Vicinal Functionalization of N-Alkoxyenamines: Tandem Umpolung Phenylation-Nucleophilic Addition Reaction Sequence

Article abstract of DOI:10.1002/ejoc.201500308

The vicinal functionalization of N-alkoxyenamines, derived in situ from aldehydes and isoxazolidines, has been achieved with the formation of two new carbon-carbon bonds by utilizing an organo-aluminum reagent and subsequent allylmagnesium bromide or tributyltin cyanide as external carbon-centered nucleophiles. By changing the second carbon nucleophile, various amine derivatives were obtained in good yields. An efficient and four-component reaction was developed. The double nucleophilic reaction of N-alkoxyenamines, derived in situ from aldehyde and isoxazolidine, afforded functionalized amines.

Full text of DOI:10.1002/ejoc.201500308

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201500308
Vicinal Functionalization of N-Alkoxyenamines: Tandem Umpolung
Phenylation–Nucleophilic Addition Reaction Sequence
Shohei Sato,[a] Norihiko Takeda,[a] Tetsuya Miyoshi,[a] Masafumi Ueda,[a] and
Okiko Miyata*[a]
Keywords: Umpolung / Nucleophilic addition / Aldehydes / Alkoxyamines / Enamines / Imines
The vicinal functionalization of N-alkoxyenamines, derived
in situ from aldehydes and isoxazolidines, has been achieved
with the formation of two new carbon–carbon bonds by
utilizing an organo-aluminum reagent and subsequent allyl-
magnesium bromide or tributyltin cyanide as external
carbon-centered nucleophiles. By changing the second
carbon nucleophile, various amine derivatives were obtained
in good yields.
of the enamine, before it decomposes. Therefore,
nucleophilic addition to the imine intermediate is efficient
when it occurs in an intramolecular manner, and cyclic
compounds such as 2,3,4-trisubstituted tetrahydroquinol-
ines,[10] 1,3-diaminotetralines,[11] and other cycloadducts[12]
are obtained by vicinal functionalization of enamines
[Scheme 1, Equation (2)]. In contrast, intermolecular
nucleophilic addition to the imine intermediate is virtually
unknown. The aforementioned approaches are generally
achieved by using a combination of an electrophile and a
nucleophile, with the exception of the radical reaction
[Scheme 1, Equations (1) and (2)]. Herein we report the suc-
cessful vicinal functionalization of an N-alkoxyenamine by
double nucleophilic reaction using two different nucleo-
philes [Scheme 1, Equation (3)]. The development of novel
vicinal functionalization utilizing a double nucleophilic re-
action clearly offers new perspectives in the chemistry of
enamines.
The concept of a double nucleophilic addition to the alk-
ene part of an enamine is outlined in Scheme 2. To intro-
duce two carbon-centered nucleophiles to the enamine de-
rivative, it is necessary that the alkene acts as a dication
equivalent for successful transformation. Therefore, we en-
visioned that N-alkoxyenamine 3, which is generated in situ
from aldehyde 1 and isoxazolidine, could act as a formal
and vicinal dication equivalent, because the umpolung reac-
tion[13] of N-alkoxyenamine 3 could generate imine B by
coordination with the first nucleophile (Nu1–M) followed
by N–O bond cleavage and simultaneous nucleophilic at-
tack of Nu1–M (Cβ-position) (Scheme 2). This imine B
would be masked in situ by the tethered metal alkoxide to
form N,O-acetal C, which would contribute to the stabiliza-
tion of imine B. The subsequent second addition of a
carbon-centered nucleophile (Nu2–M) to imine B could
then proceed to afford the α,β-disubstituted amine 2. Al-
though this reaction sequence represents the vicinal intro-
Introduction
Interest in the use of enamines and enamides in synthetic
organic chemistry has increased in recent times.[1,2] Vicinal
functionalization of the C=C double bond on enamines or
enamides is a predominant strategy for the synthesis of
various α,β-disubstituted amines, which are common motifs
of natural products and biologically active com-
pounds.[2a,2c,2f,3] Because enamides probably display a fine
balance of stability and reactivity compared with enamines,
vicinal functionalization of enamides by two carbon–
carbon bond formations has received much attention.[2a] In
particular, the sequential reaction of an enamide with an
electrophile (Cβ-position), followed by addition of a nucleo-
phile (Cα-position) to the resulting acylimine is a most reli-
able method [Scheme 1, Equation (1), Type I].[4] Several
other methods have also been developed for vicinal func-
tionalization, including transition-metal-catalyzed function-
alization [Scheme 1, Equation (1), Type I],[5,6] photoredox-
catalyzed carbotrifluoromethylation by a radical/cationic
pathway [Scheme 1, Equation (1), Type II],[7] a tandem radi-
cal reaction [Scheme 1, Equation (1), Type III],[8] and tan-
dem β-alkylation–α-arylation [Scheme 1, Equation (1),
Type IV].[9] In contrast, less is known about the vicinal
functionalization of enamines involving two carbon–carbon
bond formations due to the instability of both the enamine
substrate and the imine intermediate. Because the imine is
formed in situ by reaction of the enamine with an electro-
phile and is generally unstable, the reaction of the inter-
mediary imine with a nucleophile should proceed smoothly
for a successful vicinal functionalization of the alkene part
[a] Kobe Pharmaceutical University
Motoyamakita, Higashinada, Kobe 658-8558, Japan
E-mail: miyata@kobepharma-u.ac.jp
http://www.kobepharma-u.ac.jp/english/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500308.
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O. Miyata et al.
SHORT COMMUNICATION
Scheme 1. Vicinal functionalization of enamines and enamides.
duction of two carbon nucleophiles to N-alkoxyenamine 3, proceeded smoothly to afford α-phenylaldehyde 4a as a re-
we believe that there have been no reports on the vicinal sult of the formation of enamine 3a and subsequent phen-
functionalization of enamines by double carbon nucleo- ylation (Table 1, Entry 1). Notably, an increase in the
philes. In this report, we describe the novel vicinal function- amount of triphenylaluminum reagent (3 equiv.) led to an
alization of an N-alkoxyenamine by sequential umpolung increased yield of α-phenylaldehyde 4a (82%; Table 1, En-
β-phenylation (Nu1–M = Ph3Al) and allylation and cyan- try 2). In contrast, a significant decrease in the yield was
ation (Nu2–M = allylMgBr and Bu3SnCN).
observed when the amount of isoxazolidine was reduced
to 1 equiv. (Table 1, Entry 3). Therefore, to achieve good
conversion and yield, 2 equiv. of isoxazolidine and 3 equiv.
of triphenylaluminum were considered necessary for this re-
action.
Table 1. One-pot umpolung β-phenylation of N-alkoxyenamine 3a.
Scheme 2. Umpolung β-phenylation and sequential nucleophilic
addition to N-alkoxyenamine 3.
Entry
Isoxazolidine [equiv.]
Ph3Al [equiv.]
Yield[a] [%]
1
2
3
2
2
1
2
3
3
66
82
49
[a] Yields are for chromatographically pure product.
Results and Discussion
To accomplish this kind of vicinal introduction of carbon
nucleophiles, we first optimized the umpolung β-phen-
With the optimal reaction conditions for the umpolung
ylation of N-alkoxyenamine 3a, prepared in situ from n- reaction in hand, we next investigated the umpolung β-
hexanal (1a), with regard to the amounts of isoxazolidine phenylation of enamine 3, generated in situ from the corre-
and triphenylaluminum reagents (Table 1). This reaction sponding aldehyde and isoxazolidine through a one-pot
corresponds to the first step of the double nucleophilic reac- procedure (Table 2). The aldehyde 1b with an aliphatic long
tion of the enamine. In our previous report,[13b] we de- chain gave the corresponding α-phenylated product 4b in
scribed that the one-pot reaction involving N-alkoxyen- good yield (Table 2, Entry 1). Similarly, aldehydes 1c, 1d,
amine formation and the umpolung reaction of ketones was and 1e bearing phenyl, terminal alkenyl, and internal alk-
suitable for α-phenylation of ketones. Therefore, we selected enyl groups gave products 4c, 4d, and 4e, respectively, in
the one-pot α-phenylation of 1a as the first step to be opti- moderate to good yields (Table 2, Entries 2–4). β-Substi-
mized. The reaction of 1a with triphenylaluminum reagent tuted aldehyde 1f underwent the umpolung reaction with a
(2 equiv.) in the presence of isoxazolidine (2 equiv.) at 0 °C slightly diminished yield (Table 2, Entry 5).[14]
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Vicinal Functionalization of N-Alkoxyenamines
Table 2. Umpolung β-phenylation of various N-alkoxyenamines.[a]
ture of 5a and 6a were readily converted into α-phenylalde-
hyde 4a after purification by column chromatography on
silica gel. Thus, based on 13C NMR analysis and the experi-
mental result, we confirmed that imine 5a was generated in
situ during the umpolung reaction. These results encour-
aged us to develop a sequential β-phenylation/nucleophilic
addition to N-alkoxyenamine.
Scheme 3. Umpolung β-phenylation of N-alkoxyenamine 3a.
We next examined the phenylation of enamine 3a, pre-
pared in situ from aldehyde, and sequential nucleophilic ad-
dition to the resulting imine (Table 3). Allylation and cyan-
ation were selected as the second nucleophilic reaction for
our initial evaluation, because the products can be easily
transformed into valuable derivatives. Treatment of 3a with
Table 3. Umpolung β-phenylation and sequential nucleophilic ad-
dition of N-alkoxyenamine 3a.[a]
[a] General conditions: aldehyde
(1.0 mmol), Ph3Al (1.5 mmol), CH2Cl2, 0 °C, 2 h. [b] Yields are for
chromatographically pure product.
1 (0.5 mmol), isoxazolidine
In order to confirm the formation of N-alkoxyenamine
3a, the reaction of n-hexanal (1a) with isoxazolidine in the
presence of MgSO4 was carried out in deuterated solvent
(CD2Cl2). As a result, olefinic proton signals of (E)-N-alk-
1
oxyenamine 3a were observed in the H NMR spectrum at
δ = 5.81 (dt, J = 14.0, 1.5 Hz, 1 H) and δ = 4.96 (dt, J =
14.0, 7.0 Hz, 1 H). NMR analysis was also used to elucidate
the reaction pathway of 3a via imine intermediate 5a by
analysis of the crude mixtures after the one-pot umpolung
reaction of 1a under optimal conditions (Scheme 3). 1H and
13C NMR spectra of the crude mixtures indicated the exis-
tence of imine 5a and N,O-acetal 6a. NMR analysis of 6a
in the mixtures showed doublets for the acetal hydrogen
atom at δH = 4.28 ppm and δH = 4.19 ppm with coupling
Entry
Nu–M
Product
Yield[b] [%]
dr[c]
1
2[d]
3
4
5
AllylMgBr
AllylTMS
Et2AlCN
Bu3SnCN
LiAlH4
7a
7a
8a
8a
9a
78
n.d.[e]
56
53
82
3:1
–
1:1
1.5:1
–
3
constants of JHH = 4.0 Hz and 5.0 Hz, and singlets for the
acetal carbon atom at δC = 91.7 ppm and δC = 90.3 ppm.
Although the 13C NMR spectrum of 5a in the crude mix-
[a] General conditions: after α-phenylation of aldehyde 1a, Nu–
M (1.5 mmol) was added at 0 °C and the mixture stirred at room
temperature for further 2 h. [b] Yields are for chromatographically
pure mixtures of diastereomers. [c] Diastereomeric ratios were de-
termined by 1H NMR analysis. [d] α-Phenylaldehyde 4a was ob-
tures shows singlets for the imino carbon atom at δC
=
165.7 ppm and δC = 165.2 ppm, the imino hydrogen atom
1
of 5a could not be confirmed in the H NMR spectrum,
presumably due to overlap of imino hydrogen and ArH
signals. The crude mixtures containing the equilibrium mix- tained in 79% yield. [e] n.d. = not detected.
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O. Miyata et al.
SHORT COMMUNICATION
Ph3Al in the presence of isoxazolidine and subsequent reac- Table 4. Sequential β-phenylation–nucleophilic addition of various
N-alkoxyenamines.[a]
tion with allylmagnesium bromide gave homoallylamine 7a
in 78% yield with a 3:1 diastereoselectivity (Table 3, En-
try 1). In contrast, the addition of allyltrimethylsilane to
imine D, which is generated in situ after α-phenylation of
1a, did not proceed, and α-phenylaldehyde 4a was obtained
in 79% yield (Table 3, Entry 2). For the preparation of α-
aminonitrile 8a, we introduced a cyano group by sequential
phenylation and cyanation. As a result, both diethylalumi-
num cyanide and tributyltin cyanide gave α-aminonitrile 8a
in moderate yields with low diastereoselectivities (Table 3,
Entries 3 and 4). Furthermore, the use of LiAlH4 as a sec-
ond nucleophile after β-phenylation of 3a led to phen-
ethylamine 9a in good yield (Table 3, Entry 5). Thus, se-
quential umpolung phenylation and nucleophilic addition
of N-alkoxyenamine 3a formed in situ from 1a provided
homoallylamine 7a, α-aminonitrile 8a, and phenethylamine
9a in moderate to good yields by changing the second
nucleophile.
We then proceeded to examine the generality of the um-
polung phenylation and sequential allylation or cyanation
using a series of N-alkoxyenamines derived from aldehydes
(Table 4). We were encouraged to find that the correspond-
ing N-alkoxyenamine 3b, prepared from undecanal (1b) and
isoxazolidine, was a good substrate for the β-phenylation/
allylation and cyanation to give the desired products 7b and
8b in good yields, albeit with unsatisfactory steroselectivi-
ties (Table 4, Entries 1 and 2). Both double nucleophilic re-
actions using enamine 3c, formed in situ from 3-phenyl-
propionaldehyde (1c), also proceeded smoothly to provide
products 7c and 8c in good yields (Table 4, Entries 3 and
4). Sequential β-phenylation/allylation of the corresponding
enamines 3d and 3e of aldehydes 1d and 1e containing ter-
minal and internal olefins worked well (Table 4, Entries 5
and 7),[15] while sequential β-phenylation/cyanation of them
gave the corresponding products 8d and 8e in moderate
yields (Table 4, Entries 6 and 8). Similarly, double nucleo-
philic reactions of enamines 3f and 3g, prepared in situ
from β-branched aldehyde 1f and phenylacetoaldehyde (1g),
also worked well (Table 4, Entries 9–12). Furthermore, the
conversion of α-aminonitrile 8g into unnatural α-amino
acid 10 was readily achieved by acid hydrolysis of the cyano
group (Scheme 4).
Scheme 4. Conversion of 8g into unnatural amino acid 10.
We next examined the sequential β-phenylation and
nucleophilic addition of N-alkoxyenamine 12, which was
[a] General conditions: after α-phenylation of aldehyde 1, Nu–M
derived from cyclohexanone (11) and isoxazolidine
(1.5 mmol) was added at 0 °C and the mixture stirred at room tem-
(Scheme 5). The introduction of allyl or cyano groups to
perature for further 2 h. [b] Yields are for chromatographically pure
imine G, which was generated by umpolung β-phenylation
of enamine 12, was achieved in good yield by utilizing allyl-
mixtures of diastereomers. [c] Diastereomeric ratios were deter-
1
mined by H NMR analysis.
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Vicinal Functionalization of N-Alkoxyenamines
magnesium bromide or tributyltin cyanide, respectively. In
addition, the reduction of imine G by LiAlH4 proceeded
smoothly to give amine 15 in good yield.
[1]
[2]
For reviews on enamine chemistry, see: a) S. Mukherjee, J. W.
Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471–5569;
b) P. Melchiorre, M. Marigo, A. Carlone, G. Bartoli, Angew.
Chem. Int. Ed. 2008, 47, 6138–6171; Angew. Chem. 2008, 120,
6232–6265; c) S. Bertelsen, K. A. Jørgensen, Chem. Soc. Rev.
2009, 38, 2178–2189.
For reviews on enamide chemistry, see: a) G. Bernadat, G.
Masson, Synlett 2014, 25, 2842–2867; b) N. Gigant, L. Chaus-
set-Boissarie, I. Gillaizeau, Chem. Eur. J. 2014, 20, 7548–7564;
c) G. R. Dake, Synlett 2012, 23, 814–824; d) K. Gopalaiah,
H. B. Kagan, Chem. Rev. 2011, 111, 4599–4657; e) D. R. Car-
bey, Org. Biomol. Chem. 2008, 6, 3455–3460; f) R. Matsubara,
S. Kobayashi, Acc. Chem. Res. 2008, 41, 292–301; g) T. C. Nug-
ent, M. El-Shazly, Adv. Synth. Catal. 2010, 352, 753–819.
Selected recent examples for vicinal functionalization of en-
amides: a) R. Matsubara, N. Kawai, S. Kobayashi, Angew.
Chem. Int. Ed. 2006, 45, 3814–3816; Angew. Chem. 2006, 118,
3898–3900; b) M. Terada, K. Machioka, K. Sorimachi, Angew.
Chem. Int. Ed. 2009, 48, 2553–2556; Angew. Chem. 2009, 121,
2591–2594; c) M. Bekkaye, Y. Su, G. Masson, Eur. J. Org.
Chem. 2013, 3978–3982; d) T. Hashimoto, H. Nakatsu, Y. Taki-
guchi, K. Maruoka, J. Am. Chem. Soc. 2013, 135, 16010–
16013; e) L. He, L. Zhao, D.-X. Wang, M.-X. Wang, Org. Lett.
2014, 16, 5972–5975.
[3]
Scheme 5. Sequential β-phenylation–nucleophilic addition of N-
alkoxyenamine 12.
[4]
Selected examples of intermolecular reactions: a) S. Suga, T.
Nishida, D. Yamada, A. Nagaki, J. Yoshida, J. Am. Chem. Soc.
2004, 126, 14338–14339; b) M. Terada, K. Machioka, K. Sori-
machi, J. Am. Chem. Soc. 2007, 129, 10336–10337; c) N. Gig-
ant, I. Gillaizeau, Org. Lett. 2012, 14, 4622–4625. Selected re-
cent examples of Povarov reaction using enamide: d) H. Liu,
G. Dagousset, G. Masson, P. Retailleau, J. Zhu, J. Am. Chem.
Soc. 2009, 131, 4598–4599; e) E. Vicente-García, F. Catti, R.
Ramón, R. Lavilla, Org. Lett. 2010, 12, 860–863; f) C. Wang,
Z.-Y. Han, H.-W. Luo, L.-Z. Gong, Org. Lett. 2010, 12, 2266–
2269; g) H. Xu, S. J. Zuend, M. G. Woll, Y. Tao, E. N. Ja-
cobsen, Science 2010, 327, 986–990; h) G. Dagousset, J. Zhu,
G. Masson, J. Am. Chem. Soc. 2011, 133, 14804–14813; i) C.
Min, A. Sanchawala, D. Seidel, Org. Lett. 2014, 16, 2756–2759.
PdII-assisted intermolecular dialkylation and alkylation/acyl-
ation: a) G. M. Wieber, L. S. Hegedus, B. Åkermark, E. T.
Michalson, J. Org. Chem. 1989, 54, 4649–4653; b) J. J. Masters,
L. S. Hegedus, J. Tamariz, J. Org. Chem. 1991, 56, 5666–5671.
Transition-metal-catalyzed cyclization: a) T. J. Harrison, B. O.
Patrick, G. R. Dake, Org. Lett. 2007, 9, 367–370; b) H. Deng,
X. Yang, Z. Tong, Z. Li, H. Zhai, Org. Lett. 2008, 10, 1791–
1793; c) J. A. Kozak, J. M. Dodd, T. J. Harrison, K. J. Jardine,
B. O. Patrick, G. R. Dake, J. Org. Chem. 2009, 74, 6929–6935;
d) J. A. Kozak, B. O. Patrick, G. R. Dake, J. Org. Chem. 2010,
75, 8585–8590.
Conclusions
We have successfully developed an umpolung β-phen-
ylation–nucleophilic addition of various N-alkoxyenamines
by using two carbon-centered nucleophiles. The vicinal in-
troduction of different carbon nucleophiles to the N-alk-
oxyenamine was conveniently achieved in a single flask,
with the reaction proceeding smoothly under mild condi-
tions at ambient temperature. Further studies including the
synthesis of biologically active compounds by our method-
ology are now in progress in our laboratory.
[5]
[6]
Experimental Section
General Procedure for the β-Phenylation of N-Alkoxyenamines and
Sequential Nucleophilic Addition: Tables 3 and 4. To a solution of
aldehyde (0.5 mmol) and isoxazolidine (73 mg, 1.0 mmol) in
CH2Cl2 (3.0 mL) was added triphenylaluminum (1.0 m in dibutyl
ether, 1.5 mL, 1.5 mmol) dropwise at 0 °C under argon. After stir-
ring at 0 °C for 2 h, the second nucleophile (1.5 mmol) was added
at 0 °C. The mixture was warmed to room temperature and stirred
for 2 h. The reaction was quenched with aqueous Rochelle’s salt
(1.3 m) or saturated aqueous NaHCO3 at 0 °C. The resulting sus-
pension was extracted with CHCl3. The combined organic layers
were dried with MgSO4, filtered, and concentrated under reduced
pressure. The residue was purified by flash column chromatography
to give the amine.
[7]
[8]
A. Carboni, G. Dagousset, E. Magnier, G. Masson, Org. Lett.
2014, 16, 1240–1243.
a) T. Taniguchi, K. Iwasaki, M. Uchiyama, O. Tamura, H. Ishi-
bashi, Org. Lett. 2005, 7, 4389–4390; b) T. Taniguchi, G. Tan-
abe, O. Muraoka, H. Ishibashi, Org. Lett. 2008, 10, 197–199;
c) T. Taniguchi, H. Ishibashi, Org. Lett. 2008, 10, 4129–4131;
d) C. Poittevin, V. Liautard, R. Beniazza, F. Robert, Y. Land-
ais, Org. Lett. 2013, 15, 2814–2817.
a) J. Clayden, M. Donnard, J. Lefranc, A. Minassi, D. J. Tet-
low, J. Am. Chem. Soc. 2010, 132, 6624–6625; b) M. Tait, M.
Donnard, A. Minassi, J. Lafranc, B. Bechi, G. Carbone, P.
O’Brien, J. Clayden, Org. Lett. 2013, 15, 34–37.
[9]
[10]
a) S. Talukdar, C.-T. Chen, J.-M. Fang, J. Org. Chem. 2000, 65,
3148–3153; b) Z. Rong, Q. Li, W. Lin, Y. Jia, Tetrahedron Lett.
2013, 54, 4432–4434.
Acknowledgments
[11]
[12]
G. Dagousset, W. Erb, J. Zhu, G. Masson, Org. Lett. 2014, 16,
This work was supported by Grants-in-Aid from the Ministry of
Education, Culture, Sports, Science, and Technology of Japan
(MEXT), and the MEXT-Supported Program for the Strategic Re-
search Foundation at Private Universities.
2554–2557.
Selected recent examples of cycloaddition reactions utilizing
enamines: a) H. M. Sheldrake, T. W. Wallace, C. P. Wilson, Org.
Lett. 2005, 7, 4233–4236; b) N. Cos¸kun, J. Ma, S. Azimi, C.
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Gärtner, I. Erden, Org. Lett. 2011, 13, 5952–5955; c) E. D. An-
derson, A. S. Duerfeldt, K. Zhu, C. M. Glinkerman, D. L.
Boger, Org. Lett. 2014, 16, 5084–5087.
[14]
In the umpolung β-phenylation of N-alkoxyenamine, the use
of 2-methylpropanal as α-branched aldehyde led to the α-phen-
ylated aldehyde in 46% yield.
[13] a) T. Miyoshi, T. Miyakawa, M. Ueda, O. Miyata, Angew.
Chem. Int. Ed. 2011, 50, 928–931; Angew. Chem. 2011, 123,
958–961; b) T. Miyoshi, S. Sato, H. Tanaka, C. Hasegawa, M.
Ueda, O. Miyata, Tetrahedron Lett. 2012, 53, 4188–4191; c) T.
Miyoshi, N. Takeda, M. Fukami, S. Sato, M. Ueda, O. Miyata,
Chem. Pharm. Bull. 2014, 62, 927–932.
[15] The relative configuration of threo-7e (major diastereomer) was
determined by converting threo-7e into authentic cis-15 (see the
Supporting Information).
Received: March 6, 2015
Published Online: May 15, 2015
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Eur. J. Org. Chem. 2015, 3899–3904