Metallic chalcogenolates mediated modular Michael-aldol cascade reaction: An easy route to multi-functionalized chalcogenides and Morita-Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tet.2012.09.027

Chalcogenolate mediated Michael-aldol cascade reactions consists of a very efficient route to multi-functionalized γ-hydroxichalcogenides. Although, when selenolates are employed, these γ-hydroxichalcogenides can be readily converted into the corresponding Morita-Baylis-Hillman adducts by oxidative elimination of the selenium moiety. In this context, herein we present a complete study on the scope and limitations of this reaction.

Full text of DOI:10.1016/j.tet.2012.09.027

Tetrahedron 68 (2012) 10406e10413
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Metallic chalcogenolates mediated modular Michael-aldol cascade reaction: an
easy route to multi-functionalized chalcogenides and MoritaeBayliseHillman
adducts
a
b
c
a
,
,
*
Bruno A. Sousa , Arthur F. Keppler , Rogerio A. Gariani , Joao V. Comasseto d, Alcindo A. Dos Santos a
ꢀ
~
a
~
~
Instituto de Química, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 748, Cx.P. 26077, CEP 05508-000 Sao Paulo, Brazil
ˇ
b
~
Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC, Avenida Dos Estados, 5001, CEP 09210-170 Sao Paulo, Brazil
c GAPAM e Departamento de Química, Universidade do Estado de Santˇ a Catarina, R. Paulo Malschitzki, S/N, CEP 89219-710 Santa Catarina, Brazil
ˇ
ˇ
d
~
Universidade Federal de Sao Pulo, Campus de Diadema, Instituto de Ciencias Ambientais, Químicas e Farmaceuticas, Departamento de Ciencias Exatas e da Terra, Setor de Química,
Rua Prof. Artur Ridel, 275, CEP 09972-270, Jardim Eldorado, Diadema, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2012
Received in revised form 28 August 2012
Accepted 4 September 2012
Available online 11 September 2012
Chalcogenolate mediated Michael-aldol cascade reactions consists of a very efficient route to multi-
functionalized
g-hydroxichalcogenides. Although, when selenolates are employed, these g-hydrox-
ichalcogenides can be readily converted into the corresponding MoritaeBayliseHillman adducts by
oxidative elimination of the selenium moiety. In this context, herein we present a complete study on the
scope and limitations of this reaction.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Michael-aldol
Cascade reaction
Chalcogens
Organometallics
MoritaeBayliseHillman
1. Introduction
In this study we decided to evaluate the scope and the limita-
tions of this protocol and its complementarity to the MBH reaction.
The Michael and the aldol reactions have always been amongst
the most important and widely employed reactions in organic
synthesis.1 Another relevant feature of these two reactions is the
fact that both transformations can be performed in a cascade
fashion.2e8 For this purpose, metallic organochalcogenolates con-
sists on a key class of nucleophiles due to its high nucleophilicity
and low basicity.9 In special, when metallic selenolates are
employed as initial nucleophiles, the resulting adduct can be easily
converted into the corresponding MoritaeBayliseHillman (MBH)
adduct by syn-selenoxide elimination, as previously described by
the group.10 Since these kinds of nucleophiles can be generated in
situ by the reductive cleavage of the elemental chalcogen by the
corresponding organometallic, it is worth noting that this meth-
odology completely avoids the manipulation of chalcogen nucleo-
philes with unpleasant odors and can be applied in many different
situations.11e15
Focusing in possible synthetic applications of this methodology, we
have evaluated the behavior of different chalcogenolates, alde-
hydes, and Michael acceptors.
2. Results and discussion
Willing to investigate the cascade reaction, we proposed a sys-
tematic study in order to evaluate each of the three components
involved in this protocol and the most important effects that might
drive the reactivity (Fig. 1).
* Corresponding author. Tel.: þ55 01130919110; e-mail address: alcindo@
iq.usp.br (A.A. Dos Santos).
Fig. 1. The possible driving effects of each component of the cascade reaction.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.027

B.A. Sousa et al. / Tetrahedron 68 (2012) 10406e10413
10407
One of the most serious drawbacks of the MBH reaction is the
fact that the reaction with electron rich aldehydes, such as alkyl-
and electron-donating substituted aryl-aldehydes is quite slow in
comparison to electron-poor aldehydes, such as nitro-aromatic
ones.16 Our initial study focused on the evaluation of the behavior
of different aldehydes and chalcogenolates. In these initial experi-
ments we have chosen acrylonitrile as the standard Michael ac-
ceptor. In order to verify the influence of the electronic effect on the
secondary electrophile, some aromatic aldehydes were tested, in
which the substituents were varied from electron donating- to
electron withdrawing groups.
Table 1 (entries 1e4), the average yield of the sulfides and the
selenides produced by this protocol is the same, both leading to
the aldol products in good yields. On the other hand, the corre-
sponding tellurides were obtained in lower yields in all the cases.
It is important to note that this observation on the tellurides yields
is not only related to the reactivity of the intermediate lithium-
tellurolate, but also on the stability of the product. In all cases,
the cyano-tellurides have shown to be very unstable under various
conditions.17 It is possible to observe the decomposition of these
compounds when in solution, during the chromatography and
even when stored in low temperatures after purification. In this
case, unfortunately it is not possible to affirm that the lower yields
are due to a different reactivity without considering the pro-
nounced decomposition during the extraction and isolation
procedures.
Amongst these examples, some selenides were converted into
the corresponding MBH adducts by in situ oxidative elimination, by
quenching the reaction with hydrogen peroxide solution (30%). The
following Table 1 summarizes the obtained results.
A fair reactivity comparison can be made with aromatic alde-
hydes with different substituents and an alkyl aldehyde (Table 1,
entries 1e4). In comparison to entry 4 (benzaldehyde), the pres-
ence of an electron donating group (methoxy, entry 1) or a weak
electron-withdrawing group (chlorine, entry 2) does not strongly
affect the conversion into the expected aldol product. However,
a trend to lowest conversions can be observed when employing
more electron deficient aldehydes, such as in entry 2. In this case,
this is particularly important to the applicability of this protocol,
since no aldehyde activation is necessary and common alkyl al-
dehydes can be readily employed, leading to the expected aldol
products in good yields (Table 1, entries 3 and 5). As can be seen in
We have also optimized this protocol for the one-pot prepara-
tion of the corresponding MBH adducts, by quenching the reaction
with hydrogen peroxide solution. Some examples of MBH adducts
have been produced (Table 1, entries 6e10) and as can be seen, alkyl
and aromatics aldehydes are tolerated. It is also worth noting that
when nitro aldehydes were employed (Table 1, entries 9 and 10) the
lowest yields were observed. As depicted in the general reaction
scheme in Table 1, the aldehyde is added first into the reaction
media, since no reaction between the lithium chalcogenolate and
the aldehyde is expected. In the case of the nitro aldehydes, a re-
action between the aldehyde and the chalcogenolate clearly takes
place. As well as being visually distinct, these reactions furnish the
Table 1
Evaluation of different aldehydes and lithium chalcogenolates
OH
R1
R1
R2
nBuLi
i.
O
[nBuYLi]
Y0 = S, Se, Te Y0
THF, r.t.
CN
ii.
CN
iii. work up (H+)
or H2O2
R2 = H or nBuY
Total reaction time = 30 min
THF, -75 ºC to r.t.
Entry
1
Aldehyde
Aldol product
Chalcogen yield
Entry
6
Aldehyde
MBH adduct
Yield
O
OH
O
OH
nBuY
a 2, Y¼S, 98%
b 3, Y¼Se, 97%
c 4, Y¼Te, 65%
19, 87%
CN
OMe
CN
9
OMe
1
O
OH
OH
O
nBuY
2
3
4
5
a 6, Y¼S, 80%
b 7, Y¼Se, 88%
c 8, Y¼Te, 60%
7
21, 79%
23, 87%
25, 40%
27, 32%
CN
20
Cl
CN
Cl
5
O
O
OH
OH
a 10, Y¼S, 83%
b 11, Y¼Se, 83%
c 12, Y¼Te, 60%
8
nBuY
CN
Br
Br
22
CN
9
O
O
OH
OH
a 14, Y¼S, 91%
b 15, Y¼Se, 95%
c 16, Y¼Te, 60%
9
nBuY
CN
CN
NO2
24
NO2
13
O
O
OH
OH
NO2
NO2
18, Y¼Se, 85%
10
nBuY
6
6
CN
CN
17
26
All the reactions were conducted under nitrogen atmosphere and in a 3 mmol scale.
In all the cases in which a diastereomeric mixture was obtained, anti:syn¼3:2 d.r., calculated by 1H and 77Se NMR.

10408
B.A. Sousa et al. / Tetrahedron 68 (2012) 10406e10413
corresponding nitro-benzyl alcohol as major byproduct, probably
by a Cannizzaro type disproportionation.18
These observations lead us to conclude that all the three chalcogens
are good nucleophiles in this Michael-aldol cascade reaction. The
only exception was found when the vinyl-sulfoxide 35 was
employed as the Michael acceptor (Table 2, entry 4). In this case, the
corresponding telluride was not observed and the starting material
was completely recovered. On the other hand, the corresponding
selenide could be prepared from the sulfoxide 35 in a very good
yield. However, when the analog sulfone 33 was employed, the
expected telluride, as well as the selenide, was obtained in good
yield. It is also worth noting that the secondary amide 44 was
prepared and tested as a Michael-acceptor only its precursor (ac-
rylamide) failed to give the expected products. When acrylamide
was submitted to this established reaction conditions, the oligo-
merization of this substrate is observed as the temperature rises
and there is no consumption of the secondary electrophile (alde-
As demonstrated in this initial study on the scope of aldehydes,
the methodology is versatile and allows the use of non-activated
aldehydes. Unlike the MBH reaction, this methodology is limited
by electron deficient aldehydes, which lead to the lower yields of
the expected product. In this context, this methodology demon-
strates an important complementarity regarding the MBH reaction.
The other important component to be studied in this reaction is
the Michael acceptor (or primary electrophile). The structure of
these olefins is also of great importance regarding possible appli-
cations of this protocol in the synthesis of substances of interest.19
In this study we have evaluated especially different electron
withdrawing groups. As a standard secondary electrophile we have
chosen benzaldehyde, since it has furnished good yields and, re-
garding electronic effects on the carbonyl group benzaldehyde can
be considered as a neutral substrate. Within this study, we intended
to evaluate Michael acceptors usually employed in the MBH re-
action,16 such as esters, amides, sulfones, sulfoxides, ketones, lac-
tones, and nitriles. Also, in order to compare the stability of the
cyano-tellurides shown in Table 1 (entries 1e4), we preferably
produced the corresponding tellurides from the Michael-aldol re-
action. In those cases in which the telluride has not been obtained
in a reasonable yield, a different chalcogen was employed, giving
priority to selenium and then sulfur, respectively. The following
Table 2 summarizes some of the obtained results.
hyde). The same behavior is observed when
a,b-unsaturated ke-
tones, such as methylevinyl ketone (MVK) were employed,
suggesting that the enone itself is a more reactive secondary elec-
trophile (by conjugate addition) then the aldehyde, leading to the
oligomerization of the Michael acceptor (Scheme 1).
Not only vinylic Michael acceptors (Table 2, entries 3e8) were
employed, but also acetylenic esters (Table 2, entries 1 and 2),
which lead to the corresponding aldol product in very good yields.
It is also very important to observe that the reaction of lithium
chalcogenolates with Michael acceptors proceeded with high
stereoselectivity, since the resulting double bond is obtained ex-
clusively in the Z geometry.8,20 The geometry of the double bonds in
the compounds 29 and 31 (Table 2, entries 1 and 2) was determined
by NOESY-NMR experiment and the NOE enhancement observed
for these compounds is shown in Fig. 2.
As depicted in Table 2, we have successfully obtained several
tellurides from the Michael-aldol cascade reaction in very good
yields. In fact, these tellurides shown in Table 2 are much more
stable than the corresponding cyano-derivatives shown in Table 1.
Table 2
Evaluation of different Michael acceptors
Y0
Total reaction time = 30 min
Y0 = S, Se, Te
nBuLi
R1 = H, Me
THF, r.t.
O
R1 OH
nBuY
Ph
R1
[nBuYLi]
THF, -75 ˚C to r.t.
EWG
EWG
Entry
1
Michael acceptor
Aldol product
Chalcogen, Yield
Entry
5
Michael acceptor
Aldol product
Chalcogen, Yield
OH
OH
O
(Z)
nBuY
nBuY
MeO
29, Y¼Te, 84%
31, Y¼Te, 92%
39, Y¼Te, 81%
OEt
28
MeO
O
38
EtO
O
O
OH
OH
O
(Z)
nBuY
nBuY
MeO
2
3
6
7
41, Y¼Te, 85%
43, Y¼Te, 75%
OEt
30
MeO
O
EtO
O
O
40
OH
OH
nBuY
S
a 33, Y¼Te, 80%
b 34, Y¼Se, 83%
O
Ph
nBuY
CN
42
O
S
CN
O
Ph
32
O
OH
OH
Ph
nBuY
4
a Y¼Te, 0%
8
a 45, Y¼Te, 42%
b 46, Y¼Se, 85%
S
nBuY
(i-Pr)2N
44
O
O
Ph
b 36, Y¼Se, 93%
c 37, Y¼S, 57%
S
35
(i-Pr)2N
O
O
All the reactions were conducted under nitrogen atmosphere and in a 3 mmol scale.
In the cases in which two diastereomers were formed, anti:syn¼3:2 d.r., calculated by 1H and 125Te NMR.

B.A. Sousa et al. / Tetrahedron 68 (2012) 10406e10413
10409
carbonyl compound could be activated when a magnesium coun-
terpart is present, driving the intermediate enolate toward the al-
dol reaction with the carbonyl compound. As a proof of principle
experiment, we decided to change the organometallic compounds
used to generate the selenium nucleophile. In this case, we have
tested the use of a Grignard reagent (PhMgBr) to generate a mag-
nesium selenolate. Fortunately, our experiment was successful.
However, the behavior of this butenolide as a Michael acceptor is
very different from all the others tested substrates. The reaction still
proceeded very slowly but in very reasonable yields. The following
Table 3 summarizes the obtained results.
Table 3
Examples of b-hydroxi-butenolides
Scheme 1. Proposed lithium chalcogenolate mediated oligomerization of enones.
Se0
PhMgBr
Total reaction time = 10 h
THF, r.t.
OH
O
O
O
[PhSeMgBr]
O
R1
O
R1
-75˚C to r.t.
H2O2
47
selenoxide
elimination
Br
Mg
Fig. 2. Key NOE enhancements in the double bond geometry elucidation for com-
pounds 29 and 31.
O
O
BrMgO
R1
O
slow
R1
SePh
O
A second drawback of the MBH reaction is the fact that
b-
O
substituted Michael acceptors cannot be employed when the re-
action is performed under atmospheric pressure.16 Crotonates, for
example, requires very high pressures to be employed as Michael
acceptors in a MBH reaction. As shown in Table 2 (entries 2, 6, and
PhSe
Entry
1
MBH adduct
7),
b-substituted vinylic and acetylenic Michael acceptors have
OH
O
been successfully employed in this protocol, leading to the ex-
pected aldol products in very good yields.
O
Another very interesting class of Michael acceptors is the a,b-
49 74%
unsaturated lactones. In special, the butenolides are of particular
interest since its moiety is present in several classes of natural
products that exhibit relevant biological activity.21 Thus, we de-
cided to test a simple butenolide as a Michael acceptor in this
OH
O
2
O
cascade reaction. The commercially available
converted into the corresponding -unsaturated isomer 47 (
angelicalactone). Initially we have submitted the -angelicalactone
a-angelicalactone was
Cl
a
,b
b-
50 65%
b
to the previously established reaction conditions, employing lith-
ium n-butylselenolate as the nucleophile and benzaldehyde as the
secondary electrophile. Unfortunately, even within a 10 h reaction
time, the aldehyde was not consumed and the oligomerization of
the butenolide is observed when the solution warms back to room
temperature (Scheme 2).
OH
O
3
4
5
6
O
51 73%
This result suggested that, as the intermediate enolate 48 was
not capable of undergoing the aldol reaction with the aldehyde, this
(+)-acaterin
OH
O
O
52 78%
OH
O
O
53 68%
OH
O
O
54 70%
All the reactions were conducted under nitrogen atmosphere and in a 3 mmol scale.
In all the cases the d.r. was about 1:1.
Scheme 2. Butenolide oligomerization lithium n-butylselenolate mediated reaction.

10410
B.A. Sousa et al. / Tetrahedron 68 (2012) 10406e10413
As can be seen in Table 3, despite the negligible diaster-
eoselectivity, the -hydroxi-butenolides could be obtained in very
1.69e1.34 (m, 4H), 0.94 (t, J¼7.1 Hz, 3H). 13C NMR (50 MHz, CDCl3)
b
d: 159.92, 159.82, 132.03, 131.48, 127.69, 127.29, 119.33, 119.25,
reasonable yields. Jauch reported a similar methodology employing
the Feringa’s lactone as a Michael acceptor in a lithium selenolate
mediated MBH reaction.22e24 In this protocol the elimination of the
selenium moiety was thermally achieved. In our protocol, this
could not be reproducibly observed, and for this reason the per-
oxide must be added after the consumption of the aldehyde in
order to obtain the butenolide.
114.15, 114.09, 72.48, 72.11, 55.28, 42.04, 41.43, 32.51, 31.46, 31.14,
30.35, 21.81, 13.59. IR (KBr, cmꢀ1): 833; 1033; 1176; 1249; 1512;
2931; 3452. HRMS: requires (C15H21NNaO2S): 302.1191; found:
302.1188.
4.2. 2-((Butylselanyl)methyl)-3-hydroxy-3-(4-
methoxyphenyl)propanenitrile (3)
As the chalcogenolates presents a very low basicity, the products
of g- and a,g-di-functionalization of the b-angelicalactone was not
1H NMR (200 MHz, CDCl3)
d 7.45e7.28 (m, 2H), 7.00e6.86 (m,
observed, unlike on the MBH reaction, in which the enolization of
2H), 4.85 (dt, J¼7.0, 3.8 Hz, 1H), 3.80 (s, 3H), 3.22e2.52 (m, 6H),
the lactone is quite pronounced.16
1.72e1.45 (m, 4H), 1.10 (t, J¼7.1 Hz, 3H). 13C NMR (50 MHz, CDCl3)
d:
Like on the other cases, this protocol allows the use of alkyl
(Table 3, entries 3e6) as well as aryl (Table 3, entries 1 and 2)
aldehydes without the need of an activating group. Amongst the
examples it is worth noting that it was possible to prepare the
acaterin (Table 3, entry 4), a compound isolated from Pseudomo-
nas sp. and an acyl-CoA inhibitor in its racemic form in a single
step.
159.92, 159.82, 132.03, 131.48, 127.69, 127.29, 119.33, 119.25, 114.15,
114.09, 72.48, 72.11, 55.28, 42.04, 41.43, 32.51, 31.46, 31.14, 30.35,
21.81, 13.59. IR (KBr, cmꢀ1): 833; 1033; 1176; 1249; 1512; 1612;
2927; 2958; 3456. HRMS: requires (C15H21NNaO2Se): 350.0635;
found: 350.0633.
4.3. 2-((Butyltellanyl)methyl)-3-hydroxy-3-(4-
methoxyphenyl)propanenitrile (4)
3. Conclusions
1H NMR (200 MHz, CDCl3)
d: 7.53e7.18 (m, 2H), 7.10e6.78 (m,
We have developed a fast and high yielding route to multi-
functionalized chalcogenides and MBH adducts employing in situ
generated metallic chalcogenolates. The presented methodology
shows some interesting advantages in comparison to the classic
MBH reaction, such as the short reaction times and the substrate
scope, which presents smaller limitations. On the other hand, the
MBH reaction is known to be a very experimentally simple reaction.
In this context, our methodology is quite sensitive to the experi-
mental conditions and needs to be performed under oxygen and
moisture free conditions. Nevertheless, the complementarity of this
protocol regarding the MBH reaction and the substrate scope
makes this protocol a valuable alternative to MBH adducts and
derivatives. In this context, the asymmetric version of this reaction
is under development in our group, looking forward to apply this
methodology in the stereoselective synthesis of natural products of
interest.
2H), 4.93e4.74 (m, 1H), 3.82 (s, 3H), 3.16 (dddd, J¼26.5, 11.8, 6.2,
2.8 Hz, 2H), 2.90e2.56 (m, 4H), 1.86e1.60 (m, 2H), 1.52e1.30 (m,
2H), 0.92 (t, J¼7.2 Hz, 3H). 13C NMR (50 MHz, CDCl3)
d: 159.7, 132.0,
131.7,127.8,127.5, 120.3, 114.1,114.0, 74.5, 55.3, 44.0, 43.6, 33.9, 24.9,
13.4, 4.9, ꢀ1.2, ꢀ1.9. 125Te NMR (63 MHz, CDCl3)
d: 262.44, 258.06.
IR (KBr, cmꢀ1): 732; 833; 1033; 1176; 1249; 1303; 1512; 1612; 2835;
2870; 2927; 2958; 3452. HRMS: requires (C15H21NNaO2Te):
400.0532; found: 400.0527.
4.4. 2-((Butylthio)methyl)-3-(4-chlorophenyl)-3-
hydroxypropanenitrile (6)
1H NMR (500 MHz, CDCl3),
d
: 0.95 (t; J¼7.3 Hz; 3H); 1.45 (sex,
J¼7.3 Hz, 2H); 1.64 (qui, J¼7.3 Hz, 2H); 2.63e2.72 (m, 3H);
2.78e2.82 (m, 1H); 3.00e3.20 (q, J¼7.0 Hz, 1H); 5.00 (d, J¼6.5 Hz,
1H); 7.4 (m, 4H). 13C NMR (125 MHz, CDCl3),
d: 13.6; 21.8; 26.0;
30.2; 31.2; 32.6; 41.3; 41.9; 64.5; 71.6; 72.2; 119.0; 128.3; 129.2;
137.9. IR (film, cmꢀ1): 824, 1014,1088, 1490, 2250, 2866, 2932, 2961,
3447. HRMS: requires (C14H19NOSNa): 306.0695; found: 306.0694.
4. Experimental section
4.1. 2-((Butylthio)methyl)-3-hydroxy-3-(4-methoxyphenyl)
propanenitrile (2)
4.5. 2-((Butylselanyl)methyl)-3-(4-chlorophenyl)-3-
hydroxypropanenitrile (7)
To a stirred suspension of the elemental chalcogen (3 mmol) in
THF (45 mL), a 2 mol Lꢀ1 solution of n-butyl-lithium in hexanes
was added dropwise until the total consumption of the chalcogen
(1.0 equiv). The resulting colorless solution was cooled down to
ꢀ75 ꢁC and then an equivalent amount of the aldehyde was added
(4-anisaldehyde, 3 mmol, 0.36 mL), followed by the equimolar
addition of the Michael acceptor (acrylonitrile, 3 mmol, 0.22 mL).
The reaction is kept under stirring at ꢀ75 ꢁC for 10 min and then
the solution is allowed to warm back to room temperature (about
20 min). The reaction is then quenched with saturated NaCl so-
lution (20 mL) and then extracted with AcOEt (3ꢂ20 mL). The
combined organic phases were dried under MgSO4 and concen-
trated under reduced pressure. In those cases in which the selen-
oxide elimination step was performed, hydrogen peroxide 30%
solution (2 mL, 6 equiv) was added after quenching the reaction
with NaCl solution and the reaction mixture was kept under stir-
ring for an additional 10 min. The crude oil was purified by column
chromatography using silica gel and a hexanes/ethyl acetate (4:1)
mixture as eluent to afford 2 as a clear oil in 98% (0.8214 g) isolated
1H NMR (500 MHz, CDCl3),
d
: 0.9 (t; J¼7.3 Hz; 3H); 1.42 (sex,
J¼7.3 Hz; 2H); 1.63 (qui; J¼7.3 Hz; 2H); 2.68e2.74 (m, 3H);
2.80e2.85 (m, 1H); 3.01e3.20 (q; J¼7.0 Hz; 1H); 4.97e5.02 (d;
J¼6.5 Hz; 1H); 7.38 (m, 4H). 13C NMR (125 MHz, CDCl3),
d: 13.5;
20.5; 21.3; 22.8; 25.2; 32.3; 42.2; 42.7; 72.2; 72.5; 119.3; 119.5;
127.4; 127.9; 128.8; 128.9; 134.3; 134.4; 138.0; 138.6. 77Se NMR
(95.338 MHz, CDCl3), d
: 161.8, 163.4. IR (film, cmꢀ1): 826, 1014, 1091,
1491, 2246, 2872, 2929, 2958, 3445. HRMS: requires (C14H19NO-
SeNa): 354.0139; found: 354.0132.
4.6. 2-((Butyltellanyl)methyl)-3-(4-chlorophenyl)-3-
hydroxypropanenitrile (8)
1H NMR (500 MHz, CDCl3),
d: 0.95 (t; J¼7.3 Hz; 3H); 1.45 (sex,
J¼7.3 Hz; 2H); 1.64 (qui; J¼7.3 Hz; 2H); 2.63e2.72 (m, 3H);
2.78e2.82 (m, 1H); 3.00e3.20 (q; J¼7.0 Hz; 1H); 5.00 (d; J¼6.5 Hz;
1H); 7.4 (m, 4H). 13C NMR (125 MHz, CDCl3),
d: 13.6; 21.8; 26.0;
yield. 1H NMR (200 MHz, CDCl3)
2H), 4.97 (dt, J¼7.0, 3.8 Hz, 1H), 3.84 (s, 3H), 3.26e2.55 (m, 6H),
d
7.45e7.28 (m, 2H), 7.01e6.88 (m,
30.2; 31.2; 32.6; 41.3; 41.9; 64.5; 71.6; 72.2; 119.0; 128.3; 129.2;
137.9. IR (film, cmꢀ1): 824, 1014, 1088, 1490, 2250, 2866, 2932,

B.A. Sousa et al. / Tetrahedron 68 (2012) 10406e10413
10411
2961, 3447. HRMS: requires (C14H19NOSNa): 306.0695; found:
306.0694.
1040, 1454, 1812, 1888, 1956, 2244, 2870, 2957, 3449. HRMS: re-
quires (C14H19NOTeNa): 370.0426; found: 370.0422.
4.7. 2-((Butylthio)methyl)-3-hydroxy-4.4-
dimethylpentanenitrile (10)
4.13. 2-((Butylselanyl)methyl)-3-hydroxydecanenitrile (18)
1H NMR (200 MHz, CDCl3)
d
: 3.85 (dtt, J¼6.7, 4.2, 2.5 Hz, 1H),
1H NMR (300 MHz, CDCl3),
1.42 (sext, J¼7.2 Hz, 2H); 1.58 (qt, J¼7.2 Hz, 2H); 2.60 (t, J¼7.2 Hz,
3H); 2.88e2.97 (m, 3H); 3.50 (s, 1H). 13C NMR (75 MHz, CDCl3),
d
: 0.92 (t, J¼7.2 Hz, 3H); 1.02 (s, 9H);
3.05e2.59 (m, 5H), 2.32 (dd, J¼28.3, 6.3 Hz, 1H), 1.78e1.16 (m, 16H),
0.91 (q, J¼7.1 Hz, 6H). 13C NMR (50 MHz, CDCl3)
d
: 120.08, 119.33,
d:
71.47, 70.82, 40.89, 40.63, 35.62, 34.34, 32.41, 31.69, 29.26, 29.23,
29.10, 25.58, 25.38, 25.16, 22.84, 22.56, 21.61, 20.56, 14.03, 13.51.
13.6; 21.8; 26.0; 31.5; 32.4; 34.0; 34.3; 35.5; 77.5; 119.7. IR (film,
cmꢀ1): 743; 919; 1015; 1077; 1366; 1420; 1466; 1480; 1624; 1708;
2244; 2873; 2932; 2959; 3478.
77Se NMR (38 MHz, CDCl3) : 163.33, 161.47. IR (KBr, cmꢀ1): 1049;
d
1199; 1261; 1419; 1462; 2858; 2957; 2954; 3475. HRMS: requires
(C15H29NNaOSe): 342.1312; found: 342.1309.
4.8. 2-((Butylselanyl)methyl)-3-hydroxy-4.4-
dimethylpentanenitrile (11)
4.14. 3-Hydroxy-4.4-dimethyl-2-methylenepentanenitrile (19)
1H NMR (300 MHz, CDCl3),
d
: 0.95 (t, J¼7.3 Hz, 3H); 1.02 (s, 9H);
1H NMR (300 MHz, CDCl3),
d: 1.00 (s; 9H); 2.00 (s; 1H); 3.95 (s;
1H); 5.96 (s; 1H); 6.00 (s; 1H). 13C NMR (75 MHz, CDCl3),
d: 25.6;
1.42 (sext, J¼7.3 Hz, 2H); 1.66 (qt, J¼7.3 Hz, 2H); 2.51 (s, 1H); 2.68 (t,
J¼7.3 Hz, 2H); 2.88e3.00 (m, 3H); 3.46 (s, 1H). 13C NMR (75 MHz,
35.7; 79.8; 118.2; 124.7; 132.6. IR (film, cmꢀ1): 951; 1015; 1074;
1366; 1480; 1618; 1904; 2228; 2873; 2908; 2960; 3481.
CDCl3), d: 13.5; 22.8; 24.8; 25.1; 26.0; 32.4; 35.0; 35.6; 78.6; 119.8.
77Se NMR (95 MHz, CDCl3), : 163.5. IR (film, cmꢀ1): 721; 929; 1022;
d
1080; 1476; 2244; 2871; 2935; 2958; 3450.
4.15. 3-Hydroxy-2-methylenehexanenitrile (21)
4.9. 2-((Butyltellanyl)methyl)-3-hydroxy-4.4-
dimethylpentanenitrile (12)
1H NMR (300 MHz, CDCl3),
(m; 2H); 1.61e2.11 (m; 2H); 4.25 (dd; J¼5.3 Hz; 1H); 5.97 (s; 1H);
d
: 0.97 (t; J¼7.4 Hz; 3H); 1.34e1.52
5.99 (s; 1H). 13C NMR (75 MHz, CDCl3),
d: 13.7; 18.4; 37.8; 72.1;
1H NMR (300 MHz, CDCl3),
1.40 (sext, J¼7.2 Hz, 2H); 1.75 (qt, J¼7.3 Hz, 2H); 2.77 (t, 7.2 Hz, 3H);
2.91e3.04 (m, 3H); 3.50 (s, 1H). 13C NMR (75 MHz, CDCl3),
: 2.9;
4.9; 13.4; 25.0; 26.0; 34.0; 35.7; 36.2; 80.6; 120.2. 125Te NMR
(157.79 MHz, CDCl3),
: 251.40. IR (film, cmꢀ1): 744; 921; 1077,
d
: 0.92 (t, J¼7.3 Hz, 3H); 1.02 (s, 9H);
117.0; 127.0; 129. IR (film, cmꢀ1): 948; 1466; 1713; 2227; 2875;
2936; 2962; 3444.
d
4.16. 2-((2-Bromo-6-methylphenyl)(hydroxy)methyl)acrylo-
nitrile (23)
d
1362; 1466; 2244; 2870; 2931; 2962; 3466.
1H NMR (300 MHz, CDCl3),
d: 3.83 (s; 3H); 5.50 (s; 1H); 6.02 (s;
4.10. 2-((Butylthio)methyl)-3-hydroxy-3-phenylpropanenitrile
(14)
2H); 6.78 (d; J¼8.7 Hz; 1H); 7.41 (dd; J¼2.4 Hz; 8.7 Hz; 1H); 7.48 (d;
J¼2.4 Hz; 1H). 13C NMR (75 MHz, CDCl3),
d: 55.7; 69.4; 112.7; 113.4;
116.9; 125.3; 129.4; 130.4; 130.5; 132.6; 155.6. IR (film, cmꢀ1): 622;
1H NMR (500 MHz, CDCl3),
1.43 (m; 2H); 1.54 (m; 2H); 2.63 (m; 2H); 2.75e2.87 (m; 2H); 3.00
(m,1H); 3.61 (s; 3H); 5.03 (d, J¼Hz; 1H); 7.26e7.31 (m, 5H) 13C NMR
d
: 0.94 (dt; J¼6.5 Hz; J¼3.0 Hz; 3H);
1026; 1254; 1487; 2228; 2849; 2925; 2962; 3441.
4.17. 2-(Hydroxy(4-nitrophenyl)methyl)acrylonitrile (25)
(125 MHz, CDCl3), d: 21.8; 30.1; 31.2; 31.5; 32.5; 41.4; 42.0; 72.4;
72.8; 119.0; 119.3; 126.0; 126.4; 128.8; 128.9; 129.0; 139.4; 140.0. IR
(film, cmꢀ1): 702; 1060; 1454; 1494; 1706; 1813; 1890; 1958; 2246;
2929; 2957; 3449.
1H NMR (300 MHz, CDCl3),
d: 5.4 (s; 1H); 6.1 (s; 1H); 6.2 (s; 1H);
7.6 (t; J¼7.9 Hz; 1H); 7.7 (d; J¼7.9 Hz; 1H); 8.2 (dd; J¼7.9 Hz; 1.8 Hz;
1H); 8.2 (t; J¼1.8 Hz; 1H). 13C NMR (75 MHz, CDCl3),
d: 73.4; 116.2;
124.1; 125.4; 127.4; 130.9; 145.9; 148.1. IR (film, cmꢀ1): 1062; 1348;
4.11. 2-((Butylselanyl)methyl)-3-hydroxy-3-phenylpropanenitrile
(15)
1520; 1607; 1715; 1804; 1935; 2230; 3081; 3113; 3456.
1H NMR (500 MHz, CDCl3),
d
: 0.91 (t; J¼7.5 Hz; 3H); 1.39 (sext;
4.18. 2-(Hydroxy(3-nitrophenyl)methyl)acrylonitrile (27)
J¼7.5 Hz; 2H); 1.59e1.66 (m; 3H); 2.67e2.82 (m; 4H); 3.18e3.24
(m; 1H); 4.94e5.01 (m; 1H); 7.20 (d; J¼7.5 Hz; 1H); 7.30 (dd;
J¼8.0 Hz; J¼11.5 Hz; 2H); 7.37e7.45 (m; 2H). 13C NMR (125 MHz,
1H NMR (300 MHz, CDCl3),
d: 5.4 (s; 1H); 6.1 (s; 1H); 6.2 (s; 1H);
7.6 (d; J¼8.7 Hz; 2H); 8.2 (d; J¼8.7 Hz; 2H). 13C NMR (75 MHz,
CDCl3), d: 73.4; 116.2; 124.1; 125.4; 127.4; 130.9; 145.9; 148.1. IR
CDCl3), d: 13.5; 20.4; 21.5; 22.8; 25.2; 32.4; 42.7; 73.6; 119.4; 126.0;
(film, cmꢀ1): 1057; 1351; 1530; 2230; 2873; 2926; 3092; 3450.
126.4; 128.8; 129.5; 136.4; 136.9; 138.7; 139.4; 139.9. 77Se NMR
(95.338 MHz, CDCl3),
: 162.2 and 163.8. IR (film, cmꢀ1): 701; 1042;
d
1454; 1765; 1814; 1889; 1956; 2245; 2871; 2929; 2957; 3447.
HRMS: requires (C14H19NOSeNa): 320.0529; found: 320.0517.
4.19. (Z)-Ethyl 3-(butyltellanyl)-2-(hydroxy(phenyl)methyl)
acrylate (29)
4.12. 2-((Butyltellanyl)methyl)-3-hydroxy-3-
phenylpropanenitrile (16)
1H NMR (300 MHz, CDCl3),
d
: 0.94 (t, J¼7.5 Hz, 3H); 1.21 (t,
J¼7.2 Hz, 3H); 1.41 (sext, J¼7.5 Hz, 2H); 1.81 (qt, J¼7.5 Hz, 2H); 2.57
(t, J¼7.5 Hz, 2H); 2.71 (d, J¼4.8 Hz, 1H); 4.20 (q, J¼7.5 Hz, 2H); 5.63
(d, J¼4.2 Hz, 1H); 7.35e7.36 (m, 5H); 8.42 (s, 1H). 13C NMR (75 MHz,
1H NMR (500 MHz, CDCl3),
d
: 0.91 (t; J¼7.5 Hz; 3H); 1.36 (sext;
J¼7.5 Hz; 2H); 1.68e1.75 (m; 2H); 2.41e2.51 (m; 1H); 2.79e2.84
CDCl3), d: 9.9; 13.5; 14.2; 25.0; 33.9; 61.1; 74.7; 126.7; 127.5; 128.2;
(m; 4H); 3.11e3.27 (m; 1H); 4.91e4.93 (m; 1H); 7.36e7.43 (m; 5H).
132.2; 136.2; 142.2; 167.1. 125Te NMR (157.79 MHz, CDCl3),
d: 385.3.
13C NMR (125 MHz, CDCl3),
d
: 4.9; 5.0; 13.3; 24.9; 34.0; 43.5; 44.0;
74.9; 119.9; 120.1; 126.2; 126.5; 128.7; 128.8; 129.9; 139.5; 139.9.
125Te NMR (157.79 MHz, CDCl3), : 253.1 and 256.9. IR (film, cmꢀ1):
IR (film, cmꢀ1): 699; 1025; 1183; 1281; 1559; 1679; 1806; 1887;
1950; 2871; 2925; 2957; 3456. HRMS: requires (C16H22O3TeNa):
415.0529; found: 415.0515.
d

10412
B.A. Sousa et al. / Tetrahedron 68 (2012) 10406e10413
4.20. (Z)-Ethyl 3-(butyltellanyl)-2-(hydroxy(phenyl)methyl)
but-2-enoate (31)
NMR (125 MHz, CDCl3),
78.9; 127.4; 127.9; 128.0; 139.8; 176.2. 125Te NMR (157.79 MHz,
CDCl3),
: 171.5; 192.8. IR (film, cmꢀ1): 704, 1021, 1154, 1452, 1715,
d: 11.1; 13.4; 19.2; 24.8; 34.0; 52.1; 52.9;
d
1H NMR (300 MHz, CDCl3),
d
: 0.94 (t, J¼7.4 Hz, 3H); 1.02 (t,
2871, 2930, 2955, 3421.
J¼7.1 Hz, 3H); 1.44 (sext, J¼7.4 Hz, 2H); 1.77 (qt, J¼7.4 Hz, 2H); 2.51
(s, 3H); 2.63 (dt, J¼3.2, 7.4 Hz, 2H); 3.40 (d, J¼10.8 Hz, 1H);
4.05e4.16 (m, 2H); 6.00 (d, J¼10.8 Hz, 1H); 7.19e7.34 (m, 5H). 13C
4.26. Methyl 3-(butyltellanyl)-2-(hydroxy(phenyl)methyl)bu-
tanoate (41)
NMR (75 MHz, CDCl3), d: 7.9; 8.8; 13.4; 13.9; 23.4; 25.3; 32.9; 61.0;
70.4; 124.9; 126.7; 128.1; 131.7; 143.1; 146.7; 167.7. 125Te NMR
(157.79 MHz, CDCl3),
: 628.5. IR (film, cmꢀ1): 708; 747; 765; 1012;
1H NMR (500 MHz, CDCl3),
d
: 0.90 (t; J¼7.3 Hz; 3H); 1.38 (sext;
d
J¼7.3 Hz; 2H); 1.55e1.61 (m; 6H); 2.48e2.55 (m; 2H); 2.83 (dd;
1810; 1887; 1953; 2980; 3472. HRMS: requires (C17H24O3TeNa):
429.0685; found: 429.0684.
J¼7.5, 5.7 Hz; 1H); 2.95 (qt; J¼7.5 Hz; 1H); 3.60 (s; 3H); 5.07 (d;
J¼5.7 Hz; 1H); 7.31 (s; 5H). 13C NMR (125 MHz, CDCl3),
d: 13.5; 22.0;
23.0; 23.4; 32.3; 33.0; 51.7; 59.0; 64.1; 72.6; 127.5; 128.2; 128.5;
4.21. 3-(Butyltellanyl)-1-phenyl-2-(phenylsulfonyl)propan-1-
ol (33)
133.5; 140.3; 173.5. 77Se NMR (95.34 MHz, CDCl3),
d: 170.2; 189.7 IR
(film, cmꢀ1): 828; 1163; 1491; 1733; 3461; 2871; 2927; 2956.
1H NMR (300 MHz, CDCl3),
d
: 0.78 (t, J¼7.2 Hz, 3H); 1.12 (sext,
4.27. 3-(Butyltellanyl)-2-(hydroxy(phenyl)methyl)butanenitrile
(43)
J¼7.2 Hz, 2H); 1.36 (qt, J¼7.2 Hz, 2H); 2.19 (t, J¼7.2 Hz, 2H); 2.79 (dd,
J¼5.1, 13.2 Hz, 1H); 3.02 (dd, J¼6.6, 13.2 Hz, 1H); 3.56 (d, J¼2.7 Hz,
1H); 3.71 (t, J¼6.6 Hz, 1H); 5.53 (s, 1H); 7.28e7.33 (m, 5H);
1H NMR (300 MHz, CDCl3),
d
: 0.93 (qt, J¼7.5 Hz, 3H); 1.31e1.45
7.52e8.10 (m, 5H). 13C NMR (75 MHz, CDCl3),
d: 6.1; 13.3; 24.9; 33.7;
(m, 2H); 1.67e1.86 (m, 5H); 1.69e2.83 (m, 2H); 3.08 (dd, J¼5.1,
7.2 Hz, 1H); 3.19 (qt, J¼1.0, 7.2 Hz, 1H); 3.32e3.48 (m, 1H); 5.11 (d,
69.5; 75.2; 125.7; 128.5; 128.6; 128.9; 129.5; 133.7; 134.3; 137.2;
139.3. 125Te NMR (157.9 MHz, CDCl3), : 379.5. IR (film, cmꢀ1): 689;
d
J¼5.1 Hz, 1H); 7.46e7.50 (m, 5H). 13C NMR (75 MHz, CDCl3),
d: 4.2;
746; 1305; 1447; 2870; 2926; 2956; 3503. HRMS: requires
(C19H24O3STeNa): 485.0406; exp: 485.0404.
4.5; 10.2; 12.3; 13.3; 13.4; 20.9; 22.4; 25.1; 34.1; 50.8; 51.2; 73.4;
74.3; 118.2; 118.3; 125.9; 126.5; 128.9; 129.0; 129.1; 140.1; 140.3.
125Te NMR (157.9 MHz, CDCl3), : 454.6; 472.4. IR (film, cmꢀ1): 701;
d
4.22. 3-(Butylselanyl)-1-phenyl-2-(phenylsulfonyl)propan-1-ol
(34)
762; 1025; 1042; 1454; 2240; 2870; 2925; 2957; 3455. HRMS: re-
quires (C15H21NOTeNa): 384.0583; found: 384.0569.
1H NMR (300 MHz, CDCl3),
d
: 0.76 (t, J¼7.5 Hz, 3H); 1.04e1.25
4.28. 2-((Butylselanyl)methyl)-3-hydroxy-N,N-diisopropyl-3-
phenylpropanamide (45)
(m, 4H); 1.93e2.08 (m, 2H); 2.89 (t, J¼6.6 Hz, 2H); 2.89 (t, J¼6.6 Hz,
2H); 3.53e3.57 (m, 1H); 5.62 (s, 1H); 7.27e7.37 (m, 5H); 7.59e7.75
(m, 3H); 7.98e8.00 (m, 2H). 13C NMR (75 MHz, CDCl3),
d: 13.5; 13.6;
1H NMR (300 MHz, CDCl3),
d
: 0.43 (d, J¼6.6 Hz, 3H); 0.91 (t,
22.9; 25.6; 25.7; 32.1; 69.6; 73.8; 125.7; 128.0; 128.6; 129.0; 129.6;
J¼7.3 Hz, 3H); 1.11 (d, J¼6.6 Hz, 3H); 1.21 (d, J¼6.8 Hz, 3H); 1.34 (d,
J¼6.8 Hz, 3H); 1.38 (sext, J¼7.3 Hz, 2H); 1.67 (s, 1H); 1.74 (qt,
J¼7.3 Hz, 2H); 2.71 (t, J¼7.3 Hz, 2H); 3.10 (dd, J¼3.6, 7.4 Hz, 2H);
3.17e3.23 (m, 2H); 3.70 (qt, J¼7.0 Hz, 1H); 4.90 (dd, J¼2.9, 8.8 Hz,
1H); 5.67 (d, J¼8.8 Hz, 1H); 7.18e7.25 (m, 5H). 13C NMR (75 MHz,
134.4; 137.5; 139.5. 77Se NMR (95 MHz, CDCl3),
d: 220.9. IR (film,
cmꢀ1): 689; 734; 1319; 1448; 1700; 1774; 1816; 2871; 2927; 2956;
3505. HRMS: requires (C17H24O3TeNa): 435.0509; found: 435.0510.
4.23. 3-(Butylselanyl)-1-phenyl-2-(phenylsulfinyl)propan-1-ol
(36)
CDCl3), d: 3.0; 4.2; 13.4; 20.0; 20.3; 20.4; 21.0; 25.0; 34.2; 46.4; 49.3;
49.8; 76.6; 125.7; 127.2; 128.2; 143.7; 173.7. 125Te NMR
(157.79 MHz, CDCl3), : 212.0. HRMS: requires (C20H33NO2TeNa):
d
1H NMR (300 MHz, CDCl3),
d
: 0.82 (t, J¼7.0 Hz, 3H); 1.12 (m, 3H);
472.1471; found: 472.1469.
1.37 (qt, J¼7.0 Hz, 2H); 2.28e2.39 (m, 4H); 3.38 (dt, J¼5.5, 9.0 Hz,
1H); 5.20 (d, J¼9.0 Hz, 1H); 7.30e7.43 (m, 5H); 7.54e7.56 (m, 3H);
4.29. 2-((Butyltellanyl)methyl)-3-hydroxy-N,N-diisopropyl-3-
phenylpropanamide (46)
7.83e7.85 (m, 2H). 13C NMR (75 MHz, CDCl3),
d
: 25.8; 55.5; 120.7;
124.0; 124.7; 126.9; 129.2; 129.3; 129.4; 130.0; 131.1; 131.2; 142.8;
143.0; 143.3. 77Se NMR (95 MHz, CDCl3),
d: 154.4. HRMS: requires
1H NMR (500 MHz, CDCl3),
d: 0.88 (t, J¼7.5 Hz, 3H); 0.97 (d,
(C19H24O2SSeNa): 419.0560; found: 419.0548.
J¼6.5 Hz, 3H); 1.27 (d, J¼6.5 Hz, 3H); 1.33 (d, J¼6.5 Hz, 3H); 1.34 (qt,
J¼7.5 Hz, 2H); 1.43 (d, J¼6.5 Hz, 3H); 1.51e1.58 (m, 2H); 2.42e2.54
(m, 2H); 2.79 (dd, J¼4.0, 12.0 Hz, 1H); 3.00 (dd, J¼11.0, 12.0 Hz, 1H);
3.20 (dt, J¼4.0, 11.0 Hz, 1H); 3.42 (s, 1H); 4.15 (hept, J¼6.5 Hz, 2H);
4.90 (d, J¼4.0 Hz, 1H); 7.24e7.40 (m, 5H). 13C NMR (75 MHz, CDCl3),
4.24. 3-(Butylthio)-1-phenyl-2-(phenylsulfinyl)propan-1-ol (37)
1H NMR (300 MHz, CDCl3),
(m, 4H); 2.34e2.42 (m, 2H); 2.65e2.69 (m, 1H); 2.88 (dd, J¼3.0,
14.7 Hz, 1H); 3.22 (dd, J¼10.8, 14.7 Hz, 1H); 5.27 (s, 1H); 7.04e7.06
(m, 2H); 7.23e7.32 (m, 3H); 7.61e7.77 (m, 5H). 13C NMR (75 MHz,
d
: 0.85 (t, J¼7.2 Hz, 3H); 1.30e1.35
d: 13.5; 20.5; 20.6; 20.7; 20.8; 20.9; 22.9; 24.9; 32.5; 46.3; 49.2;
50.3; 75.2; 126.2; 127.5; 128.3; 141.7; 173.7. 77Se NMR (95 MHz,
CDCl3), : 144.4. HRMS: requires (C20H33NO2SeNa): 422.1574;
d
CDCl3),
d: 13.5; 21.8; 25.5; 31.3; 32.3; 70.2; 70.8; 124.4; 125.2; 127.5;
found: 422.1570.
128.4; 129.6; 131.3; 140.3; 141.7. HRMS: requires (C19H24O2SSeH):
349.1296; found: 349.1287.
4.30. 3-(Hydroxy(phenyl)methyl)-5-methylfuran-2(5H)-one (49)
4.25. Methyl-2-((butyltellanyl)methyl)-3-hydroxy-3-
phenylpropanoate (39)
To a stirred suspension of elemental selenium (3 mmol) in THF
(30 mL), a 2 M solution of PhMgBr in THF was added dropwise until
the total consumption of the chalcogen (1.0 equiv). The resulting
colorless solution was cooled down to ꢀ75 ꢁC and then an equiv-
alent amount of the aldehyde was added (benzaldehyde, 3 mmol,
1H NMR (500 MHz, CDCl3),
d
: 0.90 (t; J¼7.5 Hz; 3H); 1.35 (sext;
J¼7.5 Hz; 2H); 1.68 (quint; J¼7.5 Hz; 2H); 2.63 (tap, J¼7.5 Hz; 2H);
2.68 (d; J¼11.5 Hz; 1H); 2.91 (d; J¼11.5 Hz; 1H); 3.19 (d; J¼5.0 Hz;
1H); 3.73 (s, 3H); 4.90 (dap; J¼5.0 Hz; 1H); 7.27e7.31 (m, 5H). 13C
0.30 mL), followed by the equimolar addition of the
b-angel-
icalactone (3 mmol, 0.294 g). The reaction is kept under stirring at

B.A. Sousa et al. / Tetrahedron 68 (2012) 10406e10413
10413
ꢀ75 ꢁC for 10 min and then the solution is allowed to warm back to
4.35. 3-(1-Hydroxypropyl)-5-methylfuran-2(5H)-one (54)
1H NMR (200 MHz, CDCl3),
room temperature (about 20 min). The reaction is then quenched
with saturated NaCl solution (20 mL) and then hydrogen peroxide
30% solution (2 mL, 6 equiv) was added and the reaction mixture
was kept under stirring for an additional 10 min. The mixture was
extracted with AcOEt (3ꢂ20 mL). The combined organic phases
were dried under MgSO4 and concentrated under reduced pres-
sure. The crude oil was purified by column chromatography using
silica gel and a hexanes/ethyl acetate (1:1) mixture as eluent to
afford 49 as a colorless oil in 74% (0.4533 g) isolated yield. 1H NMR
d
: 7.20 (t, J¼1.5 Hz,1H), 5.17e4.96 (m,
1H), 4.44 (q, J¼5.9, 5.4 Hz, 1H), 2.60 (t, J¼5.0 Hz, 1H), 1.98e1.67 (m,
2H), 1.45 (d, J¼6.8 Hz, 3H), 0.99 (t, J¼7.4 Hz, 3H). 13C NMR (50 MHz,
CDCl3), d: 172.61, 149.51, 135.89, 77.98, 68.28, 28.46, 18.99, 9.50. IR
(film, cmꢀ1): 1114; 1319; 1743; 2920; 2920; 2966; 3417. HRMS:
requires (C8H12NaO3): 179.0684; found: 179.0679.
Acknowledgements
(200 MHz, CDCl3),
d
: 7.52e7.32 (m, 6H), 7.09 (dt, J¼7.4, 1.5 Hz, 1H),
5.60 (t, J¼1.6 Hz,1H), 5.08 (qq, J¼6.9,1.8 Hz,1H), 3.23 (s, 2H),1.45 (d,
~
ꢁ
The authors would like to thank Fundac¸ ao de Amparo a Pesquisa
J¼11.9 Hz, 2H). 13C NMR (50 MHz, CDCl3),
d: 172.47, 150.58, 150.48,
~
do Estado de Sao Paulo (FAPESP), Conselho Nacional de Desenvol-
140.17, 136.22, 136.11, 128.70, 128.36, 126.51, 126.46, 78.16, 69.14,
69.07, 18.81, 14.21. IR (KBr, cmꢀ1): 702; 829; 1014; 1083; 1195; 1319;
1747; 3414. HRMS: requires (C12H12NaO3): 227.0684; found:
227.0684.
ꢀ
~
vimento Científico e Tecnologico (CNPq) and Coordenac¸ ao de
Aperfeic¸ oamento de Pessoal de Nível Superior (CAPES) for the fi-
~
nancial support and Universidade de Sao Paulo (USP) for the pro-
vided infrastructure.
4.31. 3-((4-Chlorophenyl)(hydroxy)methyl)-5-methylfuran-
2(5H)-one (50)
Supplementary data
1H NMR (200 MHz, CDCl3),
d
: 7.40 (s, 4H), 7.06 (t, J¼1.5 Hz, 1H),
Supplementary data (copies of the 1H, 13C, 77Se and 125Te NMR
spectra) is available free of charge on www.journals.elsevier.com.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.09.027.
5.60 (dt, J¼3.5, 1.6 Hz, 1H), 5.11 (qt, J¼6.9, 1.6 Hz, 1H), 1.77 (d,
J¼6.9 Hz, 1H), 1.49e1.41 (m, 3H). 13C NMR (50 MHz, CDCl3),
d:
172.30, 150.54, 138.61, 135.83, 134.18, 128.90, 127.88, 78.22, 68.55,
18.80. IR (KBr, cmꢀ1): 540; 1014; 1087; 1195; 1319; 1408; 1489;
1747; 2981; 3414. HRMS: requires (C12H11ClNaO3): 261.0294;
found: 261.0285.
References and notes
€
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4.32. 3-(1-Hydroxyheptyl)-5-methylfuran-2(5H)-one (51)
1H NMR (200 MHz, CDCl3),
J¼6.8, 1.6 Hz, 1H), 4.51 (dt, J¼6.9, 3.5 Hz, 1H), 2.72 (s, 1H), 1.57e1.21
(m, 9H), 0.96e0.86 (m, 3H). 13C NMR (50 MHz, CDCl3),
: 172.68,
d
: 7.22 (d, J¼1.4 Hz, 1H), 5.10 (qt,
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2858; 2927; 3441. HRMS: requires (C12H20NaO3): 235.1310; found:
235.1308.
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1H NMR (500 MHz, CDCl3),
d
: 7.14 (t, J¼1.5 Hz, 1H), 5.03 (qq,
J¼6.8, 1.7 Hz, 1H), 4.48 (ddq, J¼8.2, 5.0, 1.7 Hz, 1H), 1.83e1.64 (m,
2H), 1.43 (d, J¼6.8 Hz, 4H), 1.40e1.23 (m, 11H), 0.91e0.85 (m, 3H).
13C NMR (126 MHz, CDCl3),
d: 172.32, 148.89, 136.43, 77.70, 67.12,
35.57, 31.71, 29.28, 29.09, 25.18, 22.52, 18.87, 13.89.
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(53)
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: 7.18 (t, J¼1.4 Hz, 1H), 5.08 (qt,
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3.2 Hz, 7H), 1.46 (d, J¼6.8 Hz, 3H), 1.33e0.99 (m, 6H). 13C NMR
(50 MHz, CDCl3) d: 172.70, 150.55, 134.73, 78.03, 71.88, 42.01, 29.51,
27.29, 26.29, 26.02, 25.84, 19.08. IR (KBr, cmꢀ1): 663; 1026; 1072;
1107; 1199; 1261; 1319; 1373; 1450; 1647; 1743; 2854; 2927; 2978;
3441. HRMS: requires (C12H18NaO3): 233.1153; found: 233.1147.