Double axial chirality promoted asymmetric [2,3] Stevens rearrangement of N-cinnamyl l-alanine amide-derived ammonium ylides

Article abstract of DOI:10.1039/c4cc02536a

The base-induced asymmetric [2,3] Stevens rearrangement of N-cinnamyl tetraalkylammonium ylides derived from l-alanine amides proceeds via a double axially chiral intermediate to afford the corresponding α-substituted alanine derivatives with high enantio- and diastereoselectivities. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc02536a

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Double axial chirality promoted asymmetric [2,3]
Stevens rearrangement of N-cinnamyl L-alanine
amide-derived ammonium ylides†
Cite this: Chem. Commun., 2014,
50, 6860
Received 7th April 2014,
Accepted 1st May 2014
Eiji Tayama,* Noriko Naganuma, Hajime Iwamoto and Eietsu Hasegawa
DOI: 10.1039/c4cc02536a
www.rsc.org/chemcomm
The base-induced asymmetric [2,3] Stevens rearrangement of
N-cinnamyl tetraalkylammonium ylides derived from L-alanine
amides proceeds via a double axially chiral intermediate to afford
the corresponding a-substituted alanine derivatives with high enantio-
and diastereoselectivities.
The base-induced [2,3] Stevens rearrangement of N-allylic tetra-
alkylammonium ylides is a useful transformation for organic synthesis
because it converts a readily accessible C–N bond into a new C–C
bond. The rearrangement has been applied to the synthesis of
unnatural amino acid derivatives because it proceeds via a concerted
symmetry-allowed mechanism to yield the corresponding products
with high stereoselectivities.1 However, application of the asymmetric
version of the rearrangement remains limited. The asymmetric [2,3]
Stevens rearrangement has been achieved using stoichiometric
sources of chirality, such as a chiral auxiliary2 or by N-to-C chirality
transmission of N-chiral tetraalkylammonium ylides.3 In a similar
Scheme 1 Planning of asymmetric [2,3] Stevens rearrangement via memory
of chirality (eqn (2)) based on our previous work (eqn (1)).
protocol, chiral Lewis acid-mediated [2,3] sigmatropic rearrangement eqn (1)).7 This result encouraged us to pursue asymmetric Stevens
of N-allylic tertiary amines has also been reported.4 These methods rearrangements, which proceed via formation of the corresponding
require removal of the chiral auxiliary after the reaction or preparation intermediate B, for the structural design of tetraalkylammonium
of enantiomerically enriched N-chiral tetraalkylammonium salts as salts 1 (eqn (2)). Therefore, we selected an N-cinnamyl substituent as
substrates. This disadvantage limits the scope of substrates and a migrating group and prepared N-cinnamyl pyrrolidinyl-L-alanine
products. Therefore, the development of other methods for the cyclohexyl ester-derived ammonium salt 1a because it has a structure
asymmetric rearrangement is needed. Very recently, a chiral similar to the N-tosylethenyl substituent in A (three-atom chain with
isothiourea-catalyzed asymmetric [2,3] rearrangement was reported an aromatic moiety). The base-induced [2,3] Stevens rearrangement
by Smith’s group5 to solve the limitation. Herein, we report the of 1a with 1.2 equivalents of potassium tert-butoxide in THF at 0 1C
asymmetric [2,3] Stevens rearrangement via memory of chirality as afforded the corresponding product 2a in 51% yield as a single
another protocol by the use of an a-amino acid as the chirality source.6 diastereomer. However, no asymmetric induction was observed
Recently, we reported the asymmetric a-2-tosylethenylation (Table 1, entry 1). To take advantage of the asymmetric induction,
of N,N-dialkyl-L-amino acid esters via formation of non-racemic we next attempted the rearrangement of pyrrolidine amide derivative
intermediate A, which arises from the axial chirality between the 1b because the amide moiety was previously used for asymmetric
tetraalkylammonium cation and a-carbon to carbonyl (Scheme 1, a-alkylation via memory of chirality8 or chiral Lewis acid-mediated
asymmetric [2,3] sigmatropic rearrangement.4 However, the reaction
Department of Chemistry, Faculty of Science, Niigata University, Niigata, 950-2181,
also resulted in almost no selectivity (entry 2). We thought that
asymmetric induction would be obtained by introducing additional
axial chirality from the amide moiety. Therefore, we decided to use
Japan. E-mail: tayama@chem.sc.niigata-u.ac.jp; Fax: +81 25 262 7740
† Electronic supplementary information (ESI) available: Experimental details
(including selected NMR spectra) and crystallographic data. CCDC 995319 and
1,2,3,4-tetrahydroquinoline amide as an analogue of 1-naphthyl
carbonyl. This structure was used for asymmetric a-alkylation via
995320. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c4cc02536a
6860 | Chem. Commun., 2014, 50, 6860--6862
This journal is ©The Royal Society of Chemistry 2014

View Article Online
Communication
ChemComm
Table 1 Effects of N,N-substituents and amide moieties
Table 2 Effects of migrating groups and temperature
Yielda,b eec
Temp
(1C)
Yielda,b
(%)
eec
(%)
Entry R1
R2
R3
(%)
(%)
Entry
R1
R2
R3
1
2
3
4
5
6
7
8
–(CH2)4– OcHex
–(CH2)4– Pyrrolidin-1-yl
–(CH2)4– 3,4-Dihydroquinolin-1(2H)-yl
–(CH2)5– 3,4-Dihydroquinolin-1(2H)-yl
Me Me 3,4-Dihydroquinolin-1(2H)-yl
–(CH2)5– Indolin-1-yl
–(CH2)5– 5,6-Dihydrophenanthridin-5-yl
–(CH2)5– N(Me)Ph
a
b
c
d
e
f
g
h
i
51
52
74
71
60
56
65
0d
0
o7e
42
71
30
4
81
1
2
p-Cl-Ph
p-Br-Ph
p-Me-Ph
H
H
H
H
Ph
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
CH2Ph
iBu
l
0
0
0
0
0
47
45
58
54e
76
79
69
75
62
36
64
0
71
70
62
16
5
m
n
o
p
q
d
d
d
m
n
r
3
4d
5
nPr
6
7
8
9
10
11
12
13
H
Ph
Ph
Ph
p-Br-Ph
p-Me-Ph
Ph
0
3
ꢀ40
ꢀ78
ꢀ92
ꢀ78
ꢀ78
0
81
89
91
86
85
—
—
—
9
10
11
–(CH2)5– N(Me)CHPh2
58
31
26
o7e
o2e
64
–(CH2)5– N(Me)OMe
j
k
–(CH2)5– N(Me)OtBu
a
c
Isolated yield. b Obtained as a single diastereomer. Determined by HPLC
Ph
s
0
0
d
analysis using a chiral column. [1,2] Stevens rearrangement at the piper-
a
b
idinyl ring afforded 9 (see, ref. 12). e Not baseline separation in HPLC.
Isolated yield. Unless otherwise noted, product 2 was obtained as a
c
single diastereomer. Determined by HPLC analysis using a chiral
column. E/Z = 15/85. The same diastereomer with the reaction of
1d (2d: Table 1, entry 4) was obtained as a major product (9/1 dr).
d
e
memory of chirality.9 We prepared 1c and performed the reaction
under the same conditions. The desired product 2c was obtained in
74% yield with 42% ee (entry 3) as determined by chiral HPLC. The
asymmetric induction was improved to 71% ee using piperidinyl (entry 4). The same diastereomer derived from E-cinnamyl derivative
derivative 1d (entry 4).10 However, the use of N,N-dimethyl derivative 1d (Table 1, entry 4) was obtained as a major product (ca. 9/1 dr). The
1e resulted in lower enantioselectivity (entry 5, 30% ee). These results use of N-(hex-2-en-1-yl)- or N-allyl derivatives 1p and 1q resulted in no
may indicate that the asymmetric induction was improved by the asymmetric induction (entries 5 and 6). The ee of 2d improved (up to
double axial chirality between the N–C(a) bond and the CO–N bond. 91% ee) when the rearrangement was performed at a lower tem-
To investigate the additional structural requirements, we prepared perature (entries 7–11, from ꢀ40 to ꢀ92 1C). The L-phenylalanine
amides 1f–1k and carried out their reactions. Use of indoline amide and leucine derivatives 1r and 1s, did not afford the corresponding
1f as an analogue of 1d resulted in no asymmetric induction (entry 6, [2,3] Stevens rearrangement products 2 (entries 12–13) due to the
4% ee). The rearrangement of phenanthridine amide 1g, which is same undesirable [1,2] Stevens rearrangement at the piperidinyl ring
known as a readily removable amide,11 afforded 2g in a similar yield in the reaction with 1h, which is depicted in Table 1.
with improved enantioselectivity (entry 7, 81% ee). The reaction of
Finally, the removal of the N,N-substituent and the amide moiety
N-methylaniline amide 1h as an acyclic aromatic amide did not from the product was examined (Scheme 2). The rearrangement of
afford desired product 2h due to undesirable [1,2] Stevens rearrange- 4,4-dimethoxypiperidinyl ammonium salt 3 afforded 4 in 65% yield
ment at the piperidinyl ring (entry 8).12 The use of a bulky tertiary with 9/1 dr. The enantioselectivities of the major and minor
amide, such as N-diphenylmethyl-N-methyl amide 1i, did not diastereomers were 80% ee and 81% ee, respectively. The piperidinyl
result in asymmetric induction (entry 9). Interestingly, although ring, as in 4, was removed after acid hydrolysis to aminoketone 5.
the rearrangement of Weinreb amide 1j did not exhibit any enantio- Treatment of 5 with the aminomethylated polystyrene resin14
selectivity (entry 10), O-tert-butyl analogue 1k yielded 2k in 26% afforded the corresponding primary amine 6 in 83% overall yield.
yield with 64% ee (entry 11). We tested analogous bases and other After N-benzoylation to 7 in 86% yield, the amide moiety was
solvents, such as solid potassium tert-butoxide, sodium tert-butoxide removed under mild oxidative conditions11 to afford the corres-
in THF, or potassium bis(trimethylsilyl)amide (KHMDS), dichloro- ponding oxazolone 8 in 79% yield. The absolute configuration of the
methane, tert-butyl methyl ether, acetonitrile, DMF, DMSO, and tert- major diastereomer of 8 was determined to be (4R,10S) by compar-
1
butanol, but did not observe improvements.13
ison of the H NMR spectra, the value of the optical rotation, and
To define the scope and limitations of the present asymmetric HPLC retention time with those reported for 8. Therefore, the
[2,3] Stevens rearrangement, we prepared various types of N-allylic- absolute configuration of the major diastereomer of 4 was deter-
L-amino acid amide-derived ammonium salts 1l–1s and performed mined to be (2R,3S).15 The relative stereochemistry of 4 was con-
their rearrangements (Table 2). The reaction of para-substituted- firmed by a single-crystal X-ray analysis of rac-4 prepared from rac-3.
cinnamyl derivatives 1l–1n resulted in the corresponding [2,3]
To discuss about the mechanism of this asymmetric induc-
rearrangement products 2l–2n at the same levels of the enantio- tion, a single-crystal X-ray analysis of the hexafluorophosphate
enriched form (entries 1–3). Interestingly, the rearrangement of salt of 1d (1d-PF6) was performed (Fig. 1). The analysis showed
Z-cinnamyl derivative 1o (E/Z = 15/85) created 2d with 16% ee the conformation of cinnamyl and 1,2,3,4-tetrahydroquinoline
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 6860--6862 | 6861

View Article Online
ChemComm
Communication
Notes and references
´
1 For reviews: (a) I. E. Marko, in Comprehensive Organic Synthesis, ed.
B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, ch. 3.10, vol. 3;
(b) J. B. Sweeney, Chem. Soc. Rev., 2009, 38, 1027; (c) J. A. Vanecko,
H. Wan and F. G. West, Tetrahedron, 2006, 62, 1043.
2 (a) T.-S. Zhu and M.-H. Xu, Chem. Commun., 2012, 48, 7274;
(b) E. Tayama, K. Takedachi, H. Iwamoto and E. Hasegawa, Tetra-
hedron Lett., 2012, 53, 1373; (c) E. Tayama, K. Orihara and H. Kimura,
Org. Biomol. Chem., 2008, 6, 3673; (d) J. B. Sweeney, A. Tavassoli and
J. A. Workman, Tetrahedron, 2006, 62, 11506; (e) J. A. Workman,
N. P. Garrido, J. Sançon, E. Roberts, H. P. Wessel and J. B. Sweeney,
J. Am. Chem. Soc., 2005, 127, 1066.
´
3 (a) A. P. A. Arbore, D. J. Cane-Honeysett, I. Coldham and
M. L. Middleton, Synlett, 2000, 236; (b) K. W. Glaeske and
F. G. West, Org. Lett., 1999, 1, 31; (c) K. Hiroi and K. Nakazawa,
Chem. Lett., 1980, 1077.
4 (a) J. Blid, O. Panknin, P. Tuzina and P. Somfai, J. Org. Chem., 2007,
72, 1294; (b) J. Blid, O. Panknin and P. Somfai, J. Am. Chem. Soc.,
2005, 127, 9352.
5 T. H. West, D. S. B. Daniels, A. M. Z. Slawin and A. D. Smith, J. Am.
Chem. Soc., 2014, 136, 4476.
6 For reviews: (a) J. Eames and M. J. Suggate, Angew. Chem., Int. Ed.,
2005, 44, 186; (b) H. Zhao, D. C. Hsu and P. R. Carlier, Synthesis,
2005, 1; (c) K. Fuji and T. Kawabata, Chem. – Eur. J., 1998, 4, 373.
7 E. Tayama, T. Igarashi, H. Iwamoto and E. Hasegawa, Org. Biomol.
Chem., 2012, 10, 339.
¨
8 T. Kawabata, O. Oztu¨rk, J. Chen and K. Fuji, Chem. Commun., 2003,
162.
Scheme 2 Removal of N,N-substituent and the amide moiety of 4.
9 (a) M. Branca, S. Pena, R. Guillot, D. Gori, V. Alezra and
C. Kouklovsky, J. Am. Chem. Soc., 2009, 131, 10711; (b) M. Branca,
D. Gori, R. Guillot, V. Alezra and C. Kouklovsky, J. Am. Chem. Soc.,
2008, 130, 5864; (c) T. Kawabata, K. Yahiro and K. Fuji, J. Am. Chem.
Soc., 1991, 113, 9694.
10 We performed the reaction of non-racemic substrate 1d (50% ee)
and obtained the result against the % ee of the product 2d (32% ee).
A non-liner effect was not observed.
11 (a) K. Narasaka, T. Hirose, T. Uchimaru and T. Mukaiyama, Chem.
Lett., 1982, 991; (b) T. Uchimaru, K. Narasaka and T. Mukaiyama,
Chem. Lett., 1981, 1551.
12 Undesirable [1,2] Stevens rearrangement product 9 was obtained in
55% yield as an almost single diastereomer, which was derived from
ammonium ylide C. The compound data for 9 are summarized in
the ESI.† The stereochemistry of 9 was not determined. A recent
study on competitive [2,3] and [1,2] sigmatropic rearrangements,
see: B. Biswas, S. C. Collins and D. A. Singleton, J. Am. Chem. Soc.,
2014, 136, 3740.
Fig. 1 Proposed transition state in the rearrangement of 1.
amide moieties. Thereby, we proposed that the rearrangement
would proceed on the Re-face through the exo transition state
(exo TS) leading to the (2R,3S) isomer. The formation of the
endo transition state (endo TS) leading to the (2R,3R) isomer
would be inhibited by steric repulsion with the amide moiety,16
due to which the CO–N bond is not planar by the axial chirality.
In conclusion, we have reported the base-induced asymmetric
[2,3] Stevens rearrangement of N-cinnamyl tetraalkylammonium
ylides derived from L-alanine amides, which proceeds via a
double axially chiral intermediate to afford the corresponding
a-substituted alanine derivatives with high enantio- and diastereo-
selectivities. The N,N-substituents and the amide moiety of the
rearrangement product were successfully removed.
13 The results are summarized in the ESI†.
14 (a) P. Aschwanden, C. R. J. Stephenson and E. M. Carreira, Org. Lett.,
´
2006, 8, 2437; (b) P. Renaud and I. Betrisey, Synth. Commun., 1995,
25, 3479.
15 (a) W. Chen and J. F. Hartwig, J. Am. Chem. Soc., 2013, 135, 2068;
(b) M. Kawatsura, H. Tsuji, K. Uchida and T. Itoh, Tetrahedron, 2011,
67, 7686.
16 Previous Studies about exo/endo TS: (a) A. Nash, A. Soheili and
U. K. Tambar, Org. Lett., 2013, 15, 4770; (b) A. Soheili and
U. K. Tambar, J. Am. Chem. Soc., 2011, 133, 12956. See also,
ref. 1a,b, 2d–e, 4 and 5.
This work was financially supported by the Union Tool
Scholarship Foundation.
6862 | Chem. Commun., 2014, 50, 6860--6862
This journal is ©The Royal Society of Chemistry 2014