One-pot generation of c=x bonds from methyl 2-siloxycyclopropanecarboxylates: Simple syntheses of functionalized nitriles and alkynes

Article abstract of DOI:10.1055/s-0034-1378370

Starting from methyl 2-siloxycyclopropanecarboxylates simple and efficient one-pot procedures are described that lead to β-cyanoesters and methoxycarbonyl-substituted terminal alkynes. The prepared functionalized alkynes were subjected to typical transformations such as [3+2] cycloaddition providing triazole derivatives, Sonogashira coupling, Au-catalyzed hydrophosphorylation or a copper-catalyzed coupling of methyl diazoacetate furnishing alkyne 14 and allene derivative 15. The Pauson-Khand reaction of the enyne 4c afforded a diastereomeric mixture of methyl 5-oxohexahydropentalen-2-carboxylate 16 in moderate yield.

Full text of DOI:10.1055/s-0034-1378370

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▌2265
cOlusnteer -Pot Generation of C≡X Bonds from Methyl 2-Siloxycyclopropane-
carboxylates: Simple Syntheses of Functionalized Nitriles and Alkynes
One-Pot Procedures Using Siloxycyclopropanecarboxylates
Dorian Reich, Dennis S. Müller, Luise Schefzig, Reinhold Zimmer,* Hans-Ulrich Reissig*
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany
Fax +49(30)83855367; E-mail: hans.reissig@chemie.fu-berlin.de
Received: 23.04.2014; Accepted after revision: 28.05.2014
group developed a series of efficient one-pot procedures
using methyl 2-siloxycyclopropanecarboxylates 1 as
masked 1,4-dicarbonyl compounds (Scheme 1). Easily
Abstract: Starting from methyl 2-siloxycyclopropanecarboxylates
simple and efficient one-pot procedures are described that lead to β-
cyanoesters and methoxycarbonyl-substituted terminal alkynes.
The prepared functionalized alkynes were subjected to typical available d–a cyclopropanes 1 are smoothly ring opened
transformations such as [3+2] cycloaddition providing triazole de- under mild conditions and provide γ-oxoesters enabling
3
rivatives, Sonogashira coupling, Au-catalyzed hydrophosphoryla-
the one-pot syntheses of γ-lactones A, 4,5-dihydro-
tion or a copper-catalyzed coupling of methyl diazoacetate
furnishing alkyne 14 and allene derivative 15. The Pauson–Khand
reaction of the enyne 4c afforded a diastereomeric mixture of meth-
yl 5-oxohexahydropentalen-2-carboxylate 16 in moderate yield.
4
5
3
(2H)-pyridazinones B, dipyrromethanes C, thiophene
6
7
derivatives D, Ugi four-component products E and 3-
amino)imidazo[1,2-a]pyridines F. Moreover, we re-
cently exploited the ring cleavage of perfluoroalkyl-sub-
stituted d–a cyclopropanes yielding synthetically versatile
fluorinated acyclic and cyclic products. Having already
proved the feasibility of one-pot procedures (in part as
multi-component reactions) employing 1 as synthetically
useful building blocks, we extended these studies to the
simple generation of C≡X moieties. Here we report our re-
sults on the conversion of methyl 2-siloxycyclopropanes
8,9
(
Key words: cyclopropanes, nitriles, alkynes, Bestmann–Ohira re-
agent, Click reaction, Pauson–Khand reaction, enol phosphates
10
Vicinally donor–acceptor-substituted cyclopropanes (d–a
cyclopropanes) have attracted great attention in recent
years.1 In the course of studies focusing on synthetic ap-
plications of this type of three-membered carbocycles, our
,2
1
into functionalized nitriles and alkynes, both versatile
R1
R2
O
O
R4
N
R3
O
N
A
R1
R2 R3
i. KBH4, MeOH
ii. H+
B
4
R NHNH2
CO2Me
+
CO2Me
R2
R3
R2 R3
N2
Cu or
Rh catalyst
pyrrole
acid
Me3SiO
R3
R2
OSiMe3
R1 CO2Me
NH HN
R1
1
C
Groebke
reaction
Gewald
reaction
Ugi
four-component
reaction
CO2Me
NH2
N
R4
N
t-BuNHOC
MeO2C
4
R HN
MeO C
N
CO Me
S
2
2
H
R2
R2 R3
R
R3 CO2Me
F
E
D
Scheme 1 One-pot reactions of d–a cyclopropanes 1 as key intermediates for the synthesis of γ-lactones A, 4,5-dihydro-3(2H)-pyridazinones
B, dipyrromethanes C, thiophenes D, Ugi four-component products E and 3-(amino)imidazo[1,2-a]pyridines F
SYNLETT 2014, 25, 2265–2270
Advanced online publication: 17.07.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1378370; Art ID: st-2014-s0339-c
Georg Thieme Verlag Stuttgart · New York
©

2266
D. Reich et al.
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classes of compounds of remarkable importance in organ- Table 2). The described method for the synthesis of meth-
ic synthesis. We also present a few typical subsequent re- yl pent-4-ynecarboxylates 4 is probably one of the most
actions of the prepared methoxycarbonyl-substituted flexible and simple routes to this type of intermediates.
terminal alkynes.
O
O
The nitrile group is a synthetically important functionality
that can be easily converted, for example, into amines or
into nitrogen-containing heterocycles.11 As a conse-
quence, the generation of the C≡N unit was realized by
numerous chemical transformations, including dehydra-
tions of amides or of aldoxime precursors. In this context,
we were interested to develop a simple one-pot protocol
starting from the masked 1,4-dicarbonyl compound
equivalents 1 under formation of an aldoxime immediate-
ly followed by a dehydration step. By heating the methyl
P(OMe)2
R1 R2
N2
R1 R2
R3
3
Me SiO
3
a
CO2Me
CO2Me
R3
67–98%
1
4
Scheme 3 Preparation of methyl pent-4-ynoates 4 from 1. Reagents
and conditions: (a) K CO , MeOH, r.t., overnight.
2
3
2
-siloxycyclopropanecarboxylates 1a–c in the presence of
Table 2 Synthesis of Methyl Pent-4-ynoates 4 from Methyl 2-Siloxy-
cyclopropanecarboxylates 1
hydroxylammonium chloride in formic acid at 100 °C
their direct conversion into β-cyanoesters 2a–c could be
achieved in moderate to good yields (Scheme 2, Table 1). Cyclopropane R1
Performing the reaction with less concentrated acid or ap-
R2
R3
Product Yield (%)
1
1
1
1
1
d
H
H
H
4d16a
67
98
78
85
78
plying shorter reaction times led to isolation of consider-
able amounts of the corresponding aldoxime
intermediate. The fairly low yield of nitrile 2a may be at-
tributed to its volatility; the higher substituted products 2b
and 2c could be easily handled during workup and purifi-
cation resulting in considerably higher yields.
4a16b
a
H
Me
Me
H
H
1
2
b
Me
H
H
4b16c
4e
e13
Allyl
Allyl
f13
Me
Me
4f
R1 R2
R1 R2
R3
Me3SiO
Terminal alkynes such as 4 are very versatile precursors
CO2Me
a
17,18
for many useful transformations.
Methoxycarbonyl-
N
CO2Me
R3
2
5–68%
substituted alkynes 4 could be readily converted into a se-
ries of products as exemplified in Schemes 4–7. Treat-
ment of the alkynes 4a,b,d–f with benzyl azide under
typical conditions for copper-catalyzed [3+2] cyclo-addi-
1
2
Scheme 2 Preparation of β-cyanoesters 2 from 1. Reagents and con-
ditions: (a) NH OH·HCl (1.7 equiv), HCO H, 100 °C, 6 h.
2
2
1
9
tions furnished the 3-(triazol-4-yl)-substituted carboxyl-
ic esters 5a,b,d–f in varying yields (Scheme 4, Table 3).
Applying this protocol to alkyne 4b and galactose-derived
Table 1 One-Pot Synthesis of β-Cyanoesters 2a–2c from Methyl 2-
Siloxycyclopropanecarboxylates 1a–1c
2
0,21
azide 6,
triazole derivative 7 was obtained in almost
Cyclopropane R1
R2
R3
Product Yield (%)
quantitative yield (Scheme 5). Deprotection of intermedi-
ate 7 by sodium methoxide followed by treatment with
acidic resin led to the product 8 in 83% yield. The me-
thoxycarbonyl group of 7 and 8 should also allow con-
necting these compounds to other molecules.
1
1
1
a
H
Me
Me
Me
H
2a
2b
2c
25
54
68
b
Me
Me
H
c13
Me
R1 R2
R1 R2
CO2Me
CO2Me
Having demonstrated that the ring opening of cyclopro-
panes 1 to γ-oxoesters can be combined with the smooth
generation of a C≡N moiety, we next studied the more
challenging formation of a C≡C bond with a Seyferth–
a
+
BnN3
Bn
N
R3
3
8–94%
R3
N
N
4
5
14
Gilbert homologation reaction employing the Best-
Scheme 4 Synthesis of triazoles 5 from alkynes 4. Reagents and
1
5
mann–Ohira reagent 3. Under standard reaction condi- conditions: (a) CuI, Et N, TBTA, MeCN, r.t., overnight; TBTA =
3
tris[(1-benzyl)methyl]amine.
tions (K CO as base in methanol at room temperature),
2
3
the desired transformation was readily applicable to a se-
ries of methyl 2-siloxycyclopropanecarboxylates 1 pro-
viding the expected methoxycarbonyl-substituted alkynes
Alkynes are among the most interesting components in
transition-metal-catalyzed transformations. To demon-
strate the applicability of the methoxycarbonyl-substitut-
ed alkynes 4 we subjected one of the compounds to
standard Sonogashira coupling conditions (Scheme 6).
The coupling of alkyne 4b with phenyl iodide (9) afforded
4
in good to excellent yields (Scheme 3; 67–98%). Higher
substitution did not affect the reaction outcome. A quater-
nary center adjacent to the aldehyde moiety of the inter-
mediate γ-oxoester was also tolerated (see 4b and 4f in
Synlett 2014, 25, 2265–2270
© Georg Thieme Verlag Stuttgart · New York

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One-Pot Procedures Using Siloxycyclopropanecarboxylates
2267
Table 3 Click Reaction of 4a,b,d–f with Benzyl Azide to Furnish
Triazoles 5a,b,d–f
methyl pent-4-ynecarboxylate 4a afforded the kinetically
controlled formation of enol phosphate 12 in good yield.
The synthetic usefulness of the enol phosphates is well
documented, including the transition-metal-catalyzed
Alkyne
R1
R2
R3
Product Yield (%)
21,23
processes that are well known.
An alternative func-
4
4
4
4
4
d
a
b
e
f
H
H
H
5d
5a
5b
5e
5f
58
72
49
94
38
tionalization of alkyne 4b was achieved by its copper-cat-
H
Me
Me
H
H
alyzed homologation reaction with methyl diazoacetate
2
4
13. Following a protocol developed by Kumaraswamy,
Me
H
H
reaction of 4b with 13 in the presence of Hünig base and
catalytic amounts of CuI furnished diester 14 in good
yield together with small amounts of allene derivative 15
that is probably formed by partial isomerization of the
alkyne.
Allyl
Allyl
Me
Me
the expected product 10 in 57% yield. Lee and co-workers
described the conversion of terminal alkynes into enol Finally we investigated the intramolecular Pauson–Khand
22
25
phosphates under gold catalysis. Gratifyingly, the adopt- reaction of 1,6-enyne 4e leading to a compound with bi-
ed gold(I)/silver(I)-catalyzed hydrophosphorylation of cyclo[3.3.0]octenone skeleton. The reaction of Co (CO)
2
8
Ph
Ph
CO2Me
O
O
O
O
4
a
b
CO2Me
O
O
N
N3
AcO
AcO
N
N
9
9%
OAc
OAc
6
7
b
83%
OH
HO
CO2Me
O
N
HO
N
N
HO
8
Scheme 5 Synthesis of galactose-derived triazole 7 and subsequent deprotection to 8. Reagents and conditions: (a) CuI, Et N, TBTA, MeCN,
3
r.t., overnight; (b) (i) NaOMe, MeOH, r.t., 1 d; (ii) Dowex resin, MeOH, r.t., 2 h.
PhI
9
a
CO2Me
CO2Me
5
7%
Ph
4b
10
O
(PhO)2POH
O
CO2Me
11
(PhO)2PO
CO2Me
b
7
5%
4a
12
CO2Me
CO2Me
N2
CO2Me
CO2Me
c
13
+
•
78%
CO2Me
MeO C
2
4b
14
15
(95:5)
Scheme 6 Sonogashira coupling of 4b with phenyl iodide (9), preparation of enol phosphate 12 and homologation of 4b with methyl diazo-
acetate. Reagents and conditions: (a) CuI, Pd(PPh ) Cl , Et N, DMF, r.t., 1 d; (b) Ph PAuCl, AgPF , toluene, r.t., overnight; (c) CuI, Hünig
3
2
2
3
3
6
base, MeCN, r.t., 3 h.
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2265–2270

2268
D. Reich et al.
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with alkyne 4e cleanly furnished the corresponding dico-
balt complex that was directly subjected to the treatment
with N-morpholine N-oxide (NMO) affording the expect-
ed methyl 5-oxo-hexahydropentalen-2-carboxylate 16 in
(3) Grimm, E. L.; Reissig, H.-U. J. Org. Chem. 1985, 50, 242.
(4) Reichelt, I.; Reissig, H.-U. Synthesis 1984, 786.
(
5) (a) Beyzavi, M. H.; Lentz, D.; Reissig, H.-U.; Wiehe, A.
Eur. J. Org. Chem. 2013, 269. (b) Beyzavi, M. H.; Nietzold,
C.; Reissig, H.-U.; Wiehe, A. Adv. Synth. Catal. 2013, 355,
50% yield as a mixture of two diastereomers (dr = 60:40)
1
409.
6) (a) Özbek, H.; Veljkovic, I. S.; Reissig, H.-U. Synlett 2008,
145. (b) Ngo, T. H.; Berndt, H.; Lentz, D.; Reissig, H.-U.
(Scheme 7).
(
3
J. Org. Chem. 2012, 77, 9676. (c) Ngo, T. H.; Berndt, H.;
Wilsdorf, M.; Lentz, D.; Reissig, H.-U. Chem. Eur. J. 2013,
CO2Me
a, b
O
CO2Me
1
9, 15155.
5
0% (over 2 steps)
dr = 60:40
(7) Zimmer, R.; Ziemer, A.; Gruner, M.; Brüdgam, I.; Hartl, H.;
Reissig, H.-U. Synthesis 2001, 1649.
4e
16
(
8) Veljkovic, I.; Zimmer, R.; Reissig, H.-U.; Brüdgam, I.;
Scheme 7 Intramolecular Pauson–Khand reaction of 4e to bicyclic
compound 16. Reagents and conditions: (a) Co (CO) , Et O, r.t.,
Hartl, H. Synthesis 2006, 2677.
2
8
2
(9) For other selected publications dealing with in situ
generation of 1,4-dicarbonyl compounds from d–a
cyclopropanes and their functionalizations in one-pot
procedures, see: (a) Brückner, C.; Reissig, H.-U. J. Org.
Chem. 1988, 53, 2440. (b) Brückner, C.; Reissig, H.-U.
Liebigs Ann. Chem. 1988, 465. (c) Brückner, C.; Suchland,
B.; Reissig, H.-U. Liebigs Ann. Chem. 1988, 471.
(d) Ullmann, A.; Schnaubelt, J.; Reissig, H.-U. Synthesis
1998, 1052. (e) Patra, P. K.; Reissig, H.-U. Eur. J. Org.
Chem. 2001, 4195.
overnight; (b) NMO, CH Cl , 0 °C to r.t., overnight.
2
2
In this communication we have described new applica-
tions of easily available d–a cyclopropanes of type 1 as
masked functionalized aldehydes.26 The presented two
one-pot protocols leading to nitriles 2 and alkynes 4 and
the subsequent transformations of 4 into a variety of com-
pounds again demonstrate the synthetic utility of methyl
(
10) (a) Gladow, D.; Reissig, H.-U. Helv. Chim. Acta 2012, 95,
2-siloxycyclopropanecarboxylates 1 for the rapid access
1818. (b) Gladow, D.; Reissig, H.-U. Synthesis 2013, 45,
2179. (c) Gladow, D.; Reissig, H.-U. J. Org. Chem. 2014,
79, 4492.
to functionalized products.
(
11) For a comprehensive overview on the use of nitriles in
organic chemistry, see: (a) Science of Synthesis; Vol. 19;
Murahashi, S.-I., Ed.; Georg Thieme Verlag: Stuttgart, 2004.
For selected recent publications dealing with the nitrile
synthesis from aldoximes, see: (b) Bad, M. N. S.; Behrouz,
S.; Nekoei, A.-R. Synlett 2012, 23, 1191. (c) Dev, D.;
Palakurthy, N. B.; Kumar, N.; Mandal, B. Tetrahedron Lett.
Acknowledgment
Generous support of this work by Bayer HealthCare is most grate-
fully acknowledged. We also thank Hiltrud Holzinger (Universität
Würzburg) for preliminary results concerning the one-pot nitrile
synthesis.
2
013, 54, 4397. (d) Patil, U. B.; Shendage, S. S.; Nagarkar,
Supporting Information for this article is available online
J. M. Synthesis 2013, 45, 3295. (e) Yu, L.; Li, H.; Zhang, X.;
Ye, J.; Liu, J.; Xu, Q.; Lautens, M. Org. Lett. 2014, 16, 1346;
and references cited in these reports.
at
http://www.thieme-connect.com/products/ejournals/journal/
1
0.1055/s-00000083.SunpfgIpi
o
nr
i
o
(
12) The subsequent formation of the corresponding amidoximes
from nitriles and hydroxylamine was not observed. For a
related reference, see: Lin, C.-C.; Hsieh, T.-H.; Liao, P.-Y.;
Liao, Z.-Y.; Chang, C.-W.; Shih, Y.-C.; Yeh, W.-H.; Chien,
T.-C. Org. Lett. 2014, 16, 892.
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(
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(
13) Alkylated methyl cyclopropanecarboxylates 1 are easily
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(
(
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1
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(
(
J. Chem. Soc., Perkin Trans. 1 1993, 1657. (c) Cordes, C.;
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1
968, 51, 1663.
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2
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(
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(
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Synlett 2014, 25, 2265–2270
© Georg Thieme Verlag Stuttgart · New York

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One-Pot Procedures Using Siloxycyclopropanecarboxylates
2269
2
014, 79, 1399. (d) For a total synthesis of (+)-lupinine (silica gel, Et O) followed by careful removal of the solvent
2
16b
using alkyne 4d, see ref. 16a.
(ca 500 mbar; bath temp: 35 °C) provided 4a (362 mg,
(
18) For the enyne ring-closing metathesis of 4d leading to exo-
methylene-functionalized cyclohexene product, see: Lee,
Y.-J.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc.
98%) as a pale yellow liquid.
1
H NMR (400 MHz, CDCl ): δ = 1.21 (d, J = 7.0 Hz, 3 H,
3
Me), 2.03 (d, J = 2.5 Hz, 1 H, 5-H), 2.36 (dd, J = 6.0, 12.5
Hz, 1 H, 2-H), 2.52 (dd, J = 5.7, 12.5 Hz, 1 H, 2-H), 2.87–
2.95 (m, 1 H, 3-H), 3.65 (s, 3 H, OMe). C NMR (125.8
2
009, 131, 10652.
13
(
19) (a) Chan, T. R.; Hilgraf, R.; Sharpless, K. B.; Fokin, V. V.
Org. Lett. 2004, 6, 2853. For a recent review, see: (b) Berg,
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Tetrahedron Lett. 1994, 35, 3913.
MHz, CDCl ): δ = 20.6 (q, Me), 22.7 (d, C-3), 41.2 (t, C-2),
3
51.7 (q, OMe), 68.9 (s, C-4), 87.1 (d, C-5), 171.8 (s, C-1).
Typical Procedure for Methyl 3-(1-Benzyl-1H-1,2,3-
triazol-4-yl)-3-butanoate (5a): To a solution of the alkyne
4a (0.072 g, 0.571 mmol) in MeCN (10 mL) benzyl azide
(
(
(
21) Moinizadeh, N.; Klemme, R.; Kansy, M.; Zimmer, R.;
Reissig, H.-U. Synthesis 2013, 45, 2752.
(0.051 g, 0.380 mmol), TBTA (0.028 g, 0.053 mmol), Et N
3
22) (a) Lee, P. H.; Kim, S.; Park, A.; Chary, B. C.; Kim, S.
Angew. Chem. Int. Ed. 2010, 49, 6806; Angew. Chem. 2010,
(5 μL, 0.053 mmol), and CuI (0.010 g, 0.053 mmol) were
added at r.t. and stirred overnight. After filtration of the
mixture (silica gel), concentration in vacuo and purification
by column chromatography (silica gel, hexanes–EtOAc, 8:1
→ 2:1) afforded the product 5a (0.071 g, 72%) as a yellow
1
22, 6958 . For a similar hydrophosphorylation of terminal
alkynes, see: (b) Nun, P.; Egbert, J. D.; Oliva-Madrid, M.-J.;
Nolan, S. P. Chem. Eur. J. 2012, 18, 1064.
(
23) For reviews on synthesis and recent application of enol
oil.
1
phosphates, see: (a) Lichtenthaler, F. W. Chem. Rev. 1961,
H NMR (400 MHz, CDCl ): δ = 1.30 (d, J = 7.0 Hz, 3 H,
3
6
1, 607. (b) Occhiato, E. G. Mini-Rev. Org. Chem. 2004, 1,
Me), 2.51 (dd, J = 7.6, 15.8 Hz, 1 H, 2-H), 2.78 (dd, J = 7.0,
15.8 Hz, 1 H, 2-H), 3.42 (sextet, J = 7.0 Hz, 1 H, 3-H), 3.59
149. (c) Protti, S.; Fagnoni, M. Chem. Commun. 2008, 3611.
(
d) Knappke, C. E. I.; Jacobi von Wangelin, A. Chem. Soc.
(s, 3 H, OMe), 5.45 (s, 2 H, NCH ), 7.20–7.23, 7.31–7.34 (2
2
1
3
Rev. 2011, 40, 4948. (e) Sellars, J. D.; Steel, P. G. Chem.
Soc. Rev. 2011, 40, 5170. (f) Li, B.-J.; Yu, D.-G.; Sun, C.-L.;
Shi, Z.-J. Chem. Eur. J. 2011, 17, 1728. (g) Song, R.-J.; Liu,
Y.-Y.; Wu, J.-C.; Xie, Y.-X.; Deng, G.-B.; Yang, X.-H.; Liu,
Y.; Li, J.-H. Synthesis 2012, 44, 1119. For recent
contributions on enol phosphates, see: (h) Krawczyk, E.;
Mielniczak, G.; Owsianik, K.; Luczak, J. Tetrahedron:
Asymmetry 2012, 23, 1480. (i) Barthes, N.; Grison, C.
Bioorg. Chem. 2012, 40, 48.
× m, 2 × 3 H, =CH, Ph). C NMR (100.5 MHz, CDCl ): δ =
3
20.1 (q, Me), 27.8 (d, CH), 40.9 (t, CH ), 51.4 (q, OMe), 53.9
2
(t, CH Ph), 120.0 (d, =CH), 127.9, 128.5, 129.0, 134.8 (3 ×
2
d, s, Ph), 151.9 (s, =C), 172.6 (s, C=O). IR (ATR): 3140–
–1
2845 (=C–H, C–H), 1735 (C=O) cm . HRMS (ESI–TOF):
+
m/z [M + Na] calcd for C H N NaO : 282.1213; found:
1
4
17
3
2
282.1222.
Diphenyl 4-(Diphenoxyphosphoryloxy)-3-methylpent-4-
enoate (12): Alkyne 4a (0.051 g, 0.405 mmol) was dissolved
in toluene (2 mL) and diphenyl phosphate 11 (0.084 g, 0.338
mmol), AgPF (0.004 g, 0.017 mmol) and Ph AuCl (0.008 g,
(
24) Kumaraswamy, G.; Jayaprakash, N.; Balakishnan, G. Org.
Biomol. Chem. 2011, 9, 7913.
6
3
(
25) For reviews, see: (a) Pauson, P. L. Tetrahedron 1985, 41,
0.017 mmol) were added. The solution was stirred at r.t.
overnight. After filtration through a pad of silica gel
(EtOAc), the filtrate was concentrated under reduced
pressure. The crude product was purified by column
chromatography (silica gel, hexanes–EtOAc, 6:1 → 2:1) to
5
(
2
855. (b) Schore, N. E. Chem. Rev. 1988, 88, 1081.
c) Rodríguez Rivero, M.; Adrio, J.; Carretero, J. C. Synlett
005, 26; and references cited herein. For selected examples,
see: (d) Paquette, L. A.; Borrelly, S. J. Org. Chem. 1995, 60,
912. (e) Zimmer, R.; Buchholz, M.; Collas, M.;
6
afford 12 (0.095 g, 75%) as a yellow oil.
1
Angermann, J.; Homann, K.; Reissig, H.-U. Eur. J. Org.
Chem. 2010, 4111.
H NMR (500 MHz, CDCl ): δ = 1.08 (d, J = 6.8 Hz, 3 H,
3
Me), 2.23 (dd, J = 8.2, 15.3 Hz, 1 H, CH ), 2.53 (dd, J = 6.2,
2
(
26) Typical Procedure for Methyl 3-Cyano-2,3-dimethyl-
butanoate (2c): A mixture of cyclopropane 1c (1.15 g, 5.00
15.3 Hz, 1 H, CH ), 2.79–2.87 (m, 1 H, CH), 3.65 (s, 3 H,
2
OMe), 4.66, 5.02 (m , 2 × 1 H, =CH ), 7.16–7.25, 7.32–7.36
c
2
1
3
mmol) and NH OH·HCl (486 mg, 7.00 mmol) in formic acid
(2 × m, 2 × 3 H, 2 × 2 H, Ph). C NMR (125.8 MHz, CDCl ):
δ = 17.6 (q, Me), 35.5 (dd, J = 7.3 Hz, CH), 38.4 (t, CH ),
51.6 (q, OMe), 96.9 (td, J = 2.1 Hz, =CH ), 120.1 (dd, J
= 5.2 Hz, Ph), 125.5 (d, Ph), 129.8 (d, Ph), 150.4 (d, J
CP
2
3
3
(5 mL) was heated at 100 °C for 6 h. After cooling to r.t. the
CP
2
3
3
solution was neutralized with 2 N NaOH solution followed
by extraction with CH Cl (3 × 30 mL). Purification by
CP 2 CP
2
=
2
2
2
kugelrohr distillation (80 °C, 1.3 mbar) afforded β-
7.3 Hz, Ph), 157.7 (d, J = 9.3 Hz, =C), 172.1 (s, CO ). IR
C
P
2
cyanoester 2c (524 mg, 68%) as a colorless liquid.
(ATR): 2955–2850 (=C–H, C–H), 1740 (C=O), 1665 (C=C),
1300 (P–O) cm . HRMS (ESI–TOF): m/z [M + H] calcd
1
–1
+
H NMR (400 MHz, CDCl ): δ = 1.28 (d, J = 7.2 Hz, 3 H,
3
Me), 1.34, 1.39 (2 × s, 2 × 3 H, Me), 2.51 (q, J = 7.2 Hz, 1
H, CH), 3.67 (s, 3 H, OMe). C NMR (125.8 MHz, CDCl3):
for C H O P: 377.1149; found: 377.1127. HRMS (ESI–
1
9
22
6
1
3
+
TOF): m/z [M + Na] calcd for C H NaO P: 399.0968;
19 21 6
+
δ = 13.7 (q, Me), 24.0, 25.3 (2 × q, Me), 34.5 (s, CMe ), 47.1
found: 399.0946. HRMS (ESI–TOF): m/z [M + K] calcd for
2
(
d, CH), 51.8 (q, OMe), 123.2 (s, CN), 172.9 (s, CO Me). IR
C H KO P: 415.0707; found: 415.0682.
2
19 21
6
–
1
(ATR): 2985–2845 (C–H), 2240 (C≡C), 1740 (C=O) cm .
Methyl 5-Oxo-1,2,3,3a,4,5-hexahydropentalen-2-
carboxylate (16): Enyne 4e (0.177 g, 1.16 mmol) was
dissolved in Et O (16 mL). After addition of Co (CO)
8
+
HRMS (ESI–TOF): m/z [M + Na] calcd for C H NNaO :
8
13
2
1
78.0838; found: 178.0839.
Typical Procedure for Methyl 3-Methylpent-5-yne-
carboxylate (4a): To a suspension of K CO (819 mg, 5.93
2
2
(0.398 g, 1.16 mmol), the solution was stirred for 15 h at r.t.
under an Ar atmosphere. The solution was then filtrated
2
3
mmol) in MeOH (6 mL) reagent 3 (452 mg, 2.35 mmol) and
siloxycyclopropane 1a (684 mg, 3.56 mmol) were added at
through neutral alumina (Et O) and the filtrate was
2
concentrated to dryness. The resulting crude product was
dissolved in CH Cl (10 mL) and NMO (0.178 g, 2.37
r.t. After stirring overnight, 5% aq NaHCO solution (10
3
2
2
mL) and Et O (50 mL) were added. After separation of the
mmol) was added in one portion at 0 °C. The solution was
stirred at this temperature for 18 h and then treated with 10%
HCl solution (1 mL). The separated organic phase was
washed with brine (2 × 3 mL) and dried (Na SO ). After
2
phases, the aqueous phase was extracted with Et O (3 × 50
2
mL). The combined organic layers were dried with Na SO ,
2
4
filtered and carefullyconcentrated. Column chromatography
2
4
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2265–2270

2270
D. Reich et al.
CLUSTER
removal of the solvent under reduced pressure, the residue
was purified by column chromatography (hexanes–EtOAc,
35.2*, 42.0*, 42.2 (6 × t, CH ), 43.3, 44.0*, 44.4, 46.6* (4 ×
d, CH), 52.1*, 52.2 (2 × q, OMe), 125.1, 125.6* (2 × d,
2
4:1) to afford bicyclic product 16 (0.104 g, 50%; 2
=CH), 174.6*, 175.8 (2 × s, CO Me), 187.3*, 188.1 (2 × s,
2
diastereomers = 60:40) as a colorless oil.
=C), 209.8*, 210.2 (2 × s, C=O); signals of the minor
diastereomer are marked with *. IR (ATR): 3140–2860
1
H NMR (500 MHz, CDCl ): δ = 1.37–1.52 (m, 2 H, CH ),
3
2
–1
2
.04 (dd, J = 3.1, 18.1 Hz, 0.6 H, CH ), 2.12 (dd, J = 3.4, 18.1
(=C–H, C–H), 1730 (C=O) cm . HRMS (ESI–TOF): m/z
2
+
Hz, 0.4 H, CH ), 2.42–2.50, 2.57–2.65, 2.84–3.11, 3.19–
[M + H] calcd for C H O : 181.0859; found: 181.0860.
2
10 13
3
+
3.29 (4 × m, 0.6 H, 0.4 H, 3 H, 1 H, CH, CH ), 3.69, 3.72 (2
HRMS (ESI–TOF): m/z [M + Na] calcd for C H NaO :
2
10 12 3
×
=
s, 1.2 H, 1.8 H, OMe), 5.89, 5.91 (2 × m , 0.6 H, 0.4 H,
203.0679; found: 203.0685. HRMS (ESI–TOF): m/z [M +
c
1
3
+
CH). C NMR (125.8 MHz, CDCl ): δ = 30.0*, 30.3, 34.4,
K] calcd for C H KO : 219.0418; found: 219.0426.
3
10 12
3
Synlett 2014, 25, 2265–2270
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