Asymmetric synthesis of ethoxydienamines in superbasic medium mediated by chiral sulfinyl group

Article abstract of DOI:10.1021/jo1024943

The direct addition of metalated alkoxydiene 2, obtained from α,β-unsaturated acetal 1 through a LIC-KORpromoted conjugated elimination reaction, to enantiopure sulfinimines 3 (both R and S N-sulfinyl imines) afforded Nsulfinyl alkoxydienyl amines 4 with

Full text of DOI:10.1021/jo1024943

ARTICLE
pubs.acs.org/joc
Asymmetric Synthesis of Ethoxydienamines in Superbasic Medium
Mediated by Chiral Sulfinyl Group
Marco Blangetti, Gianluca Croce,† Annamaria Deagostino, Eleonora Mussano, Cristina Prandi,* and
Paolo Venturello
Dipartimento di Chimica Generale e Chimica Organica, Universitꢀa degli Studi di Torino, Via P. Giuria, 7-10125 Torino, Italy
†Dipartimento di Scienze e Tecnologie Avanzate, Universitꢀa degli Studi del Piemonte Orientale “Amedeo Avogadro”,
Viale Teresa Michel, 11-15121 Alessandria, Italy
S Supporting Information
b
ABSTRACT: The direct addition of metalated alkoxydiene 2,
obtained from R,β-unsaturated acetal 1 through a LIC-KOR-
promoted conjugated elimination reaction, to enantiopure
sulfinimines 3 (both R and S N-sulfinyl imines) afforded N-
sulfinyl alkoxydienyl amines 4 with high diastereoselectivity.
Functionalized enantiopure alkoxydienyl amines 5 were then easily obtained upon the selective removal of the chiral auxiliary under
mild conditions. Moreover, the further hydrolysis of the alkoxydienyl moiety gave access to protected enantiopure β-keto amines 7.
’ INTRODUCTION
medium, the stereochemistry of the new stereogenic center that
is created upon addition of prochiral electrophiles. In this paper,
we report the results we obtained when metalated alkoxydienes 2
have been reacted with sulfinyl imines 3 in superbasic medium.
As far as we know, there are no references in the literature to the
diastereoselective induction effect of the sulfinyl chiral auxiliary
group in the presence of superbases.
The role of the sulfinyl group in enantioselective syntheses is
well documented in the literature, and in particular, sulfinyl
imines represent a versatile class of prochiral electrophiles in
which the presence of the electron-withdrawing sulfinyl group
activates the CdN bond to nucleophilic attack and, at the same
time, exerts powerful stereodirecting effects.1-4 Due to the
presence of the N-sulfinyl group, sulfinimines are particularly
reactive toward a variety of nucleophiles; of these, carbon
nucleophiles have been widely investigated. Hence, Grignard
reagents,5-8 cuprates,9-11 organolithium,2,12-14 cyanides,15-17
and organozincates18,19 all add to sulfinimines in a 1,2-addition
fashion to give sulfinamides. In addition, sodium, potassium, and
lithium enolates3,4 react with chiral sulfinimines to afford β-
amino esters with high yield and diastereoselectivity. Recently, β-
amino acid derivatives have been successfully obtained by the
addition of prochiral Weinreb amides to sulfinimines.20-22 The
metal seems to play a crucial role in determining the diastero-
selectivity of the reaction, and a six-membered chairlike transition
state where the metal is coordinated to the sulfinyl oxygen atom
has been evoked to explain the sense of the induction. Moreover, a
reversal of the diastereoselectivity has been realized by replacing
potassium enolates with the corresponding lithium enolates.6
These results are in agreement with the chelation-control transi-
tion-state hypothesis.
’ RESULTS AND DISCUSSION
The metalated alkoxydiene 2 was generated from crotonalde-
hyde diethyl acetal 1 in the presence of 2.2 equiv of the superbase
LIC-KOR, which is an equimolecular mixture of butyllithium
(LIC) and potassium tert-butoxide (KOR), at -78 °C as
previously reported.26 After 2 h, sulfinyl imine 3a (RS) was added
to the formed nucleophile, and the reaction was monitored by
TLC until complete consumption of the electrophile was ob-
served (Scheme 1). The reaction was then repeated using sulfinyl
imine 3a (SS) as the electrophile. In both cases, the correspond-
ing dienyl amines 4a (S, RS) or 4a (R, SS) were obtained with a
surprisingly high dr, thus indicating the excellent level of stereo-
induction occurring in superbasic medium.
The diastereomeric mixtures were then purified by flash
column chromatography, and the absolute configuration of both
enantiomers was determined by single-crystal X-ray analysis (see
the Supporting Information).
Hence, in the case of a sulfinyl imine with an R configuration
on the sulfur the major diastereoisomer formed in the nucleo-
philic addition pathway shows a S configuration on the new
formed stereogenic carbon, while the sulfinyl imine SS afforded
Within the context of our work on the study of the reactivity of
metalated alkoxydienes with electrophiles in superbasic
medium,23-25 we recently reported the synthesis of stereode-
fined alkoxy dienamines by reaction of 1-metalated-1-alkoxybu-
tadienes, these in turn obtained from R,β-unsaturated acetals in
the presence of the LIC-KOR superbase and N-protected
aldimines.26 The current challenge is to control, in the superbasic
Received: December 16, 2010
Published: February 14, 2011
r
2011 American Chemical Society
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ARTICLE
Scheme 1. Addition of Metalated Alkoxydiene 2 to N-Ben-
zylidene-p-toluenesulfinamide 3a (RS)
Scheme 2. Decomposition of Dienyl Amines 4 to Thioester
C via Sulfenate Anion A in Superbasic Medium
the R, SS diastereoisomer as the major product. The sense of this
asymmetric induction can be understood if a highly coordinated
transition state is hypothesized where both the sulfoxide oxygen
atom and the iminic nitrogen atom could coordinate one of the
metal counterions of the superbasic mixed aggregate.2,4 As a
consequence, the alkoxydienyl anion will be locked above, or
below, the plane containing the electrophile. In particular, with
an RS imine as electrophile the metalated diene appears stuck
below the imine, and the addition to the Re face becomes the
only possible pathway to afford the (S) diastereoisomer. On the
other hand, considering an SS imine, the alkoxydienyl anion
would be locked above the imine’s plane, and the addition
proceeded to the Si face, giving the R, SS diastereoisomer as the
major product.
Table 1. Synthesis of Alkoxydienyl Sulfinyl Amines at -90 °Ca
Encouraged by these results, we decided to extend the scope of
the reaction and to evaluate both the diastereoselectivity and the
yield of the addition reaction with differently substituted sulfinyl
imines. To this purpose, different enantiopure sulfinamines were
synthesized using the Andersen reagent,27 by treatment with
LHMDS in the presence of the appropriate aldehyde,28 or
alternatively according to the DAG procedure.29,30 At first, we
performed the reaction under standard conditions for this kind of
LIC-KOR-promoted eliminations, i.e., 1 equiv of 1, 2 equiv of
LIC-KOR, and 1 equiv of 3 at -78 °C, but we soon realized that
the weak point of this approach was the unsatisfactory yield of 4
in the addition reaction. Although TLC monitoring of the
reaction indicated a rapid disappearance of sulfinyl imine 3, the
1H NMR spectrum of the crude product provided evidence of
some unreacted imines 3, thioester C, and a low amount of the
desired product 4. Puzzled by these data and on the grounds that
sulfinyl imines are reported to be as electrophilic as tosyl imines
are, we tried to understand what was happening in the reaction
mixture. Supported by a recent publication,31 we considered that
the excess of superbasic reagent LIC-KOR could induce a β-
elimination reaction on the newly formed ethoxydienyl amine 4
and the generation of the sulfenate anion A (Scheme 2). This
species could act as a nucleophile and add to the sulfinyl imine 3
still present in the reaction mixture.32 A further β-elimination on
B regenerates 3 and the sulfenate anion A, which dimerizes to the
corresponding thioester C upon quenching.33
entry
Ar
imine
product
yieldb (%)
drc (%)
1
2
3
4
5
6
Ph
RS
RS
RS
RS
RS
RS
4a
4b
4c
4d
4e
4f
52
59
55
55
55
53
99:1
99:1
99:1
99:1
99:1
99:1
p-Tol
PMP
2-thienyl
cinnamyl
Piv
a The enantiomer of each of the products has been also prepared (see the
Experimental Section). Reaction conditions: 1 (3 equiv), LIC-KOR (7.5
equiv), 3 (1 equiv), -90 °C. b Yield refers to major diastereoisomer
separated by column chromatography. c Determined by 1H NMR on the
crude reaction mixture by comparison with the H spectra of each
diasteroisomer as pure compound (see the Experimental Section and
Supporting Information).
1
the cases examined the addition reaction takes place with very
high diasteromeric ratio and with satisfactory yields of purified
products.
In view of further developments, N-sulfinyl amines 4 were
then treated with TFA in MeOH: under these conditions only
the removal of the chiral auxiliary occurred so that enantiopure
alkoxydienylamines 5 were isolated in almost quantitative yields
(Table 2).34
The conversion of 5 into R,β-unsaturated ketones proved
to be troublesome. In this case, the alkoxydienyl function
is in fact resistant to acidic hydrolysis. It could be assumed
that the fast protonation of the amino group to the ammo-
nium intermediate (A) prevents the formation of the cationic
species (B) that is involved in the deprotection process
(Scheme 3).
On these bases, we realized that good conversions to the
desired product 4 could be achieved by assuring an excess of
metalated diene 2 during the whole reaction advancement, and
we consequently changed the experimental conditions, namely 3
equiv of the starting R,β-unsaturated acetal 1, very slow addition
of the electrophile (over 1.5 h) and temperatures as low as -
90 °C. Under these conditions, the yields of dienyl amines
significantly increased, ranging from 52 to 63%, while the
diastereoselectivity remained high (Table 1).
A series of attempts under different experimental conditions
led to the recovery of the unreacted starting material.35 Never-
theless, the vinyl ether function underwent hydrolysis when
Aromatic (4a-c), heteroaromatic (4d), vinylic (4e), and
aliphatic (4f) sulfinyl imines, as the R or S stereoisomer, have
been used as electrophiles in the addition reaction, and in all of
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ARTICLE
Table 2. Synthesis of Enantiopure Ethoxydienyl Amines 5a
to -78 °C, and benzaldehyde (53.0 mmol, 5.0 mL, 1.1 equiv) was added
dropwise. After being stirred for 2 h at -78 °C, the reaction mixture was
quenched with water (50 mL) and extracted with Et2O (3 ꢀ 30 mL).
The organic layer was washed with water (2 ꢀ 100 mL) and brine (100
mL), dried (Na2SO4), and concentrated to give an oil that was purified
by flash column chromatography (petroleum ether/EtOAc 9/1 þ 1%
Et3N, yield 73%). (S)-(þ)-N-Benzylidene-p-toluenesulfinamide 3a: 1H
NMR (200 MHz, CDCl3) δ 8.76 (s, 1H), 7.89-7.22 (m, 9H), 2.38 (s,
3H); [R]20D = þ117.1 (c 1.5, CHCl3).
entry
reactant
product
Ar
yieldb (%)
General Procedure for the Syntheses of N-Sulfinyl Alkox-
ydienyl Amines 4. A solution of freshly sublimated t-BuOK
(4.5 mmol, 504 mg, 7.5 equiv) in THF (10 mL) was cooled
to -78 °C. 1,1-Diethoxybut-2-ene (1.8 mmol, 259 mg, 3 equiv) in
THF (2 mL) and n-BuLi (1.6 M in hexanes, 4.5 mmol, 2.81 mL) were
added in quick succession, and the mixture was stirred for 2 h during
which time the temperature was raised to -40 °C. Afterward the
reaction was cooled to -90 °C, and a 0.20 M solution of the appropriate
sulfinimine (0.6 mmol) in THF was added dropwise over about
1.5 h. Once the addition was completed, a saturated NH4Cl solution
(10 mL) was added. The resulting mixture was extracted with Et2O
(3 ꢀ 10 mL), washed with water (10 mL) and brine (2 ꢀ 10 mL),
and dried with anhydrous K2CO3. After filtration and evaporation
of the solvent, the crude products were purified by flash column
chromatography.
1
2
3
4
5
6
4a
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
Ph
91
92
93
94
87
92
p-Tol
PMP
2-thienyl
cinnamyl
Piv
a The enantiomer of each of the products has been also prepared (see the
Experimental Section). Reaction conditions: 4 (0.5 mmol), MeOH (3
mL), 0 °C, then TFA (1.75 mmol, 3.5 equiv). Stirred for 10 min at 0 °C
and then 1 h at rt. b Yields refer to isolated products. The enantiomer of
each of the products has been also prepared (see the Experimental
Section).
Fmoc was used as a protecting function of the newly formed
amino group. In this case, Fmoc-protected dienyl amines 6 can be
easily converted to the corresponding Fmoc-protected R,β-
unsaturated ketones 7. Remarkably, all of the synthetic transfor-
mations leading to derivatives 7 occur without epimerization at
the chiral center.34
N-((S,RS,E)-2-Ethoxy-1-phenylpenta-2,4-dienyl)-4-methyl-
benzenesulfinamide (4a). Purified by flash chromatography
(alumina, Et2O/petroleum ether 1:1, Rf 0.40) to give 4a (106 mg,
1
52%) as a white solid: H NMR (200 MHz, CDCl3) δ 7.57-7.45
(m, 2H), 7.20-7.09 (m, 7H), 6.39 (dt, J = 16.5, 10.5 Hz, 1H), 5.32
(d, J = 10.5 Hz, 1H) superimposed to 5.39 (d, J = 8.0 Hz, 1H), 5.07
(d, J = 8.0 Hz, 1H) superimposed to 5.00 (dd, J = 16.5, 1.9 Hz, 1H), 4.82
(dd, J = 10.5, 1.9 Hz, 1H), 3.84 (qd, J = 7.0, 2.4 Hz, 2H), 2.29 (s, 3H),
1.21 (t, J = 7.0 Hz, 3H); 13C NMR (50.2 MHz, CDCl3) δ 154.9 (s),
140.3 (s), 140.2 (s), 139.0 (s), 129.9 (d), 128.4 (d), 127.2 (d), 126.3 (d),
125.8 (d), 124.9 (d), 112.6 (t), 101.4 (d), 62.1 (t), 52.4 (d), 20.4 (q),
13.4 (q); MS m/z 341 (Mþ, 9), 244 (16), 202 (84), 172 (88), 139 (100),
91 (89), 77 (80); [R]21D = -68.1 (c 0.9, CH2Cl2); mp 116 °C. Anal.
Calcd for C20H23NO2S: C, 70.35; H, 6.79. Found: C, 70.03; H, 6.47.
N-((R,SS,E)-2-Ethoxy-1-phenylpenta-2,4-dienyl)-4-methylbenzene-
sulfinamide was prepared by the above procedure using the correspond-
ing SS sulfinimine. Purified by flash chromatography (alumina, Et2O/
’ CONCLUSIONS
In summary, in this work we have exploited the high potential
of chiral sulfinyl imines (Davis imines) as electrophiles to obtain
enantiopure products in superbasic medium. We have demon-
strated that the addition reaction of metalated alkoxydienes to
enantiopure sulfinyl imines leads to alkoxydienyl amines with
high diastereomeric excesses, thus proving that the reactions
proceed through a highly coordinated transition state in
which both the metals of the superbasic complex can be
involved. The results we obtained are in agreement with the
“chelation-control” transition-state hypothesis,2,4 the current
theory to explain the high diastereoselective level for mono-
metallic species (Na, Li, K, Zn, Mn). Moreover, the chiral
auxiliary can be selectively removed to afford enantiopure
alkoxy dienyl amines. The change in protecting group to
Fmoc allows the hydrolysis of the vinyl ether moiety without
the loss of enantiopurity and gives ready access to keto-amino
derivatives.
petroleum ether 1:1, Rf 0.40, 129 mg, 63% yield) as a white solid: [R]21
=
D
þ68.1 (c 1.0, CH2Cl2); mp 116 °C. Spectral data identical to those
of 4a.
N-((S,RS,E)-2-ethoxy-1-p-tolylpenta-2,4-dienyl)-4-methyl-
benzenesulfinamide (4b). Purified by flash chromatography
(alumina, Et2O/petroleum ether 1:1, Rf 0.35) to give 4b (127 mg,
59%) as a white solid: 1H NMR (200 MHz, CDCl3) δ 7.52 (d, J = 8.2 Hz,
2H), 7.17 (d, J = 8.2 Hz, 2H), 7.06-6.90 (m, 4H), 6.38 (dt, J = 16.5, 10.4
Hz, 1H), 5.32 (d, J = 10.4 Hz, 1H) superimposed to 5.27 (d, J = 7.9 Hz,
1H), 5.01 (d, J = 7.9 Hz, 1H) superimposed to 4.96 (dd, J = 16.5, 1.9 Hz,
1H), 4.81 (dd, J = 10.4, 1.9 Hz, 1H), 3.76 (qd, J = 7.0, 2.3 Hz, 2H), 2.31
(s, 3H), 2.22 (s, 3H), 1.22 (t, J = 7.0 Hz, 3H); 13C NMR (50.2 MHz,
CDCl3) δ 155.1 (s), 140.2 (s, 2C), 135.9 (s, 2C), 129.9 (d), 128.4 (d),
127.9 (d), 125.7 (d), 124.9 (d), 112.5 (t), 101.3 (d), 62.1 (t), 52.4 (d),
20.3 (q), 20.0 (q), 13.4 (q); MS m/z 355 (Mþ, 29), 258 (18), 216 (98),
186 (89), 149 (100), 91 (89), 77 (49); [R]25D = -64.6 (c 1.4, CH2Cl2);
mp 121 °C. Anal. Calcd for C21H25NO2S: C, 70.95; H, 7.09. Found: C,
70.83; H, 6.89. N-((R,SS,E)-2-Ethoxy-1-p-tolylpenta-2,4-dienyl)-4-
methylbenzenesulfinamide was prepared by the above procedure using
the corresponding SS sulfinimine. Purified by flash chromatography
(alumina, Et2O/petroleum ether 1:1, Rf 0.35, 121 mg, 57% as a white
’ EXPERIMENTAL SECTION
Synthesis of Chiral Sulfinimines 3. Chiral sulfinimines were
synthesized according to the literature procedure described by Davis and
co-workers,28 starting either from Andersen reagents or DAG-p-tolue-
nesulfinates. The spectral data were in agreement with reported values.
Typical procedure for the synthesis of p-toluenesulfinimines: In a 500
mL three-necked, round-bottomed flask equipped with a magnetic stir
bar, rubber septum, and argon inlet was placed (1R,2S,5R)-(-)-menthyl
(S)-p-toluenesulfinate (14.0 g, 47.5 mmol) dissolved in 225 mL of
freshly distilled THF, and the mixture was cooled to -78 °C. A solution
of 62.0 mL of LiHMDS (62.0 mmol, 1.0 M solution in THF, 1.3 equiv)
was added dropwise via syringe, and the reaction mixture was allowed to
warm to rt with stirring. After 5 h, the reaction mixture was cooled
solid: [R]25 = þ64.6 (c 1.2, CH2Cl2); mp 121 °C. Spectral data
D
identical to those of 4b.
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Scheme 3. Removal of the Chiral Auxiliary and Hydrolysis of the Vinyl Ether Function
N-((S,RS,E)-2-Ethoxy-1-(4-methoxyphenyl)penta-2,4-
dienyl)-4-methylbenzenesulfinamide (4c). Purified by flash
chromatography (alumina, Et2O/petroleum ether 3:2, Rf 0.30) to give
4c (122 mg, 55%) as a pale yellow solid: 1H NMR (200 MHz, CDCl3) δ
7.52 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H),
6.67 (d, J = 8.8 Hz, 2H), 6.39 (dt, J = 16.5, 10.5 Hz, 1H), 5.31 (d, J = 10.5
Hz, 1H) superimposed to 5.25 (d, J = 7.9 Hz, 1H), 5.02 (d, J = 7.9 Hz,
1H) superimposed to 4.95 (dd, J = 16.5, 1.8 Hz, 1H), 4.82 (dd, J = 10.5,
1.8 Hz, 1H), 3.78 (qd, J = 7.0, 2.3 Hz, 2H) superimposed to 3.68 (s, 3H),
2.31 (s, 3H), 1.23 (t, J = 7.0 Hz, 3H); 13C NMR (50.2 MHz, CDCl3)
δ 158.6 (s), 155.9 (s), 141.1 (s), 141.0 (s), 131.9 (s), 130.7 (d), 129.2
(d), 127.8 (d), 125.7 (d), 113.4 (t), 113.3 (d), 102.0 (d), 62.9 (t), 55.0
(q), 52.9 (d), 21.1 (q), 14.2 (q); MS m/z 371 (Mþ, 8), 274 (44), 232
N-((S,RS,1E,4E)-4-Ethoxy-1-phenylhepta-1,4,6-trien-3-yl)-
4-methylbenzenesulfinamide (4e). Purified by flash chromatog-
raphy (alumina, Et2O/petroleum ether 1:1, Rf 0.30) to give 4e (120 mg,
1
55%) as a white solid: H NMR (200 MHz, CDCl3) δ δ 7.70-7.47
(m, 2H), 7.28-7.11 (m, 7H), 6.44 (dt, J = 16.6, 10.5 Hz, 1H), 6.19 (d,
J = 15.9 Hz, 1H), 6.01 (dd, J = 15.9, 6.3 Hz, 1H), 5.30 (d, J = 10.8 Hz,
1H), 5.03 (dd, J = 16.6, 2.0 Hz, 1H) superimposed to 4.94 (d, J = 6.3 Hz,
1H), 4.87 (dd, J = 10.5, 2.0 Hz, 1H) superimposed to 4.80 (d, J = 10.8
Hz, 1H), 3.78 (qd, J = 7.0, 2.5 Hz, 2H), 2.30 (s, 3H), 1.27 (t, J = 7.0 Hz,
3H); 13C NMR (50.2 MHz, CDCl3) δ 155.4 (s), 141.2 (s), 141.1 (s),
136.3 (s), 131.2 (d), 130.6 (d), 129.3 (d), 128.2 (d), 127.7 (d), 127.4
(d), 126.3 (d), 125.8 (d), 113.4 (t), 101.9 (d), 62.9 (t), 52.4 (d), 21.1
(q), 14.2 (q); MS m/z 367 (Mþ, 15), 270 (25), 229 (83), 198 (100), 139
(85), 91 (90), 77 (85); [R]20D = -78.9 (c 1.0, CH2Cl2); mp 111 °C.
Anal. Calcd for C22H25NO2S: C, 71.90; H, 6.86. Found: C, 71.64;
H, 6.73. N-((R,SS,1E,4E)-4-Ethoxy-1-phenylhepta-1,4,6-trien-3-yl)-
4-methylbenzenesulfinamide was prepared by the above procedure
using the corresponding SS sulfinimine. Purified by flash chromatogra-
phy (alumina, Et2O/petroleum ether 1:1, Rf 0.30, 123 mg, 56%) as a
white solid: [R]20D = þ78.9 (c 1.0, CH2Cl2); mp 111 °C. Spectral data
identical to those of 4e.
(100), 202 (68), 187 (98), 91 (88), 77 (97); [R]25 = -44.0 (c 0.8,
D
CH2Cl2); mp 123 °C. Anal. Calcd for C21H25NO3S: C, 67.89; H, 6.78.
Found: C, 67.80; H, 6.55. N-((R,SS,E)-2-Ethoxy-1-(4-methoxyphe-
nyl)penta-2,4-dienyl)-4-methylbenzenesulfinamide was prepared by
the above procedure using the corresponding SS sulfinimine.. Purified by
flash chromatography (alumina, Et2O/petroleum ether 3:2, Rf 0.30, 134
mg, 60% as a pale yellow solid: [R]25 = þ44.0 (c 1.6, CH2Cl2); mp
D
123 °C. Spectral data identical to those of 4c. N-((R,RS,E)-2-Ethoxy-1-
p-tolylpenta-2,4-dienyl)-4-methylbenzenesulfinamide (minor dia-
stereoisomer). Purified by flash chromatography (alumina, Et2O/
petroleum ether 1:1, Rf 0.32) to give 4c0 as a pale yellow solid:
1H NMR (200 MHz, CDCl3) δ 7.59 (d, J = 8.1 Hz, 2H), 7.27-7.08
(m, 4H), 7.00 (d, J = 8.1 Hz, 2H), 6.28 (dt, J = 16.6, 10.5 Hz, 1H), 5.47
(d, J = 10.0 Hz, 1H), 5.29 (d, J = 10.0 Hz, 1H), 5.02 (d, J = 10.5 Hz, 1H),
4.91 (dd, J = 16.6, 1.2 Hz, 1H), 4.81 (dd, J = 10.5, 1.2 Hz, 1H), 3.47 (dq,
J = 9.2, 7.0 Hz, 1H), 3.13 (dq, J = 9.2, 7.0 Hz, 1H), 2.32 (s, 3H), 2.23
(s, 3H), 1.04 (t, J = 7.0 Hz, 3H).
N-((S,RS,E)-4-Ethoxy-2,2-dimethylhepta-4,6-dien-3-yl)-4-
methylbenzenesulfinamide (4f). Purified by flash chromatogra-
phy (alumina, Et2O/petroleum ether 1:1, Rf 0.20) to give 4f (101 mg,
53%) as a pale yellow solid: 1H NMR (200 MHz, CDCl3) δ 7.47 (d, J =
8.2 Hz, 2H), 7.21 (d, J = 8.2 Hz, 2H), 6.24 (dt, J = 16.6, 10.4 Hz, 1H),
5.27 (d, J = 10.4 Hz, 1H), 4.94 (dd, J = 16.6, 1.9 Hz, 1H), 4.76 (dd, J =
10.4, 1.9 Hz, 1H) superimposed to 4.71 (d, J = 9.8 Hz, 1H), 3.79 (d, J =
9.8 Hz, 1H) superimposed to 3.68 (q, J = 7.0 Hz, 2H), 2.33 (s, 3H), 1.21
(t, J = 7.0 Hz, 3H), 0.73 (s, 9H); 13C NMR (50.2 MHz, CDCl3) δ 156.6
(s), 141.6 (s), 140.9 (s), 131.6 (d), 129.1 (d), 125.6 (d), 112.2 (t), 102.5
(d), 62.3 (t), 58.8 (t), 34.9 (s), 26.9 (q), 21.1 (q), 14.3 (q); MS m/z 321
(Mþ, 1), 264 (13), 182 (13), 139 (100), 124 (86), 96 (46), 80 (13);
N-((R,RS,E)-2-Ethoxy-1-(thiophene-2-yl)penta-2,4-dienyl)-
4-methylbenzenesulfinamide (4d). Purified by flash chromatog-
raphy (alumina, Et2O/petroleum ether 3:2, Rf 0.40) to give 4d (114 mg,
55%) as a yellow solid: 1H NMR (200 MHz, CDCl3) δ 7.57 (d, J = 8.2
Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 7.07 (dd, J = 5.1, 1.3 Hz, 1H), 6.75
(dd, J = 5.1, 3.5 Hz, 1H), 6.64 (dt, J = 3.5, 1.3 Hz, 1H), 6.27 (dt, J = 16.5,
10.6 Hz, 1H), 5.43 (d, J = 7.8 Hz, 1H), 5.32 (d, J = 10.6 Hz, 1H), 5.20
(d, J = 7.8 Hz, 1H), 5.02 (dd, J = 16.5, 1.8 Hz, 1H), 4.83 (dd, J = 10.6, 1.8
Hz, 1H), 3.78 (qd, J = 7.0, 2.3 Hz, 2H), 2.33 (s, 3H), 1.23 (t, J = 7.0 Hz,
3H); 13C NMR (50.2 MHz, CDCl3) δ 155.2 (s), 143.7 (s), 141.2 (s),
140.4 (s), 130.4 (d), 129.3 (d), 126.3 (d), 125.9 (d), 124.9 (d), 124.7
(d), 113.7 (t), 101.8 (d), 63.2 (t), 49.7 (d), 21.2 (q), 14.2 (q); MS m/z
347 (Mþ, 21), 250 (63), 208 (100), 91 (73), 55 (82); [R]21D = -45.7
(c 1.3, CH2Cl2); mp 104 °C. Anal. Calcd for C18H21NO2S2: C, 62.21; H,
6.09. Found: C, 62.09; H, 5.88.N-((S,SS,E)-2-Ethoxy-1-(thiophene-2-
yl)penta-2,4-dienyl)-4-methylbenzenesulfinamide was prepared by
the above procedure using the corresponding SS sulfinimine. Purified
by flash chromatography (alumina, Et2O/petroleum ether 3:2, Rf 0.40,
[R]21 = -66.3 (c 1.8, CH2Cl2); mp 79 °C. Anal. Calcd for
D
C18H27NO2S: C, 67.25; H, 8.47. Found: C, 67.10; H, 8.12. N-((R,SS,
E)-4-Ethoxy-2,2-dimethylhepta-4,6-dien-3-yl)-4-methylbenzenesul-
finamide was prepared by the above procedure using the corresponding
SS sulfinimine. Purified by flash chromatography (alumina, Et2O/
petroleum ether 1:1, Rf 0.20, 111 mg, 58%) as a pale yellow solid:
[R]21 = þ66.3 (c 2.2, CH2Cl2); mp 79 °C. Spectral data identical
D
to 4f.
General Procedure for the Syntheses of Alkoxydienyl
Amines 5. A solution of the appropriate N-sulfinyl alkoxydienyl amine
(0.5 mmol) in MeOH (3 mL) was cooled to 0 °C using an ice/water
bath, and TFA (1.75 mmol, 130 μL, 3.5 equiv) was added dropwise.
After 10 min, the solution was warmed to rt and stirred for an additional
time of 1 h. When the reaction was complete, the mixture was quenched
with a NaOH solution (10%). After extraction with Et2O (3 ꢀ 10 mL),
the organic layers were washed with water (10 mL) and brine (2 ꢀ 10
mL), and dried with anhydrous K2CO3. After filtration and evaporation
122 mg, 58%) as a yellow solid: [R]21 = þ45.7 (c 0.8, CH2Cl2);
D
mp 104 °C. Spectral data identical to those of 4d.
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of the solvent, the crude products were purified by flash column
chromatography.
50.2 (d), 29.5 (q), 14.2 (q); MS m/z 209 (Mþ, 46), 180 (25), 162 (38),
135 (35), 112 (100), 97 (29), 85 (44); [R]D21 = -65.8 (c 1.0, CH2Cl2).
Anal. Calcd for C11H15NOS: C, 63.12; H, 7.22. Found: C, 63.01;
H, 7.16. (S,E)-2-Ethoxy-1-(thiophene-2-yl)penta-2,4-dien-1-amine
was obtained by the above procedure starting from N-((S,SS,E)-2-
ethoxy-1-(thiophene-2-yl)penta-2,4-dienyl)-4-methylbenzenesulfina-
mide. Purified by flash chromatography (CH2Cl2, 1% Et3N, Rf 0.75,
100 mg, 96%) as a brown oil: [R]21D = þ65.8 (c 1.3, CH2Cl2). Spectral
data identical to those of 5d.
(S,E)-2-Ethoxy-1-phenylpenta-2,4-dien-1-amine (5a).
Purified by flash chromatography (Et2O/petroleum ether 7:3, 1%
1
Et3N, Rf 0.30) to give 5a (92 mg, 91%) as a yellow oil: H NMR
(200 MHz, CDCl3) δ 7.49-7.03 (m, 5H), 6.56 (dt, J = 16.6, 10.5 Hz,
1H), 5.27 (d, J = 10.5 Hz, 1H), 4.98 (dd, J = 16.6, 1.9 Hz, 1H)
superimposed to 4.97 (s, 1H), 4.79 (dd, J = 10.5, 1.9 Hz, 1H), 3.69 (qd,
J = 7.0, 2.5Hz, 2H), 1.83 (br, 2H), 1.18(t,J= 7.0Hz, 3H); 13CNMR(50.2
MHz, CDCl3). δ 158.1 (s), 142.2 (s), 130.5 (d), 127.2 (d), 125.8 (d),
125.3 (d), 111.5 (t), 100.3 (d), 61.8 (t), 52.5 (d), 13.3 (q). MS m/z 203
(S,1E,4E)-4-Ethoxy-1-phenylhepta-1,4,6-trien-3-amine
(5e). Purified by flash chromatography (CH2Cl2, 1% Et3N, Rf 0.70) to
1
(Mþ, 57), 174 (53), 158 (52), 129 (40), 106 (100), 77 (64); [R]20
=
give 5e (99 mg, 87%) as a yellow oil: H NMR (200 MHz, CDCl3)
D
-159.0 (c 1.1, CH2Cl2). Anal. Calcd for C13H17NO: C, 76.81; H, 8.43.
Found: C, 76.79; H, 8.26. (R,E)-2-Ethoxy-1-phenylpenta-2,4-dien-
1-amine was obtained by the above procedure starting from N-((R,SS,
E)-2-ethoxy-1-phenylpenta-2,4-dienyl)-4-methylbenzenesulfinamide.Pur-
ified by flash chromatography (Et2O/petroleum ether 7:3, 1% Et3N,
Rf 0.30, 100 mg, 99%) as a yellow oil: [R]20D = þ159.0 (c 0.5, CH2Cl2).
Spectral data identical to those of 5a.
δ 7.38-7.09 (m, 5H), 6.51 (dt, J = 16.6, 10.1 Hz, 1H) superimposed to
6.47 (dd, J = 16.0, 2.0 Hz, 1H), 6.24 (dd, J = 16.0, 6.3 Hz, 1H), 5.26
(d, J = 10.1 Hz, 1H), 4.99 (dd, J = 16.6, 2.1 Hz, 1H), 4.81 (dd, J = 10.1,
2.1 Hz, 1H), 4.53 (d, J = 6.3 Hz, 1H), 3.75 (q, J = 7.0 Hz, 2H), 1.73
(br, 2H), 1.26 (t, J = 7.0 Hz, 3H); 13C NMR (50.2 MHz, CDCl3) δ 158.6
(s), 136.8 (s), 131.2 (d), 129.4 (d), 128.3 (d), 127.2 (d), 126.2 (d), 112.2
(t), 100.7 (d), 62.6 (t), 52.3 (d), 14.2 (q); MS m/z 229 (Mþ, 48), 214
(S,E)-2-Ethoxy-1-p-tolylpenta-2,4-dien-1-amine (5b).
Purified by flash chromatography (CH2Cl2/petroleum ether 4:1, 1%
Et3N, Rf 0.70) to give 5b (99 mg, 92%) as a red oil: 1H NMR
(200 MHz, CDCl3) δ 7.24 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 7.9 Hz,
2H), 6.58 (dt, J = 16.6, 10.4 Hz, 1H), 5.29 (d, J = 10.4 Hz, 1H), 4.99 (ddd,
J = 16.6, 2.0, 0.7 Hz, 1H) superimposed to 4.97 (s, 1H), 4.81 (ddd, J =
10.4, 2.0, 0.4 Hz, 1H), 3.73 (qd, J = 7.0, 2.5 Hz, 2H), 2.27 (s, 3H), 1.90
(br, 2H), 1.22 (t, J = 7.0 Hz, 3H); 13C NMR (50.2 MHz, CDCl3) δ 159.0
(s), 140.2 (s), 136.3 (s), 131.4 (d, 2C), 128.7 (d, 2C), 126.0 (d), 112.2(t),
101.0 (d), 62.6 (t), 53.1 (d), 20.8 (q), 14.2 (q); MS m/z 217
(60), 200 (62), 117 (100), 84 (61), 69 (36); [R]21 = -40.4
D
(c 1.0, CH2Cl2). Anal. Calcd for C15H19NO: C, 78.56; H, 8.35. Found:
C, 78.37; H, 8.28. (R,1E,4E)-4-Ethoxy-1-phenylhepta-1,4,6-trien-
3-amine was obtained by the above procedure starting from N-((S,SS,
E)-2-ethoxy-1-(thiophene-2-yl)penta-2,4-dienyl)-4-methylbenzenesul-
finamide. Purified by flash chromatography (CH2Cl2, 1% Et3N,
Rf 0.70,96 mg, 84%) as a yellow oil: [R]21D = þ40.4 (c 1.0, CH2Cl2).
Spectral data identical to those of 5e
(S,E)-4-Ethoxy-2,2-dimethylhepta-4,6-dien-3-amine (5f).
Purified by flash chromatography (CH2Cl2, 1% Et3N, Rf 0.60) to give 5f
(84 mg, 92%) as a yellow oil: 1H NMR (200 MHz, CDCl3) δ 6.36 (dt, J =
16.6, 10.4 Hz, 1H), 5.18 (d, J = 10.4 Hz, 1H), 4.85 (ddd, J = 16.6, 2.0, 0.7
Hz, 1H), 4.66 (ddd, J = 10.4, 2.0, 0.7 Hz, 1H), 3.63 (q, J = 7.0 Hz, 2H),
3.39 (s, 1H), 1.47 (br, 2H), 1.17 (t, J = 7.0 Hz, 3H), 0.81 (s, 9H); 13C
NMR (50.2 MHz, CDCl3) δ 159.5 (s), 132.3 (d), 111.0 (t), 101.7 (d),
62.0 (t), 57.9 (d), 34.9 (s), 27.1 (q), 14.2 (q); MS m/z 183 (Mþ, 5), 126
(Mþ, 100), 188 (65), 172 (54), 120 (74), 96 (31), 77 (15); [R]22
=
D
-37.5 (c 1.0, CH2Cl2). Anal. Calcd for C14H19NO: C, 77.38; H, 8.81.
Found: C, 77.26; H, 8.79. (R,E)-2-Ethoxy-1-p-tolylpenta-2,4-dien-
1-amine was obtained by the above procedure starting from (R,SS,E)-2-
ethoxy-1-p-tolylpenta-2,4-dienyl)-4-methylbenzenesulfinamide. Purified
by flash chromatography (CH2Cl2/petroleum ether 4:1, 1% Et3N, Rf
0.70, 104 mg, 96%) as a red oil: [R]22D = þ37.5 (c 1.2, CH2Cl2). Spectral
data identical to those of 5b.
(56), 80 (100); [R]21 = þ30.4 (c 1.0, CH2Cl2). Anal. Calcd for
D
C11H21NO: C, 72.08; H, 11.55. Found: C, 71.94; H, 11.39. (R,E)-
4-Ethoxy-2,2-dimethylhepta-4,6-dien-3-amine obtained by the above
procedure starting from N-((R,SS,E)-4-ethoxy-2,2-dimethylhepta-4,6-
dien-3-yl)-4-methylbenzenesulfinamide. Purified by flash chromatogra-
(S,E)-2-Ethoxy-1-(4-methoxyphenyl)penta-2,4-dien-1-
amine (5c). Purified by flash chromatography (CH2Cl2, 1% Et3N,
Rf 0.85) to give 5c (108 mg, 93%) as a yellow oil: 1H NMR (200 MHz,
CDCl3) δ 7.23 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.8 Hz, 2H), 6.54 (dt, J =
16.6, 10.5 Hz, 1H), 5.24 (d, J = 10.8 Hz, 1H), 4.96 (dd, J = 16.6, 2.0 Hz,
1H) superimposed to 4.95 (s, 1H), 4.77 (dd, J = 10.5, 2.0 Hz, 1H), 3.73
(qd, J = 7.0, 2.5 Hz, 2H) superimposed to 3.68 (s, 3H), 1.75 (br, 2H),
1.18 (t, J = 7.0 Hz, 3H); 13C NMR (50.2 MHz, CDCl3) δ 159.2 (s),
158.3 (s), 135.3 (s), 131.4 (d), 127.2 (d), 113.4 (d), 112.2 (t), 100.9 (d),
62.6 (t), 55.0 (q), 52.8 (d), 14.2 (q); MS m/z 233 (Mþ, 96), 204 (38),
188 (45), 136 (100), 121 (38), 109 (20), 96 (29); [R]21D = -68.9 (c 1.0,
CH2Cl2). Anal. Calcd for C14H19NO2: C, 72.07; H, 8.21. Found: C,
71.94; H, 8.09. (R,E)-2-Ethoxy-1-(4-methoxyphenyl)penta-2,4-dien-
1-amine was obtained by the above procedure starting from N-((R,SS,
E)-2-ethoxy-1-(4-methoxyphenyl)penta-2,4-dienyl)-4-methylbenzene-
sulfinamide. Purified by flash chromatography (CH2Cl2, 1% Et3N,
Rf 0.85,104 mg, 89%) as a yellow oil: [R]21D = þ68.9 (c 0.4, CH2Cl2).
Spectral data identical to those of 5c.
phy (CH2Cl2, 1% Et3N, Rf 0.60, 83 mg, 91%) as a yellow oil: [R]21
-30.4 (c 1.1, CH2Cl2). Spectral data identical to those of 5f.
=
D
General Procedure for the Syntheses of N-Fmoc Alkox-
ydienyl Amines 6. A solution of 9-fluorenylmethoxycarbonyl chlor-
ide (Fmoc-Cl, 129 mg, 0.5 mmol, 1 equiv) in anhydrous Et2O (5 mL)
was cooled to 0 °C, and the appropriate alkoxydienyl amine (0.5 mmol)
was slowly added. After 10 min, the solution was warmed to rt and stirred
for 1 h, and the reaction progress was monitored by TLC. Then water
(1 mL) was added, and the reaction mixture was stirred for an additional
time of 5 min. The resulting mixture was then extracted with Et2O
(3 ꢀ 10 mL), washed with brine, and dried with anhydrous Na2SO4.
After filtration and evaporation of the solvent, crude products were
purified by column flash chromatography.
(S,E)-(9H-Fluoren-9-yl)methyl 2-ethoxy-1-phenylpenta-
2,4-dienylcarbamate (6a). Purified by flash chromatography
(alumina, EtOAc/petroleum ether 1:4, Rf 0.65) to give 6a (165 mg,
78%) as a white solid: 1H NMR (200 MHz, CDCl3) δ 7.73 (d, J = 7.2 Hz,
2H), 7.58 (d, J = 7.2 Hz, 2H), 7.43-7.14 (m, 9H), 6.67 (dt, J = 16.6, 10.4
Hz, 1H), 5.97 (d, J = 9.0 Hz, 1H), 5.75 (d, J = 9.0 Hz, 1H), 5.42 (d, J =
10.4 Hz, 1H), 5.09 (dd, J = 16.6, 1.5 Hz, 1H), 4.92 (dd, J = 10.4, 1.5 Hz,
1H), 4.44 (d, J = 6.7 Hz, 2H), 4.21 (t, J = 6.7 Hz, 1H), 3.78 (qd, J = 7.1,
2.4 Hz, 2H), 1.22 (t, J = 7.1 Hz, 3H); 13C NMR (50.2 MHz, CDCl3)
δ 155.6 (s), 154.7 (s), 143.8 (s, 2C), 143.7 (s), 141.1 (s, 2C), 130.9 (d),
128.3 (d, 2C), 127.5 (d, 2C), 127.2 (d, 2C), 126.8 (d), 126.2 (d, 2C),
(R,E)-2-Ethoxy-1-(thiophen-2-yl)penta-2,4-dien-1-amine
(5d). Purified by flash chromatography (CH2Cl2, 1% Et3N, Rf 0.75) to
1
give 5d (98 mg, 94%) as a brown oil: H NMR (200 MHz, CDCl3)
δ 7.18 (dd, J = 4.5, 1.8 Hz, 1H), 6.94 (d, J = 4.5 Hz, 1H) superimposed to
6.91 (d, J = 1.8 Hz, 1H), 6.56 (dt, J = 16.6, 10.5 Hz, 1H), 5.37 (d, J = 10.5
Hz, 1H), 5.25 (s, 1H), 5.08 (dd, J = 16.6, 1.8 Hz, 1H), 4.89 (dd, J = 10.5,
1.8 Hz, 1H), 3.74 (qd, J = 7.0, 2.4 Hz, 2H), 1.93 (br, 2H), 1.31 (t, J = 7.0
Hz, 3H); 13C NMR (50.2 MHz, CDCl3) δ 157.9 (s), 147.6 (s),
131.0 (d), 126.4 (d), 124.1 (d), 123.5 (d), 112.8 (t), 101.1 (d), 62.8 (t),
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ARTICLE
124.9 (d, 2C), 119.8 (d, 2C), 113.7 (t), 102.7 (d), 66.6 (t), 62.9 (t),
1H), 6.03 (dd, J = 16.0, 1.2 Hz, 1H), 5.36 (d, J = 6.2 Hz, 1H), 4.25 (d, J =
6.6 Hz, 2H), 4.11 (t, J = 6.6 Hz, 1H), 3.71 (s, 3H), 1.74 (dd, J = 6.9, 1.2
Hz, 3H); 13C NMR (50.2 MHz, CDCl3) δ 192.7 (s), 158.6 (s), 154.4
(s), 144.4 (d), 142.8 (s, 2C), 140.2 (s, 2C), 130.9 (d, 2C), 128.4 (s),
126.6 (d), 126.0 (d, 2C), 124.1 (d, 2C), 118.9 (d, 2C), 113.5 (d, 2C),
113.3 (d, 2C), 65.9 (t), 61.2 (d), 54.3 (q), 46.1 (d), 17.4 (q). MS m/z
427 (Mþ, 8), 328 (11), 238 (41), 223 (100), 189 (48), 77 (62), 51 (34);
52.6 (d), 47.2 (d), 14.2 (q); MS m/z 425 (Mþ, 6), 328 (14), 238 (35),
223 (26), 195 (100), 179 (23), 165 (46), 77 (68), 51 (52); [R]20
=
D
-36.6 (c 1.3, CH2Cl2); mp 86 °C. Anal. Calcd for C28H27NO3: C,
79.03; H, 6.40. Found: C, 78.88; H, 6.29.
(R,E)-(9H-Fluoren-9-yl)methyl 2-Ethoxy-1-(4-methoxy-
phenyl)penta-2,4-dienylcarbamate (6c). Purified by flash chro-
matography (alumina, EtOAc/petroleum ether 3:7, Rf 0.60) to give 6c
(193 mg, 85%) as a pale pink solid: 1H NMR (200 MHz, CDCl3) δ 7.72
(d, J = 7.3 Hz, 2H), 7.56 (d, J = 7.2 Hz, 2H), 7.44-7-07 (m, 6H), 6.80
(d, J = 8.6 Hz, 2H), 6.63 (dt, J = 16.6, 10.3 Hz, 1H), 5.90 (d, J = 9.0 Hz,
1H), 5.70 (d, J = 9.0 Hz, 1H), 5.38 (d, J = 10.3 Hz, 1H), 5.06 (dd, J =
16.6, 1.8 Hz, 1H), 4.90 (dd, J = 10.3, 1.8 Hz, 1H), 4.41 (d, J = 7.2 Hz,
2H), 4.19 (t, J = 7.2 Hz, 1H), 3.76 (q, J = 7.0 Hz, 2H) superimposed to
3.74 (s, 3H), 1.26 (t, J = 7.0 Hz, 3H); 13C NMR (50.2 MHz, CDCl3)
δ 158.7 (s), 155.6 (s), 154.9 (s), 143.8 (s), 143.7 (s, 2C), 141.1 (s, 2C),
131.8 (d, 2C), 130.9 (d, 2C), 127.4 (d, 2C), 126.8 (d), 124.8 (d, 2C),
119.8 (d, 2C), 114.1 (d, 2C), 113.6 (t), 102.4 (d), 66.6 (t), 62.9 (t),
55.1 (q), 47.1 (d), 14.2 (q); MS m/z 455 (Mþ, 3), 358 (11), 238 (39),
223 (31), 217 (19), 195 (100), 165 (44), 91 (53), 77 (61), 51 (39);
[R]20 = -62.8 (c 1.2, CH2Cl2); mp 80 °C. Anal. Calcd for
D
C27H25NO4: C, 75.86; H, 5.89. Found: C, 75.79; H, 5.82.
(R,E)-(9H-Fluoren-9-yl)methyl 2,2-Dimethyl-4-oxohept-5-
en-3-ylcarbamate (7f). Purified by flash chromatography (alumina,
EtOAc/petroleum ether 3:7, Rf 0.70) to give 7f (168 mg, 89%) as a white
solid: 1H NMR (200 MHz, CDCl3) δ 7.68 (d, J = 7.0 Hz, 2H), 7.51 (d,
J = 7.2 Hz, 2H), 7.41-7.13 (m, 4H), 6.92 (dq, J = 15.6, 6.9 Hz, 1H), 6.18
(dd, J = 15.6, 1.1 Hz, 1H), 5.54 (d, J = 9.4 Hz, 1H), 4.43 (d, J = 9.4 Hz,
1H), 4.27 (d, J = 6.7 Hz, 2H), 4.15 (t, J = 6.7 Hz, 1H), 1.84 (dd, J = 6.9,
1.1 Hz, 3H), 0.90 (s, 9H); 13C NMR (50.2 MHz, CDCl3) δ 197.9 (s),
155.2 (s), 143.4 (s), 142.9 (d), 142.8 (s), 140.3 (s, 2C), 130.5 (d), 126.6
(d, 2C), 126.0 (d, 2C), 124.1 (d, 2C), 118.9 (d, 2C), 65.9 (t), 63.2 (d),
46.2 (d), 34.4 (s), 25.8 (q), 17.4 (q); MS m/z 377 (Mþ, 11), 308 (12),
238 (38), 223 (100), 57 (40); [R]20 = -22.5 (c 1.0, CH2Cl2);
[R]21 = þ52.5 (c 1.0, CH2Cl2); mp 98 °C. Anal. Calcd for
D
D
mp 77 °C. Anal. Calcd for C24H27NO3: C, 76.36; H, 7.21. Found: C,
76.15; H, 7.08.
C29H29NO4: C, 76.46; H, 6.42. Found: C, 76.35; H, 6.37.
(R,E)-(9H-Fluoren-9-yl)methyl 4-Ethoxy-2,2-dimethylhep-
ta-4,6-dien-3-ylcarbamate (6f). Purified by flash chromatography
(alumina, EtOAc/petroleum ether 1:9, Rf 0.40) to give 6f (168 mg, 83%)
as a pale yellow solid: 1H NMR (200 MHz, CDCl3) δ 7.71 (d, J = 7.0 Hz,
2H), 7.54 (d, J = 7.2 Hz, 2H), 7.42-7.14 (m, 4H), 6.54 (dt, J = 16.5, 10.4
Hz, 1H), 5.32 (d, J = 10.4 Hz, 1H), 4.98 (dd, J = 16.5, 1.7 Hz, 1H),
4.82 (dd, J = 10.4, 1.7 Hz, 1H), 4.55 (d, J = 10.1 Hz, 1H), 4.40, (d, J =
10.1 Hz, 1H), 4.23 (t, J = 7.2 Hz, 1H), 4.07 (d, J = 7.2 Hz, 2H), 3.73 (q,
J = 7.0 Hz, 2H), 1.26 (t, J = 7.0 Hz, 3H), 0.90 (s, 9H); 13C NMR
(50.2 MHz, CDCl3). δ 155.9 (s), 155.3 (s), 143.8 (s, 2C), 141.1 (s, 2C),
131.9 (d, 2C), 127.4 (d, 2C), 126.8 (d), 124.8 (d, 2C), 119.7 (d, 2C),
112.5 (t), 103.1 (d), 66.4 (t), 62.3 (t), 47.1 (d), 35.5 (s), 26.9 (q),
14.3 (q); MS m/z 405 (Mþ, 9), 308 (21), 238 (46), 223 (31), 195 (100),
182 (22) 165 (39), 57 (44); [R]21D = -25.4 (c 1.0, CH2Cl2); mp 78 °C.
Anal. Calcd for C26H31NO3: C, 77.01; H, 7.71. Found: C, 76.89; H, 7.62.
General Procedure for the Syntheses of N-Fmoc Amino-
pentenones 7. A solution of N-Fmoc alkoxydienyl amine (0.5 mmol)
in CH2Cl2 (2 mL) was stirred in the presence of Amberlyst-15 and the
reaction monitored by TLC. When the reaction was complete, a small
amount of anhydrous K2CO3 was added, and after filtration and
evaporation of the solvent, crude products were purified by column
flash chromatography.
(S,E)-(9H-Fluoren-9-yl)methyl 2-oxo-1-phenylpent-3-en-
ylcarbamate (7a). Purified by flash chromatography (alumina,
EtOAc/petroleum ether 1:4, Rf 0.40) to give 7a (151 mg, 76%) as a
white solid: 1H NMR (200 MHz, CDCl3) δ 7.74 (d, J = 7.5 Hz, 2H),
7.56 (d, J = 5.9 Hz, 2H), 7.46-7.16 (m, 9H), 7.04 (dq, J = 16.9, 6.9 Hz,
1H), 6.37 (d, J = 6.2 Hz, 1H), 6.12 (dd, J = 16.9, 1.5 Hz, 1H), 5.50 (d, J =
6.2 Hz, 1H), 4.32 (d, J = 6.6 Hz, 2H), 4.19 (t, J = 6.6 Hz, 1H), 1.81 (dd,
J = 6.9, 1.5 Hz, 3H); 13C NMR (50.2 MHz, CDCl3) δ 192.6 (s), 154.4
(s), 144.7 (d), 142.8 (s), 142.7 (s), 140.2 (s, 2C), 135.7 (s), 128.1 (d),
127.5 (d), 127.1 (d), 126.7 (d), 126.6 (d), 126.0 (d), 124.0 (d), 118.9
(d), 65.9 (t), 61.9 (d), 46.1 (d), 17.4 (q); MS m/z 397 (Mþ, 5), 328 (9),
238 (22), 223 (100), 174 (61), 77 (78), 51 (31); [R]D20 = þ48.2 (c 1.0,
CH2Cl2); mp 81 °C. Anal. Calcd for C26H23NO3: C, 78.57; H, 5.83.
Found: C, 78.39; H, 5.71.
’ ASSOCIATED CONTENT
S
Supporting Information. Detailed experimental proce-
b
dures and copies of 1H NMR and 13C NMR spectra and X-ray
crystallographic data (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: cristina.prandi@unito.it.
’ ACKNOWLEDGMENT
We thank Regione Piemonte for financial support. We are
grateful to Prof. Ernesto G. Occhiato for helpful discussions.
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