Diversity-Oriented Approach to Normuscopyridine and Its Analogues through Ring-Closing Metathesis

Article abstract of DOI:10.1002/ejoc.201301493

Ring-closing metathesis (RCM) is a useful protocol for assembling macrocycles. To synthesize normuscopyridine, and its analogues we used RCM as a key step in our strategy. Our approach to the synthesis of pyridine macrocycles involves two routes. The first approach starts with alkenylation of 2,6-bis[(phenylsulfonyl)methyl]pyridine and involves five steps with 10 % overall yield. The second route begins with Grignard addition to pyridine-2,6-dicarbo nitrile, followed by RCM and one-pot removal of the carbonyl group before hydrogenation of the double bond in 28 % overall yield. This approach has only three steps. Neither route involves the use of protecting groups. Various points of diversification are embedded in our strategy and eight different cyclophanes were assembled by adopting a general approach to these macrocyclics. Various derivatives of muscopyridine, which is an important constituent for the perfumery industry, were assembled through ring-closing metathesis and include points for diversification that allow for variation in chain length. Reduction of carbonyl and double bonds was successfully effected in one step. Neither route involves use of protecting groups. Eight different cyclophanes were assembled.

Full text of DOI:10.1002/ejoc.201301493

FULL PAPER
DOI: 10.1002/ejoc.201301493
Diversity-Oriented Approach to Normuscopyridine and Its Analogues through
Ring-Closing Metathesis[‡]
Sambasivarao Kotha,*[a][‡‡] Gopalkrushna T. Waghule,[a][‡‡] and Mukesh E. Shirbhate[a][‡‡]
Keywords: Macrocycles / Cyclophanes / Fragrances / Metathesis / Reduction
Ring-closing metathesis (RCM) is a useful protocol for as-
sembling macrocycles. To synthesize normuscopyridine, and
its analogues we used RCM as a key step in our strategy. Our
approach to the synthesis of pyridine macrocycles involves
two routes. The first approach starts with alkenylation of 2,6-
bis[(phenylsulfonyl)methyl]pyridine and involves five steps
with 10% overall yield. The second route begins with Grig-
nard addition to pyridine-2,6-dicarbo nitrile, followed by
RCM and one-pot removal of the carbonyl group and hy-
drogenation of the double bond in 28% overall yield. This
approach has only three steps. Neither route involves the use
of protecting groups. Various points of diversification are em-
bedded in our strategy and eight different cyclophanes were
assembled by adopting a general approach to these macro-
cyclics.
Introduction
Results and Discussion
Musk is an important component of the perfumery in-
dustry. It is obtained from musk deer (Moschus moschif-
erus). Muscone and muscopyridine are the major products
whereas musk xylene, musk ambrette, musk ketone, diphen-
hydramine, and imipramine are minor products of musk.[1]
Although, several efforts have been directed toward the
preparation of these products synthetically, only a few re-
ports are available for the synthesis of normuscopyridine
and its analogues.[2,3] In view of our interest in devising new
strategies for assembling cyclophanes[4] and different
macrocycles,[5] it was considered useful to synthesize vari-
ous analogues of muscopyridine by using a general strategy.
Moreover, some of the earlier studies on normuscopyridine
synthesis are not general in nature and result in low yields.
Introducing a stereodirecting sulfone group at the α-posi-
tion of the aryl ring or changing the hybridization of the
carbon atom from sp3 to sp2 at this position may facilitate
the ring-closing metathesis (RCM) protocol by steering the
alkenyl chain into a favorable conformation. This approach
also provides an opportunity to introduce alkenyl moieties
of variable chain length in a stepwise manner. If required
the additional functionality available here can be used as
a handle for further synthetic manipulation. Consequently,
symmetrical and unsymmetrical alkenylated aryl derivatives
suitable for RCM can be assembled.
Our diversity-oriented approach to meta-pyridinophanes
and their analogues starts with arylsulfonylmethyl aro-
matics such as 2 that are derived from meta-substituted
benzylic halides 1.[6]
These sulfones may be alkenylated either in a stepwise
manner to generate mono alkenyl compounds 3 or, alterna-
tively by dialkenylation leading to symmetrically function-
alized bis-sulfone 4, from which the RCM protocol may
generate cyclized product 5. Further, desulfonylation fol-
lowed by hydrogenation can provide an entry to meta-cy-
clophane derivatives, such as 6 (Figure 1). Alternatively,
alkylation of monoalkenyl derivative 3 with a different alk-
enyl halide can generate unsymmetrically functionalized
RCM precursors 7. Analogues of normuscopyridines, such
as 9, can be assembled by attaching an alkenyl chain of a
suitable length on one arm of compound 3 followed by
RCM[7] and removal of functional groups.
Our journey to normuscopyridine starts with treatment
of readily available 2,6-lutidine dibromide (1a) with sodium
benzenesulfinate to give 2,6-bis[(phenylsulfonyl)methyl]pyr-
idine (2a) in quantitative yield.[8] Later, pentenylation of bis
sulfone 2a with 5-bromo-1-pentene in the presence of NaH
gave an inseparable mixture of the cis and trans isomers 10
and 11. Because our target is devoid of stereogenic centers,
the configuration of the sulfonyl groups is of no conse-
quence, and, therefore, we have carried out the RCM with
the diastereoisomeric mixture in the presence of Grubbs
first-generation (G-I) catalyst to generate cyclophane 12
(51% yield) and dimeric cyclophane 13 (20% yield;
Scheme 1). The dimeric nature of 13 was confirmed by
HRMS data. No detailed characterization was carried out,
and compound 13 was directly used in the desulfonation
and hydrogenation sequence. To improve the monomer/di-
[‡] A portion of this work was presented at the 14th Tetrahedron
Symposium held in Vienna, Austria, June 25–28, 2013.
[a] Department of Chemistry, Indian Institute of Technology,
Bombay, Powai, Mumbai
E-mail: srk@chem.iitb.ac.in
http://www.chem.iitb.ac.in/~srk/
[‡‡]G. T. W. and M. E. S. made an equal contribution to the paper.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301493.
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Diversity-Oriented Approach to Normuscopyridine
Figure 1. Diversity-oriented approach to normuscopyridine and its analogues.
Scheme 1. Preparation of meta-pyridinophane derivatives 15 and 16.
mer selectivity, the RCM was tested in different solvents 1-hexene in presence of NaH gave unsymmetrically func-
such as CHCl3 and CCl4. In addition, the RCM was per- tionalized pyridine derivative 18 in 61% yield. The dia-
formed with Grubbs second-generation catalyst (G-II). stereoisomeric mixture of 18 was not separable through col-
However, G-I appears to be a better option for this purpose. umn chromatography. Further, RCM of 18 with G-I gave
After a considerable amount of experimentation on the de- monomeric cyclophane 19 (37% yield) and dimeric cy-
sulfonylation protocol,[9] bisulfone 12 was subjected to re- clophane 20 (25% yield; Scheme 2). Macrocyclic bis sulfone
duction in Mg/ethanol, aided by 1,2-dibromoethane in the 19 was desulfonylated by employing similar reaction condi-
presence of trimethylsilyl chloride (TMSCl) to generate cy- tions developed earlier to deliver 21 (78% yield). Subse-
clophane derivative 14 (80% yield). Further, hydrogenation quent, hydrogenation of 21 gave (2,6)-pyridinacyclododeca-
of the double bond in cyclophane 14 with 5% Pd/C under phane 22 (94% yield). Along similar lines, dimeric product
a H2 atmosphere gave normuscopyridine 15 (84% yield).
20 consisting of diastereoisomers was subjected to the de-
Under similar reaction conditions, dimeric product 13, sulfonation and hydrogenation sequence to generate pyrid-
consisting of diastereoisomers was directly subjected to a inophane 23 in 74% yield.
desulfonation and hydrogenation sequence to deliver
To expand this strategy to other cyclophane derivatives,
macrocyclic pyridinophane 16 in 64% yield (Scheme 1).
we chose commercially available bis benzylic bromide 1b as
To prepare an analogue of normuscopyridine, bisulfone a starting material.
2a was treated with 5-bromo-1-pentene to give monoalkyl-
Thus, 1,3-bis(bromomethyl)benzene 1b was treated with
ated product 17, which on further alkylation with 6-bromo- sodium benzenesulfinate in acetonitrile in the presence of
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S. Kotha, G. T. Waghule, M. E. Shirbhate
FULL PAPER
Scheme 2. Synthesis of meta-pyridinophanes 22 and 23.
tetrapropylammonium bromide as a phase-transfer catalyst
to deliver 1,3-bis[(phenylsulfonyl)methyl]benzene 2b in 87%
yield. Bis sulfone 2b was alkylated with 5-bromo-1-pentene
in the presence of NaH to give both a monopentenylated
and a dipentenylated product depending on the number of
equivalents of the electrophile employed. Thus, two dia-
stereoisomeric dipentenylated products 24 and 25 were pre-
pared from 2b, and these two diastereoisomers were sepa-
rated by column chromatography. syn-Isomer 24 was sub-
jected to the RCM protocol to deliver monomeric ring-clos-
ing product 26 in 51% yield. In contrast, anti-isomer 25
gave dimeric product 27 in 42% yield. The structure of the
dimer was supported by HRMS data (Scheme 3).
The syn relationship of the phenyl sulfonyl groups pres-
ent in cyclophane 26 was confirmed by single-crystal X-ray
data that clearly established that the two phenyl sulfonyl
groups are situated on the same side of the benzylic carbons
and that the double bond has a trans arrangement (Fig-
ure 2).[10]
Cyclophane 26 derived from 24 was subjected to desulf-
onylation and hydrogenation to deliver saturated cy-
clophane 29 in 92% yield. Dimeric cyclophane 27, con-
sisting of a mixture of diastereoisomers was also subjected
to desulfonation followed by hydrogenation to give macro-
cyclic cyclophane 30 in 78% yield (Scheme 4).
Previously, in our laboratory we prepared the RCM pre-
cursor 33 through diallyl Grignard addition to aldehyde 31
followed by oxidation. However, RCM of dione 33 failed to
give the cyclized product.[11] During these studies it oc-
curred to us that generation of a carbonyl derivative, such
as 33, directly without involvement of an oxidation step
Scheme 3. Synthesis of meta-cyclophanes 26 and 27.
would be a better choice (Scheme 5). To this end, dicyano nard addition can deliver the dicarbonyl derivative directly
precursors 34a–34b seemed a better option because Grig- and avoid double-bond-isomerized product 33a, which was
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Diversity-Oriented Approach to Normuscopyridine
Figure 2. The molecular crystal structure of 26 with 50% prob-
ability.
Scheme 5. Synthesis of diketo precursor 33. Dimethyl formamide
(DMF).
To realize the strategy shown in Figure 3, commercially
available pyridine-2,6-dicarbonitrile 34a was treated with 5-
bromo-1-pentene in presence of Mg/tetrahydrofuran (THF)
to give dicarbonyl compound 37 in 96% yield. RCM of 37
in the presence of G-II in toluene under reflux conditions
gave cyclized product 39 as a mixture of cis-trans isomers
(56% yield). Further, reduction of ring-closed compound
39 with 5% Pd/C gave a partially reduced, racemic alcohol.
Reduction of the carbonyl group as well as the double bond
present in cyclophane 39 was successfully carried out in
one-pot under Wolff–Kishner reduction conditions in ethyl-
ene glycol (EG) to generate normuscopyridine 15 in 53%
yield.
Scheme 4. Synthesis of meta-cyclophanes 29 and 30.
Along similar lines, the Grignard reagent derived from
observed during oxidation of diol 32 to dione 33. Later, 6-bromo-1-hexene was treated with dinitrile 34a, followed
addition of CaCO3 during pyridinium chlorochromate by RCM and a Wolff–Kishner reduction sequence gave cy-
(PCC) oxidation avoided isomerization of the double bond. clophane 41, bis-homologue of normuscopyridine in 51%
We also found that the RCM precursor containing a three- yield (Scheme 6).
or four-carbon alkenyl chain is not suitable for the RCM
protocol (Figure 3).
To expand the strategy to other macrocyclic cyclophane
derivatives containing a simple benzene moiety, commer-
Figure 3. Retrosynthetic approach to a cyclophane through dicyano compound 34a–34b.
Scheme 6. Synthesis of normuscopyridine 15 and analogue 41.
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S. Kotha, G. T. Waghule, M. E. Shirbhate
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Scheme 7. Synthesis of benzene analogues of normuscopyridine 29 and 46.
mass spectrometer. Anhydrous THF, was prepared by passing it
through a column of activated alumina, then by heating to reflux
over and distillation from P2O5, and then heated to reflux with Na/
benzophenone and distilled, and stored over sodium wire. An-
hydrous toluene was obtained by distillation from P2O5 and stored
over sodium wire. Other reagents and solvents were purchased from
commercial suppliers and used without further purification.
cially available isophthalonitrile 34b was treated with 5-
bromo-1-pentene in the presence of Mg/THF to give di-
carbonyl compound 42 in 83% yield. RCM of diolefin 42
was carried out in toluene with G-II to give ring-closing
product 44 in 66% yield. Subsequent Wolff–Kishner re-
duction gave saturated cyclophane 29 in 59% yield.
Along similar lines, the Grignard reagent derived from
6-bromo-1-hexene, was treated with dinitrile 34b, and sub-
sequent RCM and Wolff–Kishner reduction gave normus-
copyridine analogues 46 in 53% yield (Scheme 7).
Monopentenylation of 2a: To a suspension of NaH (37 mg,
1.55 mmol; 55% in oil) in THF was added 2,6-bis[(phenylsulfonyl)-
methyl]pyridine (2a; 200 mg, 0.51 mmol) dissolved in dry THF
(20 mL) dropwise over a period of 30 min. Then, the reaction mix-
ture was stirred at room temp. for 30 min. Later, 5-bromo-1-
pentene (115 mg, 0.77 mmol) dissolved in dry THF (20 mL) was
added dropwise over a period of 30 min. Further, the reaction mix-
ture was stirred at room temp. for 20 h under a nitrogen atmo-
sphere. At the conclusion of the reaction (TLC monitoring), the
reaction mixture was diluted with ethyl acetate. The organic layer
was washed with brine, dried with Na2SO4 and concentrated under
reduced pressure. The crude product was purified by column
chromatography (silica gel, 10% ethyl acetate/petroleum ether) to
afford 17 (136 mg, 58% yield) and trace quantity of 10 and 11 as
an inseparable mixture.
Conclusions
In summary, we have demonstrated a new and general
synthetic strategy for the synthesis of normuscopyridine
and related compounds. Normuscopyridine and its ana-
logues prepared here did not possess any perfumery smell.
Single crystal X-ray data of 26 clearly indicate that the
stereochemical orientation of the phenyl sulfonyl groups is
syn and that the geometry of the double bond is trans. The
presence of cis substituents at the α-carbon atom of the aryl
system restricts the freedom of the alkyl chain and thus
facilitates a conformation suitable for RCM to deliver the
macrocyclic cyclophane. The trans disposition of the sulf-
onyl groups facilitates dimer formation under the same
RCM conditions. These two new and simple protocols are
capable of producing a variety of macrocyclic cyclophanes
of varying chain length.
17: (136 mg, 58% yield), m.p. 165 °C. 1H NMR (400 MHz,
CDCl3): δ = 0.93–1.14 (m, 2 H), 1.75–1.99 (m, 2 H), 2.00–2.10 (m,
1 H), 2.14–2.34 (m, 1 H), 4.15 (dd, J1 = 4, J2 = 13 Hz, 1 H), 4.31
(S, 2 H), 4.90–4.96 (m, 2 H), 5.59–5.69 (m, 1 H), 7.36–7.69 (m, 13
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 25.9, 26.0, 26.8, 27.0,
33.3, 33.3, 72.6, 115.5, 115.6, 123.7, 124.9, 128.8, 129.1, 133.6,
133.7, 137.1, 137.4, 137.5, 137.6, 137.8, 152.6, 152.9 ppm. HRMS
(Q-ToF): calcd. for C24H26NS2O4 [M + H]+ 456.1303; found
456.1291. IR (neat): ν
= = 757, 1216, 1659, 3018 cm–1.
˜
max
Dipentenylation of 2a: To a suspension of NaH (49 mg, 2.06 mmol;
55% in oil) in THF was added 2,5-bis(phenylsulfonylmethyl)pyr-
idine (2a; 200 mg, 0.52 mmol) dissolved in dry THF (50 mL) drop-
wise over a period of 30 min. Then, the reaction mixture was stirred
at room temp. for 30 min. Then, 5-bromo-1-pentene (293 mg,
2.06 mmol) in THF was added dropwise over a period of 30 min.
Further, the reaction mixture was stirred at room temp. for 20 h
under a nitrogen atmosphere. At the conclusion of the reaction
(TLC monitoring), reaction was diluted with ethyl acetate. The or-
ganic layer was washed with brine, dried with Na2SO4 and concen-
trated under reduced pressure. The crude product was purified by
column chromatography (silica gel, 10% ethyl acetate/petroleum
ether) to afford an inseparable mixture of diastereoisomers 10 and
11 (1:1 ratio; 236 mg, 65% yield).
Experimental Section
General: Analytical TLC was performed on (10ϫ5 cm) glass plate
coated with silica gel G or GF 254 (containing 13% CaSO4 as a
binder). Visualization of the spots on the TLC plate was achieved
either by exposure to I2 vapor or UV light. Column chromatog-
raphy was performed with silica gel (100–200 mesh) and the col-
umn was usually eluted with an ethyl acetate and petroleum ether
(b.p. 60–80 °C) mixture. 1H NMR and 13C NMR spectroscopic
data were recorded with Bruker 400 spectrometers with tetrameth-
ylsilane (TMS) as an internal standard and CDCl3 as a solvent.
The coupling constants (J) are given in Hertz (Hz). Chemical shifts
are expressed in parts per million (ppm) downfield from the in-
ternal reference, TMS. The standard abbreviations, s, br. s, d, t, q,
m, dd and td, refer to singlet, broad singlet, doublet, triplet, quar-
tet, multiplet, doublet of doublets, and triplet of doublets, respec-
tively. Mass spectroscopic data were recorded with a Q-ToF micro-
Dipentenylation of 2b: To a suspension of NaH (49 mg, 2.07 mmol;
55% in oil) in THF was added dropwise solution of 1,3-bis(phenyl-
sulfonylmethyl)benzene (2b; 200 mg, 0.51 mmol) dissolved in dry
THF (20 mL). Then, the reaction mixture was stirred at room
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Diversity-Oriented Approach to Normuscopyridine
temp. for 30 min. Later, 5-bromo-1-pentene (306 mg, 2.05 mmol) 12: Semi solid (48 mg, 51% yield). H NMR (400 MHz, CDCl3): δ
1
dissolved in THF (20 mL) was added dropwise over a period of
30 min, further, the reaction mixture was stirred at room temp. for
20 h. under a nitrogen atmosphere. At the conclusion of the reac-
tion (TLC monitoring), the reaction mixture was diluted with ethyl
acetate. The organic layer was washed with brine, dried with
Na2SO4 and concentrated under reduced pressure. The crude prod-
uct was purified by column chromatography (silica gel, 10% ethyl
acetate/petroleum ether) to afford 24 (77 mg, 29% yield) and 25
(79 mg, 30% yield).
24: Colorless solid (77 mg, 29% yield), m.p. 186 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.04–1.27 (m, 4 H), 1.91–2.08 (m, 6 H),
2.32–2.41 (m, 2 H), 3.98 (dd, J1 = 3.7, J2 = 11.6 Hz, 2 H), 4.95–
5.01 (m, 4 H), 5.64–5.74 (m, 2 H), 6.91–7.11 (m, 4 H), 7.32–7.40
(m, 10 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.2, 26.9, 33.2,
71.0, 115.6, 128.8, 128.8, 128.9, 129.0, 129.7, 133.0, 133.6, 137.4,
137.5 ppm. HRMS (Q-ToF): calcd. for C30H35S2O4 [M + H]+
= 0.61–0.73 (m, 2 H), 1.60–1.74 (m, 4 H), 1.91–2.07 (m, 4 H), 2.65–
2.75 (m, 2 H), 4.15 (dd, J1 = 2, J2 = 12.0 Hz, 2 H), 4.99 (m, 2 H),
6.98 (d, J = 8 Hz, 2 H), 7.41 (t, J = 8 Hz, 1 H), 7.50–7.82 (m, 10
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 24.5, 28.2, 29.7, 73.2,
127.4, 129.1, 129.2, 129.5, 131.0, 133.7, 136.5, 137.8, 151.8 ppm.
HRMS (Q-ToF): calcd. for C27H30NS2O4 [M + H]+ 496.1616;
found 496.1610. IR (KBr pellet): νmax = 734, 896, 1147, 1264, 1422,
˜
1606, 2987, 3055 cm–1.
1
19: Semi solid (35 mg, 37% yield). H NMR (400 MHz, CDCl3): δ
= 0.48–0.57 (m, 1 H), 0.77–1.21 (m, 3 H), 1.33–1.54 (m, 1 H), 1.81–
2.02 (m, 4 H), 2.07–2.46 (m, 5 H), 4.12–4.18 (dd, J1 = 6, J2 = 4 Hz,
1 H), 4.22–4.30 (dd, J1 = 4, J2 = 6 Hz, 1 H), 4.95–5.15 (m, 2 H),
6.99 (d, J1 = 8, J2 = 8 Hz, 1 H); 7.10 (d, J = 8 Hz, 1 H); 7.39–7.76
(m, 11 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 24.1, 25.8, 26.4,
27.6, 28.3, 30.2, 31.2, 73.2, 73.4, 127.0, 127.4, 129.0, 129.0, 129.2,
129.2, 129.3, 129.5, 129.7, 130.0, 130.7, 130.8 ppm. HRMS (Q-
ToF): calcd. for C28H31NS2O4 [M + H]+ 509.1694; found 509.1699.
523.1977; found 523.1976. IR (KBr pellet): νmax = 738, 1264, 1421,
˜
1606, 2987, 3054 cm–1.
IR (KBr pellet): ν
= 739, 840, 1265, 1420, 1616, 2986,
˜
max
3066 cm–1.
25: Colorless solid (79 mg, 30% yield), m.p. 190 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.08–1.26 (m, 4 H), 1.91–2.08 (m, 6 H),
2.32–2.41 (m, 2 H), 3.99 (dd, J1 = 3.7, J2 = 11.6 Hz, 2 H), 4.93–
5.00 (m, 4 H), 5.60–5.71 (m, 2 H), 6.91–7.11 (m, 4 H), 7.32–7.42
(m, 10 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.0, 26.7, 33.1,
33.1, 70.8, 115.4, 128.7, 128.8, 128.89, 129.6, 132.9, 133.5, 137.3,
137.4 ppm. HRMS (Q-ToF): calcd. for C30H35S2O4 [M + H]+
26: Colorless crystalline solid material (48 mg, 51% yield), m.p.
174 °C. 1H NMR (400 MHz, CDCl3): δ = 0.76–0.79 (m, 2 H), 1.64–
1.75 (m, 6 H), 1.94–2.11 (m, 3 H), 2.39–2.45 (m, 1 H), 3.92 (dd, J1
= 2, J2 = 12.4 Hz, 2 H), 4.99 (t, J = 2.6 Hz, 2 H), 6.70–6.73 (dd,
J1 = 1.6, J2 = 8.6 Hz, 2 H), 6.89 (t, J = 2.6 Hz, 1 H), 7.43 (t, J =
7.9 Hz, 2 H), 7.57 (t, J = 1.2 Hz, 4 H), 7.67–7.74 (m, 5 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 26.0, 26.2, 30.0, 71.2, 127.9,
128.1, 129.0, 129.2, 130.7, 132.8, 132.9, 133.6, 133.6, 137.8 ppm.
HRMS (Q-ToF): calcd. for C28H31S2O4 [M + H]+ 495.1663; found
523.1977; found 523.1975. IR (KBr pellet): νmax = 744, 1267, 1655,
˜
2923 cm–1.
Monohexenylation of 17: To
a suspension of NaH (19 mg,
0.82 mmol; 55% in oil) in THF was added monopentenyl product
17 (250 mg, 0.55 mmol) dissolved in dry THF (20 mL) dropwise
over a period of 30 min. Then, the reaction mixture was stirred at
room temp. for 30 min. Later, 6-bromo-1-hexene (134 mg,
0.82 mmol) dissolved in dry THF (20 mL) was added dropwise over
a period of 30 min. Further, the reaction mixture was stirred at
room temp. for 20 h under nitrogen atmosphere. At the conclusion
of the reaction (TLC monitoring), the reaction mixture was diluted
with ethyl acetate. The organic layer was washed with brine, dried
with Na2SO4 and concentrated under reduced pressure. The crude
product was purified by column chromatography (silica gel, 10%
ethyl acetate/petroleum ether) to afford 18 (179 mg, 61% yield).
495.1661. IR (KBr pellet): νmax = 739, 849, 1265, 1421, 1606, 2986,
˜
3054 cm–1.
13, 20, 27: Contain mixtures of isomers that were further used in
the desulfonation and hydrogenation sequence.
General Procedure for Desulfonylation Reaction: To Mg turnings
(48 mg, 2.02 mmol) activated by TMSCl (cat. amount) and 1,2-
dibromoethane (cat. amount), was added dropwise solution of
compound 12 (100 mg, 0.20 mmol) in MeOH (8 mL) at 0 °C and
kept at same temperature for 1 h. Then, the reaction mixture was
heated to reflux overnight. Next, the reaction mixture was cooled
to room temp., and diluted with Et2O (10 mL). The layers were
separated and the aqueous phase was extracted with Et2O (4ϫ
10 mL). The combined organic phase was washed with H2O and
dried with Na2SO4, filtered, concentrated and purified by column
chromatography (silica gel, 3% ethyl acetate/petroleum ether) to
obtain 14 (34 mg, 80% yield) as a pale yellow oil.
1
18: (179 mg, 61% yield). H NMR (400 MHz, CDCl3): δ = 0.80–
1.40 (m, 6 H), 1.90–2.31 (m, 8 H), 4.10–4.20 (m, 2 H), 4.90–4.97
(m, 4 H), 5.58–5.77 (m, 2 H), 7.30–7.68 (m, 13 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 25.9, 26.0, 26.1, 26.3, 26.9, 27.0, 27.2, 27.4,
28.4, 33.2, 33.3, 72.6, 72.7, 114.9, 115.5, 115.6, 123.8, 124.9, 128.9,
128.9, 129.1, 133.6, 133.6, 133.7, 137.1, 137.4, 137.5, 137.6, 137.6,
137.8, 138.4, 152.6, 152.8, 152.9, 153.0 ppm. HRMS (Q-ToF):
calcd. for C30H36NS2O4 [M + H]+ 538.2086; found 538.2064. IR
A similar procedure was adopted on 100 mg scale for desulfonation
of 19 to obtain 21 and 26 to give 28.
= 757, 1016, 1216, 1669, 3020 cm–1.
14: (34 mg, 80% yield). 1H NMR (400 MHz, CDCl3): δ = 1.22–
1.41 (m, 4 H), 1.65–1.82 (m, 4 H), 1.90–2.10 (m, 4 H), 2.71 (t, J =
6.5 Hz, 4 H), 5.35–5.43 (m, 2 H), 6.97 (d, J = 6.5 Hz, 2 H), 7.52
(t, J = 6.5 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 25.4,
28.1, 29.2, 35.6, 119.8, 130.5, 136.8, 161.1 ppm. HRMS (Q-ToF):
calcd. for C15H22N [M + H]+ 216.1752; found 216.1764. IR (neat):
(neat): ν
˜
max
General Procedure for RCM Reaction: Compound 18 (50 mg.
93 mmol) was dissolved in dry CH2Cl2 and degassed with nitrogen
for 15 min. G-I (7 mg, 5 “mol-%”) catalyst was added and the reac-
tion mixture was stirred at room temp. for 48 h. At the conclusion
of the reaction (TLC monitoring), the solvent was removed under
reduced pressure. The crude product was directly subjected to col-
umn chromatography (silica gel, 8% ethyl acetate/petroleum ether)
gave product 19 (35 mg, 37% yield) and dimeric cyclophane 20
(23 mg, 25% yield).
ν
= 896, 1265, 1421, 1639, 3986, 3054 cm–1.
˜
max
21: (35 mg, 78% yield). 1H NMR (400 MHz, CDCl3): δ = 1.04–
1.33 (m, 8 H), 1.59–1.96 (m, 6 H), 2.71–2.80 (m, 4 H), 5.04–5.11
(m, 1 H), 5.37–5.45 (m, 1 H), 6.84–6.92 (m, 2 H), 7.41 (t, J =
7.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 25.4, 26.7,
27.9, 28.8, 29.2, 31.2, 31.3, 37.4, 37.6, 120.6, 121.2, 130.4, 131.6,
136.3, 161.0, 162.0 ppm. HRMS (Q-ToF): calcd. for C16H24N [M
Similar procedure was adopted on 50 mg scale for RCM of 10 and
11 to obtain 12 and 13; RCM of 24 gives 26 further RCM of 25
gives 27.
Eur. J. Org. Chem. 2014, 984–992
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
989

S. Kotha, G. T. Waghule, M. E. Shirbhate
FULL PAPER
+ H]+ 230.1908; found 230.1909. IR (neat): νmax = 896, 1265, 1421,
7.5 Hz, 2 H), 7.48 (t, J = 7.6 Hz, 1 H) ppm. 13C NMR (100.6 MHz,
CDCl3):δ = 25.2, 26.2, 26.5, 28.0, 37.0, 120.3, 136.5, 161.7 ppm.
HRMS (Q-ToF): calcd. for C15H24N [M + H]+ 218.1908; found
˜
1639, 3986, 3054 cm–1.
28: (35 mg, 81% yield). 1H NMR (400 MHz, CDCl3): δ = 1.04–
1.33 (m, 4 H), 1.30–1.32 (m, 4 H), 1.70–1.72 (m, 4 H), 2.70–2.75
(m, 4 H), 4.98 (t, J = 3 Hz, 2 H), 6.84–6.92 (m, 3 H), 7.41 (t, J =
7.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.1, 28.0,
30.8, 34.7, 125.6, 128.2, 130.0, 131.4, 142.3 ppm. HRMS (Q-ToF):
calcd. for C16H23 [M + H]+ 215.1799; found 215.1794. IR (neat):
218.1910. IR (neat): ν
= 740, 1265, 1645 cm–1.
˜
max
22: (9.4 mg, 94% yield). 1H NMR (400 MHz, CDCl3): δ = 0.71–
0.75 (m, 2 H), 1.01–1.08 (m, 4 H), 1.20–1.32 (m, 8 H), 1.78–1.85
(m, 4 H), 2.81 (t, J = 2.5 Hz, 4 H), 6.92 (d, J = 8 Hz, 2 H), 7.47
(t, J = 8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.3,
24.4, 25.9, 26.5, 26.6, 37.1, 121.5, 136.3, 161.4 ppm. HRMS (Q-
ToF): calcd. for C16H26N [M + H]+ 232.2065; found 232.2070. IR
ν
= 896, 1265, 1421, 1639, 3986, 3054 cm–1.
˜
max
General Procedure for Desulfonylation Hydrogenation of 13, 20, and
27 Consecutively: To Mg turnings (24 mg, 1.01 mmol) activated by
TMSCl (cat. amount) and 1,2-dibromoethane (cat. amount), was
added dropwise a solution of compound 13 (100 mg, 0.10 mmol)
in MeOH (8 mL) at 0 °C and kept at same temperature for 1 h.
Then, the reaction mixture was heated to reflux overnight. Next,
the reaction mixture was cooled to room temp., and it was diluted
with Et2O (10 mL). The layers were separated and the aqueous
phase was extracted with Et2O (4ϫ 10 mL). The combined organic
phases were washed with H2O and dried with Na2SO4, filtered and
concentrated. The crude product obtained was dissolved in dry
ethyl acetate (10 mL), Pd/C (6 mg, 5%) was added, and the mixture
was stirred at room temp. under a hydrogen atmosphere (1 atm) for
12 h. At the conclusion of the reaction (TLC monitoring), the sol-
vent was evaporated under reduced pressure, and the product was
purified by column chromatography (silica gel, 10% ethyl acetate/
petroleum ether) gave hydrogenated product 16 (28 mg, 64% yield).
(neat): ν
= 894, 1265, 1645, 2983, 3054 cm–1.
˜
max
29: (9.2 mg, 92% yield). 1H NMR (400 MHz, CDCl3): δ = 0.91–
0.97 (m, 4 H), 1.09–1.25 (m, 8 H), 1.65–1.71 (m, 4 H), 2.66 (t, J =
6 Hz, 4 H), 6.99 (d, J = 7 Hz, 2 H), 7.00 (br. s, 1 H), 7.19 (t, J =
7 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 25.6, 26.3, 27.0,
28.4, 35.4, 126.1, 128.6, 130.4, 142.2 ppm. HRMS (Q-ToF): calcd.
for C16H25 [M + H]+ 217.1956; found 217.1955. IR (neat): ν
=
˜
max
740, 1265, 1645 cm–1.
General Procedure for Grignard Addition Reaction: Mg turnings
and iodine in THF were heated to reflux until the brown color
disappeared. Then, 5-bromo-1-pentene (273 mg, 1.92 mmol) was
added and mixture was stirred for 30 min. Consecutively, pyridine-
2,6-dicarbonitrile (34a; 100 mg, 0.77 mmol) was added and the re-
sulting mixture was stirred and heated to reflux for 3 h. At the
conclusion of reaction (TLC monitoring), 2 n HCl was added and
reaction mixture was stirred for 30 min. The reaction mixture was
diluted with EtOAc (10 mL) and H2O (10 mL) and the reaction
mixture was stirred well and extracted with EtOAc. The organic
layer was washed with brine and dried with Na2SO4. EtOAc was
removed under reduced pressure and the crude product obtained
was purified by column chromatography to obtain 37.
A similar procedure was adopted on 100 mg scale for desulfonation
and hydrogenation of 20 to obtain 23 and 27 to give 30.
16: (28 mg, 64% yield). 1H NMR (400 MHz, CDCl3): δ = 1.23–
1.31 (m, 10 H), 1.60–1.64 (m, 12 H), 1.90–1.95 (m, 10 H), 2.73 (m,
8 H), 6.91 (d, J = 8 Hz, 4 H), 7.45 (t, J = 8 Hz, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 28.8, 29.4, 29.5, 30.0, 38.1, 120.1,
136.5, 161.8 ppm. HRMS (Q-ToF): calcd. for C30H47N2 [M + H]+
A similar procedure was adopted on 100 mg scale with 34a with 6-
bromo-1-hexene to obtain 38 (224 mg, 97% yield). Under similar
condition and same scale, 34b with 5-bromo-1-pentene and 6-
bromo-1-hexene electrophiles gave 42 and 43, respectively.
435.3738; found 435.3739. IR (neat): νmax = 894, 1245, 1644, 2913,
˜
3154 cm–1.
23: (33 mg, 74% yield). 1H NMR (400 MHz, CDCl3): δ = 1.20–
1.22 (br. s, 20 H), 1.58–1.61 (m, 8 H), 2.20 (br. s, 8 H), 2.70 (t, J =
7 Hz, 8 H), 6.96–7.00 (m, 4 H), 7.16 (t, J = 7 Hz, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 22.8, 28.9, 29.5, 30.0, 32.1, 38.3,
120.0, 136.4, 161.8 ppm. HRMS (Q-ToF): calcd. for C32H51N2 [M
1
37: (201 mg, 96% yield). H NMR (400 MHz, CDCl3): δ = 1.85–
1.98 (m, 4 H), 2.20–2.25 (m, 4 H), 3.28 (t, J = 7.3 Hz, 4 H), 4.99–
5.09 (m, 4 H), 5.80–5.90 (m, 2 H), 7.98 (t, J = 7.5 Hz, 1 H), 8.20
(d, J = 7.7 Hz, 2 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 23.4,
33.5, 37.1, 115.4, 124.9, 138.1, 138.2, 152.6, 201.5 ppm. HRMS (Q-
ToF): calcd. for C17H21NNaO2 [M + Na]+ 294.1466; found
+ H]+ 463.4052; found 463.4067. IR (neat): νmax = 894, 1265, 1645,
˜
2983, 3054 cm–1.
30: (34 mg, 78% yield). 1H NMR (400 MHz, CDCl3): δ = 1.25–
1.27 (bd, 22 H), 1.58–1.61 (m, 10 H), 2.57 (t, J = 7 Hz, 8 H), 6.96–
7.00 (m, 6 H), 7.16 (t, J = 7 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 28.6, 29.2, 29.5, 31.3, 35.7, 125.9, 128.2, 128.7,
142.8 ppm. HRMS (Q-ToF): calcd. for C32H49 [M + H]+ 433.4834;
294.1464. IR (neat): νmax: 740, 1266, 1698, 2935, 2935, 3077, 3382,
˜
3664, 3934 cm–1.
1
38: (224 mg, 97% yield). H NMR (400 MHz, CDCl3): δ = 1.49–
1.57 (m, 4 H), 1.76–1.84 (m, 4 H), 2.10–2.17 (m, 4 H), 3.27 (t, J =
7.6 Hz, 4 H), 4.94–5.06 (m, 4 H), 5.78–5.88 (m, 2 H), 7.98 (t, J =
7.5 Hz, 1 H), 8.21 (d, J = 7.7 Hz, 2 H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 23.8, 28.8, 33.7, 37.6, 114.8, 124.9, 138.1, 138.7, 152.6,
201.6 ppm. HRMS (Q-ToF): calcd. for C19H25NNaO2 [M + Na]+
found 433.3830. IR (neat): νmax = 890, 1260, 1645, 2973, 3014 cm–1.
˜
Synthesis of Normuscopyridine 15 and Analogues 22 and 29 by Hy-
drogenation Reaction: To a solution of unsaturated cyclophane 14
(10 mg, 0.46 mmol) in dry ethyl acetate (10 mL), Pd/C (6 mg, 5%)
was added, and the mixture was stirred at room temp. under a
hydrogen atmosphere (1 atm) for 12 h. At the conclusion of the
reaction (TLC monitoring), the solvent was evaporated under re-
duced pressure, and the product was purified by column
chromatography (silica gel, 10% ethyl acetate/petroleum ether) to
give hydrogenated product 15 (8.4 mg, 84% yield).
322.1770; found 322.1777. IR (neat): νmax: 745, 1266, 1696, 2935,
˜
2935, 3054, 3377, 3689, 3944 cm–1.
1
42: (192 mg, 83% yield). H NMR (400 MHz, CDCl3): δ = 1.79–
1.87 (m, 4 H), 2.12 (q, J = 7.1 Hz, 4 H), 2.98 (t, J = 7.4 Hz, 2 H),
2.99 (t, J = 7.1 Hz, 2 H), 4.95–5.04 (m, 4 H), 5.73–5.84 (m, 2 H),
7.53 (t, J = 7.4 Hz, 1 H), 8.10 (dd, J1 = 7.8, J2 = 1.6 Hz, 2 H), 8.47
(d, J = 1.6 Hz, 1 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ =
23.1, 33.0, 37.8, 115.4, 127.4, 128.9, 132.1, 137.3, 137.8, 199.4 ppm.
HRMS (Q-ToF): calcd. for C18H23O2 [M + H]+ 271.1692; found
A similar procedure was adopted on 10 mg scale for hydrogenation
of 21 to give 22 and 28 to give 29.
15: (8.4 mg, 84% yield). 1H NMR (400 MHz, CDCl3):δ = 1.15– 271.1693. IR (neat): νmax = 738, 1267, 1687, 2934, 3055, 3357, 3690,
˜
1.18 (m, 12 H), 1.77–1.83 (m, 4 H), 2.82–2.85 (m, 4 H), 6.95 (d, J =
3945 cm–1.
990
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 984–992

Diversity-Oriented Approach to Normuscopyridine
1
43: (201 mg, 87% yield). H NMR (400 MHz, CDCl3): δ = 1.46– tracted with EtOAc. The organic layer was washed with brine solu-
1.54 (m, 4 H), 1.74–1.81 (m, 4 H), 2.11 (q, J = 7.1 Hz, 4 H), 3.02 tion and dried with Na2SO4. Organic solvent was removed under
(t, J = 7.4 Hz, 4 H), 4.95–5.05 (m, 4 H), 5.76–5.87 (m, 2 H), 7.57
reduced pressure. The crude product was purified by column
(t, J = 7.5 Hz, 1 H), 8.13 (dd, J1 = 7.8, J2 = 1.5 Hz, 2 H), 8.51 (s, chromatography (silica gel, 3% EtOAc/petroleum ether) to obtain
1 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 23.7, 28.6, 33.6, 15 (23 mg, 53% yield).
38.6, 114.8, 127.6, 129.1, 132.2, 137.4, 138.5, 199.6 ppm. HRMS
A similar procedure was adopted on 50 mg scale to obtain cy-
(Q-ToF): calcd. for C20H26NaO2 [M + Na]+ 321.1822; found
clophane derivatives 40, 44 and 45 from 41, 29 and 46, respectively.
321.1825. IR (neat): νmax = 741, 1266, 1686, 2935, 2984, 3356, 3687,
˜
3943 cm–1.
Normuscopyridine 15: 1H and 13C NMR spectroscopic data ob-
tained here is the same as that derived from the hydrogenation
route.
General Procedure for RCM Reaction: A solution of bis-alkene de-
rivative 37 (100 mg, 0.36 mmol) in dry toluene (50 mL) was de-
gassed with nitrogen for 15 min. Then, Grubbs second-generation
catalyst (14 mg, 5 “mol-%”) was added and reaction mixture was
heated to reflux overnight. At the conclusion of reaction (TLC
monitoring), the crude mixture was filtered through a Celite pad
(washed with CH2Cl2) and concentrated under reduced pressure.
The crude product was purified by column chromatography (silica
gel, 5% EtOAc-petroleum ether) to afford cyclophane derivative 39
(50 mg, 56% yield).
41: (23 mg, 51% yield). 1H NMR (400 MHz, CDCl3):δ = 1.12–1.12
(m, 4 H), 1.15–1.28 (m, 10 H), 1.69–1.76 (m, 6 H), 2.79–2.85 (m,
4 H), 6.95 (d, J = 7.5 Hz, 2 H), 7.48 (t, J = 7.5 Hz, 1 H) ppm. 13C
NMR (100.6 MHz, CDCl3): δ = 25.9, 26.1, 26.8, 27.1, 29.1, 37.7,
120.5, 136.3, 161.9 ppm. HRMS (Q-ToF): calcd. for: C17H27NK
[M + K]+ 284.1780; found 284.1782. IR (neat): ν
= 740, 1265,
˜
max
2929, 3154, 3686, 3935 cm–1.
29: 1H and 13C NMR spectroscopic data obtained here is the same
as that derived from the hydrogenation route.
A similar procedure was adopted on 100 mg scale with substrate
38, 42, and 43 individually to obtain cyclophane derivatives 40, 44
and 45, respectively.
46: (23 mg, 53% yield). 1H NMR (400 MHz, CDCl3):δ = 0.71–0.75
(m, 4 H), 1.00–1.12 (m, 4 H), 1.25–1.35 (m, 8 H), 1.65–1.71 (m, 4
H), 2.66 (t, J = 6.2 Hz, 4 H), 6.98 (dd, J1 = 1.4, J2 = 4 Hz, 2 H),
7.13 (s, 1 H), 7.18 (t, J = 7.5 Hz, 1 H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 22.8, 24.5, 25.9, 26.5, 26.6, 37.2, 126.1, 128.6, 131.4,
142.2 ppm. HRMS (Q-ToF): calcd. for C18H28K [M + K]+
39: (50 mg, 56% yield). 1H NMR (400 MHz, CDCl3): δ = 1.65–
1.72 (m, 4 H), 1.99–2.03 (m, 4 H), 3.15 (t, J = 8.0 Hz, 4 H), 5.43–
5.45 (m, 2 H), 7.88 (t, J = 7.5 Hz, 1 H), 8.06 (d, J = 12.0 Hz, 2
H) ppm. 13C NMR (100.6 MHz, CDCl3):δ = 26.1, 31.0, 34.4, 124.9,
131.6, 138.3, 152.0, 202.6 ppm. HRMS (Q-ToF): calcd. for
C15H17NNaO2 [M + Na]+ 266.1154; found 266.1151. IR (neat):
283.1823; found 283.1823. IR (neat): νmax: 740, 1265, 2929, 3054,
˜
3686, 3945 cm–1.
ν
= 741, 1266, 1965, 2928, 3054, 3681, 3939 cm–1.
˜
max
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectroscopic data for all compounds and X-ray crystal-
lographic data for 26 are provided.
40: (74 mg, 83% yield). 1H NMR (400 MHz, CDCl3): δ = 1.62–
1.66 (m, 4 H), 1.76–1.83 (m, 4 H), 2.10–2.14 (m, 4 H), 3.26 (t, J =
7.8 Hz, 4 H), 5.54–5.56 (m, 2 H), 7.98 (t, J = 7.5 Hz, 1 H), 8.15 (d,
J = 7.7 Hz, 2 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 23.8,
26.1, 31.1, 34.5, 125.0, 131.7, 138.4, 152.0, 202.7 ppm. HRMS (Q-
ToF): calcd. for C17H21NNaO2 [M + Na]+ 294.1464; found
Acknowledgments
294.1464. IR (neat): ν
= 752, 1270, 1995, 2931, 3062, 3693,
˜
max
The authors thank Council of Scientific and Industrial Research
(CSIR), New Delhi and the Department of Science and Technology
(DST), New Delhi for financial support. Sophisticated Analytical
Instrument Facility (SAIF), Mumbai is thanked for recording the
spectroscopic data. G. T. W thanks CSIR for the award of a re-
search fellowship. S. K thanks DST for the award of a J. C. Bose
fellowship. The authors thank the reviewers for valuable sugges-
tions.
3940 cm–1.
44: (54 mg, 66% yield). 1H NMR (400 MHz, CDCl3): δ = 1.75–
1.82 (m, 4 H), 2.11 (q, J = 5.4 Hz, 4 H), 2.93 (t, J = 7.6 Hz, 4 H),
5.35–5.45 (m, 2 H), 7.41–7.45 (m, 1 H), 8.04 (dd, J1 = 1.6, J2
=
7.5 Hz, 2 H), 8.44 (d, J = 1.6 Hz, 1 H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 23.6, 31.9, 37.4, 127.6, 129.1, 130.1, 131.0, 132.10,
137.3, 199.6 ppm. HRMS (Q-ToF): calcd. for C16H18NaO2 [M +
Na]+ 265.1195; found 265.1199. IR (neat): ν
= 741, 1266, 1695,
˜
max
2986, 3054, 3686, 3945 cm–1.
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45: (63 mg, 71% yield). 1H NMR (400 MHz, CDCl3): δ = 1.61–
1.67 (m, 4 H), 1.76–1.85 (m, 4 H), 2.21–2.27 (m, 4 H), 2.90–2.96
(m, 4 H), 5.49 (t, J = 3.5 Hz, 2 H), 7.59 (t, J = 7.7 Hz, 1 H), 8.20
(dd, J1 = 6.3, J2 = 1.6 Hz, 2 H), 8.27 (s, 1 H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 25.7, 28.3, 29.9, 40.3, 129.7, 130.0, 131.2,
132.6, 136.15, 200.9 ppm. HRMS (Q-ToF): calcd. for C18H22NaO2
[M + Na]+ 293.1517; found 293.1512. IR (neat): ν
= 750, 1275,
˜
max
1667, 2990, 3061, 3689, 3950 cm–1.
One-Pot Decarbonylation and Hydrogenation Procedure: To a solu-
tion of diketone cyclophane derivative 39 (50 mg, 0.20 mmol) dis-
solved in ethylene glycol (4 mL) was added hydrazine hydrate
(52 mg, 1.64 mmol) followed by solid K2CO3 (228 mg, 1.65 mmol).
The reaction mixture was heated to 120 °C for 3 h and further
heated to 180 °C for 16 h. At the conclusion of reaction (TLC mon-
itoring), reaction was diluted with EtOAc (10 mL) and H2O
(10 mL). The reaction mixture was well stirred for 15 min. and ex-
Eur. J. Org. Chem. 2014, 984–992
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
991

S. Kotha, G. T. Waghule, M. E. Shirbhate
FULL PAPER
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[11] A. Tiwari, Ph. D. Thesis, Indian Institute of Technology, Bom-
bay, 2013.
Received: October 2, 2013
Published Online: December 5, 2013
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