Catalyst-controlled site-selective asymmetric epoxidation of nerylamine and geranylamine derivatives

Article abstract of DOI:10.1039/c7cc04809b

Novel catalysts for site- and enantioselective epoxidation of nerylamine and geranylamine derivatives have been developed. Although mCPBA oxidation took place selectively at the more electron-rich double bond to give the 6,7-epoxides, these catalysts provide the 2,3-epoxides in moderate to high enantioselectivity via the oxidation of the relatively electron-deficient double bond.

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
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Catalyst-Controlled Site-Selective Asymmetric Epoxidation of
Nerylamine and Geranylamine Derivatives
Tomoya Nobutaa and Takeo Kawabatab *
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Novel catalysts for site- and enantioselective epoxidation of and Miller reported siteꢀ and enantioselective epoxidation of
nerylamine and geranylamine derivatives have been developed. polyene compounds such as farnesol, geraniol, and nerol with
Wheres mCPBA oxidation took place selectively at the more peptideꢀbased catalysts.7 Inspired by these pioneering works,
electron-rich double bond to give the 6,7-epoxides, these catalysts we planned to develop catalysts for siteꢀ and enantioselective
provides the 2,3-epoxides in moderate to high enantioselectivity epoxidation of dienyl amine derivatives.
by the oxidation of relatively electron-deficient double bond.
Epoxidation is one of the most fundamental and important
transformations in organic synthesis. Sharpless and coꢀworkers
have developed hydroxy group directed asymmetric
epoxidation of allylic alcohol using titanium tartrates.1 This
method have been extensively utilized for the synthesis of
natural products and compounds of biological importance.2 On
the other hand, only limited examples of amino group directed
selective epoxidation have been reported. In 2005, Aggarwal
and Fang reported siteꢀselective epoxidation of
Fig. 1 Catalysts for a) site-selective acylation of carbohydrates,
and b) site- and enantioselective epoxidation of dienes.
geranylammonium tosylate using oxone.3 It has been reported
that the less nucleophilic allylic double bond underwent
selective epoxidation due to the ionic and hydrogen bonding
interaction between the ammonium cation and the
peroxymonosulfate anion. In 2012, Yamamoto and coꢀworkers
reported the first example of highly enantioselective
epoxydation of allylic amine derivatives with Hf(IV)ꢀ
bishydroxamic acid complexes 4
workers also reported asymmetric epoxidation of
.
More recently, He and coꢀ
ꢀalkenyl
N
sulfonamides catalyzed by Ti(IV)ꢀchiral Schiff base
complexes.5 Here, we report asymmetric epoxydation reactions
of dienyl amine derivatives with catalystꢀcontrolled siteꢀ
selectivity.
Siteꢀselective epoxidation of polyene compounds has
recently been receiving increasing attention. Bach and coꢀ
workers reported the siteꢀ and enantioselective epoxidation of
diene compounds controlled by hydrogen bonding interaction
between the substrate and the catalyst.6 More recently, Lichtor
Fig.
2
Diasretemeric Catalyst Library for Site- and
Enantioselective Epoxidation.
We reported the siteꢀselective acylation of glucose
derivatives and diol compounds using catalyst
1
(Figure 1).8
The salient feature of the acylation of the glucose derivatives is
that the acylation takes place at the intrinsically less reactive
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C(4)ꢀOH in the presence of the intrinsically more reactive product in 55% ee through the epoxidation of the relatively
primary C(6)ꢀOH. Thus, catalystꢀcontrolled siteꢀselective electronꢀdeficient 2,3ꢀdouble bond 4a 5a=85:15, 52%
acylation was achieved independent from the intrinsic reactivity combined yield, entry 2). Similarly, epoxide 4a was obtained
of the substrate. The side chain of catalyst (yellow ellipsoid) in good siteꢀselectivity under the conditions catalyzed by
was supposed to be responsible for the siteꢀselectivity. We 2b 2d 4a 5a=66ꢀ88:12ꢀ34, 42ꢀ52% combined yields, entries
envisaged that changing the active site for acylation in catalyst 3ꢀ5). In the presence of catalysts 2a 2d, epoxidation took place
(blue circle) to the active site suitable for epoxidation with in moderate enantioselectivity with the absolute
side chains retained for substrate recognition would create a stereochemistry reflecting the axial chirality of the 6,6’ꢀ
catalyst for siteꢀselective epoxidation. We designed catalyst dinitrodiphenic acid moiety of the catalysts. No epoxidation
(
:
1
~
(
:
ꢀ
1
2
possessing a carboxylic acid moiety as an active site for was observed in the absence of DIC or the catalyst (entries 6
epoxidation based on Miller’s peptideꢀbased catalysts with a and 7).11
carboxylic acid moiety, showing excellent properties for siteꢀ
and/or enantioseletive epoxidation.7,9 A 6,6’ꢀdinitrodiphenic Table 2 Optimization of the reaction conditions with catalyst
acid moiety was chosen as an active site based on the
2
expectation that axially chiral biphenyls would be responsible
for the enantioselective reaction10 and the electron withdrawing
nitro group might increase the rate of the peracid formation as
well as the reactivity of the resulting peracid. According to the
expectation, four diastereomeric catalysts 2aꢀ2d were prepared
(Figure 2).
Table 1 Effects of catalysts on site-and enantioselectivity of
epoxidation of diene 3a
Since the most promising enantioselectivity was obtained
by the epoxidation reaction catalyzed by 2a, we next attempted
to optimize the reaction conditions with 2a (Table 2). It was
found that the lower temperature was effective for both siteꢀ
selectivity and enantioselectivity (4a
entries 1ꢀ3). While the highest siteꢀselectivity (4a
enantioselectivity (91% ee) were obtained by the reaction at –
60 C, the desired product 4a was obtained only in a low yield
:
5a=94ꢀ98:2ꢀ6, 74ꢀ91% ee,
:
5a=98:2) and
°
(28%, entry 3), probably because aqueous hydrogen peroxide
was frozen at such a low temperature. By addition of MgSO4
for the purpose of removing water from aqueous hydrogen
peroxide, the desired product 4a was obtained in an improved
yield (4a:5a=95:5, 55% yield for 4a, entry 4). Prolongation of
the reaction time to 72 h further improved the results (4a (89%
ee):5a=98:2, 72% yield for 4a, entry 5). In order to confirm the
We chose nerylamine derivative 3a bearing
pꢀ
effects of MgSO4, the control experiment at 0
°C was
methoxybenzene sulfonamide (Mbs) group as a substrate
according to Yamamoto’s achivement.4 In order to investigate
the intrinsic reactivity of the diene moiety for the epoxidation,
performed (entry 6). The epoxidation of 3a under the identical
conditions as those for entry 2 in Table 1 except for the addition
of MgSO4 gave the comparable results (4a (65% ee):5a=84:16,
53% combined yield) with those in entry 2 in Table 1. These
results suggest the dehydrative effects of MgSO4 in the reaction
3a was treated with
mCPBA in the absence of the catalyst to
give 6,7ꢀepoxide 5a as the major product (4a
:
5a=4:96) through
the epoxidation of the more electronꢀrich 6,7ꢀdouble bond
(entry 1). On the other hand, treatment of 3a with 2.5
equivalents of aqueous H2O2 and 1.0 equivalent of N,N’ꢀ
diisopropylcarbodiimide (DIC) in the presence of 10 mol% of
catalyst 2a and 10 mol% of 4ꢀdimethylaminopyridine (DMAP)
at –60
The effects of the chain length and the aryl substituents of
substrates on the epoxidation with catalyst 2a under the
optimized reaction conditions are shown in Table 3. The
reaction of Mbsꢀprotected allyilc amine derivative 3b gave the
corresponding epoxide in much higher enantioselectivity (86%
°C.
3
in CHCl3 at 0 °C for 5 h gave 2,3ꢀepoxide 4a as the major
2 | J. Name., 2012, 00, 1-3
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ee) and yield (96% yield) than that of the homoallylic surrogate
Mechanistic insights into the origin of siteꢀselectivity were
, we envisaged that
suggests that the allylic amine is an appropriate structural unit hydrogen bonding interaction between the NHꢀgroup (hydrogen
for the recognition by the catalyst 2a The effects of bond donor) of the sulfonamide group of the substrate and the
arylsulfonyl group on the amino group of nerylamine amide carbonyl group (hydrogen bond acceptor) in the side
derivatives 3a and 3d on the siteꢀ and enantioselectivity were chain on the pyrrolidine ring of the catalyst would be the key
3c (28% ee and 26% yield) (entries 1 and 2). This observation investigated. On the catalyst design of
2
.
ꢀ
g
examined (entries 3ꢀ7). Nerylamine derivatives 3a and 3d with for the siteꢀselectivity based on our previous results concerning
electronꢀdonating groups on the benzenesulfonyl group siteꢀselective acylation of diol derivatives and alkene diols.8b,c
afforded the products with high siteꢀ and enantioselectivity (
(89%ꢀ90% ee): =98ꢀ99:2ꢀ1, 74ꢀ79% yields for , entries 3 and hydrogen bond donor, the corresponding NMeMbs derivative 3j
4). Further introduction of the methoxy group on the was subject to the epoxidation reaction under the conditions in
benzenesulfonyl group diminished the siteꢀ and entry 1 of Table 2 (Scheme 1). The reaction was sluggish and
enantioselectivity (4g (77% ee):5g=95:5, 56% yield for 4g gave 2,3ꢀepoxide 4j and 6,7ꢀepoxide 5j in a 3:97 ratio and the
4
In order to estimate the importance of the NHMbs as a
5
4
,
entry 7). Epoxidation of the nerylamine derivatives 3h and 3i combined yield of 15%. The obtained 4j was found to be
showed the similar substituent effects as those of the almost racemic (4% ee). The sharp contrast to the results in
nerylamine derivatives (entries 8 and 9). The nerylamine entry 1 of Table 2 employing the corresponding N
derivatives with a cisꢀ2,3ꢀdouble gave slightly better siteꢀ and derivative 2a clearly indicates the critical importance of the
enantioselectivity =95ꢀ99:5ꢀ1, 73ꢀ89% ee) than the hydrogen bond donor in the substrate for the siteꢀselectivity and
HMbs
(4:5
corresponding trans surrogates
(4a:5a=95:5, 62ꢀ80% ee) enantioselectvity of the epoxidation.
(entries 3 vs. 8, and entries 6 vs. 9).
Table 3 The effects of the chain length and the protective groups
of on the epoxidation with 2a
3
Scheme
1 Effects of the NMe group on the site- and
enantioselectivity of the catalyzed epoxidation
We had also envisaged that the 2,5ꢀdisubstituted pyrrolidine
moiety and the axially chiral biphenyl moiety of 2a would be
responsible for the siteꢀselectivity and the enantioselectivity,
respectively. We then examined the reaction with catalyst
lacking the pyrrolidine moiety (Table 4, entry 2). In contrast to
our expectation, the epoxidation with catalyst gave 4a (34%
ee, 65% yield) and 5a in a 94:6 ratio. Catalyst was found to
6,
6
6
be as effective as catalyst 2a concerning the siteꢀselectivity,
while it was much less effective than 2a from the viewport of
enantioselectivity (Table 4, entry 1 vs. 2). These results suggest
that siteꢀselectivity may be controlled mainly by the biphenyl
moiety with the amide group, and the pyrrolidine moiety seems
to responsible for increasing the enantioselectivity of the
epoxidation. The epoxidation reactions employing catalysts
suggest that the decrease in the acidity of N Ph resulted in
decreasing the ratio of the 2,3ꢀepoxide (entries 2ꢀ4). Catalyst
without the amide hydrogen gave the 6,7ꢀepoxide as the major
isomer in a low yield (4a 5a=38:62, 29% combined yield, entry
6ꢀ8
H
9
:
5). All of these results suggests that biphenyl moiety with the
amide NH group in catalyst 2a serve as a hydrogen bond donor
to effectively promote siteꢀ and enantioselective epoxidation.
As an alternative possibility, the classical Henbestꢀtype
interaction12 between the peracid moiety and the sulfonamide
NH group could be the direct origin of the siteꢀselective
formation of the 2,3ꢀepoxide. The epoxidation reactions of
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allylic sulfonamides have also been known to proceed derivatives by organocatalysis. Epoxidation catalyzed by 2a
stereoselectively due to the hydrogen bonding interaction provides the 2,3ꢀepoxides in high siteꢀselectvity and moderate
between the sulfonamide and the peracid.13 However, this to high enantioselectivity, whereas epoxidation by
m
CPBA
seems not to be the case for the present epoxidation reactions gave the 6,7ꢀepoxides. Further applications of 2a to the
catalyzed by 2a because epoxidation of 3a with
CPBA and chemoselective oxidation might to be expected.14
that catalyzed by both gave the 6,7ꢀepoxide as the major
m
9
product (entries 5 and 6).
Notes and references
Table 4 Effects of catalyst structure on the site-selectivity of
epoxidation of 3a
1
(a) T. Katsuki and K. B. Sharpless, J. Am. Chem. Soc., 1980,
102, 5974–5976; (b) R. M. Hanson, K. B. Sharpless, J. Org.
Chem. 1986, 51, 1922–1925; (c) Y. Gao, R. M. Hanson, J. M.
Klunder, S. Y. Ko, H. Masamune and K. B. Sharpless, J. Am.
Chem. Soc., 1987, 109, 5765–5780.
2
For the selectied examples, see: (a) T. R. Hoye and Z. Ye, J.
Am. Chem. Soc., 1996, 118, 1801ꢀ1802; (b) I. Paterson, C. D.
Savi and M. Tudge, Org. Lett., 2001, 3, 3149ꢀ3152; (c) K.
A. Parker and Y. ꢀH. Lim, J. Am. Chem. Soc., 2004, 126,
15968ꢀ15969; (d) T. Ichige, Y. Okano, N. Kanoh and M.
Nakata, J. Org. Chem., 2009, 74, 230ꢀ243.
3
4
5
6
V. K. Aggarwal and G. Y. Fang, Chem. Commun., 2005,
3448ꢀ3450.
J. L. OlivaresꢀRomero, Z. Li and H. Yamamoto, J. Am.
Chem. Soc., 2012, 134, 5440−5443.
N. Ji, J. Yuan, M. Liu, T. Lan and W. He, Chem. Commun.,
2016, 52, 7731ꢀ7734.
(a) P. Fackler, C. Berthold, F. Voss and T. Bach, J. Am.
Chem. Soc., 2010, 132, 15911ꢀ15913; (b) P. Fackler, S. M.
Huber and T. Bach, J. Am. Chem. Soc., 2012, 134, 12869ꢀ
12878.
7
8
(a) P. A. Lichtor and S. J. Miller, Nat. Chem., 2012, 4, 990ꢀ
995; (b) P. A. Lichtor and S. J. Miller, J. Am. Chem. Soc.
2014, 136, 5301–5308.
,
(a) T. Kawabata, W. Muramatsu, T. Nishio, T. Shibata and H.
Schedel, J. Am. Chem. Soc., 2007, 129, 12890ꢀ12895; (b) K.
Yoshida, K. Mishiro, Y. Ueda, T. Shigeta, T. Furuta and T.
Kawabata, Adv. Synth. Catal., 2012, 354, 3291ꢀ3298; (c) M.
Yamanaka, U. Yoshida, M. Sato, T. Shigeta, K. Yoshida, T.
Furuta and T. Kawabata, J. Org. Chem., 2015, 80, 3075ꢀ3082.
(a) G. Peris, C. E. Jakobsche and S. J. Miller, J. Am. Chem.
Soc., 2007, 129, 8710ꢀ8711; (b) G. Peris and S. J. Miller,
Org. Lett., 2008, 10, 3049–3052; (c) N. C. Abascal and S. J.
Miller Org. Lett., 2016, 18, 4646–4649.
Figure 3 shows a hypothetical transition state model of the
present siteꢀ and enantioselective epoxidation. Two types of
hydrogen bonding interactions between (1) the amide carbonyl
9
group (shown in red) on the pyrrolidine ring and ꢀNHSO2ꢀ (H
10 (a) E. L. Eliel, "Stereochemistry of Carbon Compounds"
(1962) McGrawꢀHill, New York (b) A. W. Ingersoll, J. R.
Little, J. Am. Chem. Soc., 1934, 56, 2123−2126.
11 (a) R. W. Murray and K. Iyanar, J. Org. Chem., 1998, 63,
1730ꢀ1731; (b) G. Majetich, R. Hicks, G. ꢀR. Sun and P.
McGill, J. Org. Chem., 1998, 63, 2564ꢀ2573.
shown in blue) of the substrate and (2) the amide NH group in
the biphenyl moiety (H shown in green) and sulfonyl group of
the substrate are expected to be responsible for the high siteꢀ
and enantioselectivity of the catalyzed epoxidation.
12 (a) H. B. Henbest and R. A. L. Wilson, J. Chem. Soc., 1957,
1958ꢀ1965; (b) M. Freccero, R. Gandolfi, M. SarziꢀAmadé
and A. Rastelli, J. Org. Chem., 2005, 70, 9573ꢀ9583.
Fig. 3 A hypothetical transition state model
13 (a) J. ꢀE. Bäckvall, K. Oshima, R. E. Palermo and K. B.
Sharpless, J. Org. Chem., 1979, 44, 1953–1957; (b) W. R.
Roush, J. A. Straub and R. J. Brown, J. Org. Chem., 1987, 52,
5127–5136; (c) A. Jenmalm, W. Berts, K. Luthman, I.
Csöregh, and U. Hacksell, J. Org. Chem., 1995, 60, 1026ꢀ
1032; (d) D. B. Berkowitz and M. L. Pedersen J. Org. Chem.
,
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Ensor, C. L. Hill, J. P. Kirby, M. J. Dearden, S. J. Oxenford
and C. M. Rosser, Org. Lett., 2003, 5, 4955ꢀ4957; (f) S.
Raghavan and V. S. Babu, Tetrahedron, 2011, 67, 2044ꢀ
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14 J. S. Alford, N. C. Abascal, C. R. Shugrue, S. M. Colvin, D.
K. Romney and S. J. Miller, ACS Cent. Sci., 2016, 2, 733ꢀ
739.
In conclusion, we report
a
method for siteꢀ and
enantioselective epoxidation of nerylamine and geranylamine
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