Indium-promoted diastereo- and regioselective propargylation of chiral sulfinylimines

Article abstract of DOI:10.1002/ejoc.201201410

The reaction of different chiral imines 3 derived from aldehydes or ketones with the silylated propargyl bromide 4b under sonication in the presence of indium metal led mainly or exclusively to the formation of protected homopropargylamines 5 in a diaster

Full text of DOI:10.1002/ejoc.201201410

FULL PAPER
DOI: 10.1002/ejoc.201201410
Indium-Promoted Diastereo- and Regioselective Propargylation of Chiral
Sulfinylimines
M. Jesús García-Muñoz,[a] Flavia Zacconi,[a] Francisco Foubelo,*[a] and Miguel Yus*[a]
Keywords: Synthetic methods / Indium / Alkynes / Regioselectivity / Diastereoselectivity / Propargylation / Sulfinylimines
The reaction of different chiral imines 3 derived from alde-
hydes or ketones with the silylated propargyl bromide 4b un-
der sonication in the presence of indium metal led mainly or
exclusively to the formation of protected homoproparg-
ylamines 5 in a diastereoselective manner. Of special interest
are the ketimine derivatives because the new stereocenter
has a quaternary configuration. The selective deprotection of
the two protecting groups, the silicon and sulfinyl moieties,
was easily achieved by conventional methodologies.
by indium metal,[6] we report herein the regioselective prop-
argylation of the same starting imines to give the expected
chiral N-protected homopropargylic amines.[7,8]
Introduction
The addition of organometallic reagents to carbonyl
compounds and their imines is one of the most useful and
versatile methodologies for creating both a new carbon–car-
bon bond and also a new functionality, an alcohol or
amine, respectively.[1] The enantio- and/or diastereoselective
version of this process is of additional interest because at
least one new stereogenic center is generated.[2] Moreover,
when an allyl or propargyl organometallic reagent is used,[3]
the process offers the possibility of further transformation
of the unsaturation to form more carbon–carbon or car-
bon–heteroatom bonds.[4] However, in the case of proparg-
ylation, α- or γ-substitution (regioselectivity) also involves
chemoselectivity because a propargyl or allenyl moiety can
be alternatively produced, respectively (Scheme 1).[5] Con-
tinuing our studies of the diastereoselective Barbier-type
addition of allyl halides to chiral sulfinylimines promoted
Results and Discussion
The starting sulfinylimines[9] 3 were prepared according
to the standard procedure described in the literature[10] by
reaction of commercially available (R)- or (S)-tert-butane-
sulfinamide (1) with aldehydes or ketones 2 in the presence
of titanium tetraethoxide in THF (Scheme 2).
Scheme 1. Regio- and chemoselectivity in the addition of proparg-
yl/allenyl metals to carbonyl compounds and imines.
[a] Departamento de Química Orgánica, Facultad de Ciencias and
Instituto de Síntesis Orgánica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Fax: +34-965903549
E-mail: foubelo@ua.es, yus@ua.es
Scheme 2. Synthesis of starting sulfinylimines. Reagents and condi-
tions: i) Ti(OEt)4 (2 equiv.), THF, 23 °C, 12 h (for aldehydes) or
66 °C, 5 h (for ketones).
Homepage: http://iso.ua.es/es/personal/director-iso.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201410.
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To optimize the reaction, we studied the propargylation Table 1. Optimization of the reaction conditions; )))) = sonication.
of imine (R)-3c with propargyl bromides 4a and 4b under
different reaction conditions. Thus, by using a slight excess
of the imine in THF at 100 °C, the conversion was good,
but a mixture of the corresponding compounds 5 and 6 was
obtained (Table 1, entry 1). The addition of sodium iodide
under aqueous conditions did not improve either the con-
version or the selectivity (Table 1, entry 2). The use of a
mixture of DMF/Et2O as solvent gave good conversion but
low selectivity (Table 1, entry 3). Better conversion but
again low selectivity was obtained by using sonication with
or without THF (Table 1, entries 4 and 5, respectively). We
then studied the same reaction but with the bromide 4b: In
this case we found that sonication in THF gave quantitative
conversion and selectivity, as well as high diastereoselectiv-
Entry 4 (amount, Reaction conditions
Conv.
[%][a]
Products
equiv.)
5/6 [%][b]
ity (Table 1, entry 6 and footnote [d]). Without sonication,
and even under forcing conditions, the reaction did not pro-
ceed (Table 1, entry 7). Finally, and just for comparison, we
carried out two experiments with bromide 4b in which in-
dium was replaced by zinc with or without sonication; low
or complete conversion was obtained, but with low dia-
stereomeric excess in the second case (Table 1, entries 8 and
9, and footnote [e]).
1
2
4a (1.2)
4a (6)
In (1.1 equiv.), THF,
100 °C, 20 h
82
48:34
In (6 equiv.), NaI
(4 equiv.), THF/H2O,
23 °C, 20 h
49
23:26
3
4
4a (2.5)
4a (3.3)
In (3.5 equiv.), DMF- 97 (68)[c] 49:48
Et2O (1:1), 60 °C, 20 h
In (3.3 equiv.), THF,
))), 4.5 h
100
50:50
Having obtained the best conditions (Table 1, entry 6),
we carried out the reactions of aldimines 3a–i with the sil-
ylated compound 4b, obtaining in general good diastereo-
selectivities and isolated yields. Purification by column
chromatography afforded the major diastereomer in pure
form, which in all cases present the stereochemistry shown
in Table 2. Only for compounds 5a and 5h were small
amounts of the corresponding allenes detected by 1H NMR
spectroscopy (Table 2, entries 1 and 8, respectively). The use
of the enantiomer (S)-3h led to the formation of compound
5h with the expected reversed configuration at both stereo-
centers (Table 2, entry 8). Finally, it is worthy noting that
compound (R)-3f containing an electron-deficient aromatic
ring was not reactive at all in the same process under similar
reaction conditions (Table 2, entry 6).
5
6
4a (3.3)
4b (3.3)
In (3.3 equiv.), ))), 6 h 100
69:31
100
In (3.3 equiv.), THF,
))), 7 h
In (3.3 equiv.), THF,
60 °C, 7 h
100
(80)[c,d]/–
–
7
8
9
4b (3.3)
4b (3.3)
4b (3.3)
Ͻ5
Zn (3.3 equiv.), THF, 25
))), 7 h
Zn (3.3 equiv.), THF, 100
90 °C, 7 h
25/–
100[e]/–
[a] Based on the consumption of the starting material 3. [b] Based
on the 1H NMR spectra of the crude products. [c] Isolated yield
1
after column chromatography. [d] dr = 88:12 by H NMR analysis
of the reaction crude. [e] dr = 53:47 by 1H NMR analysis of the
reaction crude.
ing bromide 4b with indium metal initially gives the corre-
In the second part of this study we considered the prop- sponding propargylic intermediate I, which, by metallo-
argylation of ketimines 3j–o under the same optimized reac- tropic rearrangement, is in equilibrium with the allenylind-
tion conditions shown in Tables 1 and 2. Ketimines 3k–m ium II. Owing to the well-known stabilization effect of the
were obtained as E/Z mixtures of diastereomers (see silicon atom on α-carbanions (d orbital interaction[12]), the
Scheme 2) and used in the reactions without further purifi- most stable species is II, and considering that in allylindium
cation. This process is of additional synthetic interest be- intermediates γ addition is preferred over α addition,[13]
cause the newly created stereocenter is quaternary, these transition state IV is preferred to III, so the final product 5
types of chiral compounds not being so readily accessible is mainly or exclusively obtained (Scheme 3).
by conventional methodologies.[11] As expected, the dia-
Concerning the diastereoselectivity of the new stereocen-
stereoselectivity was modest for the cyclohexenone deriva- ter, the structure of compound 5 was assigned by compar-
1
tive 5m, and surprisingly poor for the acetophenone deriva- ing the H NMR spectra of compounds (R)-5b and (R)-5e
tive 5n (Table 3, entries 4 and 5, respectively). In the other with those reported in the literature by Chemla and Ferrei-
cases, including the butanone derivative 5k, the diastereo- ra[8b] with allenylzinc intermediates: We found that in our
selectivity was excellent (Table 3, entries 2, 3, and 6). Fi- case the configuration of the new stereocenter is opposite to
nally, as was commented upon for compound 5h, the oppo- that previously described. Thus, we concluded that nucleo-
site configuration at the new stereocenter was also observed philic attack takes place in our case at the Si face for
in the case of imine (S)-3n (Table 3, entry 5).
imines with the RS configuration and at the Re face for
From a mechanistic point of view, the formation of the imines with the SS configuration. This conclusion shows
propargylic product 5 is determined by the nature of the that both methodologies (indium- or zinc-promoted prop-
organoindium intermediate. Thus, the reaction of the start- argylation) are complementary. In the case of the reaction
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Indium-Promoted Propargylation of Chiral Sulfinylimines
Table 2. Propargylation of aldimines 3.
1
[a] Major diastereomer. [b] Diastereomeric ratio determined by H NMR analysis of the reaction crude. [c] Isolated yield after column
1
chromatography. [d] A 93:7 ratio of compound 5a and the corresponding allene 6a was revealed by H NMR analysis of the reaction
1
crude. [e] A 82:18 ratio of compound 5h and the corresponding allene 6h was revealed by H NMR analysis of the reaction crude.
with zinc, transition state V has been proposed in which the atom to both the nitrogen and oxygen atoms of the imine,
zinc atom coordinates to only the nitrogen atom of the im- so fixing a conformation in which nucleophilic attack takes
ine to form a six-membered ring in which the imine adopts place at the less hindered Si face for imines with the RS
the most stable s-cis conformation.[8a] In our case, we pro- configuration (Figure 1). However, and taking into account
pose transition state VI, also involving a six-membered the diastereoselectivity found for ethyl methyl ketone and
ring, but with the simultaneous coordination of the indium acetophenone derivatives 3k and 3n (Table 3, entries 2 and
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FULL PAPER
Table 3. Propargylation of ketimines 3.
1
[a] Major diastereomer. [b] Diastereomeric ratio determined by H NMR analysis of the reaction crude. [c] Isolated yield after column
chromatography. [d] See Scheme 2.
5, respectively), in addition to steric interactions, a compet- of the starting ketimines 3k–m (Scheme 2). It seems that at
ing mechanism involving electronic effects could not be the reaction temperature, one of the imine isomers preferen-
ruled out. It is worth noting that the diastereoselectivities tially undergoes propargylation concomitant with rapid
obtained for homopropargylic amine derivatives 5k–m imine isomer equilibration, leading to a dynamic kinetic
(Table 3, entries 2–4) greatly exceed the Z/E isomeric ratio resolution. Similar enhanced diastereoselectivities com-
pared with the E/Z isomer ratios of the starting substrate
have previously been observed for nucleophilic addition to
N-tert-butanesulfinyl ketimines.[6l,10]
In the final part of this work we studied the orthogonal
deprotection of the two protecting groups, the silicon and
sulfinyl moieties. Thus, treatment of compound 5c with po-
tassium carbonate in THF/methanol gave exclusive desil-
ylation to afford compound 7 in 83% yield. When the same
starting material was treated successively with hydrogen
Figure 1. Transition states V and VI.
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Indium-Promoted Propargylation of Chiral Sulfinylimines
Scheme 3. Proposed mechanism for the propargylation of imines 4.
Scheme 4. Selective deprotection of compound 5c.
sured (film) with a Nicolet Impact 510 P-FT spectrometer. Melting
points were recorded with an OptiMelt (Stanford Research Sys-
tems) apparatus using open-glass capillaries. Gas chromatographic
analyses (GLC) were determined with a Hewlett–Packard HP-5890
instrument equipped with a flame ionization detector (FID) and a
12 m capillary column (0.2 mm diam., 0.33 μm film thickness)
using nitrogen (2 mL/min) as carrier gas, Tinjector = 275 °C, Tdetector
= 300 °C, Tcolumn = 60 °C (3 min) and 60–270 °C (15 °C/min), P =
40 kPa as routine working conditions. 1H NMR spectra were re-
corded with a Bruker AC-300 spectrometer using CDCl3 as the
solvent and TMS as internal standard. The data is reported as [s
= singlet, d = doublet, t = triplet, q = quartet, m = multiplet or
unresolved, br. s = broad signal, coupling constant(s) in Hz, inte-
gration]. 13C NMR spectra were recorded with 1H-decoupling with
a Bruker 75 MHz spectrometer and DEPT-135 experiments were
performed to assign CH, CH2, and CH3. Optical rotations were
measured with a Perkin–Elmer 341 polarimeter (concentration is
given in g/100 mL, solvent). HRMS (EI) spectra were recorded
with a Finnigan MAT 95S spectrometer.
chloride and sodium hydroxide, desulfinylation occurred to
give amine 8 as the only reaction product (Scheme 4).
Conclusions
From the results obtained in this study we can conclude
that the indium-promoted propargylation of chiral ald-
imines and ketimines 3 with the silylated bromoalkyne 4b
is a versatile and useful methodology for preparing fully
protected chiral homopropargylic amines in an enantiopure
form. Selective deprotection of these compounds by con-
ventional procedures allowed the preparation of the corre-
sponding monoprotected compounds.
Experimental Section
General: All reactions requiring anhydrous conditions were per-
formed in oven-dried glassware under argon. Unless otherwise indi-
cated, all commercially available chemicals were purchased from
Acros or Aldrich and used without purification. N-tert-Butanesulf-
inamides (SS and RS) were a gift of Medalchemy (Ͼ99% ee by
chiral HPLC on a Chiracel AS column, 90:10 n-hexane/iPrOH,
1.2 mL/min, λ = 222 nm). TLC was performed on Merck silica gel
60 F254 using aluminium plates and visualized with phosphomolyb-
dic acid (PMA) stain. Chromatographic purification was per-
formed by flash chromatography using Merck silica gel 60 (0.040–
0.063 mm) and n-hexane/EtOAc as eluent. IR spectra were mea-
General Procedure for the Synthesis of N-tert-Butanesulfinylimines
3: Titanium tetraethoxide (2.2281 g, 2.095 mL, 10 mmol) was
slowly added to a solution of tert-butanesulfinamide (1; 0.605 g,
5 mmol) and the corresponding carbonyl compound 2 (5.5 mmol)
in dry THF (20 mL) under argon at 23 °C. The reaction mixture
was stirred for 12 h at the same temperature for aldehydes 2a–i
and at 66 °C for 5 h for ketones 2j–o. The resulting mixture was
hydrolyzed with brine (30 mL), extracted with ethyl acetate (3ϫ
15 mL), dried with anhydrous MgSO4, and the solvent evaporated
(15 Torr). The residue was purified by column chromatography (sil-
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M. J. García-Muñoz, F. Zacconi, F. Foubelo, M. Yus
FULL PAPER
ica gel, hexane/ethyl acetate) to yield pure compounds 3. Yields are
given in Scheme 2. Imines 3a,[14] 3b,[15] 3c,[16] 3d,[15] 3e,[15] 3h,[17]
3i,[18] 3j,[19] 3k,[20] 3m,[21] 3n,[15] and 3o[22] were characterized by
comparison of their physical and spectroscopic data with those re-
ported in the literature. The corresponding physical, spectroscopic,
and analytical data for imines 3f, 3g,and 3l follow.
(16), 74 (10), 73 (100), 70 (24), 69 (13). HRMS (EI): calcd. for
C15H31NOSSi [M – C4H8]+ 301.1896; found 301.1940.
(3S,RS)-N-(tert-Butylsulfinyl)-2-methyl-6-(trimethylsilyl)hex-5-yn-3-
amine (5b): White solid; m.p. 40–43 °C (hexane/CH2Cl2). [α]2D0
=
–8.3 (c = 1.01, CH2Cl2); Rf = 0.60 (hexane/EtOAc, 1:1). IR (KBr):
ν = 3449, 3263, 3123, 2959, 2929, 2898, 2870, 2174, 1473, 1466,
˜
(R)-N-(tert-Butylsulfinyl)-N-(p-nitrobenzylidene)amine
White solid; m.p. 112–113 °C (hexane/CH2Cl2). [α]2D3 = –47 (c =
1.0, CH Cl ); R = 0.34 (hexane/EtOAc, 3:1). IR (KBr): ν = 3113,
[(R)-3f]:
1429, 1366, 1248, 1008, 838, 758, 698, 646 cm–1 1H NMR
.
(300 MHz, CDCl3): δ = 3.61 (d, J = 8.0 Hz, 1 H), 3.17–3.06 (m, 1
H), 2.65 (dd, J = 17.0, 5.8 Hz, 1 H), 2.56 (dd, J = 17.0, 5.1 Hz, 1
˜
2
2
f
3025, 2948, 2914, 2360, 2341, 1584, 1529, 1343, 1087 cm–1. 1H H), 2.06–1.94 (m, 1 H), 1.24 (s, 9 H), 0.94 (d, J = 6.8 Hz, 3 H),
NMR (300 MHz, CDCl3): δ = 8.71 (s, 1 H), 8.35 (dt, J = 8.8, 0.92 (d, J = 6.8 Hz, 3 H), 0.15 (s, 9 H) ppm. 13C NMR (75 MHz,
2.1 Hz, 2 H), 8.08 (dt, J = 8.8, 2.1 Hz, 2 H), 1.32 (s, 9 H) ppm. 13
NMR (75 MHz, CDCl3): δ = 160.4 (CH), 149.4, 138.5, 129.7, 123.8
C
CDCl3): δ = 102.9, 88.2 (C), 59.8 (CH), 56.1 (C), 31.2 (CH), 25.0
(CH2), 22.8, 18.8, 18.4, 0.03 (CH3) ppm. MS (EI): m/z (%) = 231
(ArC), 58.1 (C), 22.3 (CH3) ppm. MS (EI): m/z (%) = 148 (100) (7) [M – C4H8]+, 188 (10), 184 (16), 183 (100), 140 (33), 120 (23),
[M – tBuSOH]+, 118 (16), 102 (100), 90 (27), 76 (22), 75 (40), 51 119 (65), 102 (17), 83 (10), 75 (23), 73 (85), 72 (19), 59 (11), 57
(25). HRMS (EI): calcd. for C7H4N2O2 [M – tBuSOH]+ 148.0273; (67), 56 (33), 55 (10). HRMS (EI): calcd. for C10H21NOSSi [M –
found 148.0280.
C4H8]+ 231.1113; found 231.1124.
(R)-N-(tert-Butylsulfinyl)-N-(p-hydroxybenzylidene)amine [(R)-3g]:
White solid; decomposition Ͼ208 °C. [α]2D3 = +15 (c = 1.36,
(3R,RS)-N-(tert-Butylsulfinyl)-1-phenyl-6-(trimethylsilyl)hex-5-yn-3-
amine (5c): White solid; m.p. 51–52 °C (hexane/CH2Cl2). [α]2D0
=
CH OH); R = 0.14 (hexane/EtOAc, 3:1). IR (KBr): ν = 3230–3126,
–16.1 (c = 1.01, CH2Cl2); Rf = 0.50 (hexane/EtOAc, 1:1). IR (KBr):
˜
˜
3
f
2981, 2360, 2341, 1589, 1576, 1514, 1437, 1280, 1160, 1035 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.49 (s, 1 H), 7.77 (dt, J = 8.7,
2.4 Hz, 2 H), 6.94 (dt, J = 8.7, 2.4 Hz, 2 H), 6.14 (br. s, 1 H), 1.27
(s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 161.8 (CH), 159.7,
131.6, 126.8, 115.9 (ArC), 57.7 (C), 22.5 (CH3) ppm. MS (EI): m/z
(%) = 119 (100) [M – tBuSOH]+, 91 (17), 64 (22). HRMS (EI):
calcd. for C7H5NO [M – tBuSOH]+ 119.0371; found 119.0382.
ν = 3271, 2959, 2928, 2175, 1250, 1032, 838, 759, 697 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 7.33–7.14 (m, 5 H), 3.65 (d, J =
8.1 Hz, 1 H), 3.45–3.31 (m, 1 H), 2.79–2.62 (m, 2 H), 2.71 (dd, J
= 16.9, 5.9 Hz, 1 H), 2.53 (dd, J = 16.8, 4.6 Hz, 1 H), 2.01–1.87
(m, 2 H), 1.26 (s, 9 H), 0.16 (s, 9 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 141.4 (C), 128.5, 128.3, 126.0 (CH), 102.4, 88.4, 56.0
(C), 53.9 (CH), 36.6, 31.8, 28.0 (CH2), 22.7, 0.04 (CH3) ppm. MS
(EI): m/z (%) = 293 (5) [M – 56]+, 246 (13), 245 (58), 140 (13), 91
(99), 75 (16), 73 (100).
(RS,E)-N-(tert-Butylsulfinyl)heptan-2-imine [(R)-3l]: Yellow oil.
[α]2D0 = +144 (c = 1.07, CH2Cl2); Rf = 0.59 (hexane/EtOAc, 1:1).
IR (film): ν = 2955, 2928, 2862, 1622, 1457, 1362, 1187, 1074,
(2R,RS)-N-(tert-Butylsulfinyl)-1-phenyl-5-(trimethylsilyl)pent-4-yn-
˜
669 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.35–2.44 (m, 2 H), 2-amine (5d): Yellow oil. [α]2D0 = –21.1 (c = 1.06, CH2Cl2); Rf = 0.53
2.31 (s, 3 H), 1.53–1.69 (m, 2 H), 1.26–1.38 (m, 4 H), 1.24 (s, 9 H), (hexane/EtOAc, 1:1). IR (film): ν = 3444, 3118, 3020, 2959, 2177,
˜
0.89 (t, J = 6.9 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
1473, 1456, 1426, 1364, 1249, 1081, 1052, 1026, 1003, 839, 743,
185.6 (C), 56.2 (C), 43.4, 31.3, 25.2 (CH2), 23.0 (CH3), 22.4 (CH2), 698 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.36–7.14 (m, 5 H),
22.1, 13.9 (CH3) ppm. MS (EI): m/z (%) = 161 (58) [M – C4H8]+, 3.70–3.57 (m, 2 H), 2.99 (dd, J = 13.6, 6.1 Hz, 1 H), 2.86 (dd, J =
112 (15), 105 (56), 97 (26), 96 (20), 89 (43), 82 (10), 70 (17), 64
13.6, 6.7 Hz, 1 H), 2.58 (dd, J = 16.9, 5.7 Hz, 1 H), 2.48 (dd, J =
(60), 58 (11), 57 (100), 56 (71), 55 (54), 54 (12), 53 (15), 50 (11). 16.9, 4.6 Hz, 1 H), 1.15 (s, 9 H), 0.19 (s, 9 H) ppm. 13C NMR
HRMS (EI): calcd. for C7H15NOS [M – C4H8]+ 161.0874; found
161.0886.
(75 MHz, CDCl3): δ = 137.6 (C), 129.5, 128.4, 126.6 (CH), 102.6,
88.7, 56.0 (C), 55.9 (CH), 40.9, 26.9 (CH2), 22.5, 0.04 (CH3) ppm.
MS (EI): m/z (%) = 279 (1) [M – C4H8]+, 231 (31), 188 (19), 167
(14), 140 (19), 104 (37), 98 (27), 91 (52), 75 (14), 73 (100), 71 (13).
HRMS (EI): calcd. for C14H21NOSiS [M – C4H8]+ 279.1113; found
279.1161.
General Procedure for the Propargylation of N-tert-Butanesulfin-
ylimines 3. Synthesis of Homopropargylamine Derivatives 5: A mix-
ture of N-tert-butanesulfinyl imine 3 (0.5 mmol), 3-bromo-1-tri-
methylsilyl-1-propyne (4b; 313 mg, 0.275 mL, 1.65 mmol), and in-
dium (189 mg, 1.65 mmol) was sonicated in dry THF (2 mL) for
7 h. Then the resulting mixture was hydrolyzed with H2O (5 mL)
and extracted with EtOAc (3ϫ 15 mL). The organic phase was
washed with brine (3ϫ 10 mL), dried with anhydrous MgSO4, and
the solvent evaporated (15 Torr). The residue was purified by col-
umn chromatography (silica gel, hexane/EtOAc) to yield products
5. The yields are given in Table 2 and Table 3, the physical and
spectroscopic data follow.
(1S,RS)-N-(tert-Butylsulfinyl)-1-phenyl-4-(trimethylsilyl)but-3-yn-
1-amine (5e): White solid; m.p. 80–82 °C (hexane/CH2Cl2). [α]2D0
=
–133.1 (c = 1.00, CH2Cl2); Rf = 0.52 (hexane/EtOAc, 1:1). IR
(KBr): ν = 3231, 3209, 2955, 2932, 2899, 2178, 1249, 1046, 1024,
˜
837, 757, 697 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.40–7.28
(m, 5 H), 4.56 (m, 1 H), 4.15 (br. s, 1 H), 2.74 (dd, J = 16.9, 5.1 Hz,
1 H), 2.64 (dd, J = 16.8, 8.3 Hz, 1 H), 1.24 (s, 9 H), 0.16 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 140.4 (C), 128.5, 128.0,
127.5 (CH), 102.2, 89.1 (C), 56.5 (CH), 55.7 (C), 30.3 (CH2), 22.6,
0.1 (CH3) ppm. MS (EI): m/z (%) = 217 (22) [M – C4H8]+, 202 (14),
153 (74), 144 (10), 136 (20), 129 (20), 128 (20), 77 (14), 75 (16), 74
(10), 73 (100).
(4R,RS)-N-(tert-Butylsulfinyl)-1-(trimethylsilyl)dodec-1-yn-4-amine
(5a): Colorless oil. [α]2D0 = –11.4 (c = 1.16, CH2Cl2); Rf = 0.65 (hex-
ane/EtOAc, 1:1). IR (film): ν = 3203, 2956, 2924, 2855, 2173, 1466,
˜
1363, 1249, 1052, 840, 759, 648 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 3.58 (d, J = 7.7 Hz, 1 H), 3.38–3.27 (m, 1 H), 2.65 (dd, J =
16.8, 5.7 Hz, 1 H), 2.48 (dd, J = 16.8, 5.0 Hz, 1 H), 1.65–1.50 (m,
(1S,RS)-N-(tert-Butylsulfinyl)-1-(4-hydroxyphenyl)-4-(trimethyl-
silyl)but-3-yn-1-amine (5g): Colorless oil. [α]2D0 = –120.1 (c = 1.03,
2 H), 1.39–1.24 (m, 12 H), 1.23 (s, 9 H), 0.88 (t, J = 6.8 Hz, 3 H), CH Cl ); R = 0.31 (hexane/EtOAc, 1:1). IR (film): ν = 3206, 3114,
˜
2
2
f
0.15 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 102.8, 88.2, 2958, 2899, 2179, 1616, 1600, 1517, 1458, 1248, 1170, 1021, 1006,
55.9 (C), 54.4 (CH), 34.7, 31.8, 29.4, 29.3, 29.2, 27.9, 25.6 (CH2),
22.7, 14.1, 0.04 (CH3) ppm. MS (EI): m/z (%) = 301 (7) [M –
C4H8]+, 253 (29), 189 (26), 142 (12), 140 (25), 84 (13), 77 (11), 75
834, 763, 642 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.43 (s, 1 H),
7.14 (d, J = 8.5 Hz, 2 H), 6.79 (d, J = 8.5 Hz, 2 H), 4.53–4.41 (m,
1 H), 4.29 (d, J = 1.7 Hz, 1 H), 2.68–2.59 (m, 2 H), 1.25 (s, 9 H),
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1287–1295

Indium-Promoted Propargylation of Chiral Sulfinylimines
0.16 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 156.5, 130.6 (17), 74 (16), 73 (100), 71 (27), 57 (29). HRMS (EI): calcd. for
(C), 128.8, 115.7 (CH), 102.5, 88.9 (C), 56.1 (CH), 55.8 (C), 30.1 C10H21NOSSi [M – C4H8]+ 231.1113; found 231.1121.
(CH2), 22.6, 0.07 (CH3) ppm. MS (EI): m/z (%) = 281 (8) [M –
(4R,RS)-N-(tert-Butylsulfinyl)-4-methyl-1-(trimethylsilyl)non-1-yn-
C4H8]+, 263 (10), 233 (11), 207 (16), 169 (52), 145 (16), 127 (13),
4-amine (5l): Colorless oil. [α]2D0 = –42.5 (c = 1.02, CH2Cl2); Rf =
122 (11), 121 (56), 120 (31), 75 (14), 74 (10), 73 (100). HRMS (EI):
0.55 (hexane/EtOAc, 1:1). IR (film): ν = 3183, 2956, 2933, 2863,
˜
calcd. for C13H17NOSiS [M – C4H8 – H2O]+ 263.0795; found
263.0806.
2173, 1458, 1376, 1362, 1249, 1039, 934, 839, 759, 697, 654 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.55 (s, 1 H), 2.45 (d, J = 1.3 Hz,
2 H), 1.63 (t, J = 7.6 Hz, 2 H), 1.36 (s, 3 H), 1.33–1.24 (m, 6 H),
1.22 (s, 9 H), 0.89 (t, J = 6.8 Hz, 3 H), 0.15 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 103.2, 88.2, 57.0, 55.8 (C), 40.4, 33.6, 32.1
(CH2), 25.8 (CH3), 23.1 (CH2), 22.7 (CH3), 22.5 (CH2), 14.0, 0.02
(CH3) ppm. MS (EI): m/z (%) = 273 (5) [M – C4H8]+, 225 (26), 161
(58), 154 (12), 137 (11), 112 (15), 105 (19), 97 (16), 75 (14), 74 (15),
73 (100), 57 (12), 55 (13). HRMS (EI): calcd. for C13H27NOSSi
[M – C4H8]+ 273.1583; found 273.1576.
(2R,SS)-N-(tert-Butylsulfinyl)-1-(2-bromophenyl)-5-(trimethylsilyl)-
pent-4-yn-2-amine (5h): White solid; m.p. 104–105 °C (hexane/
CH2Cl2). [α]2D0 = –14.6 (c = 1.00, CH2Cl2); Rf = 0.48 (hexane/
EtOAc, 1:1). IR (KBr): ν = 3214, 2980, 2959, 2924, 2848, 2179,
˜
1472, 1438, 1419, 1249, 1169, 1090, 1032, 1017, 837, 752, 659,
1
645 cm–1. H NMR (300 MHz, CDCl3): δ = 7.53 (d, J = 7.7 Hz, 1
H), 7.25–7.22 (m, 2 H), 7.12–6.93 (m, 1 H), 3.80–3.64 (m, 2 H),
3.14 (dd, J = 13.7, 7.1 Hz, 1 H), 3.01 (dd, J = 13.7, 5.9 Hz, 1 H),
2.73 (dd, J = 16.9, 5.5 Hz, 1 H), 2.58 (dd, J = 16.9, 3.8 Hz, 1 H),
1.09 (s, 9 H), 0.19 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
137.8 (C), 132.8, 131.7, 128.3, 127.4 (CH), 125.2, 102.3, 89.0, 56.0
(C), 55.4 (CH), 41.2, 27.8 (CH2), 22.4, 0.07 (CH3) ppm. MS (EI):
m/z (%) = 311 (15) [M – C4H8SO]+, 309 (16), 207 (11), 188 (16),
172 (12), 171 (12), 169 (12), 140 (19), 98 (22), 91 (13), 90 (11), 75
(14), 73 (100), 71 (11). HRMS (EI): calcd. for C14H20NSi79Br [M –
C4H8SO]+ 309.0548; found 309.0522.
(1S,SS)-N-(tert-Butylsulfinyl)-1-[3-(trimethylsilyl)prop-2-yn-1-yl]-
cyclohex-2-en-1-amine (5m): Yellow oil. [α]2D0 = +69.8 (c = 1.00,
CH Cl ); R = 0.43 (hexane/EtOAc, 1:1). IR (film): ν = 3203, 3022,
˜
2
2
f
2955, 2908, 2868, 2834, 2173, 1456, 1418, 1376, 1362, 1249, 1053,
839, 759, 731, 696, 646 cm–1. 1H NMR (300 MHz, CDCl3): δ =
5.96 (dt, J = 10.0, 3.6 Hz, 1 H), 5.78 (dd, J = 10.1, 0.8 Hz, 1 H),
3.82 (s, 1 H), 2.63 (d, J = 16.7 Hz, 1 H), 2.48 (d, J = 16.7 Hz, 1
H), 2.09–1.92 (m, 3 H), 1.78–1.56 (m, 3 H), 1.23 (s, 9 H), 0.15 (s,
9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 131.8, 129.9 (CH),
102.7, 88.3, 55.8, 55.3 (C), 35.5, 34.2, 25.1 (CH2), 22.7 (CH3), 18.4
(CH2), 0.0 (CH3) ppm. MS (EI): m/z (%) = 255 (2) [M – C4H8]+,
207 (17), 206 (13), 191 (25), 143 (94), 134 (19), 95 (30), 94 (17), 91
(15), 79 (17), 73 (100), 67 (25). HRMS (EI): calcd. for
C12H21NOSSi [M – C4H8]+ 255.1113; found 255.1123.
(1S,RS)-N-(tert-Butylsulfinyl)-1-(2-bromophenyl)-4-(trimethylsilyl)-
but-3-yn-1-amine (5i): Colorless oil. [α]2D0 = –111.7 (c = 1.06,
CH Cl ); R = 0.49 (hexane/EtOAc, 1:1). IR (film): ν = 3208, 2958,
˜
2
2
f
2897, 2868, 2179, 1471, 1438, 1362, 1249, 1059, 1023, 840, 755,
643 cm–1 1H NMR (300 MHz, CDCl3): δ = 7.54 (dd, J = 8.0,
.
1.1 Hz, 1 H), 7.42 (dd, J = 7.8, 1.6 Hz, 1 H), 7.33–7.27 (m, 1 H),
7.15 (td, J = 7.7, 1.7 Hz, 1 H), 5.04 (dt, J = 6.9, 4.8 Hz, 1 H), 4.23
(d, J = 4.2 Hz, 1 H), 2.90 (dd, J = 16.9, 5.1 Hz, 1 H), 2.66 (dd, J
= 16.9, 6.9 Hz, 1 H), 1.25 (s, 9 H), 0.14 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 139.6 (C), 133.0, 129.2, 129.2, 127.2 (CH),
123.3, 101.4, 89.6, 56.0 (C), 55.3 (CH), 28.6 (CH2), 22.6, 0.10
(CH3) ppm. MS (EI): m/z (%) = 297 (15) [M – C4H8SO]+, 295 (15),
233 (18), 231 (18), 184 (11), 152 (52), 128 (27), 77 (10), 75 (17), 74
(10), 73 (100). HRMS (EI): calcd. for C13H18NSi79Br [M –
C4H8SO]+ 295.0392; found 295.0392.
(2S,RS)-N-(tert-Butylsulfinyl)-2-phenyl-5-(trimethylsilyl)pent-4-yn-
2-amine (5n): Yellow oil. [α]2D0 = –64.7 (c = 1.91, CH2Cl2); Rf = 0.54
(hexane/EtOAc, 1:1). IR (film): ν = 3203, 3035, 2957, 2926, 2868,
˜
2173, 1473, 1447, 1249, 1054, 839, 760, 697 cm–1 1H NMR
.
(300 MHz, CDCl3): δ = 7.54–7.42 (m, 2 H), 7.39–7.23 (m, 3 H),
4.16 (s, 1 H), 2.88 (d, J = 16.7 Hz, 1 H), 2.65 (d, J = 16.7 Hz, 1
H), 1.88 (s, 3 H), 1.24 (s, 9 H), 0.12 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 144.1 (C), 128.2, 127.4, 126.6 (CH), 102.7,
89.2, 59.6, 56.3 (C), 37.0 (CH2), 27.1, 22.7, 0.09 (CH3) ppm. MS
(EI): m/z (%) = 279 (6) [M – C4H8]+, 231 (13), 230 (15), 216 (12),
167 (82), 158 (19), 157 (12), 150 (23), 143 (13), 128 (28), 119 (36),
104 (40), 77 (17), 75 (14), 74 (12), 73 (100). HRMS (EI): calcd. for
C14H21NOSSi [M – C4H8]+ 279.1113; found 279.1127.
(RS)-N-(tert-Butylsulfinyl)-2-methyl-5-(trimethylsilyl)pent-4-yn-2-
amine (5j): White solid; m.p. 44–47 °C (hexane/CH2Cl2). [α]2D0
=
–59.1 (c = 1.06, CH2Cl2); Rf = 0.23 (hexane/EtOAc, 1:1). IR (KBr):
ν = 3262, 2976, 2958, 2931, 2173, 1458, 1407, 1361, 1249, 1167,
˜
(1S,RS)-N-(tert-Butylsulfinyl)-1-[3-(trimethylsilyl)prop-2-yn-1-yl]-
1,2,3,4-tetrahydronaphthalen-1-amine (5o): Orange oil. [α]2D0 = –5.27
1047, 933, 837, 758 cm–1. 1H NMR (300 MHz, CDCl3): δ = 3.52
(s, 1 H), 2.42 (s, 2 H), 1.41 (s, 3 H), 1.35 (s, 3 H), 1.21 (s, 9 H),
0.15 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 103.1, 88.1,
55.6, 54.6 (C), 35.6 (CH2), 28.5, 28.1, 22.6, 0.03 (CH3) ppm. MS
(EI): m/z (%) = 217 (7) [M – C4H8]+, 170 (11), 169 (72), 162 (16),
154 (35), 153 (13), 137 (20), 106 (39), 105 (86), 97 (18), 96 (12), 88
(22), 83 (12), 75 (20), 74 (12), 73 (100), 58 (15), 57 (70). HRMS
(EI): calcd. for C9H19NOSSi [M – C4H8]+ 217.0957; found
217.0950.
(c = 0.64, CH Cl ); R = 0.31 (hexane/EtOAc, 1:1). IR (film): ν =
˜
2
2
f
3208, 2954, 2868, 2174, 1451, 1362, 1249, 1050, 839, 758, 731,
654 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.64–7.59 (m, 1 H),
7.20 (dt, J = 4.8, 3.6 Hz, 2 H), 7.12–7.07 (m, 1 H), 3.93 (s, 1 H),
2.99 (d, J = 16.9 Hz, 1 H), 2.90–2.68 (m, 2 H), 2.78 (d, J = 16.9 Hz,
1 H), 2.30–2.13 (m, 2 H), 2.02–1.91 (m, 1 H), 1.90–1.78 (m, 1 H),
1.23 (s, 9 H), 0.10 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
138.2, 137.6 (C), 129.1, 128.2, 127.7, 125.9 (CH), 103.2, 88.7, 58.4,
56.3 (C), 37.2, 34.4, 29.7 (CH2), 22.8 (CH3), 19.3 (CH2), 0.1
(CH3) ppm. MS (EI): m/z (%) = 305 (2) [M – C4H8]+, 257 (13), 256
(12), 241 (14), 193 (72), 184 (10), 167 (12), 146 (12), 145 (35), 144
(19), 141 (12), 130 (11), 117 (38), 116 (12), 115 (12), 75 (14), 74
(12), 73 (100). HRMS (EI): calcd. for C16H23NOSSi [M – C4H8]+
305.1270; found 305.1302.
(3R,RS)-N-(tert-Butylsulfinyl)-3-methyl-6-(trimethylsilyl)hex-5-yn-
3-amine (5k): Yellow oil. [α]2D0 = –46.2 (c = 1.00, CH2Cl2); Rf = 0.43
(hexane/EtOAc, 1:1). IR (film): ν = 3218, 2961, 2901, 2881, 2173,
˜
1457, 1406, 1379, 1362, 1249, 1161, 1053, 945, 923, 839, 759,
1
649 cm–1. H NMR (300 MHz, CDCl3): δ = 3.56 (s, 1 H), 2.46 (s,
2 H), 1.69 (q, J = 7.4 Hz, 2 H), 1.35 (s, 3 H), 1.22 (s, 9 H), 0.90 (t,
J = 7.4 Hz, 3 H), 0.15 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
Desilylation of Compound 5c. Synthesis of (3R,RS)-N-(tert-Butyl-
δ = 103.2, 88.2, 57.1, 55.8 (C), 33.3, 33.1 (CH2), 25.2, 22.7, 8.0, 0.0 sulfinyl)-1-phenylhex-5-yn-3-amine (7): A suspension of K2CO3
(CH3) ppm. MS (EI): m/z (%) = 231 (6) [M – C4H8]+, 183 (55), 176 (5 mg, 0.036 mmol) in methanol (4 mL) was added dropwise to a
(11), 168 (19), 154 (13), 120 (56), 119 (75), 102 (13), 97 (11), 75
solution of compound 5c (175 mg, 0.5 mmol) in THF (4 mL). The
1293
Eur. J. Org. Chem. 2013, 1287–1295
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org

M. J. García-Muñoz, F. Zacconi, F. Foubelo, M. Yus
FULL PAPER
Synlett 2009, 1543–1557; c) S. P. Nolan, Acc. Chem. Res. 2011,
44, 91–100.
reaction mixture was stirred for 12 h at room temperature and then
it was hydrolyzed with a 1 n NH4Cl aqueous solution (8 mL) and
extracted with methyl tert-butyl ether (3ϫ 15 mL). The organic
phase was dried with anhydrous MgSO4 and the solvent evaporated
(15 Torr). The residue was purified by column chromatography (sil-
ica gel, hexane/EtOAc, 2:1) to yield compound 7 as a yellow oil
(139 mg, 0.41 mmol, 83% yield). [α]2D0 = –23.5 (c = 0.83, CH2Cl2);
[5]
[6]
For related papers, see: a) B. Alcaide, P. Almendros, R. Rodrig-
uez-Acebes, J. Org. Chem. 2005, 70, 3198–3204; b) M. Banerjee,
S. Roy, Org. Lett. 2004, 6, 2137–2140; c) Y. Masuyama, A.
Watabe, Y. Kurusu, Synlett 2003, 17113–17115; d) B. Alcaide,
P. Almendros, R. Rodriguez-Acebes, J. Org. Chem. 2001, 66,
5208–5216; for reviews, see: e) S. E. Denmark, J. Fu, Chem.
Rev. 2003, 103, 2763–2793; f) see ref[3]
.
R = 0.20 (hexane/EtOAc, 1:1). IR (film): ν = 3219, 3061, 3025,
˜
f
2978, 2948, 2864, 2111, 1602, 1495, 1455, 1363, 1175, 1054,
699 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.33–7.25 (m, 2 H),
7.24–7.14 (m, 3 H), 3.55 (d, J = 8.8 Hz, 1 H), 3.47–3.32 (m, 1 H),
2.82–2.61 (m, 3 H, CH2), 2.56–2.44 (m, 1 H), 2.07 (t, J = 2.6 Hz,
1 H), 2.03–1.88 (m, 2 H), 1.26 (s, 9 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 141.3 (C), 128.5, 128.3, 126.0 (CH), 79.9, 71.7, 56.1
(C), 54.3 (CH), 36.7, 32.0, 26.7 (CH2), 22.6 (CH3) ppm. MS (EI):
m/z (%) = 221 (1) [M – C4H8]+, 157 (11), 132 (53), 117 (51), 116
(28), 101 (16), 98 (16), 92 (10), 91 (100), 77 (16), 68 (32), 67 (28),
65 (19). HRMS (EI): calcd. for C12H15NOS [M – C4H8]+ 221.0874;
found 221.0877.
a) F. Foubelo, M. Yus, Tetrahedron: Asymmetry 2004, 15,
3823–3825; b) J. C. González-Gómez, F. Foubelo, M. Yus, Syn-
lett 2008, 2777–2780; c) M. Medjahdi, J. C. González-Gómez,
F. Foubelo, M. Yus, Heterocycles 2008, 76, 569–581; d) M.
Medjahdi, J. C. González-Gómez, F. Foubelo, M. Yus, J. Org.
Chem. 2009, 74, 7859–7865; e) H. K. Dema, F. Foubelo, M.
Yus, Heterocycles 2010, 80, 125–131; f) J. C. González-Gómez,
M. Medjahdi, F. Foubelo, M. Yus, J. Org. Chem. 2010, 75,
6308–6311; g) H. K. Dema, F. Foubelo, M. Yus, Heterocycles
2011, 82, 1411–1421; h) M. Medjahdi, J. C. González-Gómez,
F. Foubelo, M. Yus, Eur. J. Org. Chem. 2011, 2230–2234; i)
H. K. Dema, F. Foubelo, M. Yus, Jordan J. Chem. 2011, 6,
247–255; j) J. C. González-Gómez, F. Foubelo, M. Yus, Org.
Synth. 2012, 89, 88–97; k) I. Bosque, J. C. González-Gómez, F.
Foubelo, M. Yus, J. Org. Chem. 2012, 77, 780–784; l) J. A. Sirv-
ent, F. Foubelo, M. Yus, Chem. Commun. 2012, 48, 2543–2545.
For the enantioselective propargylation of carbonyl com-
pounds using metals, see, for example, for In: a) T.-P. Loh, M.-
J. Lin, K.-L. Tan, Tetrahedron Lett. 2003, 44, 507–509; b) L. C.
Hirayama, K. K. Dunham, B. Singaram, Tetrahedron Lett.
2006, 47, 5173–5176; c) K.-C. Lee, M.-J. Lin, T.-P. Loh, Chem.
Commun. 2004, 2456–2457; for Mg/B: d) C. Lai, J. A. Soderqu-
ist, Org. Lett. 2005, 7, 799–802; e) E. Hernández, C. H. Burgos,
E. Alicea, J. A. Soderquist, Org. Lett. 2006, 8, 4089–4091; for
Sn/B: f) P. B. D. Ranslow, L. S. Hegedus, C. de los Rios, J. Org.
Chem. 2004, 69, 105–111; g) J. A. Marshall, M. M. Yanik, J.
Org. Chem. 2001, 66, 1373–1379; h) for a review, see: J. A. Mar-
shall, Chem. Rev. 1996, 96, 31–48; for Sn/Ti: i) H. Hanawa, D.
Uraguchi, S. Konishi, T. Hashimoto, K. Maruoka, Chem. Eur.
J. 2003, 9, 4405–4413; for Mn/Cr: j) M. Naodovic, G. Xia, H.
Yamamoto, Org. Lett. 2008, 10, 4053–4055; k) M. Inoue, M.
Nakada, Org. Lett. 2004, 6, 2977–2980; l) S. Liu, J. T. Kim,
C. G. Dong, Y. Kishi, Org. Lett. 2009, 11, 4520–4523; for Mn/
Ti: m) J. Justicia, I. Sancho-Sanz, E. Älvarez-Manzaneda, J. E.
Oltra, J. M. Cuerva, Adv. Synth. Catal. 2009, 351, 2295–2300;
for B/Cu: n) D. R. Fandrick, K. R. Fandrick, J. T. Reeves, Z.
Tan, W. Tang, A. G. Capacci, S. Rodriguez, J. J. Song, H. Lee,
N. K. Yee, C. H. Senanayake, J. Am. Chem. Soc. 2010, 132,
7600–7601; o) U. Scheneider, M. Ueno, S. Kobayashi, J. Am.
Chem. Soc. 2008, 130, 13824–13825; Si p) R. A. Brawn, J. S.
Panek, Org. Lett. 2009, 11, 4362–4365.
Desulfinylation of Compound 5c. Synthesis of (3R)-1-Phenyl-6-(tri-
methylsilyl)hex-5-yn-3-amine (8): A 6 m HCl aqueous solution
(0.100 mL, 0.6 mmol) was added to a solution of compound 5c
(70 mg, 0.2 mmol) in THF (0.2 mL) at 0 °C. The reaction mixture
was stirred at 0 °C until monitoring by TLC indicated that all the
starting material had disappeared (1.5 h). The resulting mixture
was then basified with a 1 m NaOH aqueous solution. The reaction
mixture was extracted with EtOAc (2ϫ 10 mL), the organic layer
was washed first with a 1 m NaOH aqueous solution (5 mL) and
then with H2O (5 mL), dried with anhydrous MgSO4, and finally
the solvent was evaporated (15 Torr) to yield compound 8 as a
yellow oil (35 mg, 0.14 mmol, 71% yield). [α]2D0 = +0.2 (c = 1.12,
[7]
CH Cl ); R = 0.32 (CH Cl /MeOH, 1:1). IR (film): ν = 3030, 2957,
˜
2
2
f
2
2
2853, 2171, 1495, 1454, 1249, 1030, 838, 759, 698, 646 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 7.33–7.24 (m, 2 H), 7.22–7.14 (m, 3
H), 2.98–2.85 (m, 1 H), 2.80–2.61 (m, 2 H), 2.41 (dd, J = 16.8,
4.9 Hz, 1 H), 2.27 (dd, J = 16.8, 7.0 Hz, 1 H), 1.90–1.63 (m, 4 H),
0.16 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.8 (C),
128.4, 128.3, 125.8 (CH), 104.1, 87.0 (C), 49.7 (CH), 38.4, 32.5,
29.3 (CH2), 0.09 (CH3) ppm. MS (EI): m/z (%) = 135 (11) [M –
(CH3)3SiCϵCCH2]+, 134 (100), 117 (21), 91 (57). HRMS (EI):
calcd. for C15H23NSi [M]+ 245.160; found 245.1593.
Supporting Information (see footnote on the first page of this arti-
1
cle): Spectroscopic data for imines 3a–e, 3h–k, and 3m–o, H and
13C NMR spectra of imines 3, homopropargylic amine derivatives
5, and compounds 7 and 8.
[8]
[9]
For the enantioselective propargylation of imines using allenyl-
zinc reagents, see: a) C. Botuha, F. Chemla, F. Ferreira, A.
Pérez-Luna, B. Roy, New J. Chem. 2007, 31, 1552–1567; b) F.
Chemla, F. Ferreira, Synlett 2004, 983–986; c) C. Botuha, F.
Chemla, F. Ferreira, J. Louvel, A. Pérez-Luna, Tetrahedron:
Asymmetry 2010, 21, 1147–1153; d) F. Chemla, F. Ferreira, M.
Andouin, F. Chemla, Chem. Eur. J. 2005, 11, 5269–5278; e) M.
Cyklinsky, C. Botuha, F. Chemla, F. Ferreira, A. Pérez-Luna,
Synlett 2011, 2681–2684.
Acknowledgments
The authors thank the Spanish Ministerio de Ciencia e Innovación
(MICINN) (grant numbers CTQ2007-65218, Consolider Ingenio
2010-CSD-2007-00006 and CTQ2011-24165), the Generalitat Va-
lenciana (PROMETEO/2009/039), the Fondos Europeos para el
Desarrollo Regional (FEDER)) and the University of Alicante for
financial support.
a) F. Ferreira, C. Botuha, F. Chemla, A. Pérz-Luna, Chem.
Soc. Rev. 2009, 38, 1162–1186; b) M. T. Robak, M. A. Herbage,
J. A. Ellman, Chem. Rev. 2010, 110, 3600–3740.
[10]
[11]
D. A. Cogan, J. A. Ellman, J. Am. Chem. Soc. 1999, 121, 268–
[1] M. B. Smith, J. March, March’s Advanced Organic Chemistry,
6th ed., John Wiley & Sons, New York, 2007, chapter 16.
[2] D. J. Ramón, M. Yus, Sci. Synthesis Steroselective Synthesis
2011, 2, 349–400.
[3] For a recent review, see: M. Yus, J. C. González-Gómez, F.
Foubelo, Chem. Rev. 2011, 111, 7774–7854.
269.
For recent reviews, see: a) M. Yus, D. J. Ramón, Recent Res.
Dev. Org. Chem. 2002, 6, 297–378; b) J. Christoffers, A. Baro,
Angew. Chem. 2003, 115, 1726–1728; Angew. Chem. Int. Ed.
2003, 42, 1688–1690; c) D. J. Ramón, M. Yus, Angew. Chem.
2004, 116, 286–289; Angew. Chem. Int. Ed. 2004, 43, 284–287;
d) D. J. Ramón, M. Yus, Curr. Org. Chem. 2004, 8, 149–183;
[4] See, for example: a) S. R. Chemler, Org. Biomol. Chem. 2009,
7, 3009–3019; b) E. B. Averina, T. S. Kuznetsova, N. S. Zefirov,
1294
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 1287–1295

Indium-Promoted Propargylation of Chiral Sulfinylimines
e) D. J. Ramón, M. Yus in Quaternary Stereocenters (Eds.: J.
Christoffers, A. Baro), Wiley-VCH, Weinheim, 2005, pp. 207–
241.
[17] G. S. Lemen, J. P. Wolfe, Org. Lett. 2011, 13, 3218–3221.
[18] L. Cheng, L. Liu, Y. Sui, D. Wang, Y.-J. Chen, Tetrahedron:
Asymmetry 2007, 18, 1833–1843.
[19] J. C. Lanter, H. Chen, X. Zhang, Z. Sui, Org. Lett. 2005, 7,
5905–5907.
[12] D. M. Wetzel, J. I. Brauman, J. Am. Chem. Soc. 1988, 110,
8333–8336.
[13] S. M. Capps, G. C. Lloyd-Jones, M. Murray, T. M. Peakman,
K. E. Walsh, Tetrahedron Lett. 1998, 39, 2853–2856.
[20] F. A. Davis, S. Lee, H. Zhang, D. L. Fanelli, J. Org. Chem.
2000, 65, 8704–8708.
[14] R. Almansa, D. Guijarro, M. Yus, Tetrahedron: Asymmetry [21] J. P. McMahon, J. A. Ellman, Org. Lett. 2005, 7, 5393–5396.
2008, 19, 2484–2491.
[22] J. T. Colyer, N. G. Andersen, J. S. Tedrow, T. S. Soukup, M. M.
Faul, J. Org. Chem. 2006, 71, 6859–6862.
Received: October 23, 2012
[15] G. Liu, D. A. Cogan, T. D. Owens, T. P. Tang, J. A. Ellman, J.
Org. Chem. 1999, 64, 1278–1284.
[16] L. B. Schenkel, J. A. Ellman, Org. Lett. 2004, 6, 3621–3624.
Published Online: January 24, 2013
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