Asymmetric Synthesis of (?)-Dictyopterene C' and its Derivatives via Catalytic Enantioselective Cyclopropanation

Article abstract of DOI:10.1002/bkcs.12250

An efficient and simple method for enantioselective synthesis of (?)-dictyopterene C' and its derivatives was developed on the basis of chiral oxazaborolidinium ion-catalyzed enantioselective cyclopropanation and divinylcyclopropane-cycloheptadiene rearra

Full text of DOI:10.1002/bkcs.12250

Communication
DOI: 10.1002/bkcs.12250
BULLETIN OF THE
T. Kim et al.
KOREAN CHEMICAL SOCIETY
Asymmetric Synthesis of (−)-Dictyopterene C’ and its Derivatives via
Catalytic Enantioselective Cyclopropanation
†
†
*
Taehyeong Kim, Jae Yeon Kim, Kyung Yee Park, and Do Hyun Ryu
Department of Chemistry, Sungkyunkwan University, Jangan, Suwon 16419, Korea.
E-mail: dhryu@skku.edu
*
Received January 11, 2021, Accepted February 4, 2021, Published online February 18, 2021
An efficient and simple method for enantioselective synthesis of (−)-dictyopterene C’ and its derivatives
was developed on the basis of chiral oxazaborolidinium ion-catalyzed enantioselective cyclopropanation
and divinylcyclopropane-cycloheptadiene rearrangement. Utilizing the Julia-Kocienski reaction and
Sonogashira and Suzuki coupling reactions, various 1,4-cycloheptadiene compounds were synthesized
with good results.
Keywords: cis-Cyclopropane, Enantioselectivity, Lewis acid catalyst, Rearrangement,
1
,4-Cycloheptadiene
Cyclopropane, a strained small ring, is a structural unit
found in various natural products and bioactive molecules.
enantioselective cyclopropanation for the synthesis of cis-
dicarbonyl cyclopropanes and their application to total
synthesis of (−)-dictyopterene C’ and 1,4-cycloheptadiene
derivatives (Scheme 1(b)).
1
Enantioselective formation of multisubstituted cyclopro-
panes has become a powerful strategy as such compounds
serve as versatile building blocks in organic synthesis
through ring-opening reactions. Among substituted cyclo-
propanes, optically active dicarbonyl-substituted cyclopro-
panes have been applied to various synthetic methodologies
Enantioselective cyclopropanation was first examined
with α-bromoacrolein and tert-butyl diazoacetate in the
presence of 20 mol% of COBI catalyst 1a. When the
ꢀ
cyclopropanation was performed at −78 C in propionitrile
2
as important intermediates. Therefore, considerable atten-
as solvent, cis-2 was obtained as the major product instead
of trans-2 (Table 1, entry 1) in 66% yield with moderate
diastereomeric ratio. The cis relationship between the alde-
hyde and ester groups was confirmed by nuclear Over-
hauser effect (NOE) analysis. This result differed from our
previous cyclopropanation result with α-alkyl-α-diazoesters,
that produce trans-cyclopropane as the major product
(Scheme 1(a)). When the catalyst with a 3,5-dimethyl-
tion has been devoted to development of catalytic asymmet-
ric methods for easy access to multisubstituted dicarbonyl
cyclopropanes. Metal carbenoid-mediated reactions such as
Simmons−Smith type, transition-metal-catalyzed reactions,
and ylide-based cyclopropanation have been studied inten-
sively. However, the two carbonyl groups on the cyclopro-
pane are usually in the trans-configuration with each other.
Synthetic methods forming cis-dicarbonyl-substituted
1
phenyl Ar substituent was used, the desired product was
3
cyclopropanes have rarely been reported. Feng’s group uti-
obtained with >99% ee and a small increase than phenyl
1
lized a chiral diamine catalyst to promote cyclopropanation
Ar substituted 1a in diastereomeric ratio (Table 1, entry
4
between α,β-unsaturated ketones and sulfonium ylides.
2). Next, the effect of changing the boracycle substituent
2
In 2011, we reported enantioselective cyclopropanation
(Ar ) of COBI catalyst 1 was investigated (Table 1, entries
between diazoacetates and α,β-unsaturated aldehydes in the
3–6). Gratifyingly, using COBI 1f, which has an
1-naphthyl substituent at the boron center, greatly
5
8
presence of chiral oxazaborolidinium ion (COBI) catalyst
6
a
(
Scheme 1(a)). Furthermore, we extended the substrate
improved the yield to 93% and the diastereomeric ratio is
8:1 (Table 1, entry 6). The sterically bulkier diazo tert-butyl
ester gave higher enantio- and diastereoselectivity than the
corresponding diazo ethyl ester (Table 1, entries 6 and 7).
The cyclopropanation reaction with α-chloroacrolein under
optimized conditions provided the corresponding cis-2 in
3
scope to alkyl substituents (R = alkyl) and accomplished
total synthesis of (+)-hamavellone B (Scheme 1(a)).
6b
Encouraged by these results, we planned to synthesize
the 1,4-cycloheptadiene derivatives 4 from cis-divinyl
cyclopropane compound 3 via divinylcyclopropane-
7
9
cycloheptadiene rearrangement (DVCPR) and anticipated
78% yield with 88% ee (Table 1, entry 8).
that the optically active cis-dicarbonyl cyclopropane
To identify the absolute structure of cis-cyclopropane 2,
chemical transformation of 2 to lactone 6 was performed
2
would be a suitable precursor to various divinyl cyclo-
propane compounds 3. Herein, we describe catalytic
(Scheme 2). After radical debromination using Et B as an
3
initiator, reduction of the aldehyde at low temperature led
to alcohol product 5 in 54% overall yield. Trifluoroacetic
†These authors contributed equally to this work.
Bull. Korean Chem. Soc. 2021, Vol. 42, 675–678
© 2021 Korean Chemical Society, Seoul & Wiley-VCH GmbH
Wiley Online Library
675

Communication
ISSN (Print) 0253-2964 | (Online) 1229-5949
BULLETIN OF THE
KOREAN CHEMICAL SOCIETY
Scheme 2. Synthetic method to optically active lactone 6.
ꢀ
Reagents and conditions: (a) Et
3
B, n-Bu
3
SnH, n-hexane, −78 C,
ꢀ
4
h; (b) NaBH
4
, MeOH, −78 C, 1 h, 54% (2-step overall yield);
ꢀ
(
c) TFA, CH Cl
2
2
, −78 C, 4 h, 81%.
11
6
enantioselective Diels–Alder and cyclopropanation reac-
tions. In the pretransition-state assembly 7 shown in
Figure 1, the re face of acrolein is effectively blocked by the
3
,5-dimethylphenyl group of COBI 1. As the diazoacetate
Scheme 1. Enantioselective cyclopropanation (a) α-substituted-
α-diazoesters with α,β-unsaturated aldehydes, (b) tert-butyl
diazoacetate with α-bromoacrolein and synthetic route to
approaches the β-position of acrolein, the tert-butyl ester
moiety is situated away from the aldehyde moiety of
α-bromoacrolein due to a dipole–dipole interaction between
the carbonyl groups. Therefore, nucleophilic addition of tert-
butyl diazoacetate from the si face of the α-bromoacrolein is
facilitated and leads to intermediate 8. Cyclization with loss
of nitrogen gas provides (1S,2R)-cis-cyclopropane 2 as the
major product.
To demonstrate the utility of this stereoselective cis-
dicarbonyl cyclopropane synthesis, the total synthesis of
(−)-dictyopterene C’ was carried out (Scheme 3). Since a
(Z)-configuration of the substrates results in a significant
(−)-dictyopterene C’.
acid (TFA)-catalyzed intramolecular cyclization of 5 gave
chiral cyclopropyl lactone product 6 in 81% yield. Compar-
10
ison of the optical rotation data of 6 to the literature value
confirmed the absolute (1S,2R)-configuration of 2.
The observed stereochemistry for the enantioselective
cyclopropanation reaction with COBI catalyst 1 can be ratio-
nalized by the transition-state model shown in Figure 1. The
coordination mode of α,β-unsaturated aldehydes to catalyst
12
increase of the activation barrier
Julia-Kocienski olefination was considered to introduce
for the DVCPR,
13
1
is the same as has been previously suggested for
a
Table 1. Optimization of enantioselective cyclopropanation of tert-butyl diazoacetate and α-bromoacrolein.
2
b
c
d
Entry
1
2
X
R
cis/trans
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
a
1a
1b
1c
1d
1e
1f
2a
2a
2a
2a
2a
2a
2b
2c
Br
Br
Br
Br
Br
Br
Br
Cl
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Et
4.7:1
5:1
5:1
4:1
5.9:1
8:1
66
66
66
55
62
93
99
78
93
>99
>99
>99
95
97
87
88
1f
1f
4.2:1
3.8:1
t-Bu
The reactions of tert-butyl diazoacetate (0.24 mmol) with α-bromoacrolein (0.28 mmol) were performed in the presence of 1 (20 mol%) in
ꢀ
propionitrile at −78 C for 2 h.
b
c
d
1
Determined by H NMR analysis of the crude reaction mixture.
Yield of isolated products.
Determined by HPLC analysis on a chiral stationary phase.
Bull. Korean Chem. Soc. 2021, Vol. 42, 675–678
© 2021 Korean Chemical Society, Seoul & Wiley-VCH GmbH
www.bkcs.wiley-vch.de
676

BULLETIN OF THE
Communication
KOREAN CHEMICAL SOCIETY
Scheme 4. Synthesis of various 1,4-cycloheptadiene derivatives.
Since the bromo substituent of 1,4-cycloheptadienes 12
is easily transformed into a large variety of other moieties
Figure 1. Transition-state model for the enantioselective
cyclopropanation reaction.
with Pd(0) catalysis, further chemical transformations of
0
1
2a were carried out to prepare (−)-dictyopterene C deriv-
15
atives 13 and 14 (Scheme 4). Sonogashira coupling of
2a with phenyl acetylene under modified reaction condi-
tions provided 13 in 73% yield. Suzuki coupling of 12a
the (E)-alkene substituents of 10 instead of the Wittig reac-
tion, which is known to give (Z)-alkenes. Highly trans-
selective Julia-Kocienski olefination with 1-phenyl-1H-
1
16
17
with phenyl boronic acid in the presence of Pd(PPh3)4
tetrazole
9
and potassium bis(trimethylsilyl)amide
proceeded smoothly to give phenyl 1,4-cycloheptadienes
(KHMDS) provided (E)-alkenes 10 in good to high yields.
1
4 in 99% yield without obvious loss of enantiopurity.
In conclusion, we developed COBI-catalyzed
After reduction of the tert-butyl ester group to aldehyde by
diisobutylaluminum hydride (DIBAL-H), the Wittig reac-
tion with a methylphosphonium salt using n-butyllithium
introduced the vinyl group to produce divinylcyclopropane
products 3 for DVCPR. Interestingly, while there are some
reports that high temperature is required for DVCPR, cyclo-
propane 3 was not observed under the Wittig olefination
a
enantioselective cyclopropanation for the synthesis of
optically active cis-dicarbonyl cyclopropanes, which were
successfully applied to a convenient synthetic route to chi-
ral 1,4-cycloheptadiene derivatives. The efficient synthetic
process for enantioselective synthesis of (−)-dictyopterene
C’ was accomplished in 42% overall yield and five steps
from α-bromoacrolein and tert-butyl diazoacetate. More-
over, we synthesized various 1,4-cycloheptadiene derivatives
from 2-bromo-1,4-cycloheptadienes using Sonogashira and
Suzuki coupling reactions. Further chemical transformations
of cis-dicarbonyl cyclopropane compounds are underway in
our laboratory.
ꢀ
conditions at 0 C. Apparently all the cis-3 was transformed
to 1,4-cycloheptadienes 12 through the DVCPR endo-boat-
6
c
like transition-state 11. Finally, reduction of vinyl bro-
mide 12a in the presence of palladium catalyst afforded
desired (−)-dictyopterene C’ 4 in 5 steps and 42% overall
yield. Confirmation of the synthetic (−)-dictyopterene C’
was fully established through comparison of its physical
1
13
data including H and C NMR spectra and optical rota-
1
4
Acknowledgments. This work was supported by National
Research Foundation of Korea (NRF) grants funded by the
Korean government (MSIT) (nos. NRF-2019R1A2C2087018
and 2019R1A4A2001440) and by the 111 Project (D18012).
tion data to the reported data. Based on the synthetic
route in Scheme 3, various chiral 1,4-cycloheptadiene
derivatives 12a–c were synthesized in moderate to high
yields.
References
1
. (a) R. Csuk, M. J. Schabel, Y. von Scholz, Tetrahedron
Asymmetry 1996, 7, 3505. (b) D. K. Mohapatra, A. Datta,
J. Org. Chem. 1998, 63, 642. (c) J. S. Ravi Kumar, S. Roy,
A. Datta, Bioorg. Med. Chem. Lett. 1999, 9, 513. (d) X.
Zhang, K. Hodgetts, S. Rachwal, H. Zhao, J. W. F. Wasley,
K. Craven, R. Brodbeck, A. Kieltyka, D. Hoffman, M. D.
Bacolod, B. Girard, J. Tran, A. Thurkauf, J. Med. Chem.
2
000, 43, 3923. (e) W. A. Donaldson, Tetrahedron 2001, 57,
8
589. (f) Y. Nishii, N. Maruyama, K. Wakasugi, Y. Tanabe,
Bioorg. Med. Chem. 2001, 9, 33. (g) L. A. Wessjohann, W.
Brandt, Chem. Rev. 2003, 103, 1625.
2
. (a) B. M. Trost, J. L. Gunzner, O. Dirat, Y. H. Rhee, J. Am.
Chem. Soc. 2002, 124, 10396. (b) S. D. Larsen, T. Barf, C.
Liljebris, P. D. May, D. Ogg, T. J. O’Sullivan, B. J. Palazuk,
H. J. Schostarez, F. C. Stevens, J. E. Bleasdale, J. Med.
Chem. 2002, 45, 598. (c) B. M. Trost, O. Dirat, J. L.
Gunzner, Angew. Chem. Int. Ed. 2002, 41, 841. (d) M.-X.
Zhang, P. E. Eaton, Angew. Chem. Int. Ed. 2002, 41, 2169.
(e) J. A. Miller, E. J. Hennessy, W. J. Marshall, M. A.
Scheme 3. Stereoselective synthesis of (−)-dictyopterene C’ from
optically active cyclopropane 2. Reagents and conditions: (a) 9,
ꢀ
KHMDS, DME, −78 C, 30 min; (b) DIBAL-H (1.0 M in tolu-
ꢀ
ꢀ
ene), toluene, −78 C, 10 min; (c) MePPh
3
Br, n-BuLi (2.5 M in
, NaBH , TMEDA,
n-hexane), Et
2
O, 0 C, 24 h; (d) PdCl
2
(PPh
3
)
2
4
THF, reflux, 3 h, 80%.
Bull. Korean Chem. Soc. 2021, Vol. 42, 675–678
© 2021 Korean Chemical Society, Seoul & Wiley-VCH GmbH
www.bkcs.wiley-vch.de
677

BULLETIN OF THE
Communication
KOREAN CHEMICAL SOCIETY
Scialdone, S. T. Nguyen, J. Org. Chem. 2003, 68, 7884. (f)
U. S. Sørensen, T. J. Bleisch, A. E. Kingston, R. A. Wright,
B. G. Johnson, D. D. Schoepp, P. L. Ornstein, Bioorg. Med.
Chem. 2003, 11, 197. (g) J. K. Pokorski, M. C. Myers, D. H.
Appella, Tetrahedron Lett. 2005, 46, 915. (h) K. Kagayama,
T. Morimoto, S. Nagata, F. Katoh, X. Zhang, N. Inoue, A.
Hashino, K. Kageyama, J. Shikaura, T. Niwa, Bioorg. Med.
Chem. 2009, 17, 6959. (i) S. Chanthamath, S. Takaki, K.
Shibatomi, S. Iwasa, Angew. Chem. Int. Ed. 2013, 52, 5818.
. (a) E. E. Wilson, K. X. Rodriguez, B. L. Ashfeld, Tetrahe-
dron 2015, 71, 5765. (b) D. Yin, H. Liu, C.-D. Lu, Y.-J. Xu,
J. Org. Chem. 2017, 82, 3252. (c) W. Sun, C. Peng, Z. Yao,
F. Xu, Org. Biomol. Chem. 2019, 17, 6620.
9. When the reaction was performed with α-substituted acroleins
and diazoacetates in the presence of 20 mol % of 1,
2-pyrazolines were obtained as major products. For the
details, see L. Gao, G.-S. Hwang, M. Y. Lee, D. H. Ryu,
Chem. Commun 2009, (36), 5460.
10. M. Defosseux, N. Blanchard, C. Meyer, J. Cossy, J. Org.
Chem. 2004, 69, 4626.
11. (a) D. H. Ryu, E. J. Corey, J. Am. Chem. Soc. 2003, 125, 6388.
(b) D. H. Ryu, G. Zhou, E. J. Corey, J. Am. Chem. Soc. 2004,
126, 4800. (c) D. H. Ryu, E. J. Corey, J. Am. Chem. Soc. 2005,
127, 5384. (d) M. Y. Jin, G.-S. Hwang, H. I. Chae, S. H. Jung,
D. H. Ryu, Bull. Kor. Chem. Soc. 2010, 31, 727. (e) H. I. Chae,
G.-S. Hwang, M. Y. Jin, D. H. Ryu, Bull. Kor. Chem. Soc.
2010, 31, 1047. (f) S. H. Shin, J. H. Han, S. I. Lee, Y. B. Ha,
D. H. Ryu, Bull. Kor. Chem. Soc. 2011, 32, 2885.
12. (a) G. Ohloff, W. Pickenhagen, Helv. Chim. Acta 1969, 52, 880.
(b) J. E. Baldwin, C. Ullenius, J. Am. Chem. Soc. 1974, 96,
1542. (c) H. Günther, J.-B. Pawliczek, J. Ulmen, W. Grimme,
Chem. Ber. 1975, 108, 3141. (d) J. M. Brown, B. T. Golding,
J. J. Stofko, J. Chem. Soc. Perkin Trans 1978, 2, 436. (e) M. P.
Schneider, A. Rau, J. Am. Chem. Soc. 1979, 101, 4426.
13. (a) C. Aïssa, Eur. J. Org. Chem. 2009, 2009, 1831. (b) B.
Chatterjee, S. Bera, D. Mondal, Tetrahedron Asymmetry
2014, 25, 1. (c) D. Gueyrard, Synlett 2018, 29, 34.
3
4
. For the catalytic asymmetric synthesis of cis-dicarbonyl-
cyclopropane, see J. Wang, X. Liu, S. Dong, L. Lin, X. Feng,
J. Org. Chem 2013, 78, 6322.
5
. (a) E. J. Corey, Angew. Chem. Int. Ed. 2009, 48, 2100.
(
b) S. Y. Shim, D. H. Ryu, Acc. Chem. Res. 2019, 52, 2349.
. (a) L. Gao, G.-S. Hwang, D. H. Ryu, J. Am. Chem. Soc.
011, 133, 20708. (b) S. Y. Shim, J. Y. Kim, M. Nam, G.-S.
6
2
Hwang, D. H. Ryu, Org. Lett. 2016, 8, 160. (c) S. Y. Shim,
S. M. Cho, A. Venkateswarlu, D. H. Ryu, Angew. Chem. Int.
Ed. 2017, 56, 8663. (d) S. Y. Shim, Y. Choi, D. H. Ryu,
J. Am. Chem. Soc. 2018, 140, 11184.
7
. (a) T. Hudlicky, R. Fan, J. W. Reed, K. G. Gadamasetti, Org.
React. 1992, 41, 1. (b) S. Vshyvenko, J. W. Reed, T.
Hudlicky, E. Piers, Comprehensive Organic Synthesis, 2nd
ed., Vol. 5, Elsevier B.V, Amsterdam, 2014, p. 999. (c) S.
Krüger, T. Gaich, J. Beilstein, Org. Chem. 2014, 10, 163.
. Sterically bulky Lewis acid catalyst has improved the yield due
to avoidance of some competitive reactions. For the examples
of aluminium catalyst, see (a) M. B. Boxer, H. Yamamoto,
Org. Lett 2005, 7, 3127. (b) H. Yamamoto, K. Ishihara, Acid
Catalysis in Modern Organic Synthesis, Vol. 1, Wiley-VCH,
Weinheim, 2009, p. 241. For the examples of COBI catalyst,
see (c) L. Gao, B. C. Kang, G.-S. Hwang, D. H. Ryu, Angew.
Chem. Int. Ed 2012, 51, 8322. (d) S. I. Lee, J. H. Jang, G.-S.
Hwang, D. H. Ryu, J. Org. Chem. 2013, 78, 770. (e) S. I. Lee,
G.-S. Hwang, D. H. Ryu, J. Am. Chem. Soc. 2013, 135, 7126.
14. H. Imogai, G. Bernardinelli, C. Gränicher, M. Moran, J.-C.
Rossier, P. Müller, Helv. Chim. Acta 1998, 81, 1754.
15. (a) M. Nasrollahzadeh, M. Atarod, M. Alizadeh, A.
Hatamifard, S. M. Sajadi, Curr. Org. Chem. 2017, 21, 708.
(b) G. Albano, L. A. Aronica, Eur. J. Org. Chem. 2017, 48,
7204. (c) I. Kanwal, A. Mujahid, N. Rasool, K. Rizwan, A.
Malik, G. Ahmad, S. A. A. Shah, U. Rashid, N. M. Nasir,
Catalysts 2020, 10, 443.
16. (a) Z. Lu, S. Ma, J. Org. Chem. 2006, 71, 2655. (b) H. Park,
C. H. Park, S.-T. Kang, J. H. Jeon, R. Archary, J.-Y. Lee, P.
Kim, H. Jung, C.-S. Yun, J. Y. Hwang, D. H. Ryu, S. Y.
Cho, Bull. Kor. Chem. Soc. 2017, 38, 278.
17. (a) S. Kotha, K. Lahiri, D. Kashinath, Tetrahedron 2002, 58,
9633. (b) G. A. Molander, N. Ellis, Acc. Chem. Res. 2007,
40, 275. (c) R. Martin, S. L. Buchwald, Acc. Chem. Res.
2008, 41, 1461. (d) D. E. Jose, U. S. Kanchana, T. V.
Mathew, G. Anilkumar, J. Organomet. Chem. 2020, 927,
121538.
8
(f) S. I. Lee, K. E. Kim, G.-S. Hwang, D. H. Ryu, Org. Bio-
mol. Chem. 2015, 13, 2745. (g) S. T. Kim, R. P. Pandit, J.
Yun, D. H. Ryu, Org. Lett. 2021, 23, 213.
Bull. Korean Chem. Soc. 2021, Vol. 42, 675–678
© 2021 Korean Chemical Society, Seoul & Wiley-VCH GmbH
www.bkcs.wiley-vch.de
678