1-(N-Acylamino)alkyltriphenylphosphonium salts as synthetic equivalents of N-acylimines and new effective α-amidoalkylating agents

Article abstract of DOI:10.1016/j.tetlet.2009.05.101

1-(N-Acylaminoalkyl)triphenylphosphonium salts 2a-f on reaction with DBU in MeCN are transformed into 1-(N-acylaminoalkyl)amidinium salts 3a-f. Amidinium salts 3d-f with a proton at the β-position undergo slow tautomerization into the corresponding enamid

Full text of DOI:10.1016/j.tetlet.2009.05.101

Tetrahedron Letters 50 (2009) 4606–4609
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Tetrahedron Letters
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1-(N-Acylamino)alkyltriphenylphosphonium salts as synthetic equivalents
of N-acylimines and new effective a-amidoalkylating agents
a
b
c
Roman Mazurkiewicz a, , Agnieszka Pazdzierniok-Holewa , Beata Orlinska , Sebastian Stecko
*
´
´
a Department of Organic and Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, PL 44-100 Gliwice, Poland
b Department of Chemical Organic Technology and Petrochemistry, Silesian University of Technology, Krzywoustego 4, PL 44-100 Gliwice, Poland
c Institute of Organic Chemistry of the Polish Academy of Science, Kasprzaka 44/52, PL 01-224 Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
1-(N-Acylaminoalkyl)triphenylphosphonium salts 2a–f on reaction with DBU in MeCN are transformed
into 1-(N-acylaminoalkyl)amidinium salts 3a–f. Amidinium salts 3d–f with a proton at the b-position
undergo slow tautomerization into the corresponding enamides 6d–f. The same 1-(N-acylamino)alkyltri-
phenylphosphonium salts 2d–f in the presence of Hünig’s base are transformed directly into the corre-
sponding enamides. Phosphonium salts 2, amidinium salts 3, and enamides 6 react with dialkyl
Received 20 April 2009
Revised 18 May 2009
Accepted 26 May 2009
Available online 30 May 2009
malonates in the presence of DBU to give the corresponding amidoalkylation products. a-Amidoalkyla-
Keywords:
1-(N-Acylamino)alkyltriphenyl-
phosphonium salts
tion of dialkyl malonates is not observed in the presence of (i-Pr)2EtN, yet proceeds well under these con-
ditions with more acidic nucleophiles, for example, phthalimide or benzyl mercaptan.
Ó 2009 Elsevier Ltd. All rights reserved.
N-Acylimines
8-[1-(N-Acylamino)alkyl]-1-aza-8-
azoniabicyclo[5.4.0]undec-7-ene salts
Enamides
a-Amidoalkylation
N-Acylimines, which are highly reactive, short-lived intermedi-
tored by 1H NMR. The characteristic signal of the methylene group
of the phosphonium salts at d 5.02–5.27 (dd) was replaced by a sin-
glet in the range d 4.76–4.99. The 13C NMR spectra of the reaction
mixtures also revealed the immediate disappearance of the initial
phosphonium salt and formation of free triphenylphosphine and
another compound. To identify the structures of the transforma-
tion products of phosphonium salts 2a–b, we repeated these
experiments in MeCN and carried out high-resolution mass spec-
trometry of the reaction mixtures using electrospray ionization.
In both cases the formula of the highest mass ion matched the cat-
ion of the corresponding N-acylaminomethylamidinium salt 3
formed by the amidoalkylation of DBU (Scheme 2, Table 1). Evap-
oration of MeCN and extraction of triphenylphosphine with tolu-
ene gave the pure amidinium salts 3a–b as thick oils.8 Attempts
to obtain these compounds in crystalline form failed. Further spec-
troscopic investigations of salts 3a–b fully confirmed their amidi-
nium structure.8
ates, are used in a wide variety of synthetically useful transforma-
tions.1–3 They are known as strong amidoalkylating agents that are
able to react with a range of nucleophiles to give substituted
amides,1 allylic and propargylic primary amines,1,4 b-aminoke-
tones,1 or
a
-amino acid derivatives.1,5 N-Acylimines are also
widely used, as both hetero-1,3-dienes and dienophiles in Diels–
Alder cycloaddition reactions.1,6 Most frequently, N-acylimines
are generated in situ from
a-substituted N-acylamines via base-
catalyzed or thermal elimination.1 Recently, we described simple
and efficient syntheses of 1-(N-acylamino)alkyltriphenylphospho-
nium salts (APS) 2 by hydrolysis and decarboxylation of 4-phos-
phoranylidene-5(4H)-oxazolones 1 or their alkylation products
(Scheme 1).7
Phosphonium salts 2a–f are stable, crystalline compounds,
which are easy to obtain even on kilogram scale.
In the present Letter, we report our investigations on the com-
plex interactions of 1-(N-acylamino)alkyltriphenylphosphonium
salts 2 with organic bases (DBU, Et3N, or i-Pr2EtN), as well as the
amidoalkylating properties of phosphonium salts 2 in the presence
of these bases.
2a R1 = Ph, R2 = H, X = BF4
2b R1 = t-Bu, R2 = H, X = BF4
2c R1 = Me, R2 = H, X = BF4
O
O
PPh3
R2
X
Ph3P
N-Acylaminomethyltriphenylphosphonium salts (2a–c, R2 = H)
reacted immediately when treated with DBU in CD3CN, as moni-
Lit.7
1
O
R
N
2d R1 = t-Bu, R2 = Me, X = I
N
H
2e R1 = Ph, R2 = Me, X = I
R1
2f R1 = t-Bu, R2 = CH2OMe, X = I
1
2a-f
* Corresponding author. Tel.: +48 32 2371724; fax: +48 32 2371549.
E-mail address: Roman.Mazurkiewicz@polsl.pl (R. Mazurkiewicz).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.101

R. Mazurkiewicz et al. / Tetrahedron Letters 50 (2009) 4606–4609
4607
(i-Pr)2EtN
- Ph3P
N
R
6d-f
2d-f
5d-f
O
O
N
.
- (i-Pr)2EtN HI
1
2
.
R
N
DBU HX
X
H
Scheme 4.
O
PPh3
O
X
3a-f
DBU
1
1
2
2
R
N
H
2a-f
R
R
N
R
- Ph3P
- DBU HX
3
.
R
1
R
N
H
5a-f
DBU
NuH
2
2a, 2d
3a
O
R
6d-f
(i-Pr)2EtN
NuH
1
DBU
NuH
6d R1 = t-Bu, R3 = H
6e R1 = Ph, R3 = H
2b, 2f
R
N
H
7
Nu
6f R1 = t-Bu, R3 = OMe
DBU
NuH
6d
Scheme 2.
Scheme 5.
O
O
The interaction of bases with
a-substituted 1-(N-acyla-
Et3N
mino)alkyltriphenylphosphonium salts 2d–f (R2 – H) differs in
many respects from the interactions of N-acylaminomethyltriphe-
nylphosphonium salts 2a–c (R2 = H). The first step of the reaction
of 1-(N-acylamino)alkyltriphenylphosphonium salts 2d–f with
DBU in CD3CN was closely analogous to that observed with N-acy-
laminomethyltriphenylphosphonium salts; in spite of steric conges-
t-Bu
N
H
PPh3
t-Bu
N
NEt3
BF4
BF4
H
- Ph3P
4b
2b
Scheme 3.
A similar result was obtained from a study of the reaction of N-
tion at the
a-carbon, all these phosphonium salts immediately
acylaminomethyltriphenylphosphonium salts with triethylamine.
After addition of triethylamine to a solution of N-pivaloylaminom-
ethyltriphenylphosphonium tetrafluoroborate 2b in CD3CN, we ob-
served an equilibrium between the starting phosphonium salt and
the quaternary ammonium salt 4b, which was the product of the
amidoalkylation of triethylamine (Scheme 3).9 The conversion of
phosphonium salt 2b into the ammonium salt 4b increased from
39% at a 1:1.25 molar ratio of phosphonium salt to triethylamine,
to 93% at a 1:20 molar ratio of 2b to Et3N. Attempts to isolate
the ammonium salt 4b failed, because of the reversibility of this
reaction.
formed the corresponding amidinium salts 3d–f. Amidinium salts
3d and 3f were synthesized on a larger scale, isolated and identified
as described above for compounds 3a–b (Table 1).8
In contrast to the amidinium salts 3a–c, however, salts 3d–f
underwent slow transformation into the corresponding enamides
4d–f in CD3CN, as monitored by 1H NMR. For example, in the reac-
tion of 1-(N-benzoylamino)ethyltriphenylphosphonium iodide 2e
with DBU in CD3CN at 20 °C at a 1:1.7 molar ratio of 2e to DBU,
after four hours, the 3e:6e molar ratio was 13:87 and after 24 h,
the 3e:6e ratio attained a constant value of 6:94. Similar results
were obtained with phosphonium iodides 2d and 2f. The rate of
this transformation rose with increased phosphonium salt:DBU
molar ratio. The experiments with salts 2d and 2e were repeated
on a larger scale in MeCN in order to isolate the corresponding ena-
mides in pure form, however, we were successful only in the case
of enamide 6d (Table 2, Procedure A).10 We were unable to isolate
In contrast to triethylamine, Hünig’s base [(i-Pr)2EtN], which is
considered to be a non-nucleophilic base, caused no noticeable
changes in the 1H NMR spectra of N-acylaminomethyltriphenyl-
phosphonium salts 2a–c in CD3CN.
Table 1
Transformation of phosphonium salts 2 into amidinium salts 38
APS 2
R2
Molar ratio of
Amidinium salt 3
HR-ESI-MS (m/z)
R1
X
APS 2 to DBU
Yield (%)
Formulaa
Calcd
Found
2a
2b
2d
2f
Ph
H
H
BF4
BF4
I
I
1:1
1:1
1:1.25
1:1.25
3a
3b
3d
3f
82
93
75
77
C17H24N3O
C15H28N3O
C16H30N3O
C17H32N3O2
286.1913
266.2227
280.2383
310.2489
286.1908
266.2230
280.2385
310.2491
t-Bu
t-Bu
t-Bu
Me
CH2OMe
a
Formula of the amidinium cation.
Table 2
Transformation of phosphonium salts 2 into enamides 6
APS 2
Reaction conditions
Temp. (oC)
Enamide 6
Salt
R1
R2
X
Procedure10
Time
R3
Yield (%)
Mpa (oC)
2d
2f
t-Bu
t-Bu
Me
CH2OMe
I
I
A
B
20
60
6 d
10 h
6d
6f
H
OMe
48
92–93b
81c
107–108d
a
b
c
After recrystallization from toluene.
Lit. mp 99–101 °C (from hexane).11
A mixture of Z and E isomers in a molar ratio of 66:34.
Mp of the E isomer recrystallized from toluene.
d

4608
R. Mazurkiewicz et al. / Tetrahedron Letters 50 (2009) 4606–4609
Table 3
a
-(N-Acylamino)alkyltriphenylphosphonium salts and their derivatives as amidoalkylating agents13
Amidoalkylating agent
NuH
Reaction conditions
Reaction product 7
R1
R2
R3
X
Procedure13
Base
Temp. (oC)
Time
Yield (%)
Mp (oC)
2a
3a
2b
2d
6d
2f
Ph
Ph
t-Bu
t-Bu
t-Bu
t-Bu
H
H
H
Me
—
—
—
—
H
—
BF4
BF4
BF4
I
—
I
CH2(CO2Me)2
CH2(CO2Me)2
Benzyl mercaptan
CH2(CO2Et)2
CH2(CO2Et)2
Phthalimide
C
C
D
C
C
D
DBU
DBU
(i-Pr)2EtN
DBU
DBU
60
60
20
60
60
60
1.5 h
1.5 h
4 d
1.5 h
1 h
7a
7a
7b
7d
7d
7f
64
60
92
61
82
76
94–95
45.5–46
oil
oil
—
CH2OMe
(i-Pr)2EtN
10.5 h
122–123
the enamide 6e, probably due to its polymerization during column
chromatography.
remain in equilibrium with phosphonium salts 2, the 1-(N-acyla-
mino)alkylamidinium salt 3 derived from DBU and, in the case of
phosphonium salts, with a proton at the b-position, with the corre-
sponding enamides 6. It seems that non-nucleophilic Hünig’s base
also generates N-acylimines from 1-(N-acylamino)alkyltriphenyl-
phosphonium salts, however, in this case, the reaction equilibrium
is shifted toward phosphonium salts 2a–c or enamides 6d–f.
Phosphonium salts 2d–f in CD3CN in the presence of Hünig’s
base at 20 °C underwent direct transformation into the corre-
sponding enamides 6d–f, as monitored by 1H NMR (Scheme 4).
The reaction of phosphonium salt 2f with Hünig’s base on large
scale in MeCN at 60 °C, gave a mixture of Z and E isomers of ena-
mide 6f in a molar ratio of 66:34 and in a yield of 81% (Table 2, Pro-
cedure B).10
Acknowledgment
The findings described above can be rationalized assuming that
1-(N-acylamino)alkyltriphenylphosphonium salts 2, both
a-substi-
Thefinancialhelpof theMinistryof Scienceand HigherEducation
of Poland (Grant No. N N204 238334) is gratefully acknowledged.
tuted and -unsubstituted, are transformed under the influence of
a
DBU into the corresponding N-acylimines 5 as the primary reaction
products, which in turn react with DBU to give amidinium salts 3.
Amidinium salts 3d–f with a proton at the b-position undergo slow
transformation directly, or more probably via N-acylimines, into the
corresponding enamides 6d–f. Tautomerization of N-acylimines to
the corresponding enamides is a well-known phenomenon.12
This conclusion was confirmed by the observation that both
types of N-acylaminoalkyltriphenylphosphonium salts 2 (R2 = H
and R2 – H) reacted smoothly with dialkyl malonates in the pres-
ence of DBU under the influence of microwave irradiation at
References and notes
1. Fišera, L. In N-Acylimines, Science of Synthesis, Houben-Weyl Methods of
Molecular Transformations, Thieme 2004; Vol. 27, p 349.
2. Malassa, I.; Matthies, D. Chem-Ztg. 1987, 111, 181.
3. Malassa, I.; Matthies, D. Chem-Ztg. 1987, 111, 253.
4. Zhang, L.; Wei, Ch.; Li, Ch.-J. Tetrahedron Lett. 2002, 43, 5731.
5. Foresti, E.; Palmieri, G.; Petrini, M.; Profeta, R. Org. Biomol. Chem. 2003, 1, 4275.
6. Gizecki, P.; Dhal, R.; Toupet, L.; Dujardin, G. Org. Lett. 2000, 2, 585.
´
7. Mazurkiewicz, R.; Pazdzierniok-Holewa, A.; Grymel, M. Tetrahedron Lett. 2008,
49, 1801.
60 °C to give the expected
a-amidoalkylation product (Scheme 5,
8. Experimental procedure for compounds 3: To a suspension of APS 2 (1 mmol) in
CH3CN (11 cm3), DBU (0.15 cm3, 1 mmol for 2a–b or 0.19 cm3, 1.25 mmol for
2d and 2f) was added at 20 °C. After 10 min the solvent was evaporated under
reduced pressure. The residue was extracted with toluene at room
temperature. After evaporation of the solvent and drying under reduced
pressure, the amidinium salts 3 were obtained in the yields given in Table 1.
Compound 3a: oil; IR (CH3CN, cmÀ1): 3380br, 3212br, 1668s, 1652s, 1620vs,
1532s; 1H NMR (600 MHz, CD3CN): d 7.94 (br s, 1H), 7.85–7.49 (m, 5H), 5.01 (d,
J = 6.0 Hz, 2H), 3.64–3.60 (m, 4H), 3.46–3.44 (m, 2H), 3.05–3.04 (m, 2H), 2.04–
2.01 (m, 2H), 1.75–1.73 (m, 4H), 1.68–1.66 (m, 2H); 13C NMR (150 MHz,
CD3CN): d 168.65, 168.62, 134.24, 133.21, 129.69, 128.35, 58.51, 55.88, 50.19,
47.50, 29.16, 29.00, 26.40, 23.43, 20.56.
Table 3, Procedure C).13 The isolated and purified amidinium salt
3a also reacted easily with diethyl malonate under the same con-
ditions to give the corresponding amidoalkylation product. Unex-
pectedly, N-vinylpivaloamide 6d also reacted with diethyl
malonate under these conditions to give the amidoalkylation prod-
uct 7d, in a better yield than from the corresponding phosphonium
salt 2d (Scheme 5, Procedure C, Table 3).13 It is well known that
enamides can act as a-amidoalkylation reagents, although usually
following C-protonation to an acyliminium cation.14 The results of
the two latter experiments can be explained assuming that phos-
phonium salts 2, amidinium salts 3, enamides 6, and N-acylimines
5 remain in equilibrium under the applied reaction conditions.
1-(N-Acylamino)alkyltriphenylphosphonium salts 2 did not re-
act with dialkyl malonates in the presence of Hünig’s base in
MeCN. However, the amidoalkylation reaction proceeded smoothly
under these conditions with more acidic nucleophiles, for example,
phthalimide or benzyl mercaptan (Scheme 5, Procedure D, Table
3).13 Taking these results into account, and keeping in mind that
Hünig’s base transforms phosphonium salts 2d–f into the corre-
sponding enamides, one can speculate that Hünig’s base also
generates N-acylimines from 1-(N-acylamino)alkyltriphenylphos-
phonium salts, however, in this case, the reaction equilibrium is
shifted toward phosphonium salts 2a–c or enamides 6d–f.
Compound 3b: oil; IR (CH3CN, cmÀ1): 3400br, 3220br, 1672s, 1620vs, 1520s; 1
H
NMR (300 MHz, CD3CN): d 7.24 (br s, 1H), 4.77 (d, J = 6.0 Hz, 2H), 3.61–3.58 (m,
2H), 3.53–3.49 (m, 2H), 3.46–3.42 (m, 2H), 2.98–2.94 (m, 2H), 2.02–1.93 (m,
2H), 1.79–1.65 (m, 6H), 1.15 (s, 9H); 13C NMR (75.5 MHz, CD3CN): d 180.18,
168.42, 58.17, 55.69, 50.07, 47.00, 39.33, 28.94, 28.90, 27.46, 26.37, 23.49,
20.53.
Compound 3d: IR (CH3CN, cmÀ1): 3376br, 3196br, 1676s, 1652s, 1612vs, 1508s;
1H NMR (600 MHz, CD3CN): d 7.23 (br s, 1H), 5.86 (dq, J1 = 6.7 Hz, J2 = 6.7 Hz 1H),
3.68–3.64 (m, 1H), 3.57–3.53 (m, 1H), 3.44–3.39 (m, 3H), 3.34–3.28 (m, 1H),
3.01–2.96 (m, 2H), 2.05–1.98 (m, 1H), 1.91–1.86 (m, 1H), 1.83–1.70 (m, 6H), 1.49
(d, J = 7.2 Hz 3H), 1.18 (s, 9H); 13C NMR (150 MHz, CD3CN): d 179.77, 167.50,
63.82, 55.36, 50.31, 39.91, 39.42, 28.83, 27.63, 26.65, 23.15, 20.91, 18.75.
Compound 3f: oil; 3368br, 3236br, 1676s, 1652s, 1612vs, 1520s; 1H NMR
(300 MHz, CD3CN): d 7.47 (br d, J = 6.9 Hz, 1H), 5.93 (ddd, J = 8.4 Hz, J = 7.2 Hz,
J = 4.8 Hz, 1H), 3.88 (dd, J = 10.2 Hz, J = 8.4 Hz, 1H), 3.65–3.62 (m, 2H), 3.58 (dd,
J = 10.5 Hz, J = 4.8 Hz, 1H), 3.48–3.41 (m, 4H), 3.36 (s, 3H), 3.12–2.94 (m, 2H),
1.95–1.68 (m, 8H), 1.19 (s, 9H); 13C NMR (75.5 MHz, CD3CN): d 179.89, 168.37,
70.34, 65.99, 59.42, 55.27, 50.21, 40.45, 39.42, 28.76, 28.50, 27.53, 26.35, 22.98,
20.61.
9. To a solution of APS 2b (1
l lmol or 2 lmol
mol) in CD3CN (0.8 cm3), Et3N (1.25
In conclusion, 1-(N-acylamino)alkyltriphenylphosphonium
salts 2 display strong amidoalkylating properties in the presence
of organic bases such as DBU and Hünig’s base. It can be assumed
that deprotonation and elimination of triphenylphosphine from
phosphonium salts 2 under the influence of the base lead to the
corresponding highly reactive N-acylimines, which are responsible
for the amidoalkylating properties of this reaction system. In reac-
tions carried out in the presence of DBU, unstable N-acylimines
or 20
l
mol) was added. The progress of the reaction was monitored by 1H NMR
spectroscopy.
N-pivaloylaminomethyltriethylammonium tetrafluoroborate 4b: 1H NMR
(300 MHz, CD3CN):
d 7.19 (br s, 1H), 4.52 (d, J = 7.2 Hz, 2H), 3.11 (q,
J = 7.2 Hz, 6H), 1.291 (t, J = 7.2 Hz, 3H), 1.286 (t, J = 7.2 Hz, 3H), 1.280 (t,
J = 7.2 Hz, 3H), 1.22 (s, 9H); 13C NMR (75 MHz, CD3CN): d 181.16, 61.22, 51.53,
39.81, 27.25, 7.86.
10. Procedure A: To a suspension of APS 2d (1 mmol) in CH3CN (11 cm3), DBU
(0.19 cm3, 1.25 mmol) was added. The reaction mixture was left for 6 d at rt

R. Mazurkiewicz et al. / Tetrahedron Letters 50 (2009) 4606–4609
4609
and then the solvent was evaporated under reduced pressure. The residue was
purified by column chromatography (silica gel, 1:2 EtOAc/toluene) to afford 6d
in 48% yield.
(75.5 MHz, CDCl3): d 168.69, 167.45, 133.99, 131.67, 128.58, 126.93, 52.85, 50.91,
38.26; Anal. Calcd for C13H15NO5: C, 58.86; H, 5.70; N, 5.28. Found: C, 58.91; H,
5.62; N, 5.29.
Compound 6d11: white powder, 1H NMR (600 MHz, CDCl3): d 7.30 (br s, 1H),
7.00 (ddd, J = 15.8 Hz, J = 10.8 Hz, J = 8.4 Hz, 1H), 4.62 (d, J = 15.6 Hz, 1H), 4.42
(d, J = 8.7 Hz, 1H), 1.23 (s, 9H); 13C NMR (150 MHz, CDCl3): d 175.72, 129.12,
94.92, 38.68, 27.35.
Compound 7d: IR (CH2Cl2, cmÀ1): 3444 m, 1744vs, 1728vs, 1660vs, 1512vs; 1H
NMR (600 MHz, CDCl3): d 6.81 (br d, J = 8.4 Hz, 1H), 4.68 (ddq, J = 4.2 Hz, J = 6.8 Hz,
J = 8.4 Hz, 1H), 4.26 (dq, J = 10.8 Hz, J = 7.2 Hz, 1H), 4.23 (dq, J = 11.4 Hz, J = 7.2 Hz,
1H), 4.18 (dq, J = 10.2 Hz, J = 7.2 Hz, 1H), 4.16 (dq, J = 10.2 Hz, J = 7.2 Hz, 1H), 3.57
(d, J = 4.2 Hz, 1H), 1.30 (dd, J = 7.2 Hz, J = 7.2 Hz, 3H), 1.26 (dd, J = 7.2 Hz, J = 7.2 Hz,
3H), 1.25 (d, J = 7.2 Hz, 3H), 1.17 (s, 9H); 13C NMR (150 MHz, CDCl3): d 177.52,
168.62, 167.67, 61.65, 61.50, 55.55, 44.15, 38.56, 27.36, 18.96, 13.98; HR-ESI-MS
m/z for C14H25NO5Na [M+Na+]: calcd 310.1625; found 310.1610.
Procedure B: To a suspension of APS 2f (1 mmol) in CH3CN (4 cm3), (i-Pr)2EtN
(0.26 cm3, 1.5 mmol) was added. The reaction mixture was heated in a sealed
reaction vial at 60 °C for 10 h. The solvent was evaporated under reduced
pressure and the residue was purified by column chromatography (silica gel,
1:2 EtOAc/toluene) to give two isomers of the enamide 6f. Z isomer: colorless
oil, 53%, IR (CH2Cl2, cmÀ1): 3456 m, 1664vs, 1492vs; 1H NMR (600 MHz,
CDCl3): d 7.32 (br s, 1H), 6.17 (dd, J = 10.2 Hz, J = 4.8 Hz, 1H), 5.58 (d, J = 4.8 Hz,
1H), 3.65 (s, 3H), 1.23 (s, 9H); 13C NMR (150 MHz, CDCl3): d 174.73, 133.22,
104.15, 59.96, 38.79, 27.46; HR-EI-MS m/z for C8H15NO2 [M+]: calcd 157.1103;
found 157.1096. E isomer: colorless needles; 28%; IR (CH2Cl2, cmÀ1): 3456 m,
1664vs, 1500vs; 1H NMR (600 MHz, CDCl3): d 6.82 (br s, 1H), 6.66 (d, J = 12 Hz,
1H), 6.39 (dd, J = 12 Hz, J = 9 Hz, 1H), 3.55 (s, 3H), 1.22 (s, 9H); 13C NMR
(150 MHz, CDCl3): d 175.72, 139.32, 104.94, 56.77, 38.72, 27.50; HR-EI-MS m/z
for C8H15NO2 [M+]: calcd 157.1103; found 157.1097.
Procedure D: To a stirred suspension of APS 2b or 2f (1 mmol) in CH3CN (4 cm3),
benzyl mercaptan (2 mmol) or phthalimide (1.1 mmol) and (i-Pr)2EtN (1.5 mmol)
were added. The reaction mixture was left at rt or was heated at 60 °C for the time
given in Table 3. The solvent was evaporated under reduced pressure and the
product was isolated by column chromatography (silica gel, 1:5 EtOAc/toluene) to
give compound 7b or 7f. The solid products 7b and 7f were recrystallized by
dissolving in toluene and precipitated on addition of hexane.
Compound 7b: IR (CH2Cl2, cmÀ1): 3456 m, 1664vs, 1512vs, 1500vs; 1H NMR
(300 MHz, CDCl3): d 7.38–7.23 (m, 5H), 5.69 (br s, 1H), 4.37 (d, J = 5.7 Hz, 2H), 3.79
(s, 2H), 1.09 (s, 9H); 13C NMR (75.5 MHz, CDCl3): d 178.08, 138.89, 128.76, 128.75,
127.20, 41.60, 38.58, 36.17, 27.25; Anal. Calcd for C13H19NOS: C, 65.78; H, 8.07; N,
5.90. Found: C, 65.94; H, 8.15; N, 5.92.
11. Archibald, S. C.; Fleming, I. J. Chem. Soc., Perkin Trans. 1 1993, 751.
12. Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41, 4367.
13. Procedure C: A solution of phosphonium salt (2a or 2d), or amidinium salt 3a, or
enamide 6d (1 mmol), dimethyl malonate (8 mmol) or diethyl malonate (6 mmol)
and DBU (2 mmol) in CH3CN (8 cm3) was irradiated in a sealed reaction vial at a
power of 10–12 W in a microwave reactor (CEM Matthews) at 60 °C for the time
given in Table 3. The solvent was evaporated under reduced pressure and the
product was isolated by column chromatography (silica gel, 1:5 EtOAc/toluene) to
give compound 7a or 7d. Product 7a was recrystallized from toluene.
Compound 7a: IR (CH2Cl2, cmÀ1): 3455 m, 1748vs, 1736vs, 1664vs, 1520vs; 1H
NMR (300 MHz, CDCl3): d 7.76–7.73 (m, 2H), 7.54–7.40 (m, 3H), 6.86 (br s, 1H),
3.97 (dd, J = 6.3 Hz, J = 6.0 Hz, 2H), 3.83 (t, J = 6.3 Hz, 1H), 3.78 (s, 6H); 13C NMR
Compound 7f: IR (CH2Cl2, cmÀ1): 3448 m, 1776s, 1720vs, 1676vs, 1504vs; 1H NMR
(600 MHz, CDCl3): d 7.84 (dd, J = 5.4 Hz, J = 3.0 Hz, 2H), 7.73 (dd, J = 5.3 Hz,
J = 3.0 Hz, 2H), 6.98 (br d, J = 9.6 Hz, 1H), 6.43 (ddd, J = 9.0 Hz, J = 7.8 Hz, J = 5.4 Hz,
1H), 3.80 (dd, J = 10.8 Hz, J = 7.8 Hz, 1H), 3.67 (dd, J = 10.8 Hz, J = 5.7 Hz, 1H), 3.39
(s, 3H), 1.20 (s, 9H); 13C NMR (150 MHz, CDCl3): d 177.86, 167.73, 134.17, 131.74,
123.51, 71.31, 58.96, 55.20, 38.88, 27.31; HR-ESI-MS m/z for C16H20N2O4Na
[M+Na+]: calcd 327.1315, found: 327.1330.
14. Lukyanov, S. M. In The Chemistry of Enamines, Chemistry of Functional Groups;
Rappoport, Z., Ed.; Wiley, 1994; p 1441.