Direct Access to N-tert-Butanesulfinyl Imines from Aryl Iodides, Alkenyl Alcohols, and N-tert-Butanesulfinamide

Article abstract of DOI:10.1002/ejoc.201800111

The reaction of aryl iodides, N-tert-butanesulfinamide, and allyl or homoallyl alcohol in the presence of a catalytic amount of Pd(OAc)₂, NaHCO₃ as a base, and TBAB leads to the formation of N-tert-butanesulfinyl imines in moderate yields. In this one-pot process, a sequential Heck-type arylation of the alkenol, isomerization of the double bond, and imine formation take place.

Full text of DOI:10.1002/ejoc.201800111

A Journal of
Accepted Article
Title: Direct Access to N-tert-Butanesulfinyl Imines from Aryl Iodides,
Alkenyl Alcohols and N-tert-Butanesulfinamide
Authors: Miguel Yus, Sofiane Ikhlef, Cherif Behloul, Alejandro Lahosa,
and Francisco Foubelo
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800111
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800111
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10.1002/ejoc.201800111
European Journal of Organic Chemistry
1
Direct Access to N-tert-Butanesulfinyl Imines from Aryl Iodides, Alkenyl Alcohols
and N-tert-Butanesulfinamide
Sofiane Ikhlef,[a] Cherif Behloul,*[a] Alejandro Lahosa,[b,c,d] Francisco Foubelo*[b,c,d]
and Miguel Yus*[b,d]
Keywords: Chiral sulfinyl imines · Heck-reaction · One-pot process · Isomerization · N-tert-Butanesulfinamide
The reaction of aryl iodides, N-tert-butanesulfinamide, and allyl or homoallyl alcohol in the presence of a
catalytic amount of Pd(OAC)2, NaHCO3 as a base and TBAB, leads to the formation of N-tert-butanesulfinyl
imines in moderate yields. In this one-pot process, a sequential Heck-type arylation of the alkenol, isomerization
of the double bond and imine formation takes place.
Introduction
The development of new strategies of synthesis that allow an efficient transformation of simple molecules into
more complex ones, through the generation of carbon-carbon and carbon-heteroatom bonds, is still of great
interest in organic chemistry.[1] When throughout the process a new stereogenic center is formed, it should be
done in a stereoselective way. In order to achieve this goal, the chemical yield should not be taken into account
exclusively, but waste minimization must be also considered, avoiding the use of toxic and hazardous reagents
and solvents, as well.[2] Catalytic processes in unconventional media[3] fulfill these requirements. In terms of
efficiency, multicomponent reactions[4] are also very important, because at least two consecutive transformations
occurred in the reaction flask, so that the functional group generated after the first step participates in the next
reaction, all reactants involved being from the beginning in the reaction medium. There are also one-pot
processes in which two or more reactions take place consecutively, without the need to isolate the intermediates,
although the reagents participating in the transformations can be added sequentially after each reaction step.
Both, the multicomponent reactions and the one-pot processes, in general, are interesting because the amounts of
waste, solvents, labour and time are considerably minimized. On the other hand, the chemistry of chiral N-tert-
butanesulfinyl imines[5] has experienced great advances in the last years because the reaction with different
__________________
[a]
Laboratoire des Produits Naturels d’Origine Végétale et de Synthèse Organique, Université des Frères Mentouri-Constantine
25000, Algeria
[b] Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99
03080 Alicante, Spain
E-mail: afiza72@gmail.com
foubelo@ua.es
yus@ua.es
[c]
Instituto de Síntesis Orgánica, Universidad de Alicante, Apdo. 99
03080 Alicante, Spain
[d] Centro de Innovación en Química Avanzada (ORFEO-CINQA), Universidad de Alicante, Apdo. 99
03080 Alicante, Spain
Supporting information for this article is available on the WWW under http://www.eurjoc.org/ or from the author.
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10.1002/ejoc.201800111
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nucleophilic reagents occurred in a highly diastereoselective fashion. In addition, both enantiomeric imines are
accessible in large-scale processes[6] and the tert-butanesulfinyl group is easily removed under acidic conditions.
Importantly, practical processes for recycling the chiral auxiliary upon deprotection of N-tert-butanesulfinyl
amines have also been reported.[7] In this context, we described the stereoselective allylation of N-tert-
butanesulfinyl aldimines and ketimines with allylindium species[8] and the first one-pot α-aminoallylation of
aldehydes with chiral tert-butanesulfinamide, allyl bromides, and indium,[9] which provides homoallylic amines
with high chemo- and stereoselectivities. The synthesis of these aldimines was achieved in a straightforward
manner by direct condensation of tert-butanesulfinamide with carbonyl compounds in the presence of a Lewis
acid and a water scavenger at room temperature.[10] However, more demanding reaction conditions are required
for the synthesis of the corresponding ketimines, which were accessed for the first time when the condensation
was performed in the presence of titanium tetraethoxide in refluxing THF.[10,11] New methodologies for the direct
condensation of N-tert-butanesulfinyl imines and aldehydes under the influence of pyrrolidines as
organocatalyst,[12] or different acids or bases have also been reported recently.[13] The condensation worked well
also under microwave irradiation in the presence of titanium tetraethoxide without additional solvents in short
reaction times.[14] In this context, we recently carried out the one-pot synthesis of chiral N-tert-butanesulfinyl
imines starting from commercially available or easily prepared epoxides.[15] The transformation was performed in
the presence of a Lewis acid which promoted first the isomerization of the epoxide to give a carbonyl compound,
followed by condensation with N-tert-butanesulfinamide (Scheme 1).
MgSO4, PPTS cat.
[10]
CH2Cl2, rt
t-Bu
BF3·OEt2 cat., 3Å MS
S
O
S
THF, 50 ºC
[10]
[10]
O
CuSO4, CH2Cl2, rt
Ti(OEt)4, THF, rt
R3
N
O
+
t-Bu
R3
[14]
t-Bu
NH2
R4
H
S
R4
O
N
+
O
cat., 4Å MS
CH2Cl2, rt or
60 ºC
R1
H
[12]
R1 R2
N
H
[R2 = H]
t-Bu
[10,11]
Ti(OEt)4, THF, 60-75 ºC
S
N
O
R1 R2
[13]
Ti(OEt)4, MW (40 W), 70 ºC
Scheme 1. Synthesis of N-tert-Butanesulfinyl Imines Reported Previously
Continuing our interest in this topic, and with the aim of increasing the number of methodologies which allow the
access to chiral functionalized N-tert-butanesulfinyl imines, we report here the synthesis of the corresponding 3-
arylpropanal and 4-arylbutanal derivatives starting from aryl iodides and allyl alcohol and 3-buten-1-ol,
respectively. In order to achieve this goal, a palladium-catalyzed arylation of an alkenyl alcohol with concomitant
isomerization of the double bond should occur first, followed by condensation of the resulting aldehyde with N-
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10.1002/ejoc.201800111
European Journal of Organic Chemistry
3
tert-butanesulfinamide. This two-step transformation in a one-pot process leading to the formation of chiral 3-
and 4-aryl substituted N-tert-butanesulfinyl aldimines by assembling three components is of great interest given
environmental sustainability by minimizing solvents, labour and time (Scheme 2).
Scheme 2. Proposed Synthesis of N-tert-Butanesulfinyl Imines through a One-pot Coupling of Aryl Iodides,
Alkenyl Alcohols and N-tert-Butanesulfinamide
Results and Discussion
In order to find the best reaction conditions to carry out the synthesis of N-tert-butanesulfinyl imines from an aryl
iodide 1, an alkenol 2 and (R)-N-tert-butanesulfinamide (3), we took iodobenzene (1a) and allyl alcohol (2a) as
the model compounds. The palladium-catalyzed coupling of aryl halides and allylic alcohols can be controlled to
produce selectively β-aryl carbonyl compounds or the corresponding conjugate aryl alkenols.[16] It was found that
the combination of a catalytic amount of Pd(OAc)2 with 2.5 equivalents of NaHCO3, and 1 equivalent of
tetrabutylammonium chloride (TBAC) in DMF, led almost exclusively to the carbonyl compound. However, the
use of Pd(OAc)2 with a double catalytic amount of PPh3, and 1 equivalent of AgOAc as base in the same solvent,
gave the primary expected Heck product aryl alkenol.[16] Based on these antecedents, we studied first the reaction
of iodobenzene (1a) with allyl alcohol (2a) and (R)-N-tert-butanesulfinamide (3) in a 2:3:1 ratio, in the presence
of 4 mol% of Pd(OAc)2, tetrabutylammonium bromide (TBAB) and NaHCO3 in DMF. The reaction was
performed at 60 ºC for 24 h. These conditions were almost the same that showed to be optimal for the formation
of the carbonyl compound, and led to a mixture of 8% of unreactive starting sulfinamide 3, 52% of the expected
imine 4a and 40% of the initially formed 3-phenylpropanal (5a) (Table 1, entry 1). Similar results were obtained
when MgSO4 was added to the reaction mixture to act as water scavenger, in order to facilitate the condensation
of the aldehyde 5a and the sulfinamide 3 (Table 1, entry 2). Starting sulfinamide 3 predominated in the reaction
mixture working in THF instead of DMF (Table 1, entry 3). However, the expected imine 4a was the major
component of the reaction mixture working in THF as solvent and using 4Å molecular sieves as water scavenger,
and was isolated in 46% yield after column chromatography (Table 1, entry 4). With the aim of promoting the
imine condensation, BF3·OEt2 was also added to the reaction mixture, but, unfortunately, a complex mixture of
reaction products without traces of the imine 4a and the precursor aldehyde 5a was formed (Table 1, entry 5).
Similar results to those shown on entries 1 and 2 were obtained working in DMF with 4Å molecular
sieves (Table 1, entry 6). We performed also the reaction under conventional solvent-free conditions, because
arylation of allylic alcohols proceeded effectively in ionic liquids such as TBAB.[17] The reaction of the starting
three components 1a, 2a and 3, in the presence of Pd(OAc)2, NaHCO3 and 1 equivalent of TBAB, without any
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10.1002/ejoc.201800111
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additional solvent at 80 ºC for 12 h, led to a mixture of sulfinamide 3 and imine 4a in a 33/67 ratio, the aldehyde
precursor 5a of the imine being not detected in the reaction mixture (Table 1, entry 7). Total decomposition of the
expected products was observed working at 110 ºC (Table 1, entry 8). Finally, the best result was obtained when
TBAB, Pd(OAc)2, NaHCO3 and allyl alcohol 2a were heated at 110 ºC for 4 h and after that, sulfinamide 3 was
added to the reaction mixture, which was allowed to react at 80 ºC for 8 additional h. Imine 4a was by far the
major component of the reaction mixture and was isolated in 68% yield after column chromatography
purification (Table 1, entry 9).
Table 1. Optimization of the three-component coupling of iodobenzene (1a), allyl alcohol (2a) and N-tert-
butanesulfinamide 3a
Reaction Conditions
Entry
Solvent Water Scavenger
Additive
Temperature
60 ºC
Time
24 h
24 h
24 h
24 h
24 h
24 h
12 h
12 h
4/8 h e
3/4a/5a Ratiob
8/52/40
1
2
3
4
5
6
7
8
9
DMF
DMF
THF
THF
THF
DMF
--
--
--
MgSO4
MgSO4
MS 4Å
MS 4Å
MS 4Å
--
--
60 ºC
8/63/29
--
60 ºC
65/15/20
27/73(46%)c/0
--d
--
60 ºC
BF3·OEt2
60 ºC
--
--
--
--
60 ºC
0/66/34
80 ºC
33/67/0
--
--
110 ºC
110/80 ºC e
-- d
--
--
1/82(68%) c/17
a
All the reactions were carried out with 1.0 mmol of 1a, 1.5 mmol of 2a, 0.5 mmol of 3, 0.02 mmol of
Pd(OAc)2, 1.5 mmol of TBAB, 2.5 mmol of NaHCO3, in 1.5 mL of solvent. b Ratio was determined from the
1H NMR spectrum of the crude reaction mixture. c Isolated yield after column chromatography purification. d
A complex mixture of reaction products was obtained. e The reaction was initially performed at 110 ºC for 4 h
and at 80 ºC for 8 additional h.
The scope of the reaction under the optimized conditions shown in entry 9 of Table 1 was studied next. The
expected imines 4 were obtained in moderate yields in general with values ranging from 68 to 41% (Table 2,
entries 1 and 10, respectively). In spite of the moderate yields, it merits to be mentioned that three different
processes occurred in this one-pot transformations: palladium-catalyzed coupling reaction of the aryl iodide 1 and
the alkenol 2, further isomerization of the carbon-carbon double leading first to the enol which tautomerizes to
form the corresponding aldehyde, and final condensation with sulfonamide 3. Yields were slightly higher for 3-
arylpropanal derivatives (Table 2, entries 1-8) than for those obtained using 3-buten-1-ol (2b) (Table 2, entries 9-
12). Methyl, bromine and methoxy groups are well tolerated in these transformations, independently of the
relative position respect to the iodine atom. The reaction worked also for heteroaromatic iodides, such as
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10.1002/ejoc.201800111
European Journal of Organic Chemistry
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iodothiophene (1f) (Table 2, entry 6). Unfortunately, yields were considerably lower under the optimized
reaction conditions starting from aryl bromides (see for instance entries 1 and 2 in Table 2), and imine
formation was not observed when substituted allylic alcohols 2, such as methallyl and crotyl alcohols were
used as alkylating reagents.
Table 2. Scope of the three-component coupling reaction of iodobenzene (1a), allyl alcohol (2a) and N-tert-
butanesulfinamide 3a
Aryl Iodide 1
No. Structure
N-tert-Butanesulfiniyl Imine 4
Entry
1
Alkenol 2
2a (n = 1)
No.
Structure
Yield (%)b
68 (17)c
1a
1b
4a
t-Bu
S
N
O
48 (4)c
2
3
4
2a (n = 1)
2a (n = 1)
2a (n = 1)
4b
4c
4d
H
Me
51
1c
65
1d
55
42
5
6
1e
1f
2a (n = 1)
2a (n = 1)
4e
4f
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48
7
8
1g
1h
2a (n = 1)
2a (n = 1)
4g
4h
t-Bu
S
N
O
45
H
MeO
52
41
45
49
9
1a
1b
1d
1e
2b (n = 2)
2b (n = 2)
2b (n = 2)
2b (n = 2)
4i
4j
4k
4l
10
11
12
a
All the reactions were carried out with 1.0 mmol of 1a, 1.5 mmol of 2a, 0.5 mmol of 3, 0.02 mmol of
b
Pd(OAc)2, 1.5 mmol of TBAB, 2.5 mmol of NaHCO3. Isolated yield after column chromatography
purification. Isolated yield after column chromatography purification starting from the corresponding
c
bromoarene is given in parenthesis.
We found especially interesting ortho-bromoaryl substituted imines 4e and 4l regarding synthetic applications.
They have been used as precursors of chiral tricyclic lactams 6 and 7, diastereoselective allylation of the prochiral
imine functionality and an intramolecular N-arylation involving the carbon-bromine bond being key steps of
these transformations.[18] In addition, imine 4e was also used as a reaction intermediate in the synthesis of natural
products (-)-angustureine and (-)-cuspareine (Figure 1).[19]
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OMe
OMe
N
N
Me
Me
Me
(-)-cuspareine
(-)-angustureine
t-Bu
S
N
O
N
N
H
O
Br
4e
O
6b
7b
t-Bu
Br
S
N
N
O
N
O
O
H
6l
7l
4l
Figure 1. Synthetic Applications of Imines 4b and 4l
Conclusions
In summary, N-tert-butanesulfinyl aldimines derived from 3-arylpropanal and 4-arylbutanal were prepared in a
one-pot process starting from N-tert-butanesulfinamide, aryl iodides and allyl and homoallyl alcohols,
respectively. A Heck-type palladium-catalyzed coupling involving the aryl iodide and the alkenol occurred first,
followed by isomerization of the resulting compound leading to an aldehyde, taking place finally the
condensation with the sulfinamide. The functionalized chiral imines, especially those with bromine atoms bonded
to the aromatic ring, are of potential synthetic interest as precursor of more complex molecules involving the
transformation of the present functionalities. The here presented one-pot solvent-free methodology is also of
interest taking into account environmental issues because the amounts of waste, solvents and labour are
considerably minimized if compared to classical methods.
Experimental Section
General: (RS)-tert-Butanesulfinamide was a gift of MEDALCHEMY SL (> 99% ee by chiral HPLC on a
Chiracel AS column, 90:10 n-hexane/i-PrOH, 1.2 mL/min, λ=222 nm). TLC was performed on silica gel 60 F254,
using aluminium plates and visualized with phosphomolybdic acid (PMA) stain. Flash chromatography was
carried out on hand packed columns of silica gel 60 (230- 400 mesh). Gas chromatographic analyses (GC) were
carried out in a Agilent Technologies 6890N instrument equipped with a flame ionization detector and a 30.0 m
capillary column (0.25 mm diam, 0.25 μm film thickness), using nitrogen (1.4 ml/min) as carrier gas, Tinjector
=
275°C, Tcolumn = 60 °C (3 min) and 60-270 °C (15 °C/min). Melting points are uncorrected. Optical rotations were
measured using a polarimeter with a thermally jacketed 5 cm cell at approximately 23 ºC and concentrations (c)
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10.1002/ejoc.201800111
European Journal of Organic Chemistry
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are given in g/100 mL. Infrared analyses were performed with a spectrophotometer equipped with an ATR
component; wave numbers are given in cm-1. Low-resolution mass spectra (EI) were obtained at 70 eV; and
fragment ions in m/z with relative intensities (%) in parentheses. High-resolution mass spectra (HRMS) were also
carried out in the electron impact mode (EI) at 70 eV and on an apparatus equipped with a time of flight (TOF)
analyzer and the samples were ionized by ESI techniques and introduced through an ultra-high pressure liquid
chromatography (UPLC) model. 1H NMR spectra were recorded at 300 or 400 MHz for 1H NMR and 75 or 100
MHz for 13C NMR, using CDCl3 as the solvent and TMS as internal standard (0.00 ppm). The data is being
reported as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet or unresolved, br s = broad signal,
1
coupling constant(s) in Hz, integration. 13C NMR spectra were recorded with H-decoupling at 100 MHz and
referenced to CDCl3 at 77.16 ppm. DEPT-135 experiments were performed to assign CH, CH2 and CH3. All
reactions requiring anhydrous conditions were performed in oven dried glassware under argon. Otherwise
indicated, all commercially available chemicals were purchased from Acros or Sigma-Aldrich and used without
purification.
General procedure for the synthesis of N-tert-butanesulfinyl aldimines 4: A mixture of the TBAB (0.485 g,
1.5 mmol) and Pd(OAc)2 (0.0045 g, 0.02 mmol) was stirred at 110 ºC for 15 min in a high pressure tube
under argon. When the mixture was melted, NaHCO3 (0.210 g, 2.5 mmol), the corresponding aryl iodide 1 (1.0
mmol) and alkenol 2 (1.5 mmol) were added, and stirring was continued for 4 h at the same temperature. Then,
the reaction mixture was cooled down to 80 ºC, and tert-butanesulfinamide (1, 0.061 g, 0.5 mmol) was added.
The resulting mixture was stirred at 80 ºC for 8 additional h, and after that, cooled down to room temperature,
and diluted with EtOAc (25 mL). The resulting suspension was filtered through a short path of Celite and
concentrated (15 Torr). The residue was hydrolyzed with water (10 mL), extracted with EtOAc (3×15 mL), dried
with anhydrous MgSO4 and evaporated (15 Torr). The residue was purified by column chromatography (silica
gel, hexane/EtOAc, 5:1) to yield pure compounds 4. Yields for compounds 4 are given on Table 2. Physical and
spectroscopic data follow.
23
(RS)-N-(tert-Butanesulfinyl)-3-phenylpropan-1-imine (4a):[20] Colourless oil; [α]D -208 (c 1.1, CH2Cl2); Rf
0.78 (hexane/EtOAc: 1/1); IR ν (film) 3012, 2957, 2869, 1622, 1582, 1496, 1454, 1362, 1180, 1078 cm-1; δH 8.11
(t, J = 4.2 Hz, 1H), 7.27-7.19 (m, 5H), 3.00-2.90 (m, 2H), 2.90-2.83 (m, 2H), 1.13 (s, 9H); δC 168.7 (CH), 140.3
(C), 128.6, 128.3, 126.3 (CH), 56.6 (C), 37.5 (CH2), 31.4 (CH2), 22.3 (CH3); LRMS (EI) m/z 131 (M+-C4H10SO,
34%), 92 (11), 91 (100), 65 (19), 51 (10).
(RS)-N-(tert-Butanesulfinyl)-3-(2-methylphenyl)propanimine (4b): Colourless oil; [α]D23 -115 (c 1.2, CH2Cl2);
Rf 0.78 (hexane/EtOAc: 1/1); IR ν (film) 3025, 2957, 2925, 2848 1621, 1456, 1362, 1182, 1159, 1084, 940 cm-1;
δH 8.14 (t, J = 4.3 Hz, 1H), 7.26-7.11 (m, 4H), 2.97-2.91 (m, 2H), 2.85-2.77 (m, 2H), 2.32 (s, 3H) 1.16 (s, 9H);
δC 168.65 (CH), 138.55, 135.9 (C), 130.4 , 128.5, 126.3, 126.2 (CH), 56.6 (C), 36.4, 28.8 (CH2), 22.3, 19.3
(CH3); LRMS (EI) m/z 145 (M+-C4H10SO, 28%), 105 (100), 104 (11), 103 (13), 79 (11), 77 (16), 51 (10); HRMS
(ESI): Calculated for C10H13NOS (M+-C4H8) 195.0718, found 195.0723.
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23
(RS)-N-(tert-Butanesulfinyl)-3-(3-methylphenyl)propan-1-imine (4c): Colourless oil; [α]D -81 (c 1, CH2Cl2);
Rf 0.75 (hexane/EtOAc: 1/1); IR ν (film) 3022, 2918, 2857, 1620, 1456, 1362, 1158, 1084, 914, cm-1; δH 8.11 (t, J
= 4.1 Hz, 1H), 7.20-7.15 (m, 1H), 7.02-6.99 (m, 3H), 2.96-2.91 (m, 2H), 2.88-2.81 (m, 2H), 2.32 (s, 3H), 1.13 (s,
9H); δC 168.7 (CH), 140.4, 138.2 (C), 129.3 , 128.6, 127.1, 125.4 (CH), 56.7 (C), 37.6, 31.4 (CH2), 22.4, 21.5
(CH3); LRMS (EI) m/z 145 (M+-C4H10SO, 31%), 106 (10), 105 (100), 77 (14); HRMS (ESI): Calculated for
C14H21NOS (M+) 251.1344, found 251.1334.
23
(RS)-N-(tert-Butanesulfinyl)-3-(4-methylphenyl)propan-1-imine (4d): Colourless oil; [α]D -127 (c 1,
CH2Cl2); Rf 0.78 (hexane/EtOAc: 1/1); IR ν (film) 3028, 2957, 2923, 2850 1621, 1514, 1455, 1362, 1182, 1085,
807 cm-1; δH 8.10 (t, J = 4.3 Hz, 1H), 7.13-7.04 (m, 4H), 2.94-2.90 (m, 2H), 2.85-2.80 (m, 2H), 2.31 (s, 3H), 1.13
(s, 9H); δC 168.8 (CH), 137.2 , 135.75 (C), 129.2, 128.2 (CH), 56.6 (C), 37.7 , 33.0 (CH2), 22.3, 21.0 (CH3);
LRMS (EI) m/z 145 (M+-C4H10SO, 23%), 106 (10), 105 (100), 103 (12), 77 (15); HRMS (ESI): Calculated for
C14H21NOS (M+) 251.1344, found 251.1332.
23
(RS)-N-(tert-Butanesulfinyl)-3-(2-bromophenyl)propan-1-imine (4e):[21] Colourless oil; [α]D -43 (c 1.2,
CH2Cl2); Rf 0.75 (hexane/EtOAc: 1/1); IR ν (film) 2974, 2875, 2869, 1622, 1567, 1471, 1439, 1362, 1084, 1024,
749 cm-1; δH 8.14 (t, J = 4.1 Hz, 1H), 7.53 (dd, J = 4.7 Hz, 1H), 7.27-7.23 (m, 2H), 7.11-7.05 (m, 1H), 3.12-3.06
(m, 2H), 2.90-2.83 (m, 2H), 1.17 (s, 9H); δC 168.2 (CH), 139.8 (C), 133.0, 130.4, 128.15, 127.7 (CH), 124.4, 56.7
(C), 36.0 , 31.9 (CH2), 22.4 (CH3); LRMS (EI) m/z 211 (M+-C4H8-81Br, 25%), 209 (26), 171 (97), 169 (100), 90
(23), 89 (19), 77 (10), 63 (11), 51 (10).
23
(RS)-N-(tert-Butanesulfinyl)-3-(thiophen-2-yl)propan-1-imine (4f): Colourless oil; [α]D -41 (c 1.2, CH2Cl2);
Rf 0.72 (hexane/EtOAc: 1/1); IR ν (film) 2959, 2924, 2359, 2341, 1622, 1455, 1363, 1179, 1076 cm-1; δH 8.12 (t,
J = 4.0 Hz, 1H), 7.13 (dd, J = 10.0, 5.2 Hz, 1H), 6.91 (dd, J = 5.0, 3.6 Hz, 1H), 6.84 (dd, J = 3.4, 0.9 Hz, 1H),
3.22-3.18 (m, 2H), 2.94-2.89 (m, 2H), 1.15 (s, 9H), 1.15 (s, 9H); δC 167.9 (CH), 143.0 (C), 126.85, 124.7, 123.5
(CH), 56.7 (C), 37.7 (CH2), 25.5 (CH2), 22.3 (CH3); LRMS (EI) m/z 137 (M+-C4H10SO, 22%), 97 (100), 69 (10),
53 (12); HRMS (ESI): Calculated for C11H17NOS2 (M+) 243.0752, found 243.0753.
23
(RS)-N-(tert-Butanesulfinyl)-3-(2-bromo-4-methylphenyl)propan-1-imine (4g): Colourless oil; [α]D -39 (c
1.1, CH2Cl2); Rf 0.75 (hexane/EtOAc: 1/1); IR ν (film) 3050, 2923, 2895, 1605, 1559, 1490, 1451, 1389, 1039,
910,732 cm-1; δH 8.13 (t, J = 4.2 Hz, 1H), 7.36 (s , 1H), 7.12 (d, J = 7.7 Hz, 1H), 7.05-7.03 (m, 1H), 3.06-3.02 (m,
2H), 2.86-2.82 (m, 2H), 2.29 (s, 3H), 1.17 (s, 9H); δC 168.5 (CH), 138.2, 136.6 (C), 133.5, 130.2, 128.5 (CH),
124.2, 56.8 (C), 36.3 , 31.5 (CH2), 22.4, 20.7 (CH3); LRMS (EI) m/z 275 (M+-C4H8, 30%), 273 (27), 211 (13),
209 (15), 185 (76), 183 (77), 146 (12), 131 (15), 115 (19), 104 (16), 57 (100), 41 (22); HRMS (ESI): Calculated
for C10H12Br81NOS (M+-C4H8) 274.9803, found 274.9802.
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23
(RS)-N-(tert-Butanesulfinyl)-3-(4-methoxyphenyl)propan-1-imine (4h): Colourless oil; [α]D -140 (c 1,
CH2Cl2); Rf 0.70 (hexane/EtOAc: 1/1); IR ν (film) 2956, 2931, 2825, 1612, 1510, 1462, 1363, 1244, 1177, 1082,
821 cm-1; δH 8.10 (t, J = 4.2 Hz, 1H), 7.12 (dd, J = 8.7, 0.6 Hz, 2H), 6.83 (dd, J = 8.8, 0.6 Hz, 2H), 3.78 (s, 3H),
2.94-2.89 (m, 2H), 2.85-2.79 (m, 2H), 1.14 (s, 9H); δC 168.8 (CH), 158.1, 132.45 (C), 129.4, 114.1 (CH), 56.8
(C), 55.4 (CH3), 37.9, 30.7 (CH2), 22.4 (CH3); LRMS (EI) m/z 211 (M+-C4H8, 17%), 162 (14), 121 (100), 57 (45),
41 (10); HRMS (ESI): Calculated for C14H21NO2S (M+) 267.1293, found 267.1303.
23
(RS)-N-(tert-Butanesulfinyl)-4-phenylbutan-1-imine (4i): Colourless oil; [α]D -54 (c 0.5, CH2Cl2); Rf 0.78
(hexane/EtOAc: 1/1); IR ν (film) 3028, 2925, 2849, 1622, 1582, 1421, 1371, 1264, 1155, 1076 cm-1; δH 8.09 (t, J
= 4.4 Hz, 1H), 7.31-7.26 (m, 5H), 2.71-2.67 (m, 2H), 2.57-2.52 (m, 2H), 1.98-1.95 (m, 2H), 1.20 (s, 9H); δC
169.25 (CH), 141.4 (C), 128.6, 128.3, 126.05 (CH), 56.6 (C), 35.5, 29.7, 27.1 (CH2), 22.4 (CH3); LRMS (EI) m/z
145 (M+-C4H10SO, 19%), 105 (100), 103 (12), 79 (10), 77 (15); HRMS (ESI): Calculated for C14H21NOS (M+)
251.1344, found 251.1341.
23
(RS)-N-(tert-Butanesulfinyl)-4-(2-methylphenyl)butan-1-imine (4j): Colourless oil; [α]D -111 (c 1, CH2Cl2);
Rf 0.78 (hexane/EtOAc: 1/1); IR ν (film) 3026, 2953, 2866, 1620, 1456, 1378, 1362, 1183, 1160, 1080, 740 cm-1;
δH 8.13 (t, J = 4.5 Hz, 1H), 7.28-7.12 (m, 4H), 2.73-2.68 (m, 2H), 2.65-2.58 (m, 2H), 2.33 (s, 3H), 1.99-1.91 (m,
2H), 1.22 (s, 9H); δC 169.3 (CH), 139.6, 135.85 (C), 130.3, 128.9, 126.2, 126.0 (CH), 56.6 (C), 35.9, 32.7, 25.8
(CH2), 22.4, 19.3 (CH3); LRMS (EI) m/z 159 (M+-C4H10SO, 40%), 118 (21), 117 (18), 106 (30), 105 (100), 91
(20), 79 (10), 77 (13); HRMS (ESI): Calculated for C15H23NOS (M+) 265.1500, found 265.1489.
23
(RS)-N-(tert-Butanesulfinyl)-4-(4-methylphenyl)butan-1-imine (4k): Colourless oil; [α]D -267 (c 0.5,
CH2Cl2); Rf 0.80 (hexane/EtOAc: 1/1); IR ν (film) 3050, 2960, 2926, 2830, 1622, 1514, 1456, 1421, 1364, 1265,
1073, 964 cm-1; δH 8.11 (t, J = 4.5 Hz, 1H), 7.12-7.08 (m, 4H), 2.69-2.65 (m, 2H), 2.57-2.54 (m, 2H), 2.34 (s,
3H), 1.98-1.92 (m, 2H), 1.22 (s, 9H); δC 169.3 (CH), 138.3, 135.5 (C), 129.1, 128.3 (CH), 56.55 (C), 35.5, 34.8,
27.2 (CH2), 22.4, 21.0 (CH3); LRMS (EI) m/z 159 (M+-C4H10SO, 71%), 118 (30), 117 (14), 106 (21), 105 (100),
91 (15), 77 (15); HRMS (ESI): Calculated for C15H23NOS (M+) 265.1500, found 265.1508.
(RS)-N-(tert-Butanesulfinyl)-4-(2-bromophenyl)butan-1-imine (4l):[8d] Colourless oil; [α]D23 -94 (c 1, CH2Cl2);
Rf 0.78 (hexane/EtOAc: 1/1); IR ν (film) 3052, 2957, 2923, 2875, 1621, 1514, 1455, 1362, 1182, 1085, 807 cm-1;
δH 8.11 (t, J = 4.5 Hz, 1H), 7.53 (dd, J = 9.5, 1.5 Hz, 1H), 7.24-7.22 (m , 2H), 7.07 (ddd, J = 10.1, 6.7, 2.7 Hz,
1H), 2.83-2.79 (m, 2H), 2.62-2.57 (m, 2H), 1.99-1.95 (m, 2H), 1.20 (s, 9H); δC 169.1 (CH), 140.8 (C), 133.0,
130.4, 127.9, 127.6 (CH), 124.5, 56.7 (C), 35.65 , 35.6, 25.6 (CH2), 22.5 (CH3); LRMS (EI) m/z 225 (M+-C4H8-
81Br, 30%), 223 (31), 185 (18), 184 (18), 183 (19), 182 (17), 171 (96), 170 (10), 169 (100), 144 (39), 116 (11),
115 (11), 104 (11), 103 (13), 91 (14), 90 (27), 89 (27), 77 (16), 63 (14), 51 (12).
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1
Supporting Information (see footnote on the first page of this article): Copies of H, 13C NMR and DEPT
spectra for all the reported compounds.
Acknowledgements
We thank the continued financial support from our Ministerio de Ciencia e Innovación (MCINN; projects
CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24165), the Ministerio de Economía y
Competitividad (MINECO; project CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC,
CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017), the
University of Alicante, the Ministère de l'Enseignement Supérieur et de la Recherche Scientifique Algérienne;
Direction de la Coopération et des Echanges Interuniversitaires; Programme de Formation Résidentielle à
l'Étranger au titre de l'année universitaire 2016/2017: Programme National Exceptionnel (PNE).
__________________
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Table of Contents
Chiral N-tert-butanesulfinyl aldimines are prepared in a one-pot process from aryl iodides, allyl or
homoallyl alcohols and N-tert-butanesulfinamide, through a sequential palladium-catalyzed Heck
reaction, carbon-carbon double bond rearrangement and imine condensation.
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Key Topic: Synthesis of N-tert-Butanesulfinyl Aldimines in a One-pot Process from Aryl Iodides,
Allyl or Homoallyl Alcohols and N-tert-Butanesulfinamide
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