆ5.5 Hz, 4H, H9,20; 4.52, s,

7570
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
4H, H11,22; 4.93, bs, 2H, NH; 6.59±6.65, m, 4H,
H2,4,13,15; 7.02, dd, Jˆ7.3, 1.4 Hz, 2H, H1,12; 7.19, td,
Jˆ7.9, 1.6 Hz, 2H, H3,14. 13C NMR d /75 MHz) 26.82,
27.51 /C7,8,18,19); 43.11 /C6,17); 69.41 /C9,20); 73.15
/C11,22); 110.10 /C4,15); 116.07 /C2,13); 121.63
/C12a,22a); 129.62, 129.76 /C1,3,12,14); 147.99
/C5a,15a). Mass spectrum /ESI1): m/z 355.3 /M1H)1.
43.75 /C7); 67.94 /C2); 109.82 /C9); 110.16 /C12); 116.19
/C11); 121.16 /C10); 138.48 /C8a); 146.09 /C12a). Mass
spectrum /ESI1): m/z 192.0 /M1H)1.
The dimer /6k) was isolated as a ®ne, white solid /17 mg,
20%). HPLC 40.5 min /Conditions A). /Found: C, 75.3; H,
9.1; N, 7.3. C24H34N2O2 requires C, 75.4; H, 9.0; N, 7.3%).
nmax /CH2Cl2) 3424, 3060, 2924, 1604, 1517, 1454, 1374,
1362, 1247, 1213, 1142, 1054 cm21. 1H NMR d /400 MHz)
1.49±1.67, m, 8H, H8,9,20,21; 1.74, apparent pentet,
Jˆ6.3 Hz, 4H, H10,22; 1.77±1.85, m, 4H, H7,19; 3.13, t,
Jˆ6.2 Hz, 4H, H11,23; 4.01, t, Jˆ5.5 Hz, 4H, H6,18; 4.17,
bs, 2H, NH; 6.59±6.66, m, 4H, H1,3,13,15; 6.75, dd, Jˆ7.8,
1.3 Hz, 2H, H4,16; 6.86, td, Jˆ7.6, 1.4 Hz, 2H, H2,14. 13C
NMR d /100 MHz) 26.78, 26.95 /C8,9,20,21); 29.47, 29.79
/C7,10,9,22); 43.44 /C11,23); 68.56 /C6,18); 110.21
/C1,13); 111.22 /C4,16); 116.34 /C3,15); 121.52 /C2,14);
139.13 /C12a,4a); 146.36 /C4a,16a). Mass spectrum
/ESI1): m/z 383.3 /M1H)1.
3.5.9. 1-Benzoyl-2,3,4,5,6,7-hexahydro-1H-1,7-benzodia-
zonine 25i). Reaction of 2-[/N-benzoyl)-4-formylbutyl-
amino]nitrobenzene /4i) /100 mg, 0.30 mmol) and 10%
Pd/C in MeOH /70 ml) gave a white solid /83 mg). Puri®ca-
tion gave the benzodiazonine /5i) as a yellow oil /18 mg,
22%). /Found: m/z 303.1473. /C18H20N2O1Na)1 requires
m/z 303.1473). nmax /CH2Cl2) 3422, 3055, 2934, 1633,
1
1499, 1447, 1400, 1315, 1278, 1259 cm21. H NMR d
/200 MHz) 1.49±1.67, m, 4H, H4,5; 1.76±1.89, m, 2H,
H3; 2.97±3.13, m, 1H and 3.23±3.37, m, 1H, H6; 3.62±
3.81, m, 1H and 4.61±4.74, m, 1H, H2; 6.48±6.56, m, 1H,
H8; 6.72, dd, Jˆ7.6, 1.4 Hz, 1H, H10; 6.86±6.94, m, 1H,
H9; 7.04±7.35, m, 6H, PhH, H11. 13C NMR d /50 MHz)
24.19 /C4); 27.10 /C3); 30.67 /C5); 44.36 /C2); 52.74 /C6);
118.43, 119.20, 127.18, 127.57, 128.04, 128.30, 128.54,
129.54, 129.68 /C8,9,10,11,PhCH); 130.25 /PhC);
131.87/C11a), 136.27 /C7a), 171.21 /CvO). Mass spec-
trum /ESI1): m/z 281.2 /M1H)1.
3.5.12. 10,22-Dimethyl-6,7,9,10,11,12,18,19,21,22,23,24-
dodecahydrodibenzo[e,o][1,4,11,14,7,17]tetraoxadiaza-
cycloeicosine 26l). Reaction of 2-/6-formyl-1,4-dioxa-
heptyl)nitrobenzene /4l) /50 mg, 0.19 mmol) and 10% Pd/
C gave a yellow ®lm /39 mg). Puri®cation gave the dimer
/6l) as a white solid /15 mg, 37%) mp 92.2±94.18C. /Found:
C, 69.5; H, 8.2; N, 6.6. C24H34N2O4 requires C 69.5, H 8.3,
N 6.7%). nmax /CH2Cl2) 3398, 2961, 2930, 2876, 1603,
3.5.10. 9,20-Dimethyl-6,7,10,11,17,18,21,22-octahydro-
9H,20H-dibenzo[e,h][1,4,10,13,7,16]tetraoxadiazacyclo-
octadecine 26j). Reaction of 2-/5-formyl-1,4-dioxahexyl)-
nitrobenzene /4j) /75 mg, 0.31 mmol) and 10% Pd/C
/45 mg) in MeOH /66 ml) gave a yellow residue /54 mg).
Puri®cation gave the dimer /6j) as a white solid /32 mg,
51%). /Found: m/z 387.2277. /C22H30N2O41H)1 requires
m/z 387.2284). nmax /CH2Cl2) 3410, 3056, 2924, 1603,
1
1514, 1458, 1269, 1250, 1215, 1124 cm21. H NMR d
/400 MHz) 1.03, d, Jˆ6.9 and 1.04 Hz, d, Jˆ6.9 Hz, 6H,
2£CH3; 2.12±2.19, m, 2H, H10,22; 3.07±3.15, m, 2H and
3.18±3.26, m, 2H, H11,23; 3.49±3.60, m, 4H, and 3.76±
3.85, m, 4H, H7,9,19,21; 4.12±4.19, m, 4H, H6,18; 6.60±
6.64, m, 4H, H1,3,13,15; 6.80, dd, Jˆ8.4, 1.5 Hz, 2H,
H4,16; 6.88±6.93, m, 2H, H2,14. 13C NMR d /75 MHz)
15.73 /CH3); 33.30, 33.67 /C10,22); 47.45, 47.72
/C11,23); 68.57, 68.77 /C9,21); 70.14 /C7,19); 74.77,
75.28 /C6,18); 109.91, 109.95 /C1,13); 112.21, 112.42
/C4,16): 115.67, 115.70 /C3,15); 122.06, 122.15 /C2,14);
139.53, 139.74 /C12a,24a); 145.87 /C4a,16a). Mass
spectrum /ESI1): m/z 415.0 /M1H)1.
1
1513, 1422, 1269, 1259, 1215, 1130 cm21. H NMR d
/300 MHz) 1.27, d, Jˆ6.2 Hz, 6H, 2£CH3; 3.05±3.15, m,
2H and 3.29±3.33, m, 2H, H10,21; 3.81±3.93, m, 6H,
4.04±4.07, m, 1H, 4.08±4.10, m, 1H, 4.17±4.15, m, 1H
and 4.16±4.26, m, 1H, H6,7,9,17,18,20; 6.57±6.71, m,
4H, H1,3,12,14; 6.74, td, Jˆ7.9, 1.9 Hz, 2H, H2,13; 6.77±
6.90, m, 2H, H4,15. 13C NMR d /75 MHz) 17.49, 17.65
/CH3); 48.91 /C10,21); 66.86, 67.41, 68.25, 68.51, 73.46,
73.82 /C6,7,9,17,18,20); 109.89, 110.11, 110.45, 111.25
/C1,4,12,15); 116.33, 116.40 /C3,14); 121.41, 121.68
/C2,13); 138.33, 138.62 /C11a,22a); 146.46, 146.50
/C4a,15a). Mass spectrum /ESI1): m/z 387.3 /M1H)1.
3.5.13. 2,3,6,7,8,9-Hexahydro-5H-1,4,9-benzodioxaaza-
cycloundecine 25m) and 6,7,10,11,12,13,19,20,23,24,
25,26-dodecahydro-9H,22H-dibenzo[e, p][1,4,12,15,7,18]-
tetraoxadiazacyclodocosine 26m). Reaction of 2-/7-
formyl-1,4-dioxaheptyl)nitrobenzene
/4m)
/100 mg,
0.39 mmol) and PtO2 in MeOH /88 ml) gave a viscous oil
/90 mg). The monomer /5m) was isolated as a yellow oil
/18 mg, 22%). /Found: C, 69.7; H, 8.4; N, 6.6. C12H17NO2
requires C, 69.5; H, 8.3; N, 6.8%). nmax /®lm) 3362, 2926,
2858, 1603, 1520, 1471, 1338, 1252, 1189, 1121, 1099,
3.5.11. 3,4,5,6,7,8-Hexahydro-2H-1,8-benzoxazecine 25k)
and 7,8,9,10,11,12,19,20,21,22,23,24-dodecahydro-6H,
18H-dibenzo[b,l][1,11,4,14]dioxadiazacycloeicosine 26k).
Reaction of 2-/5-formylpentyloxy)nitrobenzene /4k)
/100 mg, 0.44 mmol) and 10% Pd/C in MeOH /97 ml)
gave a white solid /75 mg). The benzoxazecine /5k) was
isolated as a white solid /6 mg, 7%). HPLC 52.1 min.
/Found: m/z 191.1309. C12H17NO requires m/z 191.1310).
nmax /CH2Cl2) 3429, 3055, 2936, 2859, 1602, 1513, 1444,
1269, 1268, 1216, 1047 cm21. 1H NMR d /200 MHz) 1.53±
1.56, m, 4H, H4,5; 1.69±1.76, m, 2H, H6; 1.80±1.87, m,
2H, H3; 3.13, t, Jˆ6.8 Hz, 2H, H7; 3.98, t, Jˆ6.3 Hz, 2H,
H2; 4.16, bs, 1H, NH; 6.58±6.66, m, 2H, H9,12; 6.74, dd,
Jˆ7.8, 1.2 Hz, 1H, H11; 6.85, td, Jˆ7.5, 1.3 Hz, 1H, H10.
13C NMR d /50 MHz) 26.17, 27.08, 29,30, 29.47 /C3,4,5,6);
1
1041, 740 cm21. H NMR d /300 MHz) 1.68±1.75, m, 2H
and 1.77±1.85, m, 2H, H6,7; 3.18±3.21, m, 2H, H8; 3.44±
3.51, m, 2H, and 3.52±3.54, m, 2H, H3,5; 4.13±4.17, m, 2H,
H2; 6.56±6.65, m, 2H, H10,12; 6.93±7.01, m, 2H, H11,13.
13C NMR d /50 MHz) 25.69, 27.31 /C6,7); 44.51 /C8);
66.84, 69.24, 72.34 /C2,3,5); 111.086 /C10); 115.46
/C13); 119.89 /C12); 124.14 /C11); 142.91 /C9a); 145.48
/C13a). Mass spectrum /ESI1): m/z 207.84 /M1H)1.
The dimer /6m) was isolated as a white solid /15 mg, 18%)
mp 136.7±138.68C. /Found: C, 69.1; H, 8.4; N, 6.7.

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7571
1
C24H34N2O4 requires C, 69.5; H, 8.3; N, 6.8%). nmax
/CH2Cl2) 3422, 3054, 2937, 2870, 1603, 1514, 1444,
2873, 1604, 1517, 1447, 1422, 1265, 1133, 1112 cm21. H
NMR d /300 MHz) 1.73±1.81, m, 2H and 1.83±1.91, m,
2H, H9,10; 3.11±3.15, m, 2H, H11; 3.53±3.57, m, 2H,
3.63±3.69, m, 2H and 3.76±3.81, m, 4H, H3,5,6,8; 4.05±
4.09, m, 2H, H2; 5.25, bs, 1H, NH; 6.53±6.59, m, 2H,
H13,15; 6.84, dd, Jˆ8.2, 1.6 Hz, 1H, H16; 6.88±6.94, m,
1H, H14,. 13C NMR d /50 MHz) 25.26, 28.16 /C9,10);
44.16 /C11); 69.27, 70.01, 70.27, 70.71, 71.14 /C2,3,
5,6,8); 110.19, 115.32, 115.45, 123.16 /C13,14,15,16);
142.80 /C12a), 145.73 /C16a). Mass spectrum /ESI1): m/z
251.0 /M1H)1.
1276, 1256, 1215, 1127 cm21 1H NMR d /300 MHz)
.
1.7±1.83, m, 8H, H10,11,23,24; 3.15, t, Jˆ6.6 Hz, 4H, H
12,25; 3.29, t, Jˆ5.9 Hz, 4H, H9,22; 3.76±3.79, m, 4H,
H7,20; 4.10±4.13, m, 4H, H6,19; 4.40, bs, 2H, NH; 6.58±
6.63, m, H1,3,14,16; 6.77, dd, Jˆ8.4, 1.5 Hz, 2H, H4,17;
6.88, td, Jˆ7.7, 1.5 Hz, 2H, H2,15; 13C NMR d /50 MHz)
26.29, 27.66 /C10,11,23,24); 43.55 /C12,25); 68.91, 69.34
/C7,9,20,22); 71.25 /C6,19); 109.99 /C1,14); 112.27
/C4,17); 115.97 /C3,16); 122.19 /C2,15); 139.29
/C13a,26a); 145.74 /C4a,17a). Mass spectrum /ESI1): m/z
415.4 /M1H)1.
The dimer /6p) was isolated as a yellow solid /5 mg, 6%).
/Found: C, 67.1; H, 8.6; N, 5.5. C28H42N2O6 requires C 66.9,
H 8.4, N 5.6%). nmax /CH2Cl2) 3379, 3048, 2933, 2872,
1604, 1518, 1478, 1448, 1368, 1336, 1278, 1258, 1226,
A similar reaction using 10% Pd/C gave the monomer /5m)
/15 mg, 19%) followed by the dimer /6m) /29 mg, 36%).
1215, 1133, 1113, 1048 cm21 1H NMR d /400 MHz)
.
3.5.14. 4-2Methylsulfonyl)-2,3,4,5,6,7,8,9-octahydro-1,4,9-
benzoxadiazacycloundecine 25n). Reaction of 2-[/N-
methylsulfonyl)-3-aza-6-formyl-1-oxaheptyl]nitrobenzene
/4n) /100 mg, 0.30 mmol) and PtO2 gave the monomer /5n)
as a white solid /31 mg, 36%). nmax /CH2Cl2) 3462, 3061,
2932, 2877, 1610, 1582, 1508, 1452, 1444, 1363, 1255,
1.75±1.82, m, 4H and 1.85±1.91, m, 4H, H13,14,29,30;
3.13±3.16, m, 4H, H15,31; 3.57, t, Jˆ5.4 Hz, 4H, 3.65±
3.67, m, 4H, 3.78±3.80, m, 4H and 3.81±3.83, m, 4H,
H7,9,10,12,23,25,26,28; 4.08±4.10, m, 4H, H6,22; 6.56±
6.59, m, 4H, H1,3,17,19; 6.85, dd, Jˆ8.1, 1.5 Hz, 2H,
H4,20; 6.90±6.94, m, 2H, H2,18. 13C NMR d /100 MHz)
25.37 /C14,30); 28.26 /C13,29); 44.12 /C15,31); 69.41,
70.12, 70.42, 70.79, 71.25 /C6,7,9,10,12,22,23,25,26,28);
110.15 /C1,17); 115.39, 115.43 /C3,4,19,20); 123.24
/C2,18); 141.06 /C16a, 32a); 145.80 /C4a,20a). Mass
spectrum /ESI1): m/z 503.1 /M1H)1.
1242, 1135, 1013 cm21 13C NMR d /50 MHz) 24.35,
.
24.76 /C6,7); 35.76 /CH3); 49.60, 49.73, 50.33 /C3,5,8);
70.35 /C2); 113.31, 122.06, 122.36, 122.68 /C10,11,
12,13); 139.19 /C9a); 151.65 /C13a). Mass spectrum
/ESI1): m/z 285.5 /M1H)1.
3.5.15. 9-Methyl-2,3,5,6,8,9,10,11-octahydro-1,4,7,11-ben-
zotrioxaazacyclotridecine 25o). Reaction of 2-/9-formyl-
1,4,7-trioxadecyl)nitrobenzene /4o) /46 mg, 0.15 mmol)
and 10% Pd/C /28 mg) in MeOH /32 ml) gave a yellow
oil /37 mg). Puri®cation gave the monomer /5o) as a colour-
less oil /26 mg, 30%). /Found: C, 67.4; H, 8.9; N, 5.4.
C14H21NO3 requires C, 66.9; H, 8.4; N, 5.6%). /Found:
m/z 252.1594. /C14H21NO31H)1 requires m/z 252.1600).
nmax /CH2Cl2) 3364, 2960, 2912, 2874, 1603, 1515, 1459,
An identical reaction of /4p) using PtO2 gave a yellow
residue /65 mg). Puri®cation gave only the monomer /5p)
as a yellow oil /48 mg, 58%).
A similar reaction of /4p) /70 mg, 0.24 mmol) and 10% Pd/
C /42 mg) in MeOH /15 ml) gave the monomer /5p)
/20 mg, 34%).
3.5.17. 11-Methyl-2,3,4,5,6,7,8,9,10,11,12,13-dodecahydro-
1,13-benzoxaazacyclopentadecine 25q) and 15,32-di-
methyl-6,7,8,9,10,11,12,13,14,15,16,17,23,24,25,26,27,
28,29,30,31,32,33,34-tetracosahydrodibenzo[b,q][1,16,
4,19]dioxadiazacyclotriacontine 26q). Reaction of 2-/10-
formylundecyloxy)nitrobenzene /4q) /100 mg, 0.31 mmol)
and PtO2 in MeOH /70 ml) gave a yellow oil /82 mg). The
monomer /5q) was isolated as a clear liquid /25 mg, 29%).
/Found C, 78.3; H, 10.5: N, 5.1. C18H29NO requires C, 78.5;
H 10.6; N, 5.1%). nmax /®lm) 3429, 3062, 2926, 2855, 1714,
1603, 1520, 1463, 1378, 1354, 1247, 1214, 1114, 1047,
1
1278, 1258, 1216, 1141, 1112, 1049 cm21. H NMR d
/300 MHz) 0.98, d, Jˆ7.3 Hz, 3H, CH3; 2.22±2.33, m,
1H, H9; 2.89, dd, Jˆ11.5, 9.6 Hz, 1H and 3.33, dd,
Jˆ11.5, 2.3 Hz, 1H, H10; 3.39, t, Jˆ8.8 Hz, 1H, 3.56±
3.58, m, 1H, 3.65±3.67, m, 1H, 3.68±3.70, m, 1H 3.70±
3.77, m, 1H and 3.78±3.81, m, 1H, H3,5,6,8; 4.04, ddd,
Jˆ10.8, 7.2, 2.4 Hz, 1H and 4.21, ddd, Jˆ10.8, 5.0,
2.4 Hz, 1H, H2; 6.55±6.61, m, 2H, H12,14; 6.84, dd,
Jˆ8.1, 1.3 Hz, 1H, H15; 6.91, td, Jˆ7.7, 1.4 Hz, 1H, H13.
13C NMR d /75 MHz) 15.74 /CH3); 32.53 /C9); 51.64
/C10); 70.10, 70.41, 71.34, 71.45 /C2,3,5,6,8); 109.99
/C12); 115.60, 115.80 /C14,15); 123.09 /C13); 141.64
/C11a); 146.78 /C15a). Mass spectrum /ESI1): m/z 252.1
/M1H)1.
1
732 cm21. H NMR d /200 MHz) 0.99, d, Jˆ6.8 Hz, 3H,
CH3; 1.25±1.56, m, 12H, H 4,5,6,7,8,9; 1.63±1.79, m, 5H,
H3,10,11; 2.70±2.81, m, 1H and 3.08±3.13, m, 1H, H12;
3.88±4.10, m, 2H, H2; 4.26, bs, 1H, NH; 6.53±6.66, m, 2H,
H14,17; 6.73, dd, Jˆ7.8, 1.5 Hz, 1H, H16; 6.85, td, Jˆ7.5,
1.6 Hz, 1H, H15. 13C NMR d /50 MHz) 18.94 /CH3); 24.54,
24.81, 25.87, 26.52, 26.52, 26.84, 27.14, 28.23, 32.10
/C3,4,5,6,7,8,9,10); 32.36 /C11); 50.01 /C12); 67.89 /C2);
109.41 /C14); 110.11 /C17); 115.80 /C16); 121.14 /C15);
138.79 /C13a); 146.11 /C17a). Mass spectrum /ESI1): m/z
276.3 /M1H)1.
3.5.16. 2,3,5,6,9,10,11,12-Octahydro-8H-1,4,7,12-benzo-
trioxaazacyclotetradecine 25p) and 6,7,9,10,13,14,15,
16,22,23,25,26,29,30,31,32-hexadecahydro-12H,28H-di-
benzo[h,v][1,4,7,15,18,21,10,24]hexaoxadiazacycloocta-
cosine 26p). Reaction of 2-/10-formyl-1,4,7-tri-
oxadecyl)nitrobenzene /4p) /100 mg, 0.34 mmol) and 10%
Pd/C in MeOH /71 ml) gave a yellow residue /75 mg). The
monomer /5p) was isolated as a yellow oil /63 mg, 75%).
/Found: C, 67.1; H, 8.6; N, 5.7. C14H21NO3 requires C, 66.9;
H, 8.4; N, 5.6%). nmax /CH2Cl2) 3384, 3054, 2986, 2936,
The dimer /6q) was isolated as a white solid /15 mg, 18%).
/Found C, 78.5; H, 10.6; N, 5.0. C36H58N2O2 requires C,
78.5; H 10.6; N, 5.1%). nmax /CH2Cl2) 3431, 3054, 2929,

7572
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
2856, 1602, 1514, 1270, 1200, 1248, 1215 cm21. 1H NMR d
/200 MHz) 0.99, d, Jˆ6.7 Hz, 6H, 2£CH3; 1.09±1.46, m,
20H, H8,9,10,11,12,25,26,27,28,29; 1.49±1.73, m, 8H,
H13,14,30,31; 1.76±1.83, m, 4H, H 7,24; 2.86±2.96, m,
2H, H15,32; 3.04, d, Jˆ5.0 Hz, 2H and 3.10, d, Jˆ4.8 Hz,
2H, H16,33; 3.99, t, Jˆ5.7 Hz, 4H, H6,23; 6.61±6.68, m,
4H, H1,3,18,20; 6.73±6.76, m, 2H, H4,21; 6.77±6.89, m,
2H, H2,19. 13C NMR d /50 MHz) 18.15 /CH3); 26.69,
26,99, 29.48, 29.67, 29.73, 29.91, 30.18 /C7,8,9,10,
11,12,13,14,24,25,26,27,28,29,30,31); 32.67 /C15,32);
56.39 /C16,33); 68.14 /C6,23), 110.55 /C1,3,18,20); 116.44
/C4,21); 121.26 /C2,19); 138.52 /C17a, 34a); 146.36 /C4a,
21a). Mass spectrum /ESI1): m/z 551.4 /M1H)1.
azatricyclo[17.3.1.18.12]tetracosa-1223),8,10,12224),19,21-
hexaene 26s). Reaction of 3-/3-formylbutyloxy)nitro-
benzene /4s) /100 mg, 0.45 mmol) and 10% Pd/C in
MeOH /100 ml) gave a white solid /67 mg). The monomer
/5s) was isolated as a yellow liquid /5 mg, 6%). /Found: m/z
178.1225. /C11H16NO1H)1 requires m/z 178.1232). nmax
/CH2Cl2) 3429, 2959, 2930, 2874, 1602, 1514, 1446,
1
1271, 1236, 1215, 1141, 1114, 1048 cm21. H NMR d
/300 MHz) 0.95, d, Jˆ6.8 Hz, 3H, CH3; 1.51±1.72, m,
2H, H4; 2.01±2.18, m, 1H, H5; 2.60±2.76, m, 1H and
3.15±3.25, m, 1H, H6; 3.82±4.01, m, 2H, H3; 6.10±6.17,
m, 3H, H9,10,11; 6.89, td, Jˆ8.1, 2.6 Hz, 1H, H12. 13C
NMR d /75 MHz) 18.34 /CH3); 27.95 /C5); 33.69 /C4,6);
49.36 /C3); 64.98 /C3); 99.11, 101.49, 107.39 /C9,10,11);
129.45 /C12); 149.21 /C8); 159.95 /C1).
3.5.18. 3,4,5,6,7,8,9,10,11,12,13,14-Dodecahydro-2H-1,14-
benzoxaazacyclohexadecine 25r) and 7,8,9,10,11,12,
13,14,15,16,17,18,25,26,27,28,2930,31,32,33,34,35,36-
tetracosahydro-6H,24H-dibenzo[b,r][1,17,4,20]dioxadi-
azacyclodotriacontine 26r). Reaction of 2-/11-formylunde-
cyloxy)nitrobenzene /4r) /100 mg, 0.31 mmol) and 10%
Pd/C in MeOH /70 ml) gave a white solid /74 mg). The
monomer /5r) was obtained as a colourless ®lm /23 mg,
27%). /Found: C, 78.2; H, 10.4; N, 5.3. C18H29NO requires
C, 78.5; H, 10.6; N, 5.1%). HPLC 41.68 min. nmax /®lm)
3431, 2927, 2856, 1602, 1521, 1445, 1246, 1213, 1048,
The dimer /6s) was isolated as a ®ne, white solid /31 mg,
39%). HPLC 48.14 min. /Found: C 74.5, H 8.5, N 7.9.
C22H30N2O2 requires C 74.5, H 8.5, N 7.9%). nmax
/CH2Cl2) 3448, 3054, 2931, 1616, 1511, 1269, 1262,
1
11196, 1165, 1062 cm21. H NMR d /200 MHz) 0.84, d,
Jˆ6.7 Hz, 6H, 2£CH3; 1.50±1.71, m, 4H, H4,15; 1.99±
2.18, m, 2H, H5,16; 2.62±2.78, m, 2H and 3.11±3.20, m,
2H, H6,17; 3.82±4.01, m, 8H, H3,14, NH; 6.06±6.20, m,
6H, H9,10,11,20,21,22; 6.89, td, Jˆ8.0, 2.6 Hz, 2H,
H23,24. 13C NMR d /50 MHz) 18.34 /CH3); 27.91, 28.23
/C4,15); 33.77 /C5,16); 49.31, 49.55 /C6,17); 64.88, 65.35
/C3,14); 99.11, 99.83, 101.49, 107.39, 107.67 /C9,10,
11,20,21,22); 129.42, 129.53 /C23,24); 149.08 /C8,19);
159.89 /C1,12). Mass spectrum: /ESI1): m/z 355.2
/M1H)1.
1
731 cm21. H NMR d /200 MHz) 1.31, bs, 4H and 1.41,
bs, 10H, H5,6,7,8,9,10,11; 1.49±1.56, m, 2H, H4; 1.64±
1.74, m, 2H, H12; 1.75±1.82, m, 2H, H3; 3.18, t,
Jˆ5.4 Hz, 2H, H13; 4.03, t, Jˆ5.2 Hz, 2H, H2; 4.30, bs,
1H, NH; 6.59±6.65, m, 2H, H15,18; 6.70±6.75, m, 1H,
H17; 6.84, td, Jˆ7.6, 1.3 Hz, H16. 13C NMR d /50 MHz)
24.77, 25.19, 25.64, 25.83, 26.73, 27.12, 27.61, 28.52, 29.42
/C3,4,5,6,7,8,9,10,11,12); 42.40 /C13); 67.56 /C2); 109.48,
109.78 /C15,18); 115.85 /C17); 120.99 /C16); 138.62
/C14a); 146.19 /C18a). Mass spectrum /EI): m/z 276
/M11, 20%), 275/85), 148/12), 123/30), 122/100),
120/68), 109/48), 95/20), 94/11), 93/11), 78/12), 77/15),
69/11), 67/12), 65/12), 55/43); /ESI1): m/z 276.2 /M1H)1.
3.5.20. 2-Oxa-8-azabicyclo[7.3.1]trideca-1213),9,11-triene
25t) and 2,14-dioxa-8,20-diazatricyclo[19.3.1.19,13]hexa-
cosa-1225),9,11,13226),21,23-hexaene 26t). Reaction of 3-
/4-formylbutyloxy)nitrobenzene /4t) /150 mg, 0.67 mmol)
and 10% Pd/C in MeOH /150 ml) gave an orange solid
/120 mg). The monomer /5t) was isolated as a colourless
liquid /12 mg, 10%). HPLC 43.61 min. /Found: m/z
178.1227. /C11H15NO1H)1 requires m/z 178.1232). nmax
/CH2Cl2) 3438, 3044, 2921, 2854, 1613, 1602, 1508,
The dimer /6r) was isolated as a white solid /17 mg, 19%).
HPLC 39.09 min. /Found: C, 78.2; H, 10.6; N, 5.1.
C38H66N2O2 requires C, 78.3; H, 11.4; N, 4.8%). nmax
/CH2Cl2) 3425, 3054, 2929, 2855, 1602, 1513, 1280,
. d
1475, 1286, 1268, 1201, 1165 cm21 1H NMR
/200 MHz) 1.52±1.71, m, 4H, and 1.79, pentet, Jˆ6.2 Hz,
2H, H4,5,6; 3.74, bs, 1H, NH; 3.17, t, Jˆ6.6 Hz, 2H, H7;
3.98, t, J, 6.0 Hz, 2H, H3; 6.10±6.18, m, 3H, H10,11,12;
7.02, t, Jˆ8.0 Hz, 1H, H13. 13C NMR d /50 MHz) 24.05,
29.14, 29.27 /C4,5,6); 43.95 /C7); 67.54 /C3); 99.28,
102.24, 106.83 /C10,11,12); 129.85 /C13); 149.89 /C9);
160.42 /C1).
1
1230, 1215 cm21. H NMR d /300 MHz) 1.29, bs, 28H,
1.47±1.50, m, 4H, 1.61±1.68, m, 4H and 1.74±1.81, m,
4H, H7,8,9,10,11,12,13,14,15,16, 25, 26,27, 28,29, 30, 31,
32, 33,34; 3.13, t, Jˆ6.3 Hz, 4H, H17,35; 3.99, t, Jˆ5.7 Hz,
4H, H6,24; 6.61±6.66, m, 4H, H1,3,19,21; 6.74±6.76, m,
2H, H4,22; 6.83±6.88, m, 2H, H2,20. 13C NMR d
/200 MHz) 26.65, 27.14, 29.27, 29.38, 29.51, 29.62, 29.73
/C7,8,9,10,11,12,13,14,15,16,25,26,27,28,29,30,31,32, 33,34);
43.52 /C17,35); 68.38 /C6,24); 109.94, 110.71
/C1,3,19,21); 116.09 /C4,22); 121.27 /C2,20); 138.91
/C18a,36a); 146.26 /C4a, 22a). Mass spectrum /EI): m/z
552 /M111, 20%), 551/M1, 60), 123/13), 122/100),
120/22), 110/15), 109/15), 91/10), 69/18), 55/42).
The dimer /6t) was isolated as a white solid /20 mg, 17%).
HPLC 35.8 min. /Found: m/z 355.2387. /C22H30N2O21H)1
requires m/z 355.2386). nmax /CH2Cl2) 3436, 3055, 2941,
2864, 1616, 1601, 1510, 1475, 1339, 1299, 1296, 1268,
1
1200, 1163 cm21. H NMR d /400 MHz) 1.46±1.62, m,
8H and 1.71, pentet, Jˆ6.4 Hz, 4H, H4,5,6,16,17,18; 3.10,
t, Jˆ6.7 Hz, 4H, H7,19; 3.67, bs, 2H, NH; 3.91, t, Jˆ6.1 Hz,
2H, H3,15; 6.07±6.15, m, 6H, H10,11,12,22,23,24; 6.94, t,
Jˆ8.0 Hz, 2H, H25,26. 13C NMR d /100 MHz) 23.07,
28.19, 28.46 /C4,5,6,16,17,18); 43.53 /C7,19); 66.88
/C3,15); 99.00, 102.78, 106.74 /C10,11,12,22,23,24);
129.91 /C25,26); 147.68 /C9,21); 160.19 /C1,13). Mass
spectrum /ESI1): m/z 355.3 /M1H)1.
A similar reaction using PtO2 gave a yellow ®lm /88 mg).
Puri®cation gave the monomer /5r) /31 mg, 36%) followed
by the dimer /6r) /9 mg, 11%).
3.5.19. 5-Methyl-2-oxa-7-azabicyclo[6.3.1]dodeca-1212),
8,10-triene 25s) and 5,16-dimethyl-2,13-dioxa-7,18-di-

T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
7573
3.5.21. 2,13-Dioxa-8,19-diazatricyclo[18.2.2.29,12]hexa-
cosa-10,11,20,22,23,25-hexaene 26u). Reaction of 4-/4-
formylbutyloxy)nitrobenzene /4u) /100 mg, 0.48 mmol)
and PtO2 in MeOH /100 ml) gave a colourless residue
/90 mg). The dimer /6u) was obtained as a white solid
/9 mg, 11%). /Found: m/z 355.2382. /C22H30N2O21H)1
requires m/z 355.2386). nmax /CH2Cl2) 3430, 3054, 2936,
2862, 1734, 1604, 1513, 1480, 1278, 1259, 1235, 1128,
142.82 /C11,24); 151.28 /C1,14). Mass spectrum /ESI1):
m/z 415.3 /M1H)1.
3.5.23.
2,5,8,18,21,24-Hexaoxa-13,29-diazatricyclo-
[28.2.2.214,17]hexatriaconta-4,16,30,32,33,35-hexaene
26w). Reaction of 4-/10-formyl-1,4,7-trioxadecyl)nitro-
benzene /4w) /100 mg, 0.34 mmol) and PtO2 gave a yellow
residue /80 mg). Puri®cation gave the dimer /6w) as a
colourless ®lm /22 mg, 26%). /Found: C, 66.8; H, 8.3; N,
5.7. C28H42O6N2 requires C, 66.9; H, 8.4; N, 5.6%). nmax
/CH2Cl2) 3055, 2928, 2869, 1648, 1604, 1514, 1457,
1
1106, 1076 cm21. H NMR d /400 MHz) 1.53±1.55, m,
8H, and 1.72, apparent pentet, Jˆ5.8 Hz, 4H,
H4,5,6,15,16,17; 2.91, bs, 2H, NH; 3.12, t, Jˆ6.2 Hz, 4H,
H7,18; 3.84, t, Jˆ5.9 Hz, 4H, H3,14; 6.44, dd, Jˆ8.8,
2.3 Hz, 4H, H10,21,23,26; 6.59, dd, Jˆ8.9, 2.2 Hz, 4H,
H11,22,24,25. 13C NMR d /100 MHz) 21.37, 25.45, 27.02
/C4,5,6,15,16,17); 44.08 /C7,18); 67.21 /C3,14); 115.23,
115.83 /C10,11,21,22,23,24,25,26); 141.10 /C9,20);
151.07 /C1,12). Mass spectrum /ESI1): m/z 355.0 /M1H)1.
1
1353, 1278, 1256, 1236, 1109, 1068 cm21. H NMR d
/300 MHz) 1.67±1.81, m, 8H, H10,11,26,27; 3.13, t,
Jˆ6.8 Hz, 4H, H12,28; 3.59, t, Jˆ5.2 Hz, 4H, 3.71±3.74,
m, 8H and 3.99±4.03, m, 8H, H3,4,6,7,9,19,20,22,23,25;
6.48, dd, Jˆ8.9, 2.3 Hz, 4H, H15,31,33,36; 6.65, dd,
Jˆ8.9, 2.3 Hz, 4H, H16,32,34,35. 13C NMR d /75 MHz)
26.78, 27.01 /C10,11,26,27); 44.90 /C12,28); 69.13,
69.54, 70.95 /C3,4,6,7,9,19,20,22,23,25); 114.54 /C15,31,
33,36); 116.59 /C16,32,34,35); 142.82 /C14,30); 151.28
/C1,17). Mass spectrum /ESI1): m/z 503 /M1H)1.
Further elution gave 4-/5-hydroxypentyloxy)aniline as a
yellow liquid which solidi®ed on standing /40 mg, 45%).
/Found: m/z 196.1330. /C11H17NO21H)1 requires m/z
196.1338). nmax /CH2Cl2) 3616, 3448, 3373, 3054, 2939,
1
2870, 1610, 1512, 1475, 1260, 1237, 1058, 1029 cm21. H
3.5.24. 6,7,9,10,18,19,20,21-Octahydro-5H-dibenzo[b,k]-
[1,4,7,10,13]tetraoxaazacycloheptadecine 28). Reaction
of 2-{7-[2-/3-formylpropyloxy)phenyl-1,4,7-trioxaheptyl}-
nitrobenzene /7) /100 mg, 0.26 mmol) and 10% Pd/C in
MeOH /54 ml) gave a solid residue /71 mg). Puri®cation
gave /8) as a white, crystalline solid /58 mg, 65%) mp
133.8±135.38C. /Found: C, 69.3; H, 7.3; N, 4.0.
C20H25NO4 requires C, 69.5; H, 7.3; N, 4.1%). nmax
/CH2Cl2) 3421, 3048, 2932, 2874, 1603, 1506, 1470,
NMR d /300 MHz) 1.49±1.56, m, 2H and 1.57±1.68, m,
2H, H30,40; 1.72±1.82, m, 2H, H20; 3.32, bs, 1H, OH; 3.66,
t, Jˆ6.3 Hz, 2H, H50; 3.89, t, Jˆ6.4 Hz, 2H, H10; 6.63, dd,
Jˆ8.8, 2.3 Hz, 2H, H2,6; 6.73, dd, Jˆ8.9, 2.3 Hz, 2H, H3,5.
13C NMR d /100 MHz) 22.39 /C30); 29.20 /C40); 32.50
/C20); 62.85 /C50); 68.57 /C10); 115.75 /C3,5); 116.45
/C4,6); 139.94 /C1); 152.29 /C4).
1
1453, 1453, 1271, 1253, 1222, 1125, 1064, 1048 cm21. H
3.5.22. 2,5-Dioxa-10-azabicyclo[9.2.2]pentadeca-11,13,
14-triene 25v) and 2,5,15,18-tetraoxa-10,23-diazatricyclo-
[22.2.2.211,14]triaconta-11,13,24,26,27,29-hexaene 26v).
Reaction of 4-/7-formyl-1,4-dioxaheptyl)nitrobenzene /4v)
/95 mg, 0.38 mmol) and PtO2 in MeOH /79 ml) gave a
yellow residue /77 mg). The monomer /5v) was obtained
as a yellow ®lm /4 mg, 7%). /Found: C, 69.8; H, 8.2; N,
6.8. C12H18NO2 requires C, 69.5; H, 8.3; N, 6.8%). /Found:
m/z 208.1329. /C12H18NO21H)1 requires m/z 208.1338).
nmax /CH2Cl2) 3360, 3049, 2929, 2869, 1603, 1519, 1471,
1457, 1330, 1278, 1256, 1236, 1189, 1121, 1109,
NMR d /300 MHz) 1.81±1.98, m, 4H, H7,8; 3.34, t,
Jˆ5.5 Hz, 2H, H6; 3.81±3.84, m, 2H and 3.93±3.96, m,
2H, H17,19; 4.07, t, Jˆ5.3 Hz, 2H and 4.18±4.20, m, 4H,
H 9,6,20; 4.91, bs, 1H, NH; 6.57±6.65, m, 2H, H4,13; 6.84±
6.96, m, 6H, H1,3,11,12,13,14. 13C NMR d /75 MHz)
25.90, 26.63 /C7,8); 42.34 /C6); 68.59, 69.42, 69.70,
69.90, 70.37 /C9,16,17,19,20); 110.31 /C4); 113.60,
113.62, 114.95, 115.59 /C1,2,11,14); 120.94, 121.41,
122.95 /C3,12,13); 140.67 /C4a); 145.765 /C21a); 148.97,
149.34 /C10a,15a). Mass spectrum /ESI1): m/z 383.4
/M1K)1.
1
1041 cm21. H NMR d /400 MHz) 1.67±1.73, m, 2H and
1.74±1.80, m, 2H, H7,8; 3.13, t, Jˆ6.9 Hz, 2H, H9; 3.59, t,
Jˆ5.6 Hz, 2H, 3.71±3.73, m, 2H and 4.01±4.03, m, 2H,
H3,4,6; 6.47, dd, Jˆ8.9, 2.3 Hz, 2H, H12,14; 6.66, dd,
Jˆ9.0, 2.3 Hz, 2H, H13,15. 13C NMR d /100 MHz) 26.78,
26.97 /C7,8); 44.72 /C9); 69.19, 69.52, 70.91 /C3,4,6);
114.37 /C12,14); 116.66 /C13,15); 143.07 /C11); 151.16
/C1).
A similar reaction using PtO2 gave /8) 47% yield.
3.6. Template-assisted reactions with H2
The general procedure for hydrogenation of /4m) using 10%
Pd/C was followed.
The dimer /6v) was obtained as a yellow ®lm /25 mg, 32%).
/Found: C, 69.6; H, 8.5; N, 5.1. C24H34N2O4 requires C,
69.5, H, 8.3, N, 6.8%). /Found: 415.2580. /C24H34N2O41H)1
requires 415.2597). nmax /CH2Cl2) 2929, 2871, 1723, 1608,
Reaction of 2-/2-formyl-1,4-dioxaheptyl)nitrobenzene /4m)
/46 mg, 0.18 mmol), 10% Pd/C /30 mg) and Ag/OTf)
/45 mg, 0.17 mmol) in MeOH /37 ml) gave an orange resi-
due /66 mg) which was dissolved in a mixture of CH2Cl2/
MeOH. 10% NaCl /aq.) solution was added to give AgCl as
a white precipitate and the residue was chromatographed to
give the monomer /5m) /11 mg, 30%).
1
1514, 1458, 1358, 1265, 1260, 1235, 1127, 1069 cm21. H
NMR d /300 MHz) 1.68±1.82, m, 8H, H7,8,20,21; 3.13, t,
Jˆ6.8 Hz, 4H, H9,22; 3.59, t, Jˆ5.2 Hz, 4H, 3.71±3.74, m,
4H and 3.99±4.03, m, 4H, H3,4,6,16,17,19; 6.48, dd, Jˆ8.9,
2.3 Hz, 4H, H12,25,27,30; 6.65, dd, Jˆ8.9, 2.3 Hz, 4H,
H13,26,28,29. 13C NMR
d /75 MHz) 26.78, 27.01
Acknowledgements
/C7,8,20,21); 44.90 /C9,22); 69.13, 69.54, 70.95 /C3,4,6,
16,17,19); 114.54 /C12,25,27,30); 116.59 /C13,26,28,29);
We thank the Australian Research Council for support and

7574
T. Ventrice et al. / Tetrahedron 57 .2001) 7557±7574
18. Cuny, G. D.; Buchwald, S. L. J. Am. Chem. Soc. 1993, 115,
2066±2068.
provision of a postgraduate award to T. V. and Johnson
Matthey Pty Ltd for a loan of precious metals. We also
thank Professor Len Lindoy and Dr Gang Wei, The
University of Sydney, for metal-ion binding studies and
Dr Peter Nichols, Monash University, for molecular
modelling studies.
19. Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of
Organic Compounds, Vol. 11; Wiley: New York, 1994; pp.
675±684 /Chapter 11).
20. Insight II /v. 4.0.0) /Discover) Molecular Modelling System;
Molecular Simulations Inc., 9685 Scranton Road, San Diego,
CA 92121-3752, USA.
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