Target cum flexibility: An alkyne [2+2+2]-cyclotrimerization strategy for synthesis of trinem library

Article abstract of DOI:10.1016/j.tetlet.2010.10.123

A rapid access to the central 4,5,6-tricyclic core of 4,5,6-trinems has been achieved by employing the alkyne [2+2+2]-cyclotrimerization as the key and final reaction in the synthesis.

Full text of DOI:10.1016/j.tetlet.2010.10.123

Tetrahedron Letters 52 (2011) 38–41
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Target cum flexibility: an alkyne [2+2+2]-cyclotrimerization strategy for
synthesis of trinem library
⇑
C. V. Ramana , Mangesh P. Dushing, Sradhanjali Mohapatra, Rosy Mallik, Rajesh G. Gonnade
National Chemical Laboratory (CSIR, India), Dr. Homi Bhabha Road, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid access to the central 4,5,6-tricyclic core of 4,5,6-trinems has been achieved by employing the
alkyne [2+2+2]-cyclotrimerization as the key and final reaction in the synthesis.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 17 June 2010
Revised 15 October 2010
Accepted 25 October 2010
Available online 30 October 2010
Effective methods that address the complex molecular ensem-
ble and also provide flexibility in modulating the pharmacokinetics
are important tools in the modern drug discovery programs.
to synthesize. In order to investigate in this direction, the diynes 1–
3 were selected as the model substrates to check the feasibility of
this approach and also to understand the substituent influence on
1
1
0
Engagement of the intermolecular (cyclo)additions as the key skel-
etal constructs at the penultimate stages in a target oriented syn-
thesis will provide enormous versatility for altering the target
the regioselectivity.
Synthesis of diynes 1–3 was started with the optimization of
the conditions for the addition of an alkynyl anion at the C(4)-po-
sition of 4AA to prepare the intermediate alkynes 5–7. The alkyne 5
has been prepared earlier via the addition of lithiated trimethyl-
2
properties and is one of the ongoing programs in our group. Here-
in, we exemplify the potential of such an approach by selecting the
trinem skeleton as a target and the key bicycloannulation as the fi-
nal step. Tricyclic b-lactam antibiotics, referred to as trinems, are a
new class of broad spectrum antibacterial agents.3 When com-
pared with conventional carbapenems, trinems have good resis-
tance to beta-lactamases and dehydropeptidases and offer
1
1
silyl acetylene followed by desilylation. To have a simple and
practical method for accessing the alkynes on large scales, we
opted for the addition of alkynyl Grignard reagents. After substan-
tial optimization of the reaction conditions, the ethylnylmagne-
sium chloride (generated by passing dry acetylene gas to a
4
superior stability in the stomach and intestine. A handful of non-
conventional fused polycyclic b-lactams have been described with
interesting anti-bacterial activities (Fig. 1).
OH
S
In this context, various approaches for cycloannulations on the
b-lactam have been documented among which the ring-closing
H
H
N
5
metathesis (RCM) approach has been employed by several groups.
N
N
OMe
OMe
O
O
O
Our attention has been drawn to the 6-(1-hydroxyethyl)-cyclono-
CO H
CO Na
CO Na
2
2
2
6
cardicin developed by the researchers at Merck. This benzannulat-
Sanfetrinem
ed trinem has shown promising activity against a wide range of
pathogens including both Gram positive (Staphylococcus aureus,
Strep. pyogenes, Bacillus subtilis) and Gram negative (Escherichis coli,
Pseudomonas, Proteus morgani, etc.) and thus is a potential lead for
further exploration in anti-bacterial therapeutics. We have been
interested in providing a strategy which should facilitate the place-
ment of a wide range of functional groups and appendages on the
aromatic ring without diverting from the original target oriented
route. Keeping this in mind, the central trinem skeleton has been
OH
R
N
OH
H H
N
O
CO Na
N
2
O
CO Na
2
CO H
2
6-(1-Hydroxyethyl)-
cyclonocardicin
R = acyl group
R'
7
–
R
disconnected so as to employ trimerization as the key reaction.
R''
HO H H
9
HO
H
H
N
R
Since the cyclotrimerization was planned as the final step, this
strategy should effectively address a rapid synthesis of the trinem
library as various alkynes are commercially available and are easy
R''
+
N
O
[2+2+2]-
cyclotrimerization
R'
O
⇑
Corresponding author. Tel.: +91 20 25902577; fax: +91 20 25902629.
E-mail address: vr.chepuri@ncl.res.in (C.V. Ramana).
Figure 1. Some tricyclic b-lactam antibiotics and proposed cyclotrimerization
approach for benzannulated 4,5,6-trinems.
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.123

C. V. Ramana et al. / Tetrahedron Letters 52 (2011) 38–41
39
solution of preformed n-BuMgCl in THF) was added to azetidin-
-one 4 to get 5 in excellent yield. Under similar conditions by
using 1-octyne and phenyl acetylene, the other two alkynyl azedi-
tines 6 and 7 have been prepared in very good yields and on multi-
gram scales. The N-propargylation of compounds 5–7 was carried
out by using propargyl bromide and KOH in the presence of n-
substituted diynes 2 and 3 with phenyl acetylene were not facile
with Wilkinson’s catalyst. When the catalysts B and C were
employed, the reactions proceeded smoothly at rt and gave the
corresponding trinems (Table 1) in good yields. The trimerization
of n-hexyl substituted diyne 2 gave mainly the 1,3-isomer 12a.
The product distribution was independent of the catalyst em-
ployed. With the phenyl substituted diyne 3, the trimerization
gave exclusively the 1,3-product 13a. The regioselectivity noticed
with the trimerization of diynes 2 and 3 endorse them for further
exploration in constructing the homochiral trinem libraries. The at-
tempted cyclotrimerization reactions of the alkynes 1–3 with sym-
metrically disubstituted akynes bis-(trimethylsilyl)acetylene,
dimethyl acetylenedicarboxylate, and diphenylacetylene met with
failure. With 2-butyne-1,4-diol as a substrate, the requisite trimer-
2
4
Bu NI in THF to afford the corresponding diynes 8–10 which were
subsequently treated with TBAF to provide the final diynes 1–3
5
c
(Scheme 1).
Using phenyl acetylene as a substrate, the feasibility of cyclotri-
merization of the diynes 1–3 has been examined by screening
available Rh- and Ru-based catalysts. With the simple diyne 1,
the reaction was facile with Wilkinson’s catalyst (A).12 The two re-
gio-isomeric trinems 11a/11b were formed in equal proportions. A
marginal improvement in the product yields could be seen when
1
5
ization product 14 from the cyclotrimerization of the diyne 1
could be obtained only with the Wilkinson’s catalyst. But with
the diynes 2 and 3, none of the three catalysts resulted in the tri-
merziation product.
*
13
the catalysts Cp RuCl(cod) (B)
and [Rh(cod)
2 4
]BF /(R)-BINAP
1
4
(
C) were employed, albeit without any substantial improvement
in the regioselectivity. The cyclotrimerization of the mono-
10
With the optimized catalyst and conditions of the cyclotrimer-
ization reactions with phenylacetylene, next we did proceed with
the synthesis of a small collection of trinems by employing easily
available alkynes as the co-partners for the cyclotrimerization.
Tables 1 and 2 show the versatility of our strategy. The cyclotri-
merization reactions of diyne 1 were carried out by employing
the Wilkinson’s catalyst. The reaction with acetylene was con-
ducted in a sealed tube at 80 °C (entry 15, Table 2). With a wide
range of terminal alkynes employed, the requisite cyclotrimeriza-
tion products were obtained in good to excellent yields, however,
as 1:1 inseparable regiomeric mixture. For the structural analysis,
compounds 16a, 18b, and 19b were separated by preparative
TLC and their constitutions were confirmed with the help of exten-
sive 2D NMR experiments. For example, a combination of observa-
tions obtained from NOESY, HSQC, and HMBC studies helped to
deduce the structure of compound 19b. The proton resonating at
R
TBSO
H
OAc
NH
TBSO
Mg, n-BuCl, THF
H
NH
O
R
O
,
0 ºC
20 min
5
6
7
(R = H, 86%)
4
AA (4)
(R = C H13, 83%)
6
(R = Ph, 89%)
KOH, Bu NI
4
1
6
17
18
Br
H
THF, 0 ºC-rt
2.5 h
R
R
HO
H
TBSO
TBAF, THF
rt,1 h
7
.23 ppm as a singlet was found to be connected to the aromatic
N
N
O
carbon C(8) in HSQC. In HMBC, correlations were observed be-
tween C(8)–H and C(12) (38.8 ppm). The C(12)–H appeared as a
triplet at 3.87 ppm and showed cross peaks with C(8)
O
1
2
3
(R = H, 90%)
(R = C H13, 87%)
(R = Ph, 89%)
8 (R = H, 70%)
9 (R = C H13, 75%)
10 (R = Ph, 77%)
6
6
(
124.1 ppm) and C(10) (129.0 ppm). There was no connectivity ob-
served between C(11) (123.1 ppm) and C(12)–H. This confirmed
the position of the side chain to be at C(9). The through-space
Scheme 1. Synthesis of diynes 1–3.
Table 1
Examination of the cyclotrimerization reaction of diynes 1–3 with phenylacetylene
R'
R
R
OH
H
HO
Catalyst and Conditions:
H
H
N
H
N
R''
A) Rh(PPh ) Cl (5 mol%), toluene-EtOH
3
3
B) Rh(cod) BF -(R)-BINAP, (5 mol%), CH Cl
Ph
2
4
2
2
C) Cp*RuCl(cod) (5 mol%), CH Cl
2
O
2
O
R = H, Ph or C H
6
13
11a (R = R' = H, R'' = Ph)
1
1
1
1b (R = R''= H, R' = Ph)
n
2a (R= C H13, R' =H, R'' = Ph)
6
3a (R = R'' = Ph, R' = H)
Entry
Diyne
R=
Method
Temp/time (°C/h)
Product(s)
a:b
Yield (%)
1
2
3
4
5
6
7
8
9
1
1
1
2
2
2
3
3
3
H
H
H
n-C
n-C
n-C
Ph
A
B
C
A
B
C
A
B
C
80/12
rt/7
rt/4
80/18
rt/7
rt/4
80/24
rt/7
rt/4
11a, 11b
11a, 11b
11a, 11b
12
12
12
13
13
13
1:1
1:1
1:1
—
—
—
—
—
—
64
68
80
6
H
6
H
6
H
13
13
13
No reaction
78
—
No reaction
80
81
Ph
Ph

4
0
C. V. Ramana et al. / Tetrahedron Letters 52 (2011) 38–41
Table 2
Scope of cyclotrimerization reaction of diynes 1–3
R
R
R
R'
OH
R'
OH
OH
Ph
R' = n-C21H43
OH
R'
A/B/C
R'
30 (C, 77%)
N
(5 mol%)
N
N
O
O
O
N
NH2
a
b
O
Conditions:
A) Rh(PPh ) Cl, toluene-EtOH, reflux, 6-8 h
3
3
R' =
H
B) Rh(cod) BF -(R)-BINAP, CH Cl , rt, 6-8 h
2
4
2
2
C) Cp*RuCl(cod), CH Cl , rt, 3-5 h
25 (C, 80%)
31 (C, 83%)
2
2
(
6:1)
H
n-C H
6 13
OH
R'
O
R' =
H
n-C H
5
11
26 (B, 78%)
1
5 (A, 70%)
16 (A, 55%)
N
N
(1:1)
O
O
Cl
O
O
HN
2
7 (C, 79%)
32 (C, 71%)
9:1)
N
(
R' =
n-C14
H
C H OH
2 4
CH OH
29
2
H
OH
O
TMS
19 (A, 60%)
20 (A, 48%)
21 (A, 52%)
OBn
1
7 (A, 62%)
1:1)
1
8 (A, 55%)
(1:1)
(
(1:1)
(2:3)
(1:1)
2
8 (C, 86%)
33 (C, 69%)
C H
O
O
6
11
OH
R'
HN
C H OH
2
4
R' =
n-C H
6 13
N
H
N
29 (C, 73%)
H
OTBS
O
23 (B, 79%)
8:1)
O 24 (B, 71%)
22 (C, 83%)
3
4 (C, 53%)
(
(3:1)
H
H
H
12 13
H
H 8
12 13
H
9
H 8
H 8
OH
H
H
OH
H
C11H23
OH
OH
9
9
H
H
H
H
H
H
H
10
1
2
10
3
4
10
3
4
3
4
1
1
11
11
N
N
N
5
H
5
H
5
H
O
O
O
H H
H H
H H
a)
b)
c)
d)
Figure 2. Observed through spatial contacts in the NOESY spectra of compounds (a) 16a, (b) 18b, (c) 19b and (d) ORTEP structure of compound 16a.
connectivity observed between C(8)–H and C(12)–H in the NOESY
spectrum further substantiated the assigned regiochemistry. In
similar lines, the structure of the compound 16a was confirmed
by NOE studies. For example, the C(4)–H showed through spatial
interactions with both the C(8)–H and C(5)–H. The C(5)–H gave
an additional NOE signal with C(11)–H. In addition, the cross peaks
between C(12)–H/C(9)–H and C(12)–H/C(11)–H, and the absence
of cross peak between C(12)–H/C(8)–H confirmed the attachment
of alkyl side chain to C(10) carbon (Fig. 2b). Due to the aniosotrpic
deshielding effect of the lactam carbonyl, the diastereotropic
with diyne 3. Various functional groups are tolerant under the
reaction conditions. The products 27 and 31 obtained from the
cyclotrimerization of diyne 3 with 5-chloropent-1-yne and 3-ethy-
nylaniline are quite attractive, as these products provide a suitable
functional group handle for further diversification with simple
chemical maneuvering.
In summary, a [2+2+2] alkyne cyclotrimerization reaction was
employed successfully to construct the central 4/5/6 tricyclic
framework of 6-(1-hydroxyethyl)-cyclonocardicin trinems. Intro-
duction of different substituents to the structure was achieved eas-
ily by simply employing a suitable alkyne at the final event of
bicyclo-annulation, and thus are allowed to prepare a focussed li-
brary of trinem like small molecules easily. Further studies toward
the synthesis of carboxylate appended trinems and ring size mod-
ifications are in progress. Their synthesis and the biological activi-
ties will be reported in due course.
5
c
methylene protons C(5) were well separated (ca. 0.8 ppm). The
single crystal X-ray crystallographic studies of 16a (Fig. 2d) further
confirmed the assigned structure.1
9–21
Some of the representatives
through-space interactions noticed in the NOE spectrum of com-
pound 19b have been presented in Figure 2c.
The scope of the cyclotrimerization reactions with the substi-
tuted diynes 2 and 3 was next explored. With terminal alkynes,
the cyclotrimerization of diynes 2 and 3 was achieved smoothly
at rt. The regioselectivity was excellent with the diyne 3 trimeriza-
tions. In case of diyne 2, along with the anticipated 1,3-regiomer,
the 1,2-isomer was also obtained as a minor product. A variety of
terminal alkynes have been employed for the cyclotrimerization
Acknowledgments
We thank the Department of Science and Technology (SR/S5/
GC-20/2007) for funding and UGC and CSIR (New Delhi) for the re-
search fellowships granted to R.M. and M.P.D.

C. V. Ramana et al. / Tetrahedron Letters 52 (2011) 38–41
41
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Supplementary data ( H, 13C DEPT, MS and 2D NMR Spectra of
selected compounds) associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.123.
1
7
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d
6
): d 1.30 (d, J = 6.3 Hz, 3H), 3.01 (dd, J = 2.3, 6.5 Hz, 1H), 4.05 (d, J = 14.5 Hz,
H), 4.13–4.16 (m, 1H), 4.60 (s, 2H), 4.63 (s, 2H) , 4.79 (d, J = 14.5 Hz, 1H), 4.85
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(
(
s, 1H), 5.05 (br s, 2H), 5.14 (br s, 1H), 7.33 (s, 1H), 7.47 (s, 1H); 13C NMR
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3 6
+ DMSO-d ): d 20.4 (q), 49.8 (t), 58.4 (d), 59.5 (t, 2C), 62.9 (d),
6
6.0 (d), 120.2 (d), 120.8 (d), 137.1 (s), 137.9 (s), 138.0 (s), 139.0 (s), 177.6 (s)
+
ppm; ESI-MS m/z: 286.1 (46%, [M+Na] ). Anal. Calcd for C14
.51; N, 5.32. Found: C, 63.88; H, 6.37; N, 5.37.
6. Spectral data of compound 16a: Colorless needles, yield: 55%; ½
CHCl ); IR (CHCl
160, 1135, 1045, 929, 881 cm
4
H17NO : C, 63.87; H,
7
1
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6
25
D
1
a
ꢀ
: 28.5 (c 1,
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Genet, J.-P.; Bhatnagar, N. Tetrahedron Lett. 2001, 42, 2461–2464; (g) Barrett,
A. G. M.; Ahmed, M.; Baker, S. P.; Baugh, S. P. D.; Braddock, D. C.; Procopiou, P.
A.; White, A. J. P.; Williams, D. J. J. Org. Chem. 2000, 65, 3716–3721; (h) Tarling,
C. A.; Holmes, A. B.; Markwell, R. E.; Pearson, N. D. J. Chem. Soc., Perkin Trans. 1
3
3
) m: 3404, 3019, 2960, 2859, 2400, 1752, 1618, 1457, 1332,
ꢁ
1 1
1
;
H
NMR (400 MHz, CDCl
3
): d 0.89 (t,
J = 6.9 Hz, 3H), 1.29–1.37 (m, 4H), 1.42 (d, J = 6.3 Hz, 3H), 1.60 (quintet,
J = 7.8 Hz, 2H), 2.15 (br s, 1H), 2.61 (t, J = 7.6 Hz, 2H), 3.15 (dd, J = 2.4, 5.9 Hz,
1
7
H), 4.08 (br d, J = 14.6 Hz, 1H), 4.34 (quintet, J = 6.3 Hz, 1H), 4.84–4.89 (m, 2H),
.05 (s, 1H), 7.12 (br d, J = 7.8 Hz, 1H), 7.25 (d, J = 7.8 Hz, 1H); C NMR
13
(
100 MHz, CDCl
3
): d 14.0 (q), 21.8 (q), 22.5 (t), 31.3 (t), 31.4 (t), 35.7 (t), 51.8 (t),
5
1
3
9.7 (d), 65.4 (d), 67.1 (d), 122.9 (d), 123.2 (d), 128.3 (d), 136.9 (s), 142.5 (s),
+
+
43.3 (s), 179.0 (s); ESI-MS m/z: 274.1 (45%, [M+H] ); 296.0 (40%, [M+Na] ),
+
12.0 (30%, [M+K] ). Anal. Calcd for C17
H
23NO
2
: C, 74.69; H, 8.48; N, 5.12.
Found: C, 74.48; H, 8.45; N, 5.23.
7. Spectral data of compound 18b, Thick liquid, yield: 55%; ½aꢀ : ꢁ18.4 (c 1,
D
25
1
ꢁ1
1
CHCl
CDCl
.59 (quintet, J = 7.2 Hz, 2H), 1.96 (br s, 1H), 2.60 (t, J = 7.8 Hz, 2H), 3.16 (dd,
J = 2.5, 6.2 Hz, 1H), 4.07 (br d, J = 14.4 Hz, 1H), 4.34 (quintet, J = 6.2 Hz, 1H),
3
3
); IR (CHCl ) m: 3406, 3019, 2927, 1757, 1133 cm ; H NMR (400 MHz,
1
999, 1695–1701; (i) Barrett, A. G. M.; Baugh, S. P. D.; Braddock, D. C.; Flack,
3
): d 0.87 (t, J = 6.8 Hz, 3H), 1.25–1.32 (m, 22H), 1.42 (d, J = 6.3 Hz, 3H),
K.; Gibson, V. C.; Giles, M. R.; Marshall, E. L.; Procopiou, P. A.; White, A. J. P.;
Williams, D. J. J. Org. Chem. 1998, 63, 7893–7907; (j) Barrett, A. G. M.; Baugh, S.
P. D.; Gibson, V. C.; Giles, M. R.; Marshalla, E. L.; Procopioub, A. P. Chem.
Commun. 1997, 155–156; (k) Barrett, A. G. M.; Baugh, S. P. D.; Gibson, V. C.;
Giles, M. R.; Marshall, E. L.; Procopioub, P. A. Chem. Commun. 1996, 2231–
1
13
4
2
3
1
3
.83–4.87 (m, 2H) , 7.09–7.14 (m, 3H); C NMR (100 MHz, CDCl ): d 14.1 (q),
2.0 (q), 22.7 (t) , 29.4 (t, 2C) , 29.5 (t) , 29.6 (t) , 29.7 (t, 5C), 31.7 (t) , 31.9 (t) ,
5.8 (t) , 51.7 (t) , 59.9 (d), 65.5 (d), 67.1 (d), 122.8 (d), 123.3 (d), 128.4 (d),
39.6 (s), 139.8 (s), 143.2 (s), 178.8 (s); ESI-MS m/z: 400.4 (8%, [M+H] ), 422.4
2
232.
(a) Christensen, B. G.; Heck, J. V.; Szymonifka, M. J. U.S. Patent 4 174,848, 1983.;
b) Heck, J. V.; Szymonifka, M. J.; Christensen, B. G. Tetrahedron Lett. 1982, 23,
+
6
.
.
+
(
100%, [M+Na] ). Anal. Calcd for C26
H
41NO
2
: C, 78.15; H, 10.34; N, 3.51. Found:
(
C, 78.28; H, 10.57; N, 3.34.
1
5
519–1522; (c) Christensen, J. V.; Heck, B. G. Tetrahedron Lett. 1981, 22, 5027–
030.
25
1
8. Spectral data of compound 19b: Colorless oil, yield: 60%; ½
CHCl ); IR (CHCl
NMR (200 MHz, CDCl
aꢀ : ꢁ26.2 (c 1,
D
ꢁ1 1
3
3
)
m: 3422, 3018, 2932, 1752, 1457, 1330, 1044, 928 cm
; H
7
For selected reviews see: (a) Zhou, L. S.; Li, S.; Kanno, K.; Takahashi, T.
Heterocycles 2010, 80, 725–738; (b) Tanaka, K. Chem. Asian J. 2009, 4, 508–518;
3
): d 1.42 (d, J = 6.3 Hz, 3H), 1.88 (br s, 2H), 2.89 (t,
J = 6.6 Hz, 2H), 3.18 (dd, J = 2.4, 6.3 Hz, 1H), 3.87 (t, J = 6.6 Hz, 2H), 4.07 (dd,
J = 2.2, 14.2 Hz, 1H), 4.34 (quintet, J = 6.3 Hz, 1H), 4.84–4.91 (m, 2H), 7.18 (s,
(
c) Shibata, T.; Tsuchikama, K. Org. Biomol. Chem. 2008, 1317–1323; (d) Agenet,
N.; Buisine, O.; Slowinski, F.; Gandon, V.; Aubert, C.; Malacria, M. In Organic
Reactions; RajanBabu, T. V., Ed.; John Wiley & Sons: Hoboken, 2007; Vol. 68, pp
1
5
H), 7.23 (s, 1H), 7.27 (s, 1H); 13C NMR (100 MHz, CDCl
3
): d 21.9 (q), 38.8 (t),
1.6 (t), 59.9 (d), 63.5 (t), 65.4 (d), 67.1 (d), 123.1 (d), 124.1 (d), 129.0 (d), 138.8
1–302; (e) Gandon, V.; Aubert, C.; Malacria, M. Chem. Commun. 2006, 2209–
2217; (f) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741–
4767; (g) Gandon, V.; Aubert, C.; Malacria, M. Curr. Org. Chem. 2005, 9, 1699–
1712; (h) Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503–519; (i) Rubin, M.;
+
(
s), 140.1 (s), 140.5 (s), 178.8 (s) ppm; ESI-MS m/z: 246.9 (9%, [M+H] ), 269.9
+
(
10%, [M+Na] ). Anal. Calcd for C14
8.19; H, 6.67; N, 5.39.
9. X-ray intensity data of compound 16a was collected on a Bruker SMART APEX
CCD diffractometer with graphite-monochromatized (Mo = 0.71073 Å)
3
H17NO : C, 68.00; H, 6.93; N, 5.66. Found: C,
6
1
Sromek, A. W.; Gevorgyan, V. Synlett 2003, 2265–2291; (j) Aubert, C.; Buisine,
O.; Petit, M.; Slowinski, F.; Malacria, M. Pure Appl. Chem. 1999, 71, 1463–1470;
K
a
radiation at room temperature. All the data were corrected for Lorentzian,
polarization and absorption effects using Bruker’s SAINT and SADABS
programs. SHELX-97 (G. M. Sheldrick, SHELX-97 program for crystal structure
(
k) Schore, N. E. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, p 1129.
8
.
For recent total synthesis employing [2+2+2] cyclotrimerization, see: (a)
McIver, A. L.; Deiters, A. Org. Lett. 2010, 12, 1288–1291; (b) Yuan, C. X.; Chang,
C. T.; Axelrod, A.; Siegel, D. J. Am. Chem. Soc. 2010, 132, 5924–5925; (c) Li, P. F.;
Menche, D. Angew. Chem., Int. Ed. 2009, 48, 5078–5080; (d) Alayrac, C.;
Schollmeyer, D.; Witulski, B. Chem. Commun. 2009, 1464–1466; (e) McIver, A.;
Young, D. D.; Deiters, A. Chem. Commun. 2008, 4750–4752; (f) Moser, M.;
Banfield, S. C.; Rinner, U.; Chapuis, J.-C.; Pettit, G. R.; Hudlicky, T. Can. J. Chem.
20
solution and refinement, University of Gottingen, Germany, 1997) was used
2
for structure solution and full-matrix least-squares refinement on F . Hydrogen
atoms were included in the refinement as per the riding model.
0. Sheldrick, G. M. SHELX-97 program for crystal structure solution and refinement,
University of Gottingen, Germany, 1997.
1. The crystallographic data has been deposited with the Cambridge
Crystallographic Data Centre as deposition No. CCDC 791182. Copies of the
data can be obtained, free of charge, on application to the CCDC, 12 Union
Road,Cambridge CB2 1EZ, UK [fax: +44 (1223) 336033; e-mail:
deposit@ccdc.cam.ac.uk].
2
2
2
006, 84, 1313–1337; (g) Moser, M.; Sun, X.; Hudlicky, T. Org. Lett. 2005, 7,
5
669–5672; (h) Anderson, E. A.; Alexanian, E. J.; Sorensen, E. J. Angew. Chem.,
Int. Ed. 2004, 43, 1998–2001; (i) McDonald, F. E.; Smolentsev, M. V. Org. Lett.
002, 4, 745–748; (j) Witulski, B.; Zimmermann, A.; Gowans, N. D. Chem.
Commun. 2002, 8, 2984–2985.
2