Regioselective Synthesis of α,α-Difluorocyclopentanone Derivatives: Domino Nickel-Catalyzed Difluorocyclopropanation/Ring-Expansion Sequence of Silyl Dienol Ethers

Article abstract of DOI:10.1021/acs.orglett.5b02726

Silyl dienol ethers prepared from α,β-unsaturated ketones underwent nickel-catalyzed difluorocyclopropanation of the electron-rich alkene moiety with trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate. The subsequent vinylcyclopropane-cyclopentene rear

Full text of DOI:10.1021/acs.orglett.5b02726

Letter
pubs.acs.org/OrgLett
Regioselective Synthesis of α,α-Difluorocyclopentanone Derivatives:
Domino Nickel-Catalyzed Difluorocyclopropanation/Ring-Expansion
Sequence of Silyl Dienol Ethers
Tatsuya Aono, Hisashi Sasagawa, Kohei Fuchibe, and Junji Ichikawa*
Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
S
* Supporting Information
ABSTRACT: Silyl dienol ethers prepared from α,β-unsatu-
rated ketones underwent nickel-catalyzed difluorocyclopropa-
nation of the electron-rich alkene moiety with trimethylsilyl
2,2-difluoro-2-(fluorosulfonyl)acetate. The subsequent vinyl-
cyclopropane−cyclopentene rearrangement afforded silyl 5,5-
difluorocyclopent-1-en-1-yl ethers in good yields. The
obtained five-membered silyl enol ethers were demonstrated to be versatile intermediates for the synthesis of di- and
monofluorinated cyclopentanones and cyclopentenones. A nickel difluorocarbene complex is proposed as a key intermediate in
the difluorocyclopropanation.
Scheme 1. Strategy for the Domino Synthesis of α,α-
Difluorocyclopentanone Derivatives
yclopentanones are an important structural motif found in
1
Cmany natural and artificial compounds.
Since the
introduction of fluorine substituents is known to increase the
biological activities of the original molecules,2 the pharmaceutical
utilities of cyclopentanones with fluorine substituents at the
position α to the carbonyl group have been taken into
consideration (Figure 1).3,4
VCP rearrangements of fluorine-free vinylcyclopropanes,
including siloxy-substituted ones,7 are typically conducted at
high temperatures (300−550 °C).6 As an advantage, fluorine
substitution allows the rearrangement conditions to be benign
and renders the C−C bond cleavage regioselective. Dolbier
reported that 1,1-difluoro-2-vinylcyclopropanes underwent facile
VCP rearrangement at 200−275 °C to selectively afford 3,3-
difluorocyclopent-1-enes.8 Recently, Percy conducted the
reaction of the difluorinated vinylcyclopropanes with an ester
moiety at 100 °C.9 These advantages of fluorine substitution in
cyclopropane rings are ascribed to two primary reasons:10 (i)
increased ring strain11 and (ii) elongation of the C−C bond distal
to the geminal fluorine substituents.12 We expected that the VCP
rearrangement of 2-siloxy-substituted 1,1-difluoro-2-vinylcyclo-
propanes would readily proceed, providing the desired domino
synthesis of α,α-difluorocyclopentanone derivatives.
The difluorocyclopropanation of silyl enol ethers is an issue in
this strategy and needs to be addressed. In general,
difluorocyclopropanations of alkenes have been extensively
studied for decades using systems such as CHClF2/KOH,13
CClF2CO2Na,14 or PhHgCF3/NaI15 to generate free difluor-
ocarbene;16 these methods are affected by strongly basic
conditions, high reaction temperature, and the need for toxic
reagents, respectively. Although useful methods for the
Figure 1. α-Fluorinated cyclopentanone derivatives whose biological
activities have been studied.3a,c
To date, α,α-difluorocyclopentanone derivatives have been
synthesized via two methods: double-electrophilic fluorination of
cyclopentanones5 and deoxygenative fluorination of cyclo-
pentanones followed by oxidation.3b These strategies involve
considerable effort because they require the construction of the
carbon skeleton and the introduction of fluorine. We envisioned
that the concise synthesis of α,α-difluorinated cyclopentanones
would be facilitated by the combination of the difluorocyclo-
propanation of silyl dienol ethers and vinylcyclopropane−
cyclopentene rearrangement (VCP rearrangement, Scheme
1).6 Silyl dienol ethers, which are prepared from α,β-unsaturated
ketones, are subjected to difluorocyclopropanation. The
resulting 1,1-difluoro-2-vinylcyclopropanes bearing a siloxy
group undergo subsequent VCP rearrangement to afford silyl
5,5-difluorocyclopent-1-en-1-yl ethers (i.e., the domino synthesis
of α,α-difluorocyclopentanone derivatives).
Received: September 20, 2015
© XXXX American Chemical Society
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DOI: 10.1021/acs.orglett.5b02726
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Organic Letters
Letter
generation of free difluorocarbene have been reported in the past
few years,16b systems for the difluorocyclopropanation of silyl
enol ethers are still limited,17 probably due to their instabilities.
Thus, we investigated the difluorocyclopropanation of silyl
enol ethers with trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)-
acetate (TFDA)18 and found the first example of the metal-
catalyzed difluorocyclopropanation of silyl enol ethers (Table 1,
NHC-catalyzed generation of free difluorocarbene,19 TFDA was
treated with imidazolium, imidazolinium, or triazolium salts 3−5
(5 mol %) along with sodium carbonate (0.2 equiv) in the
presence of silyl enol ether 1a to afford 2a in 53%, 56%, or 46%
yield, respectively (entries 2−4). Further examination revealed
that the use of a metal catalyst increased the yield of
cyclopropane 2a. Tetrakis(triphenylphosphine)nickel, -palladi-
um, and -platinum catalysts afforded 2a in 12−59% yields at 100
°C (entries 5−7). The use of electron-donating pincer-type
NHC complexes of those metals further improved the yields
(entries 8−13). In particular, nickel complex 6a was the most
effective to prepare 2a, resulting in 73% yield (entry 8).20 This
method was also successfully applied to other substrates.
Sterically hindered or cyclic silyl enol ethers 1b,c afforded the
corresponding products 2b,c in 63% and 78% yields, respectively
(eqs 1 and 2).
a
Table 1. Catalyst Optimization
b
b,c
entry
catalyst
2a (%)
TFDA (equiv)
0.62
d
1
NaF
31
2
3 + Na2CO3 (0.2 equiv)
53
3
4 + Na2CO3 (0.2 equiv)
56
4
5 + Na2CO3 (0.2 equiv)
46
5
Ni(PPh3)4
30
6
Pd(PPh3)4
59
7
Pt(PPh3)4
12
8
6a
72 (73)
37
9
6b
10
11
12
13
14
7a
64
7b
68
7c
62
8
62
To eliminate the possibility that the pincer-type NHC ligand
served as a catalyst for the decomposition of TFDA, silyl enol
ether 1a was treated with TFDA in the presence of
bis(imidazolium) salt 9 (5 mol %) and sodium carbonate (0.2
equiv, entry 14). The product 2a was obtained in 45% yield,
suggesting that the difluorocyclopropanation was more
efficiently catalyzed by nickel. One reasonable mechanism for
the metal-catalyzed difluorocyclopropanation is that the reaction
proceeded via a nickel difluorocarbene complex, [LNiCF2]2+
(L = pincer-type NHC ligand), which was supported by HRMS
analysis of its aminolysis product, [LNiCN(2,6-dimethyl-
phenyl)]2+ (see the Supporting Information).21−23
9 + Na2CO3 (0.2 equiv)
45
a
b
TFDA = FSO2CF2CO2SiMe3. TBS = Sit-BuMe2. 19F NMR yield
based on (CF3)2C(C6H4p-Me)2. Isolated yield is shown in
parentheses. Recovery. Silyl enol ether 1a was completely consumed.
c
d
Importantly, there have been several reports on the
preparation of transition-metal difluorocarbene complexes,24
whereas their synthetic applications are quite rare.25 We propose
that the difluorocyclopropanation proceeds through a transition-
metal difluorocarbene complex, which is an unprecedented
catalytic application of the difluorocarbene complexes in organic
synthesis.
Having successfully carried out the nickel-catalyzed difluor-
ocyclopropanation of silyl enol ethers, the domino difluorocy-
clopropanation/VCP rearrangement sequence was examined
(Table 2). Silyl dienol ether 10a was treated with 2 equiv of
TFDA in the presence of 5 mol % of nickel complex 6a in toluene
at 100 °C (entry 1). Chemoselective cyclopropanation
proceeded on the oxygenated electron-rich alkene moiety
followed by the expected ring expansion, affording 11a in 61%
yield along with vinylcyclopropane 12 in 16% yield. The
vinylcyclopropane intermediate was completely converted to the
desired cyclic silyl enol ether by conducting the reaction at 140
°C.26 Upon treatment with 2 equiv of TFDA in the presence of 5
mol % of 6a at 140 °C, silyl dienol ether 10a afforded 11a in 83%
yield (entry 2). Silyl ethers 10b,c, which bear electron-rich and
-deficient aryl groups (R1), smoothly underwent the domino
process to afford the corresponding products 11b,c in 80% and
Figure 2. List of catalyst candidates (Mes = 2,4,6-trimethylphenyl).
Figure 2). TFDA was originally designed to generate free
difluorocarbene upon treatment with a fluoride ion. Silyl enol
ether 1a was treated with TFDA (2 equiv) in the presence of
sodium fluoride (5 mol %) at 100 °C (entry 1). The desired
difluorocyclopropane 2a was obtained, although the yield was
only 31% (19F NMR), and a substantial amount of TFDA (0.62
equiv) remained unreacted. Since we previously reported the
B
DOI: 10.1021/acs.orglett.5b02726
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Letter
Table 2. Synthesis of Silyl 5,5-Difluorocyclopent-1-en-1-yl
Ethers via Domino Difluorocyclopropanation/VCP
Rearrangement
Scheme 2. Synthesis of α,α-Difluorocyclopentanone
Derivatives
a
entry
10
R1
R2
R3
yield (%)
b
c,d
1
10a
10a
10b
10c
10d
10e
10f
Ph
Ph
H
H
61, 11a
83, 11a
80, 11b
79, 11c
71, 11d
73, 11e
74, 11f
74, 11g
60, 11h
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
Me
C6H4p-Me
C6H4p-Cl
n-Pr
H
H
H
Ph
Me
Ph
Br
Ph
10g
10h
10i
Ph
e
9
−(CH2)4−
Ph
f
g
10
H
54, 11i
a
b
c
TBS = Sit-BuMe2. 100 °C, 40 min. 19F NMR yield based on
d
Scheme 3. Synthesis of Di- and Monofluorocyclopentenone
Derivatives
(CF3)2C(C6H4p-Me)2. Vinyl(difluoro)cyclopropane 12 was obtained
in 16% yield. 20 mol % 6a, NaH (2 equiv), 100 °C. 10i (E:Z =
34:66). Single trans diastereomer. Siloxydiene 13 was obtained in
e
f
g
27% yield.
79% yields (entries 3 and 4), respectively. The reaction of
alkylated substrate 10d also worked well to give the product 11d
in 71% yield (entry 5). Substrates 10e−g, which bear
substituents at the internal position (R2), similarly afforded the
products 11e−g in 73−74% yields (entries 6−8). Silyl enol ether
10h, derived from cyclohexenyl methyl ketone, afforded the
bicyclic silyl enol ether 11h in 60% yield (entry 9).27 When the
substrate 10i, bearing a methyl group as R3, was employed, the
corresponding product 11i was obtained in 54% yield as a single
trans diastereomer along with siloxydiene 13 (27%) as a 1,5-
hydrogen shift product (entry 10).8a,b,28 Thus, the VCP
rearrangement of siloxy-substituted difluorovinycyclopropanes
was successfully accomplished for the first time.
Cyclic silyl enol ethers 11 were transformed to demonstrate
their utility for the synthesis of substituted α,α-difluorocyclo-
pentanones. The hydrolysis of 11a under acidic conditions
afforded α,α-difluorocyclopentanone 14 in 80% yield (Scheme
2); this ketone was unstable toward chromatographic
purification (silica gel and basic alumina) and distillation.
Treatment of 14 with tosylhydrazine afforded the corresponding
hydrazone 15 in 74% yield (a). The single-crystal X-ray structure
analysis of 15 confirmed that the difluoromethylene unit was
introduced at the position adjacent to the carbonyl group (see
the Supporting Information). Cyclopentanone 14 was also
derivatized to the corresponding oxime 16 in 87% yield (based
on 11a) with hydroxylamine hydrochloride in a one-pot
operation (b). Treatment of cyclopentanone 14 with sodium
borohydride afforded cyclopentanol 17 as a diastereomeric
mixture in quantitative yield (cis/trans = 64:36, c).29
diluted conditions (7 × 10−4 mol/L) gave difluorinated
cyclopentenone 18 in 86% yield (d).30 Oxidation of 11a with
m-chloroperbenzoic acid (mCPBA) gave the corresponding
epoxide 19 in 85% yield as a diastereomeric mixture (78:22). Its
desilylation with potassium hydrodifluoride led to the formation
of 3-fluorinated 2-hydroxycyclopent-2-en-1-one 20 in 54% yield
(e).31 The oxygenated cyclopentenone skeleton of 20 is found in
cyclotene that is used as a food additive with a caramel-like
flavor.32
In summary, the novel metal-catalyzed difluorocyclopropana-
tion of silyl enol ethers was accomplished using a pincer-type
nickel complex. The sequential difluorocyclopropanation/VCP
rearrangement of silyl dienol ethers provided synthetically useful
derivatives of di- and monofluorinated cyclopentanones and
cyclopentenones in good yields.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b02726.
Furthermore, the oxidative treatment of 11 afforded function-
alized fluorine-containing cyclopentenones (Scheme 3). Treat-
ment of 11a with N-bromosuccinimide (NBS) under highly
Experimental procedures and spectra of new compounds
(PDF)
C
DOI: 10.1021/acs.orglett.5b02726
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
760. (d) Song, X.; Chang, J.; Zhu, D.; Li, J.; Xu, C.; Liu, Q.; Wang, M.
Org. Lett. 2015, 17, 1712.
AUTHOR INFORMATION
Corresponding Author
■
(18) (a) Tian, F.; Kruger, V.; Bautista, O.; Duan, J.-X.; Li, A.-R.;
Dolbier, W. R., Jr.; Chen, Q.-Y. Org. Lett. 2000, 2, 563. (b) Dolbier, W.
R., Jr.; Tian, F.; Duan, J.-X.; Li, A.-R.; Ait-Mohand, S.; Bautista, O.;
Buathong, S.; Marshall Baker, J.; Crawford, J.; Anselme, P.; Cai, X. H.;
Modzelewska, A.; Koroniak, H.; Battiste, M. A.; Chen, Q.-Y. J. Fluorine
Chem. 2004, 125, 459.
(19) (a) Fuchibe, K.; Koseki, Y.; Sasagawa, H.; Ichikawa, J. Chem. Lett.
2011, 40, 1189. (b) Fuchibe, K.; Koseki, Y.; Aono, T.; Sasagawa, H.;
Ichikawa, J. J. Fluorine Chem. 2012, 133, 52. (c) Fuchibe, K.; Bando, M.;
Takayama, R.; Ichikawa, J. J. Fluorine Chem. 2015, 171, 133.
(20) (a) Inamoto, K.; Kuroda, J.-i.; Hiroya, K.; Noda, Y.; Watanabe, M.;
Sakamoto, T. Organometallics 2006, 25, 3095. (b) Inamoto, K.; Kuroda,
J.-i.; Sakamoto, T.; Hiroya, K. Synthesis 2007, 2007, 2853.
(21) When 6b was treated with TFDA (1.2 equiv) in the presence of
2,6-dimethylaniline (10 equiv), the ion corresponding to the isonitrile
complex was observed as a major product by HRMS analysis. See: Clark,
G. R.; Hoskins, S. V.; Jones, T. C.; Roper, W. R. J. Chem. Soc., Chem.
Commun. 1983, 719. Free isonitrile was generated only in 4% yield (1H
NMR analysis) when free difluorocarbene was generated in the presence
of 2,6-dimethylaniline (10 equiv).
(22) We compared the reactivities of silyl (di)enol ethers, alkynes, and
alkenes in the presence or absence of the metal complex. The observed
differences in reactivity suggest that the active species of our metal-
catalyzed system was not free carbene. See the Supporting Information.
(23) For the cyclopropanation of alkenes with nonfluorinated
nickel(II) and nickel(0) carbene complexes, see: (a) Nakamura, A.;
Yoshida, T.; Cowie, M.; Otsuka, S.; Ibers, J. A. J. Am. Chem. Soc. 1977,
99, 2108. (b) Davidson, J. G.; Barefield, E. K.; Derveer, D. G. V.
*E-mail: junji@chem.tsukuba.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research is supported by MEXT KAKENHI (Grant No.
24106705, J.I.), JSPS KAKENHI (Grant No. 15K05414, K.F.),
and Asahi Glass Foundation (K.F.).
REFERENCES
■
(1) Trost, B. M. Chem. Soc. Rev. 1982, 11, 141. (b) Heasley, B. Curr.
Org. Chem. 2014, 18, 641.
(2) (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity,
Applications; Wiley-VCH: Weinheim, 2004. (b) Uneyama, K. Organo-
fluorine Chemistry; Blackwell: Oxford, 2006.
(3) (a) Iguchi, K.; Kaneta, S.; Tsune, C.; Yamada, Y. Chem. Pharm. Bull.
1989, 37, 1173. (b) Meegalla, S. K.; Doller, D.; Liu, R.; Sha, D.; Lee, Y.;
Soll, R. M.; Wisnewski, N.; Silver, G. M.; Dhanoa, D. Bioorg. Med. Chem.
Lett. 2006, 16, 1702. (c) Fah, C.; Hardegger, L. A.; Baitsch, L.;
Schweizer, W. B.; Meyer, S.; Bur, D.; Diederich, F. Org. Biomol. Chem.
2009, 7, 3947.
(4) For our previous work on fluorocyclopentenones, see: Ichikawa, J.
Pure Appl. Chem. 2000, 72, 1685.
(5) (a) Nakano, T.; Makino, M.; Morizawa, Y.; Matsumura, Y. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1019. (b) Pravst, I.; Zupan, M.; Stavber, S.
Synthesis 2005, 2005, 3140. (c) Baudoux, J.; Cahard, D. Org. React. 2007,
69, 347.
Organometallics 1985, 4, 1178. (c) Kunzi, S. A.; Toro, J. M. S.; Hartog,
̈
T.; Chen, P. Angew. Chem., Int. Ed. 2015, 54, 10670.
(6) (a) Wong, H. N. C.; Hon, M. Y.; Tse, C. W.; Yip, Y. C.; Tanko, J.;
Hudlicky, T. Chem. Rev. 1989, 89, 165. (b) Baldwin, J. E. Chem. Rev.
(24) For isolated difluorocarbene complexes, see: (a) Clark, G. R.;
Hoskins, S. V.; Roper, W. R. J. Organomet. Chem. 1982, 234, C9.
(b) Koola, J. D.; Roddick, D. M. Organometallics 1991, 10, 591.
(c) Grushin, V. V.; Marshall, W. J. J. Am. Chem. Soc. 2004, 126, 3068.
(d) Hughes, R. P.; Laritchev, R. B.; Yuan, J.; Golen, J. A.; Rucker, A. N.;
Rheingold, A. L. J. Am. Chem. Soc. 2005, 127, 15020. (e) Martínez-
2003, 103, 1197. (c) Hudlicky, T.; Kutchan, T. M.; Naqvi, S. M. Org.
́
React. 1985, 33, 247.
(7) (a) Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95,
289. (b) Girard, C.; Amice, P.; Barnier, J. P.; Conia, J. M. Tetrahedron
Lett. 1974, 15, 3329. (c) Rousseau, G.; Slougui, N. Tetrahedron Lett.
1983, 24, 1251.
(8) (a) Dolbier, W. R., Jr.; Sellers, S. F. J. Am. Chem. Soc. 1982, 104,
2494. (b) Dolbier, W. R., Jr.; Sellers, S. F. J. Org. Chem. 1982, 47, 1. See
also: (c) Mitsch, R. A.; Neuvar, E. W. J. Phys. Chem. 1966, 70, 546.
(d) Smart, B. E.; Krusic, P. J.; Roe, D. C.; Yang, Z.-Y. J. Fluorine Chem.
2002, 117, 199.
́ ́ ́
Salvador, S.; Menjon, B.; Fornies, J.; Martín, A.; Uson, I. Angew. Chem.,
Int. Ed. 2010, 49, 4286. (f) Huang, D.; Koren, P. R.; Folting, K.;
Davidson, E. R.; Caulton, K. G. J. Am. Chem. Soc. 2000, 122, 8916. See
also ref 21. For spectroscopically observed difluorocarbene complexes,
see: (g) Reger, D. L.; Dukes, M. D. J. Organomet. Chem. 1978, 153, 67.
(h) Richmond, T. G.; Crespi, A. M.; Shriver, D. F. Organometallics 1984,
3, 314.
(9) Orr, D.; Percy, J. M.; Tuttle, T.; Kennedy, A. R.; Harrison, Z. A.
Chem. - Eur. J. 2014, 20, 14305.
(25) (a) Trnka, T. M.; Day, M. W.; Grubbs, R. H. Angew. Chem., Int. Ed.
2001, 40, 3441. (b) Takahira, Y.; Morizawa, Y. J. Am. Chem. Soc. 2015,
137, 7031.
(26) Although the nickel-catalyzed VCP rearrangement of vinyl-
cyclopropanes was reported, the effect of nickel catalyst 6a was not
obvious in our system. See: (a) Ryu, I.; Ikura, K.; Tamura, Y.; Maenaka,
J.; Ogawa, A.; Sonoda, N. Synlett 1994, 1994, 941. (b) Wang, S. C.;
Tantillo, D. J. J. Organomet. Chem. 2006, 691, 4386.
(10) Dolbier, W. R., Jr.; Battiste, M. A. Chem. Rev. 2003, 103, 1071.
(11) Experimental and theoretical studies indicate that the strain
energy of 1,1-difluorocyclopropane and the parent cyclopropane are
35.7−42.4 and 26.5−28.7 kcal/mol, respectively. See: (a) Liebman, J. F.;
Greenberg, A. Chem. Rev. 1976, 76, 311. (b) Khoury, P. R.; Goddard, J.
D.; Tam, W. Tetrahedron 2004, 60, 8103.
(12) Experimental and theoretical studies indicate that the lengths of
the C−C bonds distal and proximal to the geminal fluorine substituents
in 1,1-difluorocyclopropane are 1.553 and 1.464 Å, respectively, while
the length of the C−C bonds in the parent cyclopropane is 1.510 Å.
(13) (a) Miller, T. G.; Thanassi, J. W. J. Org. Chem. 1960, 25, 2009.
(b) Shen, T. Y.; Lucas, S.; Sarett, L. H. Tetrahedron Lett. 1961, 2, 43.
(14) (a) Birchall, J. M.; Cross, G. W.; Haszeldine, R. N. Proc. Chem. Soc.
1960, 81. (b) Knox, L. H.; Velarde, E.; Berger, S.; Cuadriello, D.; Landis,
P. W.; Cross, A. D. J. Am. Chem. Soc. 1963, 85, 1851.
(27) The VCP rearrangement of 10h in the absence of NaH resulted in
partial decomposition of the vinylcyclopropane intermediate.
(28) (a) Ellis, R. J.; Frey, H. M. J. Chem. Soc. 1964, 5578. (b) Roth, W.
R.; Konig, J. Liebigs Ann. 1965, 688, 28.
̈
(29) Oxime formation (a) and sodium borohydride reduction (c) of
ketone 14 in a one-pot operation gave poor results.
(30) Harrington, P. E.; Li, L.; Tius, M. A. J. Org. Chem. 1999, 64, 4025.
(31) Harrington, P. E.; Murai, T.; Chu, C.; Tius, M. A. J. Am. Chem. Soc.
2002, 124, 10091.
(15) (a) Seyferth, D.; Hopper, S. P.; Darragh, K. V. J. Am. Chem. Soc.
1969, 91, 6536. (b) Seyferth, D.; Hopper, S. P. J. Org. Chem. 1972, 37,
4070.
(32) Naoshima, Y.; Yamaguchi, M.; Kawai, M.; Ichimoto, I.; Ueda, H.
Agric. Biol. Chem. 1974, 38, 2273.
(16) (a) Brahms, D. L. S.; Dailey, W. P. Chem. Rev. 1996, 96, 1585.
(b) Ni, C.; Hu, J. Synthesis 2014, 46, 842.
(17) (a) Wu, S.-H.; Yu, Q. Acta Chim. Sin. 1989, 7, 253. (b) Oshiro, K.;
Morimoto, Y.; Amii, H. Synthesis 2010, 2010, 2080. (c) Kosobokov, M.
D.; Levin, V. V.; Struchkova, M. I.; Dilman, A. D. Org. Lett. 2015, 17,
D
DOI: 10.1021/acs.orglett.5b02726
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