Reactivity of tert-butanesulfinamides in palladium-catalyzed allylic substitutions Dedicated to Professor Maria José Calhorda in occasion of her 65th birthday.

Article abstract of DOI:10.1016/j.jorganchem.2013.11.026

The performance of tert-butanesulfinamides as nitrogen nucleophiles in Pd(0)-catalyzed allylic substitution reactions has been investigated. Metalated N-alkyl and N-acetyl sulfinamides have been identified as suitable partners for the reaction with π-allyl-palladium complexes. The cross-coupling of N-acetyl tert-butanesulfinamide with 2- or 3-substituted linear allylic carbonates is achieved in the presence of Pd(OAc)₂ (5 mol%) and dppe (7.5 mol%) and does not require an additional base. The reaction proceeds in high yields (59-98%) to produce the corresponding E-configured linear allylic sulfinamides in a totally regioselective and highly diastereoselective manner. The sulfur atom remains configurationally stable throughout the allylation process, and thus the coupling products are obtained in enantiomerically pure form.

Full text of DOI:10.1016/j.jorganchem.2013.11.026

Journal of Organometallic Chemistry 760 (2014) 124e129
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Reactivity of tert-butanesulfinamides in palladium-catalyzed allylic
substitutions
,
Laetitia Mistico a, Emel Ay a b, Vaizanne Huynh a, Aurelie Bourderioux a, Fabrice Chemla a,
,
a
Franck Ferreira a, Julie Oble a, Alejandro Perez-Luna a , Giovanni Poli ,
*
, ,
1
Guillaume Prestat a
*
a Institut Parisien de Chimie Moléculaire, UMR 7201, FR 2769, UPMC Univ Paris 06, CNRS, Bâtiment F 2ème et., Case 183, 4 place Jussieu, F-75005 Paris,
France
b Université de Haute Alsace, ENSCMu, Laboratoire de Chimie Organique et Bioorganique, 3 rue Alfred Werner, 68093 Mulhouse Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The performance of tert-butanesulfinamides as nitrogen nucleophiles in Pd(0)-catalyzed allylic substi-
tution reactions has been investigated. Metalated N-alkyl and N-acetyl sulfinamides have been identified
Received 27 September 2013
Received in revised form
18 November 2013
as suitable partners for the reaction with
p-allylepalladium complexes. The cross-coupling of N-acetyl
tert-butanesulfinamide with 2- or 3-substituted linear allylic carbonates is achieved in the presence of
Pd(OAc)2 (5 mol%) and dppe (7.5 mol%) and does not require an additional base. The reaction proceeds in
high yields (59e98%) to produce the corresponding E-configured linear allylic sulfinamides in a totally
regioselective and highly diastereoselective manner. The sulfur atom remains configurationally stable
throughout the allylation process, and thus the coupling products are obtained in enantiomerically pure
form.
Accepted 19 November 2013
Dedicated to Professor Maria José Calhorda
in occasion of her 65th birthday.
Keywords:
Sulfinamide
Palladium
Ó 2013 Elsevier B.V. All rights reserved.
Allylic substitution
Amination
1. Introduction
An impressive body of work has been devoted to the prepa-
ration of elaborated enantiopure tert-butanesulfinamides and the
The use of the chiral amine reagent tert-butanesulfinamide 1a
(Scheme 1) has attracted a great deal of attention over the last
decade and has found applications in an increasingly growing
number of research fields [1]. In the context of asymmetric syn-
thesis, it is now a well-established tool for the preparation of chiral
non-racemic amines. Rapid access to both enantiomeric forms of
tert-butanesulfinamide, high levels of stereodiscrimination and
easy removal of the sulfinyl moiety under mild acidic conditions
constitute major advantages to the use of the N-tert-butanesulfinyl
group as chiral auxiliary. Furthermore, tert-butanesulfinamides
have also found promising applications in the field of asymmetric
catalysis, where they have been successfully used as ligands for
transition metal catalysts or organocatalysts [1].
area has been recently reviewed extensively [1,2]. The vast ma-
jority of synthetic approaches entails the condensation of 1a with
a carbonyl derivative and the subsequent reaction at the electro-
philic carbon atom of the corresponding sulfinimine thereby
produced [2]. Quite surprisingly, the complementary synthetic
strategies utilizing tert-butanesulfinamides as chiral nitrogen nu-
cleophiles have received far less attention [3]. Furthermore, their
use as partners in metal-catalyzed amination reactions is an
interesting prospect that has only been successfully exploited very
recently. Arylation of tert-butanesulfinamide with aryl- and het-
eroaryl halides has been reported using Cu [4] and Pd [5] catalysts.
tert-Butanesulfinamides have also been shown to be efficient
partners for the Pd-catalyzed Wacker-type aerobic oxidative
cyclization of tethered alkenes [6]. Finally, the Pd-catalyzed [3 þ 2]
cycloaddition of N-tert-butanesulfinimines with trimethylene-
methane is as well a related process that involves a carboneni-
trogen bond formation [7].
* Corresponding authors. Tel.: þ33 144275571; fax: þ33 144277567.
E-mail addresses: alejandro.perez_luna@upmc.fr (A. Perez-Luna), guillaume.
prestat@parisdescartes.fr (G. Prestat).
In this context, and given the recent interest in allylic N-tert-
butanesulfinamides as hybrid ligands for asymmetric catalysis [8],
we have considered the use of tert-butanesulfinamides as nitrogen
1
Current address: Laboratoire de Chimie et Biochimie Pharmacologiques et
Toxicologiques (UMR 8601), Université Paris Descartes, 45 rue des Saints-Pères,
75006 Paris, France.
0022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.11.026

L. Mistico et al. / Journal of Organometallic Chemistry 760 (2014) 124e129
125
Table 1
Pd(0)-catalyzed allylic substitution of allyl acetate by metalated sulfinamides.
Entry
Substrate
R1
Base
Product
Yielda
b
b
1
2
3
4
5
6
7
1a
1a
1b
1b
1c
1c
1c
H
H
Bn
Bn
COMe
COMe
COMe
K2CO3
nBuLic
K2CO3
nBuLic
nBuLic
NaHe
2a
2a
2b
2b
2c
2c
2c
11%
8%d
No reaction
83%
83%
95%
Scheme 1. Proposed strategy to prepare enantiopure allylic sulfinamides.
nucleophiles in Pd(0)-catalyzed allylic substitution reactions [9]
(Scheme 1). To the best of our knowledge, the only precedent for
such a transformation is that of Pyne and co-workers. These au-
thors reported that lithiated 1a reacts with cyclohex-2-enyl ethyl
carbonate in the presence of 5 mol% [Pd(PPh3)4] to afford the cor-
responding sulfinamide, albeit in poor yield and diaster-
eoselectivity [10]. Furthermore, the substitution product was
described to undergo rapid hydrolysis in the presence of silica-gel.
Intrigued by this reported unstability, we decided to reinvestigate
this reaction using other nitrogen-substituted sulfinamides and
acyclic electrophiles. Hereafter, we disclose our first findings con-
cerning this approach.
b
K2CO3
70%
a
Yield of isolated product after column chromatography.
K2CO3 (3 equiv) was added to the reaction medium.
b
c
n
Deprotonation conditions: BuLi (1 equiv), THF, ꢀ30 ꢁC, 0.5 h.
d
e
85% of acetylated product 2c was also isolated.
Deprotonation conditions: NaH (1 equiv), THF, 0 ꢁC, 0.5 h.
Having identified metalated sulfinamides as competent nucle-
ophiles for allylic substitution, we considered to use the BSA [N,O-
bis(trimethyl)acetamide]/AcOK system [11] as an alternative to the
discrete pre-formation of the metalated nucleophiles (Table 2).
Pleasingly, sulfinamide 1a underwent allylation with allyl acetate in
refluxing THF using the Pd(OAc)2/dppe catalytic system in the
presence of BSA (1.1 equiv) and AcOK (10 mol%). N-Allyl tert-
butanesulfinamide 2a was isolated in 56% yield, despite the for-
mation of 16% of N,N-diallyl tert-butanesulfinamide (entry 1).
While no reaction was observed with benzyl-substituted sulfina-
mide 1b (entry 2), efficient allylic substitution was restored in the
case of the acetyl-substituted sulfinamide 1c (entry 3).
2. Results and discussion
2.1. Allylic substitution with allyl acetate
Initially, we decided to identify nucleophiles derived from tert-
butanesulfinamide that would be well-suited to react with stan-
dard
p-allylepalladium complexes. Towards this end, we selected
as archetypal reaction the allylic substitution of allyl acetate
(3 equiv), using as catalytic system a combination of Pd(OAc)2
(5 mol%) and dppe [1,2-bis(diphenylphosphino)ethane] (7.5 mol%)
in THF (Table 1). In the presence of K2CO3, allylation of sulfinamides
1a or 1b was at most very sluggish (entries 1 and 3), thereby
indicating that N-alkyl tert-butanesulfinamides are not nucleo-
These results suggest that the in situ generated N-(trime-
thylsilyl)acetamide is basic enough to deprotonate unsubstituted
tert-butanesulfinamide 1a and N-acyl-substituted 1c, thereby effi-
ciently generating a nucleophile suitable for the substitution to
occur. Conversely, this silylated base does not metalate N-benzyl
tert-butanesulfinamide 1b.
philic enough to intercept the
p-allyl complex intermediate in
these conditions. By contrast, their corresponding lithium salts,
obtained by treatment with 1 equiv nBuLi, took part readily in the
nucleophilic substitution. For unsubstituted sulfinamide 1a, the
expected product 2a was only obtained in 8% yield as the process
was hampered by the competitive acylation reaction of the lithium
salt of 1a with the ester moiety of allyl acetate (entry 2). However,
in the case of substituted sulfinamide 1b, the allylated compound
2b was isolated in 83% yield (entry 4). Finally, starting from acetyl-
substituted pronucleophile 1c, the allylation product 2c was ob-
tained in good 70e95% yields either by reacting the pre-formed
lithium or sodium salts of 1c (entries 5 and 6), or in the presence
of K2CO3 (entry 7). For these last reaction conditions, it is likely that
the carbonate base is strong enough to deprotonate 1c (quantita-
tively or at least to a great extent), thereby generating in situ the
reactive nucleophile.
2.2. Allylic substitution with allylic carbonates
We considered next to use allylic carbonates as electrophilic
partners. Given that N-acetyl tert-butanesulfinamide 1c undergoes
allylation in the presence of K2CO3, we reasoned that in this case an
additional base might be avoided as the carbonate leaving group
could be basic enough to deprotonate the starting material and thus
generate the nucleophile for the coupling reaction (Scheme 3).
Worthy of mention, the unforeseen acylation of the lithium salt
of 1a in the presence of allyl acetate led us to consider a one-pot
strategy leading to the sequential acylation/allylation of tert-buta-
nesulfinamide 1a (Scheme 2). Treatment of 1a with nBuLi, followed
by the addition of methyl acetate led to the formation of the lithium
salt 3 that was then engaged directly in the palladium(0)-catalyzed
allylation. Product 2c was obtained in excellent 95% yield using only
a slight excess of allyl acetate.
Scheme 2. One-pot acylation/allylation of tert-butanesulfinamide 1a.

126
L. Mistico et al. / Journal of Organometallic Chemistry 760 (2014) 124e129
carbonates incorporating 1,10,2-trisubstituted alkenes such as
prenyl carbonate (entry 8), for which no reaction was observed.
Finally, we considered the prospect of taking advantage of the
tert-butanesulfinyl group as stereodirecting group in the reaction
with racemic secondary allylic carbonates. Most disappointingly, in
this case the process was hampered by a significant lack of reac-
tivity. Out of several allyl carbonates tested, only 1,3-diphenyl-3-
ethoxycarbonyloxy-propene (ꢂ)-9 led to somewhat interesting
results (Scheme 4). The best conditions, resulting from an extended
screening of catalytic systems, reaction conditions and solvents (see
Supporting information) consisted in the use of 3 equiv of (ꢂ)-9 in
DMF at 80 ꢁC in the presence of Pd(OAc)2 (5 mol%), dppe (7.5 mol%),
and gave the substitution product 10 in 41% yield as a mixture of
diastereoisomers [13].
Table 2
Pd(0)-catalyzed allylic substitution of allyl acetate by sulfinamides in the presence of
BSA/AcOK.
Entry
Substrate
R1
Product
Yielda
1
2
3
1a
1b
1c
H
Bn
COMe
2a
2b
2c
56%b
0%
84%
2.3. Orthogonal deprotection of N-allylic N-acetyl tert-
butanesulfinamide
a
Yield of isolated product after column chromatography.
b
16% of N,N-diallyl tert-butanesulfinamide 2d (R1 ¼ allyl) were also isolated.
An interesting aspect of N-acetyl tert-butanesulfinamides is the
possibility to orthogonally cleave each of the nitrogen-protecting
groups. As illustrated in the case of 8, treatment with dry HCl in
methanol provides the corresponding allylic acetamide 12 in
excellent yield. Alternatively, cleavage of the acetyl moiety with
NaOH in MeOH leads to the corresponding allylic tert-butane-
sulfinamide 11. Therefore, from a synthetic standpoint, in the
context of Pd-catalyzed allylic substitution reactions, N-acetyl tert-
butanesulfinamide 1c can thus be regarded either as a chiral
equivalent of acetamide or as an equivalent of tert-
butanesulfinamide.
Moreover, the preparation of allylic sulfinamide 11 provided us
with a means to check the stereochemical integrity of the tert-
butanesulfinyl moiety in the Pd(0)-catalyzed allylic substitution
reaction conditions. We were concerned by this issue because we
reasoned that the acetyl group could stabilize a putative O-meta-
lated imidate-type tautomeric form [14] of metalated 1c and
thereby possibly cause its racemization. There are only a few re-
ports on the use of metalated enantiopure N-acyl tert-butane-
sulfinamides [15,16] and their configurational stability at the
temperature required to perform the allylic substitution reaction is
a matter that has not been addressed.
Gratifyingly, N-acetyl tert-butanesulfinamide was found to un-
dergo allylation in THF at 70 ꢁC by reaction with allyl methyl car-
bonate in the presence of Pd(OAc)2 (5 mol%) and dppe (7.5 mol%).
Using only 1.2 equiv of electrophile, 2c was isolated in 94% yield
(Table 3, entry 1). Encouraged by this positive result we then
studied the scope of the transformation (Table 3).
We first considered a range of primary carbonates. Under the
same conditions as above, methallyl carbonate underwent allylic
substitution smoothly and allylic sulfinamide 4 was isolated in 86%
yield (entry 2). 1,2-Disubstituted allylic carbonates behaved effi-
ciently, in a totally regioselective and highly diastereoselective way.
In the case of 3-alkyl-substituted allyl carbonates (entries 3e6), the
corresponding linear allylic sulfinamides 5e7 were isolated in 59e
98% yield and E/Z ratio higher than 94:06 [12]. The process was
stereoconvergent, as the same diastereoselectivity in favor of the E
isomer was obtained regardless of the configuration of the starting
alkene (compare entries 3,5 vs 4,6). A similar behavior was also
observed with cinnamyl carbonate, the linear E-configurated ally-
lation product 8 being isolated in 81% yield without Z isomer
detection. By contrast, the process could not be applied to allylic
The specific optical rotation value of allylic sulfinamide 11 pre-
pared according to our methodology was ½a D25
ꢀ49.4 (c 0.89,
ꢃ
CHCl3). As the reported specific optical rotation values for enan-
tiopure 11 are much lower and not consistent [8d,e], we decided to
synthesize an enantiomerically pure sample of it from enantiopure
(R)-tert-butanesulfinamide 1a and cinnamaldehyde, following a
reported protocol [8e] (Scheme 6). The ½a D25
value of ꢀ48.7 (c 0.90,
ꢃ
CHCl3) measured for this sample was the same within experimental
error as the one measured for that prepared using our methodology
(Scheme 5). As a consequence, we can conclude that 11 deriving
from the present allylation procedure is enantiomerically pure and,
as a corollary, that the sulfur atom remains configurationally stable
throughout the allylation process.
3. Conclusion
In summary, we have investigated the use of N-tert-butane-
sulfinamides as coupling partners in Pd(0)-catalyzed allylic sub-
stitution reactions. From a fundamental viewpoint, we have
identified metal salts of N-substituted tert-butanesulfinamides as
excellent nucleophiles for the reaction with
p-allylepalladium
complexes. From a synthetic perspective, we have developed a mild
and simple catalytic system to perform the cross-coupling of N-
acetyl tert-butanesulfinamide with linear allylic carbonates in the
absence of added base. The acetyl group of the coupling products
Scheme 3. Proposed mechanism for the Pd(0)-catalyzed allylic substitution of allylic
carbonates by N-acetyl tert-butanesulfinamide.

L. Mistico et al. / Journal of Organometallic Chemistry 760 (2014) 124e129
127
Table 3
Pd(0)-catalyzed allylic substitution of allylic carbonates by N-acetyl tert-butane-
sulfinamide.
R1
OCOMe
(1.2 equiv)
Pd(OAc)2 (5 mol%)
dppe (7,5 mol%)
O
S
O
O
S
O
N
Me
R1
N
H
Me
THF, 70 °C
Scheme 5. Orthogonal deprotection of 8.
1c
can be readily removed, thereby providing a new entry to enan-
tiopure linear allylic tert-butanesulfinamides that are promising
hybrid ligands for asymmetric catalysis [8bee,g]. By contrast,
racemic secondary carbonates were found to be rather poor
coupling partners, affording low overall yields (up to 41%) and low
levels of asymmetric induction (dr up to 69:31).
Entry
1
Carbonate
Product
Yielda
94%
E/Z ratio
O
S
O
N
Me
e
OCOMe
2c
4. Experimental section
O
S
O
O
N
N
Me
Me
2
3
86%
76%
e
OCOMe
OCOMe
Experiments involving organometallic compounds were carried
out in dried glassware under a positive pressure of dry argon. All
solvents were distilled to remove stabilizers and dried with a Sol-
vent Purification System. 1H NMR and 13C NMR spectra were
recorded with a Bruker AM 300 MHz or a Bruker AVANCE 400
4
5
O
S
94:6
97:3
spectrometer. Chemical shifts are reported in
d relative to an in-
ternal standard of residual chloroform (
d
¼ 7.27 for 1H NMR and
77.16 for 13C NMR). IR spectra were recorded with an ATR diamond
spectrophotometer. High resolution mass spectra (HRMS) were
O
S
O
O
obtained on a Bruker MicrOTOF. [
2000 polarimeter.
a]D were measured on a JASCO P-
N
N
Me
Me
OCOMe
6
7
4
5
98%
67%
4.1. (RS)-N-Acetyl tert-butanesulfinamide (1c)
O
S
Under argon, nBuLi (8.8 mL, 1.9 M in hexanes, 16.5 mmol) was
added drop wise to a solution of (RS)-tert-butanesulfinamide (2.0 g,
16.5 mmol) in THF (80 mL) kept at ꢀ35 ꢁC. Methyl acetate (4.0 mL,
49.5 mmol) cooled at 0 ꢁC was then added. The cooling bath was
removed and the reaction was stirred overnight. The reaction was
quenched with solid Na2SO4$10H2O (5 g), filtered (solid rinsed with
CH2Cl2) and concentrated under reduced pressure. The crude was
recrystallized in THF and washed with pentane to afford (RS)-N-
acetyl tert-butanesulfinamide (1c) (2.23 g, 83%) as a white solid.
Spectroscopic data were in good agreement with previously re-
96:4
96:4
OCOMe
O
S
O
O
N
N
Me
OCOMe
7
8
6
7
59%
81%
ported data [16]. ½a D20
ꢀ379.2 (c 1.0, CHCl3).
ꢃ
4.2. Pd(0)-catalyzed allylic substitution of allyl acetate by
metalated sulfinamides, preparation of 2b from 1b is representative
[Table 1, entry 4]
O
S
Me
Ph
Ph
>98:2
OCOMe
OCOMe
4.2.1. Metalation
Under argon, to
a stirred solution of (RS)-N-benzyl-2-
methylpropane-2-sulfinamide [17] (1b) (211 mg, 1 mmol) in THF
(5 mL) kept at ꢀ30 ꢁC, nBuLi (2.1 M in hexane, 0.48 mL, 1 mmol),
8
e
No reaction
e
a
Yield of isolated product after column chromatography.
Scheme 4. Pd(0)-catalyzed allylic substitution of (ꢂ)-9 by N-acetyl tert-butanesulfi-
namide 1c.
Scheme 6. Synthesis of the allylic sulfinamide 11 in enantiomerically pure form by
reduction of the parent a-b unsaturated imine [8e].

128
L. Mistico et al. / Journal of Organometallic Chemistry 760 (2014) 124e129
was added drop wise. The reaction mixture was stirred for 30 min
at 0 ꢁC.
4.02 (m, 1H), 3.99 (m, 1H), 2.24 (s, 3H), 1.25 (s, 9H); 13C NMR (CDCl3,
100 MHz, 300 K):
d 172.4, 134.3, 118.0, 60.7, 41.4, 23.8, 23.3; HRMS
(ESI): m/z [M ꢀ Na]þ calcd for C9H17NO2SNa: 226.0872; found:
4.2.2. Allylic substitution
226.0874. ½a 2D0
þ77.6 (c 0.92, CHCl3).
ꢃ
Under argon, THF (250 mL) was added to a mixture of Pd(OAc)2
(11 mg, 0.05 mmol) and dppe [1,2-bis(diphenylphosphino)ethane]
(30 mg, 0.075 mmol). The white slurry was stirred until it became
yellow and allyl acetate (0. 33 mL, 3.0 mmol) was added. Metalated
1b was next added via cannula and the resulting solutionwas stirred
at rt overnight. AcOEt (10 mL) and aqueous HCl (1 M, 4 mL) were
then added. The layers were separated, the aqueous one being
extracted with AcOEt (ꢄ3). The combined organic layers were
washed with brine (ꢄ3), dried over MgSO4 and the solvents evap-
orated under reduced pressure. Purification by flash chromatog-
raphy (AcOEt/cyclohexane ¼ 20:80 then 30:70) afforded (RS)-N-
allyl-N-benzyl-2-methylpropane-2-sulfinamide (2b) (208 mg, 83%) as
a white solid. IR (neat): 1495,1476,1416,1360 cmꢀ1; 1H NMR (CDCl3,
4.5. (RS)-N-Acetyl-N-methylallyl-2-methylpropane-2-sulfinamide (4)
IR (neat): 2969, 1668, 1072 cmꢀ1 1H NMR (CDCl3, 400 MHz,
;
325 K): d 4.88 (m,1H), 4.74 (s,1H), 3.92 (m,1H), 3.84 (AB system,1H,
J ¼ 17.2 Hz), 2.17 (s, 3H), 1.67 (s, 3H), 1.19 (s, 9H); 13C NMR (CDCl3,
100 MHz, 325 K):
d 172.3, 140.8, 111.2, 60.7, 43.8, 23.2, 22.8, 20.3;
HRMS (ESI): m/z [M ꢀ Na]þ calcd for C10H19NO2SNa: 240.1029;
found: 240.1025. ½a D20
þ91.2 (c 1.0, CHCl3).
ꢃ
4.6. (RS)-N-Acetyl-N-((E)-but-2-enyl)-2-methylpropane-2-
sulfinamide (5)
300 MHz):
d
7.33e7.26 (m, 5H), 5.80 (m,1H), 5.18 (d,1H, J ¼ 10.1 Hz),
Isolated as a E/Z ¼ 94:06 mixture of isomers. IR (neat): 2963,
5.12 (d, 1H, J ¼ 17.1 Hz), 4.32 (AB system, 1H, J ¼ 17.1 Hz), 4.14 (AB
system, 1H, J ¼ 17.1 Hz), 3.72 (dd, 1H, J ¼ 15.8, 5.7 Hz), 3.39 (dd, 1H,
1673, 1088 cmꢀ1; 1H NMR (CDCl3, 400 MHz, 325 K) E isomer:
d 5.60
(dqt, 1H, J ¼ 15.2, 6.4, 1.2 Hz), 4.82 (m, 1H), 3.96e3.85 (m, 2H), 2.18
J ¼ 15.8, 6.8 Hz),1.20 (s, 9H); 13C NMR (CDCl3, 75 MHz):
d 137.4,134.4,
(s, 3H), 1.63 (dq, 3H, J ¼ 6.4, 1.2 Hz), 1.20 (s, 9H); 13C NMR (CDCl3,
129.0 (2C), 127.7, 118.3, 59.0, 51.8, 50.3, 23.5; HRMS (ESI): m/z
100 MHz, 325 K) E isomer: d 171.9, 129.1, 126.9, 60.3, 40.5, 23.3, 23.0,
[M ꢀ Na]þ calcd for C14H21NOSNa: 274.1242; found: 274.1236.
17.3; HRMS (ESI): m/z [M ꢀ Na]þ calcd for C10H19NO2SNa: 240.1029;
found: 240.1026. ½a D20
þ68.8 (c 1.0, CHCl3).
ꢃ
4.3. Pd(0)-catalyzed allylic substitution of allyl acetate by
sulfinamides in the presence of BSA/AcOK, preparation of 2a from 1a
is representative [Table 2, entry 1]
4.7. (RS)-N-Acetyl-N-((E)-pent-2-enyl)-2-methylpropane-2-
sulfinamide (6)
In a sealed-tube under argon, THF (250
m
L) was added to a
Isolated as a E/Z ¼ 97:03 mixture of isomers. IR (neat): 2965,
mixture of Pd(OAc)2 (11 mg, 0.05 mmol) and dppe [1,2-
bis(diphenylphosphino)ethane] (30 mg, 0.075 mmol). The white
slurry was stirred until it became yellow and allyl acetate (0. 33 mL,
1677, 1092 cmꢀ1; 1H NMR (CDCl3, 400 MHz, 325 K) E isomer:
d 5.62
(dtt, 1H, J ¼ 15.6, 6.4, 1.2 Hz), 5.42 (m, 1H), 4.00e3.80 (m, 2H), 2.19
(s, 3H), 2.00 (m, 2H), 1.21 (s, 9H), 0.93 (t, 3H, J ¼ 7.6 Hz); 13C NMR
3.0 mmol) was added.
A
solution of (RS)-2-methyl-2-
(CDCl3, 100 MHz, 325 K) E isomer: d 171.9, 136.1, 124.7, 60.2, 40.5,
propanesulfinamide (1a) (121 mg, 1.0 mmol) in THF (5 mL) was
introduced via cannula at rt. N,O-Bis(trimethyl)acetamide (BSA)
(0.27 mL, 1.1 mmol) and AcOK (9.8 mg, 0.1 mmol) were added and
the reaction mixture was heated at 70 ꢁC overnight. AcOEt (5 mL)
and aqueous HCl (1 M, 4 mL) were then added. The layers were
separated, the aqueous one being extracted with AcOEt (ꢄ3). The
combined organic layers were washed with brine (ꢄ3), dried over
MgSO4 and the solvents evaporated under reduced pressure. Pu-
rification by flash chromatography (AcOEt/cyclohexane gradient)
afforded (RS)-N-allyl-2-methylpropane-2-sulfinamide (2a) (90 mg,
56%) as a colorless oil. Spectroscopic data were in good agreement
with previously reported data [8d,e].
25.1, 23.3, 23.1, 13.2; HRMS (ESI): m/z [M ꢀ Na]þ calcd for
C
11H21NO2SNa: 254.1185; found: 254.1188. ½a D20
þ71.9 (c 1.0, CHCl3).
ꢃ
4.8. (RS)-N-Acetyl-N-((E)-hex-2-enyl)-2-methylpropane-2-
sulfinamide (7)
Isolated as a E/Z ¼ 96:04 mixture of isomers. IR (neat): 2958,
1675, 1091 cmꢀ1; 1H NMR (CDCl3, 400 MHz, 325 K) E isomer:
d 5.58
(m, 1H), 5.42 (m, 1H), 4.00e3.85 (m, 2H), 2.18 (s, 3H), 1.97 (m, 2H),
1.34 (m, 2H), 1.21 (s, 9H), 0.84 (t, 3H, J ¼ 7.6 Hz); 13C NMR (CDCl3,
100 MHz, 325 K) E isomer: d 171.9, 134.4, 125.8, 60.2, 40.5, 34.1, 23.3,
23.0, 22.1,13.4; HRMS (ESI): m/z [M ꢀ Na]þ calcd for C12H23NO2SNa:
268.1342; found: 268.1347. ½a D20
þ68.6 (c 1.1, CHCl3).
ꢃ
4.4. Pd(0)-catalyzed allylic substitution of allylic carbonates by N-
acetyl tert-butanesulfinamide, preparation of 2c from 1c is
representative [Table 3, entry 1]
4.9. (RS)-N-Acetyl-N-((E)-cinnamyl)-2-methylpropane-2-
sulfinamide (8)
Ina sealed-tube underargon, THF (250
m
L)was addedto a mixture
Isolated as a E/Z >98:02 mixture of isomers. 7.35e7.14 (m, 5H),
6.52 (d, J ¼ 16.0 Hz, 1H), 6.17 (dt, J ¼ 16.0, 6.1 Hz, 1H), 4.24e4.08 (m,
2H), 2.24 (s, 3H), 1.25 (s, 9H); 13C NMR (CDCl3, 100 MHz, 325 K) E
of Pd(OAc)2 (11 mg, 0.05 mmol) and dppe [1,2-bis(diphenyl
phosphino)ethane] (30 mg, 0.075 mmol). The white slurry was stir-
red until it became yellow and allyl methyl carbonate (0.14 mL,
1.2 mmol) was added. A solution of (RS)-N-acetyl-tert-butanesulfi-
namide (1c) (163 mg, 1.0 mmol) in THF (5 mL) was introduced via
cannula at rt. The reaction mixture was heated at 70 ꢁC overnight.
AcOEt (5 mL) and aqueous HCl (1 M, 4 mL) were then added. The
layers were separated, the aqueous one being extracted with AcOEt
(ꢄ3). The combined organic layers were washed with brine (ꢄ3),
dried over MgSO4 and the solvents evaporated under reduced
pressure. Purification by flash chromatography (AcOEt/cyclohexane
50:50) afforded (RS)-N-acetyl-N-allyl-2-methylpropane-2-sulfinamide
isomer:
d 172.0, 136.7, 133.6, 128.7, 127.9, 126.6, 125.6, 60.6, 40.9,
29.8, 23.6, 23.3. HRMS (ESI): m/z [M
ꢀ
Na]þ calcd for
þ32.6 (c 1.1, CHCl3).
C
15H21NO2SNa: 302.1185; found: 302.1187. ½a D20
ꢃ
4.10. (RS)-N-Acetyl-N-((E)-1,3-diphenylallyl)-2-methylpropane-2-
sulfinamide (10)
In a sealed-tube under argon, DMF (250
mL) was added to a
mixture of Pd(OAc)2 (14 mg, 0.06 mmol) and dppe [1,2-
bis(diphenylphosphino)ethane] (36 mg, 0.09 mmol). The white
slurry was stirred until it became yellow and (ꢂ)-1,3-diphenyl-3-
ethoxycarbonyloxy-propene 9 (1.03 g, 3.66 mmol) was added. A
(2c) (190 mg, 94%) as a white solid. IR (neat): 2960,1669,1083 cmꢀ1
1H NMR (CDCl3, 400 MHz, 300 K):
5.82 (m, 1H), 5.21e5.16 (m, 2H),
;
d

L. Mistico et al. / Journal of Organometallic Chemistry 760 (2014) 124e129
129
solution of (R)-N-acetyl-tert-butanesulfinamide (1c) (200 mg,
Appendix A. Supplementary data
1.22 mmol) in DMF (5 mL) was introduced via cannula at rt. The
reaction mixture was heated at 80 ꢁC for 6 h. AcOEt (5 mL) and
water (4 mL) were then added. The layers were separated, the
aqueous one being extracted with AcOEt. The combined organic
layers were washed with water and brine, dried over MgSO4 and
the solvents evaporated under reduced pressure. Purification by
flash chromatography (AcOEt/cyclohexane 20:80) afforded the title
compound (10) as a mixture of diastereoisomers (dr ¼ 68:32) as a
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2013.11.026.
References
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d 7.52e
7.21 (m, 10H), 7.00 (dd, 1Hminor, J ¼ 16.4, 8.4 Hz), 6.75e6.74 (m,
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d 172.4,
140.8, 139.7, 137.0, 136.6, 135.5, 134.0, 130.1, 128.9, 128.6, 128.5,
128.3, 128.2, 128.0, 127.8, 127.7, 127.2, 127.1, 126.9, 126.8, 126.6, 61.0,
60.5, 57.1, 55.4, 25.0, 24.8, 23.5, 23.2. HRMS (ESI): m/z [M ꢀ Na]þ
calcd for C21H25NO2SNa: 378.1498; found: 378.1502.
4.11. (RS)-N-(Cinnamyl)-2-methylpropane-2-sulfinamide (11)
In a round-bottom flask, to a solution of (RS)-N-acetyl-N-((E)-
cinnamyl)-2-methylpropane-2-sulfinamide (8) (100 mg, 0.36
mmol) in MeOH (5 mL) was added NaOH (43.2 mg, 1.08 mmol). The
reaction mixture was refluxed for 4 h and then cooled. AcOEt (5 mL)
and aqueous HCl (1 M, 1 mL) were added, the layers separated, and
the aqueous one was extracted with AcOEt (ꢄ3). The combined
organic layers were washed with brine, dried over MgSO4 and the
solvents evaporated under reduced pressure. Purification by flash
chromatography (AcOEt/cyclohexane 20:80 to 40:60) afforded the
title compound 11 (67 mg, 79%) as a white solid. Spectroscopic data
were in good agreement with previously reported data [8d,e].
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a 2D5
ꢃ
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NMR signals at 300 K. Product characterization by NMR analysis was
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major isomer was attributed on the basis of the 3J coupling constant be-
4.12. N-Cinnamylacetamide (12)
In a round-bottom flask, to a solution of (RS)-N-acetyl-N-((E)-cin-
namyl)-2-methylpropane-2-sulfinamide (8) (53 mg, 0.19 mmol) in
dry MeOH (5 mL) kept at 0 ꢁC was added HCl (4 M in dioxane, 0.5 mL,
0.5 mmol). The reaction mixture was stirred at 0 ꢁC for 2 h and then
sat. NaHCO3 (3 mL) was added. The MeOH was evaporated under
reduced pressure and the resulting mixture was extracted with
CH2Cl2 (ꢄ3). The combined organics were washed with brine, dried
over MgSO4, and the solvents evaporated under reduced pressure to
provide the title compound 12 (33 mg, 99%). Spectroscopic data were
in good agreement with previously reported data [18].
tween the vicinal vinylic protons (>15.0 Hz) characteristic of
configuration.
a trans
[13] The presence of two diastereomers was unambiguously established by car-
rying the NMR experiments at 325 K. The absolute configuration of the newly
created stereocenter of the two diastereomeric products was not determined.
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structure: V.A. Blaschette, D. Rinne, H.C. Marsmann Z. Anorg. Allg. Chem. 420
(1976) 55e64.
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Acknowledgments
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[18] T. Leikoski, P. Wrigstedt, J. Helminem, J. Matikainen, J. Sipila, J. Yli-Kauha-
luoma, Tetrahedron 69 (2013) 839e843.
GP and EA thank ENSCMu and Actelion for a grant “Actelion
Chair in Innovative Organic Chemistry”.