Organocatalytic enantioselective formal C(sp2)-H alkylation

Article abstract of DOI:10.1021/ja5117556

An organocatalytic enantioselective formal C(sp²)-H alkylation is reported. This alkylative desymmetrization of prochiral 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a bifunctional tertiary aminourea derivative, utilizes air-stable and inexpensive nitroalkanes as the alkylating agents, and delivers synthetically versatile five-membered carbocycles containing an all-carbon quaternary stereogenic center remote from the reaction site in excellent enantioselectivity.

Full text of DOI:10.1021/ja5117556

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Communication
Organocatalytic Enantioselective Formal C(sp2)-H Alkylation
Madhu Sudan Manna, and Santanu Mukherjee
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja5117556 • Publication Date (Web): 31 Dec 2014
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Organocatalytic Enantioselective Formal C(sp2)−H Alkylation
Madhu Sudan Manna, and Santanu Mukherjee*
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Department of Organic Chemistry, Indian Institute of Science, Bangalore - 560012, India
Supporting Information Placeholder
Scheme 1. Catalytic Enantioselective Alkylative Desymme-
trization of Cyclopentene-1,3-diones
ABSTRACT: An organocatalytic enantioselective formal
C(sp2)–H alkylation is reported. This alkylative desymmetrization
of prochiral 2,2-disubstituted cyclopentene-1,3-dione is catalyzed
by a bifunctional tertiary aminourea derivative, utilizes air-stable
and inexpensive nitroalkanes as the alkylating agents, and delivers
synthetically versatile five-membered carbocycles containing an
all-carbon quaternary stereogenic center remote from the reaction
site in excellent enantioselectivity.
The importance of chiral cyclopentanes as synthetically useful
building blocks and common structural motifs of complex targets
has stimulated considerable research activities on their enantiose-
lective synthesis.1 Among various methods for accessing these
enantioenriched carbocyclic frameworks, desymmetrization of
prochiral or meso compounds through catalytic enantioselective
transformations represents a powerful strategy.2 The biggest ad-
vantage of such asymmetric desymmetrization reactions lies in
their ability in controlling stereochemistry remote from the reac-
tion site. This aspect becomes particularly prominent for the crea-
tion of all-carbon quaternary stereogenic centers.
Inspired by the wide abundance of five-membered carbocyclic
frameworks in bioactive natural products3 and the challenges in
the enantioselective generation of all-carbon quaternary stereo-
genic centers,4 we have recently developed a highly efficient de-
symmetrization protocol for 2,2-disubstituted cyclopentene-1,3-
diones through a direct vinylogous nucleophilic addition of de-
conjugated butenolides.5 This reaction delivers densely functiona-
lized products containing three stereogenic centers with excellent
diastereo- and enantioselectivity. The construction of multiple
stereocenters through a single operation bears its own advantage
in creating stereochemical diversity. However, a desymmetriza-
tion reaction, in its strict sense, should proceed without the crea-
tion of any additional stereocenter and should result in the mini-
mum variation of the existing functionalities. Pursuing our interest
along this direction, we sought an alkylative desymmetrization
reaction of prochiral cyclopentene-1,3-diones (Scheme 1A). Such
a C(sp2)–H alkylation would not only create an all-carbon quater-
nary stereogenic center remote from the reaction site, but would
also represent an ideal desymmetrization. This type of reactions is
conventionally carried out using a two-step sequence consisting of
an asymmetric conjugate addition of a metalloalkyl or equivalent
species followed by oxidation (Scheme 1B).6 To this end, the
highly diastereo- and enantioselective Cu-catalyzed addition of
metalloalkyl reagents to cyclopentene-1,3-diones, developed by
Mikami and co-workers is particularly noteworthy.2c Despite im-
mense popularity of this strategy, a prominent drawback lies in
the limited accessibility and relatively high cost of the organome-
tallic alkyl source, besides demanding reaction conditions.
We became interested in a direct and step-economic enantiose-
lective alkylative desymmetrization of prochiral cyclopentene-
1,3-diones using an easily accessible, inexpensive and air-stable
alkyl source. The initial breakthrough towards finding such an
alkylating agent emerged as the fortunate consequence of our
futile attempt to facilitate a double Michael reaction of A for ge-
nerating a tricyclic compound B (Scheme 1C). Using nitrome-
thane as the nucleophile, this base-mediated reaction, instead
produced a methylated analog C as an equimolar mixture of two
atropisomers.7 This formal C(sp2)–H methylation reaction pre-
sumably proceeds via an addition-elimination-isomerization
pathway (Scheme 1C). Despite their growing application in enan-
tioselective synthesis,8 nitroalkanes, to the best of our knowledge,
have never been used as an alkyl source. This is particularly sur-
prising since the propensity of nitro as a leaving group is well
documented in the literature.9
Encouraged by this unexpected findings and considering the
easy accessibility and stability of a wide range of nitroalkanes, we
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embarked into applying this concept for the enantioselective al-
was conducted in CHCl3 at 25 °C (Table 1, entry 1). However, the
combination of 10 mol% of the Takemoto catalyst11 (I) and 1.5
equiv. of Na2CO3 resulted in complete conversion of 1a within 20
h and furnished the desired product 3aa with 20:80 er (Table 1,
entry 2). Encouraged by this moderate yet promising level of
enantioselectivity, a number of similar bifunctional catalysts were
evaluated.7 Cinchona alkaloid-derived thioureas were proved to
be good catalyst candidates (entries 3-5), particularly dihydroqui-
nine derived thiourea IV, which increased the enantioselectivity to
88:12 er (entry 5). Reaction medium offered some assistance7 and
the best results were obtained in trifluorotoluene (PhCF3), both in
1
2
3
4
5
6
7
8
kylative desymmetrization of prochiral 2,2-disubstituted cyclo-
pentene-1,3-diones (Scheme 1D). The results of this successful
enantioselective formal C(sp2)−H alkylation are presented through
this communication.
Our initial task was to identify a suitable catalyst system. We
reasoned that an enantiogroup-differentiating conjugate addition
(of nitroalkane or the corresponding nitronate) to cyclopentene-
1,3-diones is necessary to transform the prochiral center into an
all-carbon quaternary stereogenic center. Tertiary amino-
(thio)urea based bifunctional compounds were chosen as the cata-
lyst candidate to accomplish this task, given their widespread
precedence in activating nitroalkanes for various enantioselective
transformations.10
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Table 2. Scope of the Desymmetrization with respect to
Cyclopentene-1,3-dionea,b,c
Table 1. Catalyst Evaluation and Reaction Optimization
entry cat.
solvent
temp time conv. (%)a erb
(°C)
25
25
25
25
25
25
0
−10
−10
−10
−10
−20
−10
(h)
24
20
15
36
20
12
40
55
72
48
48
72
1
2
3
4
5
6
7
8
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
<5
>95
>95
>95
>95
>95
>95
>95
-
-
I
II
20:80
81.5:18.5
86:14
88:12
90:10
94:6
95:5
95:5
97:3
III
IV
IV
IV
IV
IV
V
VI
V
VII
9c
10
11
12
13
85
>95 (88)d
>95
94.5:5.5
97.5:2.5
6:94
b
aReactions were carried out on a 0.1 mmol scale. Yields correspond
>95
>95 (84)d
to the isolated yield. cEr was determined by HPLC analysis on a chiral
stationary phase. Value in parenthesis indicates the er after a single
48
d
aConversion of 1a as determined by H NMR of the crude reaction
1
recrystallization. eReaction was performed at 0 °C.
b
mixture. Enantiomeric ratio (er) was determined by HPLC analysis
on a chiral stationary phase. cUsing 5.0 equiv. nitromethane (2a).
dValues in parentheses represent isolated yield after column chroma-
tography.
terms of the enantioselectivity and the reaction rate (entry 6). The
latter factor allowed us to reduce the reaction temperature down to
−10 °C, when the product was obtained with 95:5 er (entry 8).
Reduction in the amount of nitromethane did not affect the enan-
tioselectivity, although the reaction rate was decreased signifi-
cantly (entry 9). The urea derivative V was found to be even more
efficient (entry 8 vs 10) and the dihydro-cinchona derivatives
were generally found to be superior compared to their dehydro
analogs.7 We have also tested the corresponding (E)-styryl deriva-
tive VI, without any beneficial effect (entry 11). Further im-
provement in er is possible by carrying out the reaction at −20 °C,
albeit at the expense of reaction rate (entry 12). Considering the
practicality, −10 °C was chosen as the working temperature for
the subsequent studies. We were pleased to find that the other
product antipode (ent-3aa) could be accessed with a reasonably
2
An important issue had to be resolved at the outset of this in-
vestigation: an equimolar amount of external base is necessary for
quenching the nitrous acid byproduct (see Scheme 1C) to prevent
catalyst poisoning. However, this external (achiral) base must not
catalyze the (non-selective) conjugate addition on its own.
It is against this backdrop, we began our studies with prochiral
2-benzyl-2-methylcyclopent-4-ene-1,3-dione 1a as the test sub-
strate and nitromethane (2a) as the alkylating agent (Table 1). A
survey of a small collection of bases7 revealed Na2CO3 to be the
suitable external base as no product formation could be detected
in the presence of 1.5 equiv. of Na2CO3 alone, when the reaction
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high er using the corresponding pseudoenantiomeric catalyst VII
After achieving the formal enantioselective C(sp2)−H methyla-
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3
4
5
6
7
8
under the optimized reaction conditions (entry 13).
tion with various 2,2-disubstituted cyclopentene-1,3-diones, we
turned our attention to alkylations using other nitroalkanes. The
results are summarized in Table 3. In this case only 4.0 equivalent
of nitroalkane was sufficient to reach a reasonable reaction rate.
Simple alkyl (3ab-ac, 3fb), benzylic (3ad-ae) as well as homo-
benzylic groups (3af-ag) were smoothly introduced in moderate
to good yield and in most cases with high er. Functionalized ni-
troalkanes containing amine (2h), amide (2i), alcohol (2j) and α,β-
unsaturated ketone (2l) could also be employed. Although the
products containing amine and amide functionalized alkyl groups
(3ah-ai) could be obtained with acceptable er, drastically reduced
enantioselectivities were observed in the case of 2-hydroxyethyl
(3aj) and 4-heptenone (3al). However, the TBS-protected
2-hydroxyethyl group could be introduced with good enantiose-
lectivity (3ak).
With the optimum catalyst identified and the reaction condi-
tions established (Table 1, entry 10), the generality of this alkyla-
tive desymmetrization reaction was explored. We initially focused
on elucidating the scope of cyclopentene-1,3-diones towards me-
thylation using nitromethane (2a). As revealed in table 2, a wide
range of 2,2-disubstituted cyclopentene-1,3-diones having differ-
ent substitution pattern at the quaternary center underwent facile
methylative desymmetrization under our optimized reaction con-
ditions. The substrates having the combination of a methyl, and
various sterically and electronically tuned benzylic substituents
were found to be the most suitable, and furnished the alkylated
products (3aa−ja) uniformly in high yield and with good to excel-
lent er in most cases (Table 2A). As exemplified with 3aa, essen-
tially enantiopure product could be obtained after a single recrys-
tallization. The single crystal X-ray analysis of 3aa revealed the
absolute configuration of our products,12 which was confirmed by
synthetic transformation to the known compounds (see Scheme
2A). The scope is not limited to benzylic substituents as similar
level of enantioselectivity was maintained with other cyclopen-
tene-1,3-diones containing allylic (Table 2B), alkyl and benzhy-
drylic substituents at the quaternary stereocenter (Table 2C). Not-
ably lower enantioselectivity observed in the case of 2-
chlorobenzyl (3ia) and phenyl-substituted diones (3oa) points out
the current limitation of our protocol. The combination of ethyl
and benzhydryl substrate was also studied: the corresponding
methylated product (3ra) was obtained with lower er (cf. 3pa) as
the reaction had to be conducted at 0 °C to achieve a reasonable
reaction rate.
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Having successfully developed
a formal enantioselective
C(sp2)-H alkylation, we directed our efforts to demonstrate the
synthetic utility of the resulting desymmetrized cyclopentene-1,3-
diones. Hydrogenation under Pd-catalysis proved to be complete-
ly diastereoselective, as illustrated by two examples (Scheme 2A).
The low yields of 4a-b are due to the formation of considerable
amount of the corresponding debenzylated products under the
reaction conditions. The relative and absolute stereochemistry of
4a-b have previously been confirmed by Mikami et al.2c and in
turn established the absolute configuration of our alkylated prod-
ucts. Reaction under Luche condition surprisingly led to the regi-
oselective reduction of the more hindered keto group of 3aa, even
though the reaction was found to be only moderately diastereose-
lective (5:1 dr). However, the diastereomerically pure alcohol 5
could be isolated in 55% yield after chromatographic purification
without any erosion of er (Scheme 2B). Weitz-Scheffer-type
epoxidation13 of 3aa, on the other hand, furnished 6 as a single
diastereomer in 78% yield (Scheme 2B).
Table 3. Scope of the Desymmetrization with regard to
Nitroalkanea,b,c
Scheme 2. Synthetic Transformations of the Desymme-
trized Adducts
In addition to the synthetic transformations discussed above,
the alkylated products were subjected to a second alkylation with
a different nitroalkane (Scheme 3). Using Cs2CO3 as the base,
these reactions required somewhat demanding conditions, but the
products containing unsymmetrical tetrasubstituted olefins were
obtained in excellent yield. For example, the methylated adduct
3aa upon reaction with nitroethane furnished (–)-7 in 90% yield.
More importantly, by simply reversing the sequence of nitroal-
kanes, the other product enantiomer can be accessed under the
influence of the same catalyst enantiomer: the ethylated adduct
3ab on treatment with nitromethane produced (+)-7 in 87% yield
(Scheme 3A). As a brief demonstration of the applicability of this
double alkylation protocol, we have synthesized the core structure
b
aReactions were carried out on a 0.1 mmol scale. Yields correspond
to the isolated yield. cEr was determined by HPLC analysis on a chiral
stationary phase.
3
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(8) of antibiotic natural product (+)-madindoline B14 in a single
lore) for his help with the X-ray structure analysis. We also thank
1
2
3
4
5
6
7
8
step from one of our desymmetrized products, 3na (Scheme 3B).
Thus, treatment of 3na with nitrobutane (2c) and Cs2CO3 under
refluxing toluene provided 8 in high yield after 12 h without com-
promising its stereochemical integrity. The stereoisomeric natural
product, madindoline A, can in principle be obtained similarly by
changing the sequence of nitrobutane and nitromethane.
Prof. N. Suryaprakash and Mr. Sachin Rama Chaudhari (SIF,
IISc, Bangalore) for their help with 1D-NOE.
REFERENCES
(1) For reviews, see: (a) Vaidya, T.; Eisenberg, R.; Frontier, A. J. Chem-
CatChem 2011, 3, 1531. (b) Habermann, J. Curr. Org. Chem. 2010,
14, 1139. (c) Kurteva, V. B.; Afonso, C. A. M. Chem. Rev. 2009, 109,
6809. (d) Shibata, T. Adv. Synth. Catal. 2006, 348, 2328. (e) Trost, B.
M. Angew. Chem., Int. Ed. 1986, 25, 1.
Scheme 3. Double Alkylation and the Synthesis of the Core
Structure of Madindolines
9
O
O
(A)
(2) For selected examples, see: (a) Werner, T.; Hoffmann, M.; Desh-
mukh, S. Eur. J. Org. Chem. 2014, 6630. (b) Prévost, S.; Dupré, N.;
Leutzsch, M.; Wang, Q.; Wakchaure, V.; List, B. Angew. Chem., Int.
Ed. 2014, 53, 8770. (c) Aikawa, K.; Okamoto, T.; Mikami, K. J. Am.
Chem. Soc. 2012, 134, 10329. (d) Mori, K.; Katoh, T.; Suzuki, T.; No-
ji, T.; Yamanaka, M.; Akiyama, T. Angew. Chem., Int. Ed. 2009, 48,
9652. (e) Yeung, Y.-Y.; Chein, R.-J.; Corey, E. J. J. Am. Chem. Soc.
2007, 129, 10346. (f) Wadamoto, M.; Phillips, E. M.; Reynolds, T. E.;
Scheidt, K. A. J. Am. Chem. Soc. 2007, 129, 10098. (g) Shintani, R.;
Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. J. Am. Chem.
Soc. 2005, 127, 54. (h) La, D. S.; Sattely, E. S.; Ford, J. G.; Schrock,
R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2001, 123, 7767. (i) Ohshi-
ma, T.; Kagechika, K.; Adachi, M.; Sodeoka, M.; Shibasaki, M. J.
Am. Chem. Soc. 1996, 118, 7108. For a review, see: (j) Manna, M. S.;
Mukherjee, S. Org. Biomol. Chem. 2015, 13, 18-24.
(3) For selected reviews, see: (a) Das, S.; Chandrasekhar, S.; Yadav, J. S.;
Grée, R. Chem. Rev. 2007, 107, 3286. (b) Biellmann, J.-F. Chem. Rev.
2003, 103, 2019. (c) Silva Jr., L. F. Tetrahedron 2002, 58, 9137. (d)
Faulkner, D. J. Nat. Prod. Rep. 2002, 19, 1. (e) Mehta, G.; Srikrishna,
A. Chem. Rev. 1997, 97, 671.
(4) For reviews, see: (a) Hawner, C.; Alexakis, A. Chem. Commun. 2010,
46, 7295. (b) Trost, B. M.; Jiang, C. Synthesis 2006, 369. (c) Christof-
fers, J.; Baro, A. Adv. Synth. Catal. 2005, 347, 1473. (d) Christoffers,
J.; Baro, A. Quaternary Stereocenters: Challenges and Solutions for
Organic Synthesis; Wiley-VCH: Weinheim, 2005.; (e) Douglas, C. J.;
Overman, L. E. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 5363.
(5) Manna, M. S.; Mukherjee, S. Chem. Sci. 2014, 5, 1627.
(6) (a) Kerr, W. J.; Pearson, C. M.; Thurston, G. J. Org. Biomol. Chem.
2006, 4, 47. (b) Matsuo, J.-i.; Aizawa, Y. Chem. Commun. 2005,
2399.
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Et
MeNO2
Cs2CO3
Me
Me
Ph
Ph
EtNO2
120 °C, 4 h
O
Me
Me
V
O
O
(10 mol%)
Me
3aa (97:3 er)
( )-7, 90% yield
Ph
Na2CO3
PhCF3
10 °C
O
O
Me
O
1a
Cs2CO3
Me
Me
Ph
Ph
MeNO2
110 °C, 6 h
EtNO2
Et
Et
O
O
3ab (95:5 er)
(+)-7, 87% yield
(B)
O
n-BuNO2 (2c)
Cs2CO3
O
n-Bu
n-Bu
Me
OH
Me
3na
(96:4 er)
OTBS
N
H
toluene (0.1 M)
120 °C, 12 h
80% yield
Me
Me
O
O
O
8, 96:4 er
(+)-madindoline B
Overall, we have developed an enantioselective alkylative de-
symmetrization of prochiral 2,2-disubstituted cyclopentene-1,3-
diones catalyzed by a dihydroquinine-based bifunctional urea
derivative. Using easily accessible, inexpensive and air-stable
nitroalkanes as the alkylating agent, this formal C(sp2)-H alkyla-
tion represents a near-ideal desymmetrization and delivers prod-
ucts containing an all-carbon quaternary stereogenic center in
good to excellent yields and with high enantioselectivities. The
mild reaction conditions allow for the introduction of various
functionalized alkyl groups. The possibility of a second alkylation
and its applications has also been demonstrated. This report, to
our knowledge, is the first example of the use of nitroalkanes as
the alkylating agent. We expect these findings to be of broader
consequences and applicable to other alkylative and related trans-
formations. Investigations along these lines are currently under-
way in our laboratory.
(7) See Supporting Information for details.
(8) (a) Aitken, L. S.; Arezki, N. R.; Dell’Isola, A.; Cobb, A. J. A. Synthe-
sis 2013, 45, 2627. (b) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri,
A.; Petrini, M. Chem. Rev. 2005, 105, 933.
(9) (a) Tamura, R.; Kamimura, A.; Ono, N. Synthesis 1991, 423. (b) Ba-
kuzis, P.; Bakuzis, M. L. F.; Weingartner, T. F. Tetrahedron Lett.
1978, 19, 2371. (c) Danishefsky, S.; Prisbylla, M. P.; Hiner, S. J. Am.
Chem. Soc. 1978, 100, 2918. (d) Seebach, D.; Hoekstra, M. S.; Prot-
schuk, G. Angew. Chem., Int. Ed. Engl. 1977, 16, 321. (e) Strumza, J.;
Altschuler, S. Isr. J. Chem. 1963, 1, 106. For reviews, see: (f) Hali-
mehjani, A. Z.; Namboothiri, I. N. N.; Hooshmand, S. E. RSC Adv.
2014, 4, 48022. (g) Ono, N. The Nitro Group in Organic Synthesis;
Wiley-VCH: New York, 2001; p 182. Also see: ref. 8b.
(10) For representative examples, see: (a) Qian, H.; Yu, X.; Zhang, J.;
Sun, J. J. Am. Chem. Soc. 2013, 135, 18020. (b) Quintavalla, A.; Lan-
za, F.; Montroni, E.; Lombardo, M.; Trombini, C. J. Org. Chem.
2013, 78, 12049. (c) Vakulya, B.; Varga, S.; Csámpai, A.; Soós, T.
Org. Lett. 2005, 7, 1967. (d) Okino, T.; Nakamura, S.; Furukawa, T.;
Takemoto, Y. Org. Lett. 2004, 6, 625.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, compound characterization data, HPLC
traces and crystallographic data for 3aa (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
(11) Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125,
12672.
(12) CCDC 1034440 contains the crystallographic data for 3aa (also
available as Supporting Information). These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www. ccdc.cam.ac.uk/data_request/cif.
sm@orgchem.iisc.ernet.in
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
(13) Weitz, E.; Scheffer, A. Chem. Ber. 1921, 54, 2344.
(14) Sunazuka, T.; Hirose, T.; Shirahata, T.; Harigaya, Y.; Hayashi, M.;
Komiyama, K.; Ōmura, S.; Smith, A. B. J. Am. Chem. Soc. 2000, 122,
2122.
We gratefully acknowledge financial support from DST, CSIR
and DAE. M.S.M thanks CSIR for a doctoral fellowship. Thanks
are expressed to Mr. Amar. A. Hosamani (SSCU, IISc, Banga-
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