Demonstration of 11-21-Membered Intramolecular Sulfonium Ylides: Regio- and Diastereoselective Synthesis of Spiro-Oxindole-Incorporated Macrocycles

Article abstract of DOI:10.1002/ejoc.201600008

An expeditious and convenient method for the generation of 11-21-membered intramolecular macrocyclic sulfonium ylides using catalytic Rh₂(OAc)₄ is presented. Using this approach, a wide variety of sulfur-macrocycles incorporating the

Full text of DOI:10.1002/ejoc.201600008

DOI: 10.1002/ejoc.201600008
Full Paper
Sulfonium Ylides
Demonstration of 11–21-Membered Intramolecular Sulfonium
Ylides: Regio- and Diastereoselective Synthesis of Spiro-
Oxindole-Incorporated Macrocycles
Sengodagounder Muthusamy,*[a] Karuppu Selvaraj,[a] and Eringathodi Suresh[b]
Abstract: An expeditious and convenient method for the gen- diastereoselectivity. Interestingly, tetracyclic macrocycles were
eration of 11–21-membered intramolecular macrocyclic sulf-
onium ylides using catalytic Rh2(OAc)4 is presented. Using this
approach, a wide variety of sulfur-macrocycles incorporating
the oxindole unit were produced in good yields and with high
also attained in good yields and with good regioselectivity us-
ing the disclosed sulfonium ylides. Ring-opening reactions of
tetracyclic macrocycles were also demonstrated.
Introduction
forming strategy in the synthesis of several natural products.[2]
Inter- and intramolecular sulfonium ylide reactions[3] employing
Reactions of diazocarbonyl compounds with metal catalysts metallo-carbenoids have been investigated for several cyclic as
constitute a widely illustrated approach in producing metallo- well as acyclic compounds. However, only a few reports have
carbenoids, which enable an assortment of reactions, such as discussed the synthesis of macrocycles via metallo-carbenoid-
cyclopropanations, C–H or heteroatom–H insertions, and ylide mediated sulfonium ylides. Davies[4] and co-workers have re-
formations.[1] Rhodium- or copper-carbenoids can efficiently re- ported the formation of four–ten-membered intramolecular
act with sulfides to generate sulfonium ylides; subsequent [1,2]- sulfonium ylides in the presence of Rh2(OAc)4 catalyst as a way
Stevens rearrangement has been applied as a key C–C bond to synthesize a wide variety of stable sulfonium ylides. More
Scheme 1. Reactions of intramolecular macrocyclic sulfonium ylides.
[a] School of Chemistry, Bharathidasan University,
recently, Kido[5] and co-workers reported the synthesis of vinyl-
Tiruchirappalli 620024, India
substituted lactones via the application of nine-membered in-
tramolecular cyclic sulfonium ylides. Recently, we reported[6]
the rhodium(II) acetate-catalyzed generation of nine- to thir-
teen-membered intramolecular macrocyclic sulfonium ylides
and their reactions (Scheme 1). However, we failed to demon-
strate the production of greater than thirteen-membered intra-
E-mail: muthu@bdu.ac.in
http://www.bdu.ac.in/schools/chemistry/chemistry/dr_s_muthusamy.php
[b] Analytical Division and Centralized Instrument Facility, CSIR - Central Salt
and Marine Chemicals Research Institute,
Bhavnagar, Gujarat 364002, India
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600008
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molecular macrocyclic sulfonium ylides. Generally, macrocycles hydroxybenzaldehydes, 2-hydroxynaphthaldehyde or hydroxy-
have been synthesized using high dilution techniques[7]/tem- acetophenone 1 using dibromoalkanes in the presence of
plates[8] and have received a great deal of attention due to their K2CO3/DMF to afford[12] corresponding bromo compounds 2
large number of applications.[9] From a synthetic point of view,
there are many methods available for the synthesis of oxindoles
bearing quaternary carbon centers; coupling reactions and cy-
clization methods are among the most prominent. In particular,
reactions of compounds bearing a thio group at the oxindole
3-position have been widely investigated.[10,11] We sought to
develop new methods for the construction of oxindoles bearing
quaternary carbon centers with a thio group at the 3-position
using transition metal-catalyzed reactions of intramolecular
macrocyclic sulfonium ylides. Based on the above limitations
and our desire to generate greater than thirteen-membered
sulfonium ylides, we herein demonstrate a mild and convenient
method for making a wide variety of sulfur macrocycles incor-
porating an oxindole unit. Rh2(OAc)4 serves as a catalyst ena-
bling reactions with high regio- and diastereoselectivity that
proceed through 11–21-membered macrocyclic sulfonium ylide
intermediates.
(Scheme 2). The carbonyl group was then protected using a
literature precedented procedure to afford the thiol-protected
bromo compounds 3. Subsequent N-alkylation of 3-diazoox-
indoles 4 with 3 in the presence of K2CO3/DMF furnished the
appropriate diazoamides 5a–p in 80–91 % yield (Scheme 2 and
Table 1).
To further our ongoing efforts to construct[6,13] functional-
ized sulfur macrocycles, we investigated the metal-catalyzed
decomposition of diazoamides 5 involved in generating macro-
cyclic sulfonium ylides. In this reaction, solvents and tempera-
ture play an important role in dictating product distribution.
Thus, reactions of diazoamide 5a were examined in various or-
ganic solvents. In line with our previous report,[6,13] the reaction
of diazoamide 5a with rhodium(II) acetate dimer catalyst in di-
chloromethane was performed at room temperature but did
not yield desired product 6a. In general, the decomposition of
the diazo group bearing a sulfide unit requires high tempera-
ture and long reaction times because the catalyst activity of
Rh2(OAc)4 is diminished by sulfur atoms.[14] Based on this obser-
vation, solvents and reaction temperature were changed. In the
Results and Discussion
To demonstrate the utility of macrocyclic sulfonium ylides, re- next attempt, diazoamide 5a in 1,2-dichloroethane at 40 °C
quired diazoamides 5a–p were assembled by O-alkylation of gave only a 40 % yield of macrocycle 6a. The reaction was re-
Scheme 2. Synthesis of diazoamides 5a–p.
Table 1. Summary of syntheses for diazoamides 5a–p.
Entry
Product
n
m
Aldehydes/ketones
R1
R2
R3
X
Yield [%][a]
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
6
5
9
5
6
2
2
3
2
2
2
3
6
7
0
0
2
1
1
2
1
1
1
2
2
1
1
1
1
1
1
1
2-hydroxybenzaldehyde
3-hydroxybenzaldehyde
3-hydroxybenzaldehyde
2-hydroxynaphthaldehyde
2-hydroxynaphthaldehyde
2-hydroxynaphthaldehyde
3-hydroxybenzaldehyde
2-hydroxybenzaldehyde
2-hydroxyacetophenone
2-hydroxyacetophenone
2-hydroxyacetophenone
2-hydroxyacetophenone
2-hydroxyacetophenone
2-hydroxyacetophenone
2-hydroxyacetophenone
2-hydroxyacetophenone
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
4-OCH3
4-OCH3
4-OCH3
H
H
H
H
H
H
H
H
H
H
Cl
H
H
H
H
Br
S
S
90
87
82
88
85
80
67
88
84
90
85
84
86
80
80
78
O
S
O
O
S
H
H
H
H
H
H
H
H
H
H
H
H
H
S
S
9
10
11
12
13
14
15
16
O
O
O
O
O
O
O
[a] Yield of the isolated product.
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peated with 1 mol-% of rhodium(II) acetate dimer as a catalyst
in refluxing benzene to furnish 16-membered macrocycle 6a
having the spiro-1,4-dithiepane unit. Compound 6a was ob-
tained as a single diastereomer (Scheme 3) in 95 % yield via
intramolecular macrocyclic sulfonium ylide formation followed
by a Stevens rearrangement.[6] In the present reaction, the de-
composition proceeded quickly at reflux and the reaction was
completed within 30 min. However, a low yield of the product
was observed when the reaction was carried out using
Cu(acac)2. The results show that Rh2(OAc)4 is superior to
Cu(acac)2 for promoting formation of macrocycle 6a. The struc-
ture of 6a was confirmed by 1H and 13C NMR spectroscopy
and mass spectrometry analyses. In addition, the structure and
stereochemistry of compound 6a were determined by X-ray
crystal structure analysis (Figure 1). No other isomers were de-
tected by either 1H NMR or HPLC analyses of the crude reaction
mixture.
Our principal aim is to synthesize interesting macrocyclic sys-
tems via the use of sulfonium ylides. With the optimized reac-
tion conditions in hand, we subsequently tested the compatibil-
ity of this reaction with various substrates; the results are pre-
sented in Scheme 3. The use of macrocycles 6b and 6c, bearing
Figure 1. ORTEP view of macrocycle 6a with 50 % probability of ellipsoids.
Scheme 3. Diastereoselective synthesis of macrocycles 6a–i. [a] Reaction conditions: 5a (1 mmol), 1 mol-% of Rh2(OAc)4, solvent (15 mL). [b] Yield of the
isolated product.
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a methoxy group para to the aldehyde, led to higher yields
than did substrates lacking the methoxy group and did so in a
completely diastereoselective manner. Naphthyl ring annulated
spiro-1,4-oxathiane, -dithiepane macrocycles 6d, 6e and 6f also
were generated in good yields (Scheme 3). Similar methodol-
ogy was applied to generate macrocycles 6g and 6h in good
yields and reaction of diazoamide 5i tethered to hydroxyaceto-
phenone furnished corresponding methyl-substituted product
6i, also in good yield. The stereochemistry for compounds 6b–
i was tentatively assigned on the basis of the crystal structure
obtained for 6a. However, reactions with the benzophenone
derivative did not furnish product.
Next, diazoamides 5j–n were prepared from mercaptoethan-
ol-protected acetophenone derivatives instead of the appropri-
ate dithiol-protected substrates. Initially, diazoamide 5j was
subjected to the optimized reaction conditions (see above);
however, this reaction did not yield the expected [1,2]-rear-
ranged macrocycle with a spiro-oxindole unit. Instead, we ob-
served the regioselective formation of interesting tetracyclic
Figure 2. ORTEP view of tetracyclic macrocycle 7a with 50 % probability of
ellipsoids.
In all the above reactions, we did not observe the formation
of any [1,2]-rearrangement products. The length of the spacer
plays an important role in this transformation. However, the
reaction of diazoamides 5o and 5p, with shorter spacers, under
similar conditions furnished products 8a and 8b in 83 % and
85 % yields, respectively, via Stevens rearrangement with com-
plete regio- and diastereoselectivity (Scheme 5). No tetracyclic
products of type 7 were observed when using 5o and 5p as
starting materials.
1
macrocycle 7a in high yield (Scheme 4). The H NMR spectrum
of 7a shows the newly formed exocyclic double bond by way
of two doublets at δ = 3.92 and 4.03 ppm, respectively, and a
singlet for the CH proton at δ = 4.26 ppm. The 13C NMR spec-
trum of 7a shows a CH-carbon at δ = 46.1 ppm corresponding
to the indole-3-carbon and the newly formed quaternary
carbon at δ = 86.1 ppm. In addition, the structure of compound
7a was unambiguously determined by X-ray crystallographic
analysis (Figure 2). Encouraged by these results, we evaluated
the substrate scope for this synthetic approach using various
sizes of tetracyclic macrocycles; the results are shown in
Scheme 4.
Scheme 5. Regio- and diastereoselective synthesis of spiro-1,4-oxathianes 8a
and 8b.
Spiro-macrocycles 6 are produced in line with our earlier re-
port.[6] The mechanism for regioselective formation of tetra-
cyclic macrocycles 7 and macrocycles 8 having the spiro-oxind-
ole is depicted in Scheme 6. Reaction of diazo compounds 5
with rhodium(II) acetate dimer as a catalyst might produce cor-
responding rhodium carbenoids 9. The initially formed transient
rhodium(II) carbenoids 9 may then undergo reaction with the
thioether sulfur to form sulfonium ylides 10. Further, the ab-
straction of a proton from a neighbouring methyl group pro-
ducing the exocyclic double bond followed by C–S bond cleav-
age would yield tetracyclic macrocycles 7 (Scheme 6, path a).
However, sulfonium ylides 10 with relatively short spacers may
undergo Stevens rearrangement affording spiro-macrocycles 8
(Scheme 6, path b).
Scheme 4. Regioselective synthesis of tetracyclic macrocycles 7a–e. [a] Reac-
tion conditions: 5 (1 mmol), 1 mol-% of Rh2(OAc)4, solvent (15 mL). [b] Yield
of the isolated product.
To explore the reactivity of tetracyclic macrocycles 7, we ex-
amined their hydration reactions using acids/H2O. It is well
Reaction of the chloro-substituted diazoamide gave corre- known that exocyclic olefins react with water in the presence of
sponding tetracyclic macrocycle 7b in high yield (Scheme 4). acid catalyst to afford the corresponding secondary or tertiary
We then generalized this reaction by regioselectively synthesiz- alcohols. Based on this reasoning, the reaction of macrocycle
ing several tetracyclic macrocycles 7b–e up to the 23-mem- 7a was performed with pTsOH·H2O in DCM as a solvent. The
bered ring using various spacer lengths.
reaction was completed within a few minutes to yield the Mark-
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ovnikov addition product hemiacetal 12 as an intermediate via
protonation on enol ether 7a followed by nucleophilic attack
of water upon oxonium species 11. It was found that com-
pound 12 is very labile and was converted to acyclic compound
13a in 90 % yield through hemiacetal decomposition of inter-
mediate 12 (Scheme 7). The hydration reaction of compound
7a was also accomplished in the presence of moist DCM sol-
vent. In this case, the complete conversion of product 13a was
achieved without adding any acid to 7a. To understand the
role of water during the reaction a controlled experiment was
performed using NMR techniques. Towards this end, macro-
cyclic compound 7a was dissolved in CDCl3, placed in the NMR
1
tube and the H-NMR spectrum was recorded. Next, a drop of
water was added to 7a using a capillary tube in the NMR tube
and NMR spectra recorded at specific time intervals. Review of
the NMR data revealed that 7a was slowly converted into 13a
over the course of 1 h (Figure 3). This experiment indicates that
the hydration reaction likely requires only traces of some acidic
impurity available in CDCl3. Acyclic product 13a was obtained
without using any purification techniques. Subsequent ring-
opening reactions of 7b–d were also carried out; corresponding
acyclic products 13b–d were obtained in good yields
(Scheme 7).
Scheme 6. Proposed mechanism for regioselective formation of tetracyclic
macrocycles 7 and macrocycles 8 having spiro-oxindole unit.
In order to study the effect of diastereoselectivity in an inter-
molecular reaction, a reaction of 1 equiv. thioacetal 15 and
Scheme 7. Ring-opening reactions of tetracyclic macrocycles 7a–d. [a] Reaction conditions: Compound 7 (1 mmol), a drop of H2O in 5 mL of DCM solvent.
[b] Yield of the product 13.
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Figure 3. 1H-NMR analyses conversion spectrum of compound 7a to 13a in NMR tube. [a] 1H-NMR spectrum of 7a in CDCl3. [b] 1H-NMR spectrum of 7a 0.5 h
after addition of H2O. [c] 1H-NMR spectrum after 1 h indicating complete conversion to 13a.
Scheme 8. Synthesis of spiro-1,4-dithianes 16a,b in an intermolecular manner.
1.2 equiv. 3-diazooxindole 14 in the presence of 1 mol-% rho- Experimental Section
dium(II) acetate dimer under optimized conditions (see above)
General Methods: The melting points are uncorrected. Infrared
was performed. This reaction furnished ring enlarged spiro-1,4-
dithianes 16a,b in 90 % yield as a diastereomeric mixture
(86:14, in favor of 16a) (Scheme 8).
spectra were recorded using ATR technique with a Bruker Alpha FT-
1
IR spectrophotometer. H and 13C NMR spectra were recorded with
a Bruker 400 MHz FT-NMR spectrometer (model: Avance DPX 400)
at room temperature (25 °C). The chemical shift (δ) and coupling
constant (J) values are given in parts per million and Hertz, respec-
tively. Tetramethylsilane (TMS) was used as an internal standard for
Conclusions
1
all H NMR studies. Carbon types were determined from DEPT-135
In conclusion, we have demonstrated a facile method by which
to generate 11–21-membered macrocyclic sulfonium ylides in
the presence of catalytic Rh2(OAc)4. Subsequent Stevens rear-
rangement afforded 11–21-membered sulfur macrocycles incor-
porating an oxindole unit without using high dilution/template
techniques. Interestingly, synthesis of tetracyclic macrocycles
from mercaptoethanol-protected diazo compounds was also
delineated in a regioselective manner.
and 13C NMR experiments. High resolution mass analyses were per-
formed using electrospray ionization (ESI) technique with Orbitrap
LC-MS and microTOF-Q II spectrometers. X-ray analyses were per-
formed with a Bruker Smart Apex II diffractometer. Solvents were
purified by distillation prior to use according to usual methods.
DCM was dried using P2O5. DMF was purified through vacuum dis-
tillation using CaH2 and stored over molecular sieves (4 Å). Thin-
layer chromatography was performed using silica/alumina plates
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and components were visualized by observation under iodine/UV NMR (CDCl3, 400 MHz): δ = 1.38–1.42 (m, 6 H), 1.50–1.54 (m, 2 H),
light at 254 nm. Column chromatography was performed over silica
gel (100–200 mesh)/neutral alumina, for column elution process
hexane/EtOAc mixture was used as the eluent unless otherwise
1.68–1.72 (m, 2 H), 1.81–1.88 (m, 2 H), 1.99–2.10 (m, 1 H), 2.20–2.25
(m, 1 H), 2.95 (dt, J1 = 13.6, J2 = 3.6 Hz, 2 H), 3.14 (td, J1 = 14.4, J2 =
1.6 Hz, 2 H), 3.80 (t, J = 7.2 Hz, 2 H), 4.13 (t, J = 6.4 Hz, 2 H), 6.45
stated. All air sensitive reactions were conducted in oven-dried (s, 1 H), 6.91 (d, J = 7.6 Hz, 1 H), 7.05 (td, J1 = 7.6, J2 = 0.8 Hz, 1 H),
glassware under a positive pressure of an argon or nitrogen with
magnetic stirring.
7.13–7.21 (m, 3 H), 7.33 (td, J1 = 8.0, J2 = 0.8 Hz, 1 H), 7.51 (td, J1 =
7.2, J2 = 1.2 Hz, 1 H), 7.71–7.75 (m, 2 H), 9.07 (d, J = 8.4 Hz, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 25.9, 26.1, 26.8, 28.1, 29.2,
29.3, 29.5, 33.3, 40.7, 44.8, 60.7, 70.2, 108.9, 114.8, 116.9, 118.3,
120.6, 121.9, 123.8, 125.4, 125.7, 126.6, 128.2, 129.8, 130.3, 132.9,
133.9, 152.5, 166.7 ppm. C30H33N3O2S2 (531.73): calcd. C 67.76, H
6.26, N 7.90; found C 67.93, H 6.35, N 7.75.
General Procedure for Diazoamides 5a–p: To an oven-dried flask,
a solution containing appropriate diazo compound 4 (250 mg,
1 mmol) and potassium carbonate (543 mg, 2.5 mmol) in dry DMF
was made under argon atmosphere. To this reaction mixture, a solu-
tion of appropriate bromo thioacetals (1.2 mmol) in dry DMF was
slowly added over a period of 10 min and then a catalytic amount
of tetrabutylammonium iodide was added. The progress of the re-
action was monitored using TLC. After completion of the reaction,
DMF was removed under reduced pressure. The reaction mixture
was then extracted with dichloromethane (3 × 25 mL) and the com-
bined organic layers washed with water (3 × 25 mL), brine (2 ×
25 mL) and dried (anhydrous Na2SO4). The solvent was removed
under reduced pressure and the resulting residue purified using
silica gel column chromatography (hexanes/ethyl acetate, 80:20) to
afford respective diazoamides 5a–p.
Diazoamide 5e: Red thick oil (690 mg), yield 85 %. IR (neat): νmax
=
˜
2970, 2885, 2101, 1732, 1620, 1455, 1339, 1146, 1040, 726 cm–1. H
NMR (CDCl3, 400 MHz): δ = 1.26–1.48 (m, 10 H), 1.66–1.71 (m, 2 H),
1.77–1.86 (m, 2 H), 3.34–3.37 (m, 1 H), 3.45–3.52 (m, 1 H), 3.80 (t,
J = 7.6 Hz, 2 H), 3.89–3.95 (m, 1 H), 4.04–4.22 (m, 2 H), 4.73–4.77
(m, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 7.04–7.08 (m, 2 H), 7.15–7.20 (m,
3 H), 7.33 (t, J = 7.2 Hz, 1 H), 7.45–7.46 (m, 1 H), 7.74 (d, J = 8.0 Hz,
1 H), 7.78 (d, J = 9.2 Hz, 1 H), 7.51 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 25.9, 26.1, 26.8, 28.0, 29.2, 29.3, 29.4, 33.3,
40.6, 44.9, 60.5, 70.1, 108.8, 114.8, 116.8, 118.3, 120.5, 121.9, 123.8,
125.4, 125.6, 126.6, 128.2, 129.8, 130.3, 132.9, 134.0, 152.5,
166.7 ppm. C30H33N3O3S (515.66): calcd. C 69.87, H 6.45, N 8.15;
found C 69.68, H 6.33, N 8.30.
1
Diazoamide 5a: Red thick oil (747 mg), yield 90 %. IR (neat): νmax
=
˜
2988, 2945, 2132, 1754, 1664, 1323, 1165, 1080, 777, 760 cm–1. H
NMR (CDCl3, 400 MHz): δ = 0.82–0.95 (m, 1 H), 1.23–1.48 (m, 9 H),
1.66–1.73 (m, 2 H), 1.77–1.87 (m, 2 H), 1.90–1.95 (m, 1 H), 2.10–2.16
(m, 1 H), 2.86 (dt, J1 = 14.0, J2 = 4.0 Hz, 2 H), 3.06 (td, J1 = 14.4, J2 =
2.0 Hz, 2 H), 3.37 (s, 3 H), 3.81 (t, J = 7.2 Hz, 2 H), 3.95 (t, J = 6.4 Hz,
1
Diazoamide 5f: Red thick oil (580 mg), yield 80 %. IR (neat): νmax
=
˜
2980, 2934, 2131, 1715, 1616, 1290, 1265, 1109, 935, 745 cm–1. H
NMR (CDCl3, 400 MHz): δ = 1.42–1.50 (m, 2 H), 1.54–1.63 (m, 2 H),
1.69–1.76 (m, 2 H), 2.88 (dt, J1 = 14.0, J2 = 3.6 Hz, 2 H), 3.08 (td, J1 =
14.4, J2 = 2.0 Hz, 2 H), 3.73 (t, J = 7.2 Hz, 2 H), 4.01 (t, J = 6.4 Hz, 2
H), 5.67 (s, 1 H), 6.84 (dd, J1 = 8.4, J2 = 2.8 Hz, 2 H), 6.95 (t, J =
7.6 Hz, 1 H), 7.14–7.21 (m, 3 H), 7.22 (td, J1 = 8.4, J2 = 1.2 Hz, 1 H),
7.50 (dd, J1 = 8.4, J2 = 2.0 Hz, 1 H), 7.55–7.57 (m, 2 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 25.4, 25.7, 27.2, 28.9, 40.2, 43.9, 43.9,
60.4, 68.1, 109.8, 111.8, 116.9, 118.3, 120.5, 121.8, 123.8, 125.4, 125.6,
126.6, 128.2, 129.8, 130.3, 132.9, 133.9, 152.5, 166.7 ppm.
C26H25N3O3S (459.56): calcd. C 67.95, H 5.48, N 9.14; found C 67.72,
H 5.42, N 9.10.
1
2 H), 5.59 (s, 1 H), 6.40 (d, J = 2.4 Hz, 1 H), 6.47 (dd, J1 = 8.4, J2
=
2.4 Hz, 1 H), 6.92 (d, J = 7.6 Hz, 1 H), 7.06 (t, J = 7.6 Hz, 1 H), 7.15–
7.18 (m, 2 H), 7.47 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 25.4, 26.0, 26.9, 28.1, 29.1, 29.2, 29.5, 32.6, 40.8, 43.5,
55.3, 60.6, 68.6, 99.6, 104.8, 108.9, 116.9, 118.3, 120.3, 121.9, 125.4,
129.7, 133.9, 156.1, 160.6, 166.7 ppm. C28H35N3O2S2 (525.72): calcd.
C 63.97, H 6.71, N 7.99; found C 63.80, H 6.60, N 7.88.
Diazoamide 5b: Red thick oil (684 mg), yield 87 %. IR (neat): νmax
=
˜
2983, 2933, 2137, 1717, 1626, 1292, 1261, 1110, 938, 743 cm–1. H
NMR (CDCl3, 400 MHz): δ = 1.36–1.46 (m, 8 H), 1.68–1.71 (m, 2 H),
1.78–1.87 (m, 2 H), 3.29–3.36 (m, 2 H), 3.44–3.52 (m, 2 H), 3.80 (t,
J = 7.2 Hz, 2 H), 3.83 (s, 3 H), 4.02 (t, J = 6.8 Hz, 2 H), 5.61 (s, 1 H),
6.76 (d, J = 8.0 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 7.01–7.09 (m, 3 H),
7.16–7.20 (m, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 25.9, 26.8,
28.1, 29.1, 29.2, 29.23, 40.2, 40.7, 56.1, 56.6, 60.7, 68.9, 108.9, 111.2,
112.6, 116.9, 118.3, 120.2, 121.9, 125.4, 132.0, 133.9, 148.5, 149.3,
166.7 ppm. C26H31N3O3S2 (497.67): calcd. C 62.75, H 6.28, N 8.44;
found C 62.90, H 6.18, N 8.32.
1
Diazoamide 5g: Red thick oil (450 mg), yield 67 %. IR (neat): νmax
=
˜
2965, 2880, 2112, 1730, 1619, 1454, 1340, 1142, 1043, 728 cm–1. H
NMR (CDCl3, 400 MHz): δ = 1.42–1.50 (m, 2 H), 1.66–1.77 (m, 4 H),
3.21–3.29 (m, 2 H), 3.36–3.44 (m, 2 H), 3.77 (t, J = 7.2 Hz, 2 H), 3.86
(t, J = 6.0 Hz, 2 H), 5.51 (s, 1 H), 6.68 (dd, J1 = 8.4, J2 = 1.6 Hz, 1 H),
6.86 (d, J = 7.6 Hz, 1 H), 6.97–7.01 (m, 3 H), 7.08–7.18 (m, 3 H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 23.5, 27.9, 28.9, 40.2, 40.6, 56.2,
60.7, 67.6, 108.9, 114.0, 114.1, 116.9, 118.4, 120.2, 121.9, 125.4, 129.4,
133.8, 141.9, 159.1, 166.8 ppm. C22H23N3O2S2 (425.56): calcd. C
63.97, H 6.71, N 7.99; found C 63.80, H 6.62, N 7.88.
1
Diazoamide 5c: Red thick oil (697 mg), yield 82 %. IR (neat): νmax
=
˜
2936, 2861, 2131, 1753, 1691, 1322, 1165, 1081, 760, 567 cm–1. H
NMR (CDCl3, 400 MHz): δ = 1.26–1.33 (m, 14 H), 1.41–1.46 (m, 2 H),
1.65–1.73 (m, 2 H), 1.78–1.87 (m, 2 H), 3.17–3.20 (m, 1 H), 3.24–3.30
(m, 1 H), 3.80 (t, J = 7.6 Hz, 2 H), 3.84 (s, 3 H), 3.88–3.94 (m, 1 H),
4.02 (t, J = 6.8 Hz, 2 H), 4.49–4.53 (m, 1 H), 5.98 (s, 1 H), 6.81 (d, J =
8.0 Hz, 1 H), 6.92 (d, J = 7.6 Hz, 1 H), 6.98 (dd, J1 = 8.0, J2 = 2.0 Hz,
1 H), 7.04 (d, J = 2.0 Hz, 1 H, Ar H), 7.07 (d, J = 7.6 Hz, 1 H), 7.16–
7.19 (m, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 25.9, 26.8, 28.1,
28.5, 28.9, 29.1, 29.2, 29.2, 32.6, 33.1, 40.1, 40.7, 56.1, 56.5, 60.7, 68.9,
108.9, 111.2, 112.6, 116.9, 118.3, 120.2, 121.9, 125.4, 132.0, 133.9,
148.5, 149.3, 166.7 ppm. C30H39N3O4S (537.71): calcd. C 67.01, H
7.31, N 7.81; found C 67.19, H 7.40, N 7.94.
1
Diazoamide 5h: Red thick oil (630 mg), yield 88 %. IR (neat): νmax
=
˜
2978, 2886, 2113, 1730, 1615, 1449, 1336, 1142, 1039, 728 cm–1. H
NMR (CDCl3, 400 MHz): δ = 1.42–1.59 (m, 4 H), 1.71–1.96 (m, 5 H),
2.11–2.15 (m, 1 H), 2.86 (dt, J1 = 14.4, J2 = 3.2 Hz, 2 H), 3.06 (td, J1 =
14.4, J2 = 2.0 Hz, 2 H), 3.83 (t, J = 7.2 Hz, 2 H), 3.99 (t, J = 6.4 Hz, 2
H), 5.67 (s, 1 H), 6.82 (d, J = 8.4 Hz, 1 H), 6.93 (t, J = 6.4 Hz, 2 H),
7.06 (t, J = 7.6 Hz, 1 H), 7.15–7.26 (m, 3 H), 7.56 (dd, J1 = 7.6, J2 =
1.2 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 25.4, 25.8, 26.6,
28.1, 29.1, 32.4, 40.6, 43.9, 60.7, 68.3, 108.9, 111.9, 116.9, 118.4,
120.9, 121.9, 125.4, 127.6, 129.1, 129.3, 133.8, 154.9, 166.7 ppm.
C24H27N3O2S2 (453.62): calcd. C 63.55, H 6.00, N 9.26; found C 63.33,
H 6.15, N 9.18.
1
Diazoamide 5d: Red thick oil (739 mg), yield 88 %. IR (neat): νmax
=
Diazoamide 5i: Red thick oil (600 mg), yield 84 %. IR (neat): νmax =
˜
˜
1
1
3054, 2985, 2108, 1714, 1609, 1468, 1349, 1264, 728, 700 cm–1. H 2937, 2859, 2132, 1750, 1693, 1320, 1161, 1087, 764, 564 cm–1. H
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Full Paper
NMR (CDCl3, 400 MHz): δ = 1.59–1.66 (m, 2 H), 1.76–1.83 (m, 2 H),
1.86–1.20 (m, 4 H), 1.96 (s, 3 H), 2.71–2.81 (m, 4 H), 3.85 (t, J =
6.8 Hz, 2 H), 3.99 (t, J = 6.0 Hz, 2 H), 6.87–6.94 (m, 3 H), 7.06 (t, J =
7.6 Hz, 1 H), 7.15–7.26 (m, 3 H), 7.90 (dd, J1 = 7.6, J2 = 1.6 Hz, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 23.7, 24.8, 27.8, 28.5, 29.0,
29.1, 40.6, 52.0, 60.7, 68.0, 108.9, 113.4, 116.8, 118.4, 119.7, 121.9,
4.42 (m, 1 H), 6.85–6.93 (m, 3 H), 7.06 (td, J1 = 7.2, J2 = 0.8 Hz, 1 H),
7.15–7.21 (m, 3 H), 7.42 (dd, J1 = 7.6, J2 = 1.6 Hz, 1 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 26.3, 26.9, 28.1, 29.3, 29.3, 29.4, 29.5,
30.8, 33.4, 40.8, 60.7, 68.1, 70.8, 92.6, 108.9, 111.8, 116.9, 118.4,
120.1, 121.9, 122.9, 125.4, 128.2, 134.0, 134.9, 155.3, 166.7 ppm.
C28H35N3O3S (493.66): calcd. C 68.12, H 7.15, N 8.51; found C 68.28,
125.4, 128.7, 130.6, 131.1, 133.9, 157.2, 166.7 ppm. C24H27N3O2S2 H 7.08, N 8.46.
(453.62): calcd. C 63.55, H 6.00, N 9.26; found C 63.36, H 5.90, N
Diazoamide 5o: Red thick oil (624 mg), yield 80 %. IR (neat): νmax
=
˜
2936, 2092, 1685, 1606, 1468, 1351, 1230, 1040, 756 cm–1. H NMR
(CDCl3, 400 MHz): δ = 1.20 (s, 3 H), 2.91–2.38 (m, 2 H), 2.95–2.99 (m,
1 H), 3.13–3.19 (m, 1 H), 4.05–4.18 (m, 4 H), 4.20–4.27 (m, 1 H), 4.42–
4.47 (m, 1 H), 6.84 (d, J = 8.0 Hz, 1 H), 6.94 (t, J = 7.2 Hz, 1 H), 7.07
(t, J = 7.2 Hz, 1 H), 7.15–7.25 (m, 4 H), 7.47 (dd, J1 = 7.6, J2 = 1.2 Hz,
1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 28.3, 31.1, 33.5, 38.4, 60.8,
65.4, 70.9, 92.5, 109.3, 111.9, 116.7, 118.3, 120.6, 122.0, 123.1, 125.6,
128.3, 134.0, 134.8, 154.8, 166.8 ppm. C21H21N3O3S (395.47): calcd.
C 63.78, H 5.35, N 10.63; found C 63.60, H 5.24, N 10.49.
1
9.12.
Diazoamide 5j: Red thick oil (600 mg), yield 90 %. IR (neat): νmax
=
˜
2934, 2090, 1688, 1608, 1465, 1357, 1236, 1045, 755 cm–1. H NMR
(CDCl3, 400 MHz): δ = 1.62–1.72 (m, 2 H), 1.78–1.87 (m, 2 H), 1.88
(s, 3 H), 1.91–1.96 (m, 2 H), 2.88–2.92 (m, 1 H), 3.03–3.10 (m, 1 H),
3.87 (t, J = 6.8 Hz, 2 H), 3.97–4.08 (m, 3 H), 4.36–4.41 (m, 1 H), 6.84
(d, J = 8.0 Hz, 1 H), 6.89 (td, J1 = 7.6, J2 = 0.8 Hz, 1 H), 6.95 (d, J =
7.6 Hz, 1 H), 7.05 (td, J1 = 8.4, J2 = 0.8 Hz, 1 H), 7.14–7.20 (m, 3 H),
7.42 (dd, J1 = 7.6, J2 = 1.6 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 23.8, 27.8, 29.0, 30.8, 33.4, 40.6, 60.7, 67.6, 70.8, 92.5, 109.0,
111.8, 116.9, 118.4, 120.2, 121.9, 123.0, 125.4, 128.2, 133.9, 134.9,
155.1, 166.7 ppm. C23H25N3O3S (423.52): calcd. C 65.23, H 5.95, N
9.92; found C 65.41, H 5.84, N 9.85.
1
Diazoamide 5p: Red thick oil (620 mg), yield 78 %. IR (neat): νmax
=
˜
2938, 2090, 1688, 1607, 1465, 1350, 1233, 1039, 759 cm–1. H NMR
(CDCl3, 400 MHz): δ = 1.19 (s, 3 H), 2.90–2.39 (m, 2 H), 2.93–3.02 (m,
1 H), 3.16–3.20 (m, 1 H), 4.04–4.19 (m, 4 H), 4.20–4.26 (m, 1 H), 4.40–
4.46 (m, 1 H), 6.83 (d, J = 8.0 Hz, 1 H), 6.90 (t, J = 7.2 Hz, 1 H), 7.05
(t, J = 7.2 Hz, 1 H), 7.16–7.27 (m, 3 H), 7.49 (dd, J1 = 7.6, J2 = 1.2 Hz,
1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 28.3, 31.1, 33.5, 38.3, 60.8,
65.3, 70.9, 92.5, 109.2, 111.8, 116.7, 118.4, 120.6, 122.0, 123.1, 125.7,
128.3, 133.9, 134.8, 154.8, 166.8 ppm. C21H20BrN3O3S (474.37): calcd.
C 53.17, H 4.25, N 8.86; found C 53.01, H 4.14, N 8.74.
1
Diazoamide 5k: Red thick oil (504 mg), yield 85 %. IR (neat): νmax
=
˜
2928, 2089, 1682, 1607, 1462, 1350, 1239, 1047, 752 cm–1. H NMR
(CDCl3, 400 MHz): δ = 1.61–1.69 (m, 2 H), 1.77–1.85 (m, 2 H), 1.88
(s, 3 H), 1.90–1.96 (m, 2 H), 2.88–2.92 (m, 1 H), 3.05–3.11 (m, 1 H),
3.86 (t, J = 6.8 Hz, 2 H), 3.96–4.08 (m, 3 H), 4.38–4.43 (m, 1 H), 6.84
(dd, J1 = 8.4, J2 = 0.8 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 6.90 (td, J1 =
7.6, J2 = 0.8 Hz, 1 H), 7.13 (dd, J1 = 8.4, J2 = 2.0 Hz, 1 H), 7.17 (d,
J = 1.6 Hz, 1 H), 7.19–7.21 (m, 1 H), 7.42 (dd, J1 = 8.0, J2 = 2.0 Hz, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 23.6, 27.8, 29.0, 30.8, 34.0,
40.8, 60.9, 67.5, 70.8, 92.5, 109.7, 111.7, 118.2, 118.4, 120.2, 122.9,
125.4, 127.3, 128.2, 132.4, 134.8, 155.1, 166.2 ppm. C23H24ClN3O3S
(457.97): calcd. C 60.32, H 5.28, N 9.18; found C 60.48, H 5.42, N
9.29.
1
General Procedure for Macrocycles 6a–i Having Spiro-oxindole
Unit: A solution of diazoamide 5a–i (100 mg, 1.0 mmol) and rho-
dium(II) acetate dimer (1 mol-%) in dry benzene (10 mL) was stirred
at reflux conditions for 30–50 min. The progress of the reaction was
monitored using TLC. After completion of the reaction, the reaction
mixture was concentrated under reduced pressure and purified by
column chromatography (SiO2, hexane/ethyl acetate 75: 25) to af-
ford respective macrocycles 6a–i.
Diazoamide 5l: Red thick oil (581 mg), yield 84 %. IR (neat): νmax
=
˜
Macrocycle 6a: White solid (84 mg), yield 88 %; m.p. 151–152 °C.
2924, 2099, 1682, 1604, 1458, 1358, 1235, 1043, 744 cm–1. H NMR
(CDCl3, 400 MHz): δ = 1.44–1.52 (m, 2 H), 1.57–1.67 (m, 2 H), 1.73–
1.89 (m, 4 H), 1.91 (s, 3 H), 2.88–2.93 (m, 1 H), 3.05–3.11 (m, 1 H),
3.84 (t, J = 7.2 Hz, 2 H), 3.96–4.08 (m, 3 H), 4.37–4.41 (m, 1 H), 6.
84–6.95 (m, 3 H), 7.04–7.08 (m, 1 H), 7.15–7.25 (m, 3 H), 7.42 (dd,
J1 = 7.6, J2 = 0.8 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 26.0,
26.6, 28.1, 29.8, 30.8, 33.4, 40.7, 60.7, 67.8, 70.8, 92.6, 108.9, 111.8,
116.9, 118.4, 120.2, 121.9, 122.9, 125.4, 128.2, 133.9, 134.9, 155.2,
166.7 ppm. C24H27N3O3S (437.55): calcd. C 63.55, H 6.00, N 9.26;
found C 63.72, H 6.15, N 9.34.
1
IR (neat): νmax = 2923, 2855, 1709, 1606, 1352, 1200, 1165, 1044,
˜
1
736 cm–1. H NMR (CDCl3, 400 MHz): δ = 0.82–0.90 (m, 4 H), 1.09–
1.14 (m, 1 H), 1.21–1.56 (m, 8 H), 1.71–1.74 (m, 1 H), 1.98–1.08 (m,
1 H), 2.43–2.87 (m, 1 H), 2.30–3.13 (m, 4 H), 3.59–3.66 (m, 1 H), 3.63
(s, 3 H), 3.91–3.96 (m, 1 H), 4.03–4.10 (m, 1 H), 4.18–4.23 (m, 1 H),
5.27 (s, 1 H), 5.99 (dd, J1 = 8.8, J2 = 2.4 Hz, 1 H), 6.33 (d, J = 2.8 Hz,
1 H), 6.53 (d, J = 8.4 Hz, 1 H), 6.66 (d, J = 8.0 Hz, 1 H), 7.08 (td, J1 =
7.6, J2 = 0.8 Hz, 1 H), 7.25 (td, J1 = 7.6, J2 = 1.2 Hz, 1 H), 7.90 (dd,
J1 = 7.2, J2 = 0.8 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 21.8,
23.1, 25.0, 25.3, 26.9, 27.4, 28.0, 28.6, 33.6, 36.9, 38.3, 50.6, 55.2, 57.9,
66.1, 98.5, 103.6, 108.3, 119.8, 121.9, 126.3, 128.8, 129.2, 130.7, 142.8,
Diazoamide 5m: Red thick oil (650 mg), yield 86 %. IR (neat): νmax
=
˜
2928, 2094, 1682, 1606, 1465, 1358, 1236, 1044, 747 cm–1. H NMR 155.6, 159.5, 177.6 ppm. HRMS (ESI): calcd. for C28H35NO3S2 [M +
1
(CDCl3, 400 MHz): δ = 1.35 (s, 8 H), 1.51–1.56 (m, 2 H), 1.68–1.73 (m,
2 H), 1.82–1.91 (m, 2 H), 1.92 (s, 3 H), 2.90–2.92 (m, 1 H), 3.06–3.12
(m, 1 H), 3.81 (t, J = 7.2 Hz, 2 H), 3.96–4.09 (m, 3 H), 4.39–4.41 (m,
1 H), 6.85–6.93 (m, 3 H), 7.04–7.08 (m, 1 H), 7.15–7.25 (m, 3 H), 7.42
(d, J = 8.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 26.2, 26.9,
28.1, 29.2, 29.3, 29.4, 30.8, 33.4, 40.8, 60.6, 68.1, 70.8, 92.6, 108.9,
111.8, 116.9, 118.3, 120.1, 121.8, 122.9, 125.4, 128.2, 134.0, 134.9,
155.3, 166.7 ppm. C27H33N3O3S (479.63): calcd. C 67.61, H 6.93, N
8.76; found C 67.78, H 6.88, N 8.72.
Na]+ 520.1956, found 520.1949.
Crystal Data for Macrocycle 6a: C28H35NO3S2, M = 497.69,
0.28 × 0.09 × 0.06 mm, orthorhombic, space group Pcba with a =
16.404(2) Å, b = 9.8784(12) Å, c = 31.474(4) Å, α = 90.00, ꢀ = 90.00,
(2), γ = 90.00, V = 5100.1(11) Å3, T = 150(2) K, R1 = 0.0756, wR2 =
0.1703 on observed data, z = 8, Dcalcd. = 1.296 mg cm–3, F(000) =
2128, Absorption coefficient: 0.239 mm–1, λ = 0.71073 Å, 5289 re-
flections were collected on a smart apex CCD single crystal diffrac-
tometer 4330 observed reflections [I ≥ 2σ(I)]. The largest difference
peak and hole: 0.843 and –0.341 e Å–3, respectively. The structure
was solved by direct methods and refined by full-matrix least-
squares on F2 using SHELXL-97 software.
Diazoamide 5n: Red thick oil (624 mg), yield 80 %. IR (neat): νmax
=
˜
2929, 2092, 1685, 1607, 1462, 1358, 1231, 1048, 746 cm–1. H NMR
(CDCl3, 400 MHz): δ = 1.25–1.42 (m, 10 H), 1.50–1.58 (m, 2 H), 1.66–
1.73 (m, 2 H), 1.81–1.91 (m, 2 H), 1.93 (s, 3 H), 2.90–2.93 (m, 1 H),
3.06–3.12 (m, 1 H), 3.80 (t, J = 7.2 Hz, 2 H), 3.96–4.08 (m, 3 H), 4.37–
1
Macrocycle 6b: White solid (78 mg), yield 83 %; m.p. 142–143 °C.
IR (neat): νmax = 2927, 2858, 1705, 1605, 1511, 1462, 1358, 1137,
˜
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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1
736 cm–1. H NMR (CDCl3, 400 MHz): δ = 0.61–0.70 (m, 1 H), 0.75–
7.54 (d, J = 9.2 Hz, 1 H), 7.55–7.60 (m, 1 H), 7.67 (d, J = 8.0 Hz, 1 H),
9.30 (d, J = 9.2 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 19.9,
22.8, 24.0, 27.2, 39.0, 52.8, 53.4, 63.5, 64.3, 79.1, 107.8, 112.0, 120.7,
0.87 (m, 1 H), 1.02–1.11 (m, 1 H), 1.20–1.45 (m, 8 H), 1.89–1.97 (m,
1 H), 2.84–2.93 (m, 1 H), 3.10–3.18 (m, 2 H), 3.55–3.64 (m, 2 H), 3.70
(s, 3 H), 3.98–4.12 (m, 2 H), 4.36–4.41 (m, 1 H), 4.95 (s, 1 H), 6.14 121.6, 123.4, 125.4, 125.9, 126.2, 128.0, 128.1, 128.3, 129.3, 129.7,
(dd, J1 = 8.4, J2 = 2.0 Hz, 1 H), 6.43 (d, J = 8.4 Hz, 1 H), 6.76 (d, J =
7.6 Hz, 1 H), 6.83 (d, J = 2.0 Hz, 1 H), 7.16 (t, J = 7.6 Hz, 1 H), 7.32
(td, J1 = 7.6, J2 = 0.8 Hz, 1 H), 8.58 (dd, J1 = 7.2, J2 = 0.8 Hz, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 22.3, 22.4, 24.9, 25.6, 25.7,
26.0, 33.0, 38.7, 52.0, 52.0, 55.9, 67.3, 108.9, 111.2, 115.6, 119.3,
121.9, 125.8, 128.5, 129.5, 131.1, 141.9, 146.1, 149.2, 173.4 ppm.
HRMS (ESI): calcd. for C26H31NO3S2 [M + Na]+ 492.1643, found
492.1640.
133.2, 141.4, 153.1, 180.5 ppm. HRMS (ESI): calcd. for C26H25NO3S
[M + Na]+ 454.1453, found 454.1454.
Macrocycle 6g: White solid (70 mg), yield 75 %; m.p. 214–215 °C.
IR (neat): νmax = 2925, 2852, 1706, 1609, 1512, 1467, 1260, 1143,
˜
1
736 cm–1. H NMR (CDCl3, 400 MHz): δ = 0.83–0.93 (m, 1 H), 1.56–
1.26 (m, 1 H), 1.35–1.51 (m, 2 H), 1.61–1.69 (m, 1 H), 1.78–1.86 (m,
1 H), 2.94–2.97 (m, 1 H), 3.17–3.24 (m, 2 H), 3.48–3.63 (m, 2 H), 3.91–
4.04 (m, 2 H), 4.25–4.30 (m, 1 H), 4.96 (s, 1 H), 6.51 (d, J = 7.6 Hz, 1
H), 6.56 (d, J = 8.0 Hz, 1 H), 6.68 (dd, J1 = 8.0, J2 = 1.6 Hz, 1 H), 6.82
(t, J = 7.6 Hz, 1 H), 6.91 (s, 1 H), 7.10 (t, J = 7.6 Hz, 1 H), 7.20 (t, J =
7.6 Hz, 1 H), 8.34 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 22.3, 25.5, 26.1, 30.0, 31.8, 40.6, 50.6, 52.8, 68.9, 108.3, 119.0,
120.3, 121.4, 122.0, 125.6, 128.5, 128.6, 130.7, 137.7, 141.9, 158.3,
174.4 ppm. HRMS (ESI): calcd. for C22H23NO2S2 [M + Na]+ 420.1068,
found 420.1070.
Macrocycle 6c: White solid (78 mg), yield 82 %; m.p. 175–176 °C.
IR (neat): νmax = 2926, 2854, 1706, 1605, 1513, 1462, 1262, 1140,
˜
1
735 cm–1. H NMR (CDCl3, 400 MHz): δ = 0.80–0.88 (m, 2 H), 1.06–
1.28 (m, 15 H), 1.43–1.58 (m, 2 H), 1.68–1.73 (m, 1 H), 2.61 (d, J =
14.0 Hz, 1 H), 3.10–3.17 (m, 1 H), 3.33–3.38 (m, 1 H), 3.65–3.68 (m,
1 H), 3.70 (s, 3 H), 3.79–3.85 (m, 2 H), 4.30 (td, J1 = 12.4, J2 = 2.0 Hz,
1 H), 4.66 (d, J = 13.2 Hz, 1 H), 5.22 (s, 1 H), 6.38 (d, J = 1.2 Hz, 1
H), 6.55 (d, J = 8.4 Hz, 1 H), 6.66–6.69 (m, 2 H), 7.09–7.13 (m, 1 H),
7.22–7.26 (m, 1 H), 8.00 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 24.3, 24.7, 25.0, 25.7, 26.3, 26.5, 26.8, 27.2, 27.2, 27.8,
39.8, 51.9, 56.0, 67.8, 70.4, 84.9, 108.7, 110.1, 112.0, 120.6, 122.1,
125.1, 128.4, 129.2, 131.3, 142.5, 147.6, 149.4, 172.8 ppm. HRMS
(ESI): calcd. for C30H39NO4S [M + H]+ 510.2678, found 510.2676.
Macrocycle 6h: White solid (74 mg), yield 79 %; m.p. 186–187 °C.
IR (neat): νmax = 2927, 2865, 1702, 1605, 1487, 1352, 1237, 1167,
˜
1
730 cm–1. H NMR (CDCl3, 400 MHz): δ = 0.82–0.89 (m, 1 H), 1.12–
1.19 (m, 1 H), 1.27–1.33 (m, 1 H), 1.56–1.64 (m, 1 H), 1.73–1.91 (m,
4 H), 2.04–2.12 (m, 1 H), 2.38–2.43 (m, 1 H), 2.69–2.73 (m, 1 H), 3.06–
3.19 (m, 2 H), 3.25–3.30 (m, 1 H), 3.84–3.91 (m, 1 H), 4.04–4.15 (m,
2 H), 4.28–4.35 (m, 1 H), 5.24 (s, 1 H), 6.59 (d, J = 8.4 Hz, 1 H), 6.63–
6.66 (m, 2 H), 6.89 (t, J = 7.6 Hz, 1 H), 6.94 (td, J1 = 8.4, J2 = 1.2 Hz,
1 H), 7.08 (t, J = 7.6 Hz, 1 H), 7.16 (dd, J1 = 7.6, J2 = 1.2 Hz, 1 H),
7.39 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 23.1,
25.0, 25.0, 26.5, 28.9, 33.3, 37.5, 38.0, 53.6, 59.2, 67.4, 108.5, 110.7,
119.3, 121.8, 126.5, 127.3, 128.0, 128.2, 128.6, 131.8, 141.65, 153.7,
177.2 ppm. HRMS (ESI): calcd. for C24H27NO2S2 [M + Na]+ 448.1381,
found 448.1362.
Macrocycle 6d: White solid (74 mg), yield 78 %; m.p. 238–239 °C.
IR (neat): νmax = 2925, 2859, 1698, 1603, 1463, 1352, 1240, 1070,
˜
1
740 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.32–1.49 (m, 7 H), 1.63–
1.77 (m, 4 H), 1.87–1.96 (m, 1 H), 2.07–2.18 (m, 1 H), 2.42–2.47 (m,
1 H), 2.61–2. 65 (m, 1 H), 2.97–3.01 (m, 1 H), 3.32–3.38 (m, 1 H),
3.63–3.71 (m, 2 H), 3.94–4.00 (m, 2 H), 4.15–4.22 (m, 1 H), 6.11 (s, 1
H), 6.40 (td, J1 = 7.6, J2 = 0.4 Hz, 1 H), 6.64 (d, J = 8.0 Hz, 1 H), 7.23
(d, J = 7.6 Hz, 1 H), 6.95 (td, J1 = 8.0, J2 = 1.2 Hz, 1 H), 7.04 (d, J =
8.8 Hz, 1 H), 7.33 (td, J1 = 8.0, J2 = 0.8 Hz, 1 H), 7.55–7.61 (m, 2 H),
7.67 (d, J = 8.4 Hz, 1 H), 9.25 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 23.3, 23.8, 25.1, 25.2, 26.0, 26.3, 28.0, 30.7,
34.4, 34.7, 40.3, 50.0, 62.6, 69.4, 108.0, 114.1, 119.6, 121.7, 121.8,
123.5, 123.7, 125.2, 126.4, 128.2, 128.3, 128.8, 129.5, 129.5, 129.8,
133.9, 141.7, 153.1, 175.8 ppm. HRMS (ESI): calcd. for C30H33NO2S2
[M + H]+ 504.2031, found 504.2050.
Macrocycle 6i: White solid (75 mg), yield 80 %; m.p. 193–194 °C. IR
(neat): νmax = 2922, 2857, 1698, 1603, 1482, 1355, 1234, 1172, 1057,
˜
1
737 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.33–1.41 (m, 1 H), 1.64–
1.84 (m, 3 H), 1.95–2.03 (m, 1 H), 2.12–2.30 (m, 3 H), 2.40 (s, 3 H),
3.00–3.13 (m, 3 H), 3.37–3.43 (m, 1 H), 3.61–3.69 (m, 1 H), 3.82–3.85
(m, 1 H), 3.96–4.01 (m, 1 H), 4.09–4.15 (m, 1 H), 6.53 (d, J = 8.0 Hz,
1 H), 6.63–6.73 (m, 3 H), 6.94 (td, J1 = 8.4, J2 = 1.2 Hz, 1 H), 7.03 (t,
J = 6.8 Hz, 1 H), 7.52 (s, 1 H), 7.84 (dd, J1 = 8.0, J2 = 1.2 Hz, 1 H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 22.8, 23.7, 23.3, 24.8, 28.7, 29.6, 31.3,
38.6, 60.5, 62.9, 66.2, 108.0, 111.4, 119.3, 121.0, 125.6, 127.8, 128.0,
129.7, 130.0, 132.2, 141.3, 156.2, 174.3 ppm. HRMS (ESI): calcd. for
Macrocycle 6e: White solid (76 mg), yield 80 %; m.p. 239–240 °C.
IR (neat): νmax = 2923, 2855, 1705, 1462, 1352, 1239, 1096, 1042,
˜
1
743 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.26–1.45 (m, 7 H), 1.62–
1.84 (m, 6 H), 3.21–3.29 (m, 2 H), 3.43–3.48 (m, 1 H), 3.42–3.48 (m,
1 H), 3.89–3.94 (m, 1 H), 4.03–4.08 (m, 1 H), 4.15–4.22 (m, 1 H), 4.33–
4.00 (m, 1 H), 4.00–4.49 (m, 1 H), 6.14 (s, 1 H), 6.42 (t, J = 7.6 Hz, 1
H), 6.61 (d, J = 7.6 Hz, 1 H), 6.72 (d, J = 7.6 Hz, 1 H), 6.96 (td, J1 =
7.6, J2 = 0.8 Hz, 1 H), 7.01 (d, J = 8.8 Hz, 1 H), 7.33 (t, J = 6.8 Hz, 1
H), 7.49–7.53 (m, 1 H), 7.61 (d, J = 8.8 Hz, 1 H), 7.17 (d, J = 8.0 Hz,
1 H), 9.30 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ =
23.3, 24.8, 25.0, 25.9, 26.0, 26.4, 27.6, 29.3, 40.3, 52.7, 64.0, 70.9, 76.9,
108.0, 115.9, 121.7, 123.7, 125.9, 126.5, 128.1, 128.5, 129.0, 129.8,
130.3, 133.2, 142.7, 155.2, 177.5 ppm. HRMS (ESI): calcd. for
C30H33NO3S [M + Na]+ 488.2259, found 488.2260.
C
24H27NO2S2 [M + H]+ 426.1561, found 426.1567.
General Procedure for Tetracyclic Macrocycles 7a–e: Rhodium(II)
acetate dimer (1 mol-%) catalyst was added to a stirred solution of
dry benzene (5 mL) under nitrogen atmosphere at reflux conditions.
An appropriate solution of diazoamides 5j–n (100 mg, 1.0 mmol) in
dry benzene (5 mL) was added dropwise over 30–60 min. Then, the
reaction was monitored using TLC. The solvent was removed under
reduced pressure after the reaction was completed. The residue
was subjected to silica gel column (100–200 mesh) chromatography
using hexanes/EtOAc to furnish respective tetracyclic macrocycles
7a–e.
Macrocycle 6f: White solid (72 mg), yield 76 %; m.p. 218–219 °C. IR
(neat): ν
= 2925, 2856, 1702, 1605, 1462, 1353, 1237, 1095,
˜
max
1
746 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.47–1. 54 (m, 1 H), 1.62–
1.87 (m, 4 H), 1.96–2.04 (m, 1 H), 3.13–3.21 (m, 1 H), 3.28–3.42 (m,
2 H), 3.69–3.73 (m, 1 H), 4.07–4.11 (m, 1 H), 4.20–4.34 (m, 2 H), 4.48–
4.55 (m, 1 H), 5.98 (s, 1 H), 6.29 (t, J = 7.6 Hz, 1 H), 6.49 (d, J =
7.6 Hz, 1 H), 6.62 (d, J = 7.6 Hz, 1 H), 6.86 (d, J = 9.2 Hz, 1 H), 6.92
(td, J1 = 7.6, J2 = 0.8 Hz, 1 H), 7.34 (td, J1 = 7.6, J2 = 0.8 Hz, 1 H),
Tetracyclic Macrocycle 7a: White solid (86 mg), yield 92 %; m.p.
211–212 °C. IR (neat): νmax = 3454, 2930, 2858, 1708, 1601, 1464,
˜
1350, 1301, 1235, 1042, 752 cm–1
.
1H NMR (CDCl3, 400 MHz): δ =
1.13–1.61 (m, 2 H), 1.66–1.77 (m, 2 H), 1.80–1.92 (m, 2 H), 2.51–2.68
(m, 2 H), 3.38–3.45 (m, 2 H), 3.70–3.77 (m, 1 H), 3.88–3.99 (m, 2 H),
3.92 (d, J = 2.4 Hz, 1 H), 4.03 (d, J = 2.4 Hz, 1 H), 4.21–4.28 (m, 1 H),
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4.26 (s, 1 H), 6.80–6.86 (m, 3 H), 7.10 (t, J = 7.6 Hz, 1 H), 7.16 (dd,
J1 = 7.6, J2 = 1.6 Hz, 1 H), 7.22 (td, J1 = 8.4, J2 = 2.0 Hz, 1 H), 7.28
(t, J = 7.6 Hz, 1 H), 7.44 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 24.2, 27.0, 27.8, 30.2, 40.9, 46.1, 66.3, 68.2, 86.1, 108.7,
1.6 Hz, 1 H), 7.29 (t, J = 7.8 Hz, 1 H), 7.36–7.39 (m, 2 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 22.67, 25.87, 26.16, 27.08, 28.31, 28.49,
28.72, 29.18, 29.72, 44.64, 67.29, 68.27, 87.58, 108.69, 111.96, 119.89,
122.68, 125.30, 125.44, 126.14, 129.18, 129.44, 143.56, 156.65,
112.5, 120.3, 123.0, 125.3, 127.3, 127.7, 129.3, 129.8, 130.4, 143.9, 157.60, 175.55 ppm. HRMS (ESI): calcd. for C28H35NO3S [M + Na]+
156.5, 159.4, 174.4 ppm. HRMS (ESI): calcd. for C23H25NO3S [M + H]+ 466.2416, found 466.2410.
396.1633, found 396.1630.
Compound 8a: White solid, yield 83 %; m.p. 191–192 °C. IR (neat):
Crystal Data for Tetracyclic Macrocycle 7a: C23H25NO3S, M =
νmax = 2928, 2850, 1691, 1605, 1484, 1367, 1234, 1171, 1059,
˜
1
395.50, 0.45 × 0.32 × 0.24 mm, triclinic, space group P1 with a =
751 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.76–1.80 (m, 1 H), 2.02–
¯
8.6848(7) Å, b = 9.7801(8) Å, c = 12.7044(11) Å, α = 107.8050(10),
ꢀ = 93.5390(10), γ = 94.2270(10), V = 1020.57(15) Å3, T = 273(2) K,
R1 = 0.0357, wR2 = 0.0893 on observed data, z = 2, Dcalcd. = 1.287 mg
cm–3, F(000) = 420, Absorption coefficient: 0.182 mm–1, λ =
2.10 (m, 1 H), 2.19 (s, 3 H), 2.48 (d, J = 13.2 Hz, 1 H), 3.51–3.58 (m,
2 H), 4.31–4.48 (m, 4 H), 4.62 (t, J = 10.8 Hz, 1 H), 6.52–6.57 (m, 2
H), 6.64 (t, J = 7.6 Hz, 1 H), 6.74 (t, J = 7.6 Hz, 1 H), 6.97 (t, J =
7.6 Hz, 1 H), 6.70 (t, J = 7.6 Hz, 1 H), 7.49 (d, J = 8.0 Hz, 1 H), 7.61
0.71073 Å, 4360 reflections were collected on a smart apex CCD (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 17.4, 21.3,
single crystal diffractometer 4083 observed reflections [I ≥ 2σ(I)].
23.5, 39.3, 54.7, 60.7, 66.3, 78.1, 108.4, 110.8, 114.1, 120.4, 127.7,
The largest difference peak and hole: 0.300 and –0.233 e Å–3, re- 128.1, 129.1, 130.3, 133.2, 135.3, 140.3, 152.2, 174.8 ppm. HRMS
spectively. The structure was solved by direct methods and refined
(ESI): calcd. for C21H21NO3S [M + H]+ 368.1320, found 368.1329.
by full-matrix least-squares on F2 using SHELXL-97 software.
Compound 8b: White solid, yield 85 %; m.p. 183–184 °C. IR (neat):
Tetracyclic Macrocycle 7b: White solid (83 mg), yield 88 %; m.p.
ν
= 2923, 2855, 1696, 1606, 1480, 1358, 1230, 1170, 1054,
˜
max
1
208–209 °C. IR (neat): νmax = 3456, 2931, 2857, 1706, 1602, 1464,
736 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.74–1.78 (m, 1 H), 1.99–
˜
1348, 1306, 1232, 1038, 753 cm–1
.
1H NMR (CDCl3, 400 MHz): δ =
2.08 (m, 1 H), 2.17 (s, 3 H), 2.48 (d, J = 13.6 Hz, 1 H), 3.46–3.49 (m,
1.39–1.56 (m, 2 H), 1.67–1.89 (m, 4 H), 2.52–2.69 (m, 2 H), 3.35–4.41 2 H), 4.31–4.46 (m, 4 H), 4.60 (t, J = 12.4 Hz, 1 H), 6.40 (d, J = 8.0 Hz,
(m, 1 H), 3.45–3.50 (m, 1 H), 3.75–3.82 (m, 1 H), 3.89–3.99 (m, 2 H),
4.00 (d, J = 2.4 Hz, 1 H), 4.04 (d, J = 2.4 Hz, 1 H), 4.21–4.28 (m, 1 H),
4.26 (s, 1 H), 6.78 (d, J = 8.4 Hz, 1 H), 6.81 (d, J = 8.4 Hz, 1 H), 6.86
(td, J1 = 7.2, J2 = 0.4 Hz, 1 H), 7.17–7.28 (m, 3 H), 7.44 (d, J = 0.8 Hz,
1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 24.2, 27.0, 27.6, 30.2, 41.1,
45.9, 66.1, 68.1, 86.2, 109.6, 112.5, 120.4, 125.6, 127.6, 128.5, 129.0,
129.3, 129.9, 130.4, 142.41, 156.5, 159.4, 174.0 ppm. HRMS (ESI):
calcd. for C23H24ClNO3S [M + Na]+ 452.1063, found 452.1059.
1 H), 6.56 (d, J = 8.0 Hz, 1 H), 6.72 (t, J = 7.6 Hz, 1 H), 6.93 (t, J =
7.2 Hz, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 7.49 (d, J = 7.6 Hz, 1 H), 7.71
(s, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 17.4, 21.3, 23.5, 39.4,
54.7, 60.7, 66.2, 78.1, 108.4, 110.8, 114.0, 120.4, 127.7, 128.1, 129.1,
130.3, 133.2, 135.3, 140.3, 152.2, 174.8 ppm. HRMS (ESI): calcd. for
C
21H20BrNO3S [M + H]+ 446.0426, found 446.0418.
General Procedure for Ring-Opening Reaction of Tetracyclic
Macrocycles 7a–d: To a solution of the appropriate tetracyclic
macrocycles 7a–d (100 mg, 1.0 mmol) in DCM (5 mL) at room tem-
perature was added a drop of water. This reaction mixture was
stirred for 10 min. The reaction was diluted with equal amount of
Tetracyclic Macrocycle 7c: White solid (84 mg), yield 90 %; m.p.
243–244 °C. IR (neat): νmax = 3456, 2933, 2862, 1706, 1606, 1460,
˜
1348, 1302, 1228, 1040, 754 cm–1
.
1H NMR (CDCl3, 400 MHz): δ =
1.34–1.50 (m, 4 H), 1.64–1.78 (m, 4 H), 2.58–2.71 (m, 2 H), 3.34–3.40 water and ethyl acetate. The aqueous phase was extracted. The
(m, 1 H), 3.54–3.61 (m, 1 H), 3.70–3.77 (m, 1 H), 3.84–3.94 (m, 3 H),
4.09 (s, 1 H) 4.18–4.25 (m, 1 H), 4.27 (s, 1 H), 6.79–6.86 (m, 3 H), 7.11
(t, J = 7.6 Hz, 1 H), 7.19 (t, J = 6.4 Hz, 2 H), 7.29 (t, J = 7.6 Hz, 1 H),
combined organic extracts were washed with brine, desiccated with
Na2SO4 and the solvent removed under reduced pressure. The
crude product was purified by column chromatography on silica
7.45 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 26.4, gel using hexane/EtOAc as an eluent to obtain ring-opening prod-
26.7, 27.0, 27.8, 28.8, 40.5, 46.0, 66.5, 68.7, 86.1, 108.8, 113.7, 120.5, ucts 13a–d.
123.0, 125.3, 126.9, 127.9, 129.2, 129.7, 130.3, 143.7, 156.6, 159.1,
Compound 13a: Colourless thick oil (90 mg), yield 90 %. IR (neat):
174.7 ppm. HRMS (ESI): calcd. for C24H27NO3S [M + H]+ 410.1790,
νmax = 3459, 2932, 2866, 1709, 1604, 1459, 1355, 1300, 1240, 1044,
˜
found 410.1784.
1
754 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.54–1.62 (m, 2 H), 1.75–
Tetracyclic Macrocycle 7d: White solid (77 mg), yield 82 %; m.p.
1.83 (m, 2 H), 1.87–1.94 (m, 2 H), 2.57 (s, 3 H), 2.85–2.92 (m, 1 H),
2.97–3.03 (m, 1 H), 3.72–3.89 (m, 5 H), 4.05 (t, J = 6.4 Hz, 2 H), 4.40
(s, 1 H), 6.84 (d, J = 8.0 Hz, 1 H), 6.92 (d, J = 8.4 Hz, 1 H), 6.97 (t, J =
231–232 °C. IR (neat): νmax = 3458, 2931, 2857, 1701, 1608, 1467,
˜
1352, 1307, 1236, 1040, 750 cm–1
.
1H NMR (CDCl3, 400 MHz): δ =
1.26–1.50 (m, 10 H), 1.63–1.75 (m, 4 H), 2.84–2.93 (m, 2 H), 3.34– 7.2 Hz, 1 H), 7.10 (t, J = 7.6 Hz, 1 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.41–
3.50 (m, 1 H), 3.87–4.00 (m, 4 H), 4.07–4.14 (m, 1 H), 4.23 (d, J = 7.45 (m, 2 H), 7.71 (dd, J1 = 7.6, J2 = 1.6 Hz, 1 H) ppm. 13C NMR
1.6 Hz, 1 H), 4.29 (s, 1 H), 4.46 (d, J = 1.6 Hz, 1 H), 6.82–6.88 (m, 3
H), 7.07 (t, J = 7.6 Hz, 1 H), 7.21 (t, J = 8.0 Hz, 1 H), 7.26–7.31 (m, 2
H), 7.39 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ =
25.4, 26.0, 27.1, 27.5, 27.8, 28.2, 28.6, 40.0, 45.0, 67.1, 68.4, 87.2,
108.7, 112.8, 120.1, 122.7, 125.3, 125.7, 126.9, 129.2, 129.4, 129.7,
143.7, 156.6, 158.0, 175.2 ppm. HRMS (ESI): calcd. for C27H33NO3S
[M + Na]+ 474.2079, found 474.2073.
(CDCl3, 100 MHz): δ = 23.6, 27.1, 28.8, 32.0, 35.7, 40.2, 45.4, 62.2,
68.1, 108.6, 112.3, 120.5, 123.1, 125.6, 126.2, 128.3, 129.2, 130.4,
133.7, 142.9, 158.3, 177.0, 199.9 ppm. HRMS (ESI): calcd. for
C23H27NO4S [M + H]+ 414.1739, found 414.1738.
Compound 13b: Colourless thick oil (94 mg), yield 94 %. IR (neat):
νmax = 3419, 2925, 2859, 1703, 1598 1479, 1348, 1292, 1164, 1056,
˜
1
755 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.52–1.60 (m, 2 H), 1.73–
Tetracyclic Macrocycle 7e: White solid (75 mg), yield 79 %; m.p.
1.80 (m, 2 H), 1.87–1.94 (m, 2 H), 2.58 (s, 3 H), 2.86–2.92 (m, 1 H),
2.98–3.04 (m, 1 H), 3.72–3.83 (m, 5 H), 4.05 (t, J = 6.4 Hz, 2 H), 4.40
(s, 1 H), 6.76 (d, J = 8.4 Hz, 1 H), 6.92 (d, J = 8.4 Hz, 1 H), 6.98 (t, J =
204–205 °C. IR (neat): νmax = 3453, 2932, 2855, 1705, 1604, 1460,
˜
1356, 1307, 1237, 1040, 757 cm–1
.
1H NMR (CDCl3, 400 MHz): δ =
1.20–1.50 (m, 12 H), 1.63–1.76 (m, 4 H), 2.91–2.97 (m, 1 H), 3.07– 7.6 Hz, 1 H), 7.27 (d, J = 6.8 Hz, 1 H), 7.41–7.45 (m, 2 H), 7.71 (d, J =
3.14 (m, 1 H), 3.35–3.41 (m, 1 H), 3.87–4.00 (m, 4 H), 4.09–4.16 (m,
1 H), 4.30 (s, 1 H), 4.33 (d, J = 2.0 Hz, 1 H), 4.61 (d, J = 2.0 Hz, 1 H),
6.8 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 23.5, 27.0, 28.8,
31.9, 35.7, 40.3, 45.3, 62.2, 68.1, 109.5, 112.3, 120.6, 126.0, 127.9,
128.4, 128.55, 129.2, 130.4, 133.6, 141.4, 158.2, 176.6, 199.9 ppm.
6.82–6.89 (m, 3 H), 7.06 (t, J = 7.2 Hz, 1 H), 7.22 (td, J1 = 8.0, J2
=
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HRMS (ESI): calcd. for C23H26ClNO4S [M + H]+ 448.1349, found
448.1338.
Acknowledgments
This research was supported by the Department of Science and
Technology (DST), New Delhi. K. S. thanks University Grants
Commission (UGC), New Delhi (Research Fellowship in Sciences
for Meritorious Students). The authors thank DST for providing
Compound 13c: Colourless thick oil (92 mg), yield 92 %. IR (neat):
νmax = 3419, 2930, 2861, 1674, 1603, 1457, 1358, 1294, 1238, 1047,
˜
1
756 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.43–1.59 (m, 4 H), 1.69–
1.77 (m, 2 H), 1.82–1.89 (m, 3 H), 2.61 (s, 3 H), 2.85–2.91 (m, 1 H), the 400 MHz NMR facility under the FIST program.
2.97–3.01 (m, 1 H), 3.67–3.88 (m, 4 H), 4.05 (t, J = 6.4 Hz, 2 H), 4.39
(s, 1 H), 6.84 (d, J = 8.0 Hz, 1 H), 6.92 (d, J = 8.4 Hz, 1 H), 6.97 (t, J =
7.6 Hz, 1 H), 7.10 (t, J = 7.2 Hz, 1 H), 7.30 (t, J = 8.0 Hz, 1 H), 7.41–
7.44 (m, 2 H), 7.71 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 25.9, 26.6, 27.2, 29.1, 32.0, 35.6, 40.3, 45.4, 62.1, 68.3,
108.6, 112.3, 120.5, 123.1, 125.5, 126.2, 128.4, 129.2, 130.4, 133.6,
143.0, 158.4, 176.9, 199.9 ppm. HRMS (ESI): calcd. for C24H29NO4S
[M + Na]+ 450.1715, found 450.1712.
Keywords: Diastereoselectivity · Rhodium · Regioselectivity ·
Ylides · Sulfur heterocycles · Macrocycles · Cyclization
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Compound 13d: Colourless thick oil (89 mg), yield 89 %. IR (neat):
νmax = 3424, 2926, 2856, 1674, 1602, 1458, 1357, 1293, 1236, 1018,
˜
752 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = δ = 1.26–1.49 (m, 9 H),
1.67–1.75 (m, 3 H), 1.80–1.87 (m, 2 H), 2.62 (s, 3 H), 2.85–2.91 (m, 1
H), 2.97–3.02 (m, 1 H), 3.70 (t, J = 7.6 Hz, 2 H), 3.82 (s, 3 H), 4.05 (t,
J = 6.4 Hz, 2 H), 4.39 (s, 1 H), 6.84 (d, J = 8.0 Hz, 1 H), 6.90–6.99 (m,
2 H), 7.09 (t, J = 7.6 Hz, 1 H), 7.26–7.32 (m, 1 H), 7.41–7.45 (m, 2 H),
7.73 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 26.2,
26.8, 27.3, 29.1, 29.2, 29.3, 32.0, 35.7, 40.5, 45.5, 62.2, 68.5, 108.7,
112.3, 120.4, 123.0, 125.5, 126.3, 128.4, 129.2, 130.4, 133.6, 143.1,
158.5, 176.9, 200.0 ppm. HRMS (ESI): calcd. for C27H35NO4S [M +
Na]+ 492.2184, found 492.2173.
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278–295.
Compound 16a: White solid (72 mg), yield 72 %; m.p. 172–173 °C.
IR (neat): νmax = 3451, 2927, 2854, 1701, 1605, 1470, 1347, 1308,
˜
1
1231, 1044, 754 cm–1. H NMR (CDCl3, 400 MHz): δ = 2.91–2.98 (m,
1 H), 3.17–3.25 (m, 1 H), 3.61–3.71 (m, 2 H), 4.37 (d, J = 16.0 Hz, 1
H), 5.07 (d, J = 16.4 Hz, 1 H), 5.10 (s, 1 H), 6.38 (d, J = 7.6 Hz, 1 H),
6.42–6.44 (m, 2 H), 6.96–7.26 (m, 10 H), 8.58 (d, J = 8.0 Hz, 1 H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 25.8, 32.7, 43.7, 52.2, 52.2, 109.8,
122.3, 125.8, 126.2, 127.1, 127.2, 128.3, 128.6, 128.7, 128.9, 130.6,
134.6, 137.1, 141.4, 173.4 ppm. HRMS (ESI): calcd. for C24H21NOS2
[M + H]+ 404.1143, found 404.1148.
Compound 16b: White solid (18 mg), yield 18 %; m.p. 174–175 °C.
IR (neat): νmax = 3450, 2928, 2855, 1700, 1606, 1469, 1347, 1308,
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˜
1
1230, 1044, 755 cm–1. H NMR (CDCl3, 400 MHz): δ = 2.71–2.75 (m,
1 H), 3.12–3.14 (m, 1 H), 3.44–3.50 (m, 1 H), 4.18–4.25 (m, 1 H), 4.66
(d, J = 16.0 Hz, 1 H), 4.83 (s, 1 H), 4.93 (d, J = 15.6 Hz, 1 H), 6.38 (d,
J = 7.2 Hz, 1 H), 6.97–7.11 (m, 9 H), 7.20–7.22 (m, 3 H), 7.39 (d, J =
7.2 Hz, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 26.3, 32.2, 43.5,
47.3, 51.9, 109.1, 122.3, 123.8, 127.1, 127.3, 127.9, 128.1, 128.5, 128.6,
128.7, 129.1, 135.4, 137.1, 141.8, 174.6 ppm. HRMS (ESI): calcd. for
C24H21NOS2 [M + H]+ 404.1143, found 404.1150.
CCDC 1437706 (for 6a) and 1437707 (for 7a) contain the supple-
mentary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre.
Supporting Information (see footnote on the first page of this
article): Copies of 1H, 13C and DEPT-135 NMR spectra for selected
compounds.
Received: January 4, 2016
Published Online: March 9, 2016
Eur. J. Org. Chem. 2016, 1849–1859
www.eurjoc.org
1859
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim