Regioselective mo-catalyzed hydrostannations as key steps in the synthesis of functionalized amino alcohols and heterocycles

Article abstract of DOI:10.1002/ejoc.200700126

Molybdenum catalyzed hydrostannation of suitable protected propargylic amino alcohols provides the corresponding functionalized vinyl stannanes, which are useful synthetic intermediates for the combinatorial synthesis of amino alcohols and heterocycles. W

Full text of DOI:10.1002/ejoc.200700126

FULL PAPER
DOI: 10.1002/ejoc.200700126
Regioselective Mo-Catalyzed Hydrostannations as Key Steps in the Synthesis
of Functionalized Amino Alcohols and Heterocycles
[a]
[a]
Hechun Lin and Uli Kazmaier*
Dedicated to Prof. P. Hofmann on the occasion of 60th birthday
Keywords: Cross coupling / Hydrostannation / Metathesis / Molybdenum / Stannanes
Molybdenum catalyzed hydrostannation of suitable pro- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
tected propargylic amino alcohols provides the correspond-
ing functionalized vinyl stannanes, which are useful syn-
thetic intermediates for the combinatorial synthesis of amino
alcohols and heterocycles.
Germany, 2007)
Introduction
fully applied to the synthesis of protected (PG: protecting
group) stannylated γ,δ-unsaturated amino acids 4 (Fig-
ure 1), which can be further modified, e.g. by Stille coupling
reactions giving rise to amino acids with interesting func-
Vinylstannanes are interesting building blocks in organic
synthesis, easily available for example by hydrostannations
[
1]
[
5]
of alkynes. For this purpose either radical or transition
metal catalyzed versions have been developed during the
tionalized side chains.
[
2]
last decades. A major drawback of both protocols results
form the difficulties to control the stereo- and regioselective
outcome of the reaction in case of unsymmetrical alkynes.
Recently, our group has developed a new catalyst based on
[
3]
molybdenum. Mo(CO) (CNtBu) (MoBl ) was found to
3
3
3
Figure 1. Stannylated amino acid.
be an excellent catalyst for highly regio- and stereoselective
hydrostannations of functionalized alkynes such as 1
(
Scheme 1), preferentially affording the α-stannylated prod-
[
4]
ucts 2.
Results and Discussion
In principle, these amino acids can easily be reduced to
the corresponding amino alcohols, which are also valuable
building blocks. But we were also interested to see, if we
can obtain suitable protected derivatives such as 6 directly
from chiral alkynes such as 5. This alkyne can easily be
Scheme 1. Hydrostannation of alkyne 1. Reaction conditions: a)
Bu SnH (3 equiv.), hydroquinone (10 mol-%), Mo(CO) (CNtBu)
2 mol-%), THF, 60 °C, 4 h.
[
6]
obtained from -serine in 5 steps. Reginato et al. could
show, that the β-isomer 7 can selectively be obtained via the
3
3
3
(
addition of Bu Sn(Bu)Cu(CN)Li and subsequent partial
3
[
7]
hydrolysis. To get access to the other regioisomer 6 we
subjected alkyne 5 to our molybdenum-catalyzed hydro-
stannation conditions (Scheme 2). Hydroquinone was
added to the reaction mixture to suppress radical hydro-
These α-regioisomers are not available under radical con-
ditions or by using other metal catalysts, at least not with
these yields and selectivities. This protocol has been success-
stannation. And indeed, in the presence of 2% MoBl the
3
[
a] Universität des Saarlandes, Institut für Organische Chemie,
Im Stadtwald, Geb. C4.2, 66123 Saarbrücken, Germany
Fax: +49-681-302-2409
reaction was finished after 24 h (THF, 60 °C), and the stan-
nylated products were obtained in high yield as a 9:1 re-
gioisomeric mixture, which could easily be separated by
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
[
8]
flash chromatography.
Eur. J. Org. Chem. 2007, 2839–2843
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2839

H. Lin, U. Kazmaier
FULL PAPER
Scheme 2. Hydrostannation of alkyne 5. Reaction conditions: (a)
3 3 3
Bu SnH (3 equiv.), hydroquinone (10 mol-%), Mo(CO) (CNtBu)
(2 mol-%), THF, 60 °C, 24 h.
With pure stannane 6 in hand, we subjected it to several
cross coupling reactions (Scheme 3). Excellent yields were
obtained with benzyl and allyl bromide giving rise to 8 and
9
in a very clean conversion. Different is the situation with
aryl halides which show a tendency to undergo ipso-substi-
tution via a Heck-type mechanism.[
5b,9]
Therefore, in the
case of 10 the yield dropped to around 60%. Iodoalkenes
Scheme 4. Modifications of cross coupling products. Reaction con-
are also versatile substrates as shown with the coupling of
ditions: a) CH
b) CH (CN) (2 equiv.), LiI (2 equiv.), DME, ∆, 24 h; c) 1) 20 mol-
1 as a single isomer in good yield.[11] In principle, further % pTsOH, MeOH, H O, ∆, 48 h; 2) NEt (1 equiv.), Boc O
2 2
(COOEt) (2 equiv.), LiI (2 equiv.), DME, ∆, 24 h;
[
10]
(
1
Z)-β-iodoacrylate, which provided the conjugated diene
2
2
2
3
2
(
1 equiv.).
modifications at the double bonds should be possible,
which is also true for the coupling products obtained with
acyl halides. Both aromatic and aliphatic acyl chlorides are
suitable coupling partners and the vinylogeous ketones 12
and 13 are good candidates for subsequent Michael ad-
ditions.
The ketale unit of the coupling products in principle can
selectively be removed without affecting the Boc-protecting
group (68% yield for the cleavage of 8), but the yields was
slightly better (82%) if some additional Boc O was added
2
after the reaction.
To have an even more flexible access towards these unsat-
urated alcohols it might be interesting to carry out the Stille
couplings directly with the stannylated free alcohol. Be-
cause the stannylated ketale 6 would definitely not survive
the acidic cleavage conditions, we subjected alcohol 20 also
to our hydrostannation conditions (Scheme 5). And indeed,
a similar yield and regioselectivity of 21 was obtained as
with ketale 6. The alcohol 21 was afterwards converted into
several other derivatives, such as allyl ether 22 and the tosy-
lated 23, which was further transformed into protected
stannylated diamine 24. Interestingly, no decomposition of
the vinyl stannane subunit was observed under all these re-
action conditions, probably because all reactions were car-
ried out in a basic medium.
Attempts to subject the stannylated dienes to a ring clos-
ing metathesis (RCM) using either “Grubbs I” or “Grubbs
Scheme 3. Cross coupling reactions of stannylated amino alcohol
[13]
II” catalyst failed.
Only migration of the double bond
derivative 6. General reaction conditions: 2 mol-% [(allyl)PdCl]
2
,
[
14]
was observed, but no cyclization. With respect to the ste-
rically demanding tin substituent, this result is not really
surprising. The chances to get the heterocyclic systems
should increase if the Stille coupling is carried out prior to
the ring closing metathesis. Therefore, both dienes 22 and
4
mol-% PPh , 2 equiv. halide, THF, 60 °C, overnight; a) BnBr; b)
3
Allyl bromide; c) PhI; d) (Z)-ethyl 3-iodoacrylate; e) acetyl chlo-
ride; f) PhCOCl.
For example, in the presence of LiI malonates and ma- 24 were coupled (Scheme 6), each with benzyl bromide and
lononitrile could be added to these ketones under neutral acetyl chloride to get two different types of alkenes. Both
[
12]
conditions,
Scheme 4). The best yield was obtained in the addition of only the substrates 25 and 26 with the electron rich double
malononitrile, and in this case the diastereomers of 16 bond underwent RCM, while the vinylogeous ketones 29
could be separated by chromatography. and 30 did not. This can be explained by electronic factors,
but without significant diastereoselectivity types of Stille couplings proceeded with good yields, but
(
2840
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2839–2843

Regioselective Mo-Catalyzed Hydrostannation
FULL PAPER
Conclusions
In conclusion, we have shown that hydrostannation of al-
kynes such as 5 gives rise to synthetically interesting interme-
diates, which can easily be converted into functionalized
amino alcohols and heterocyclic structures. The vinylstan-
nanes 6 obtained can be subjected to various Stille-type coup-
lings, including the reactions with acyl halides. The coupling
products themselves can be further modified as exemplified
with Michael additions and ring closing metatheses.
Experimental Section
General Remarks: All reactions were carried out in oven-dried
glassware (100 °C) under argon. All solvents were dried before use.
Scheme 5. Synthesis and conversions of stannylated amino alcohol
THF was distilled from LiAlH and stored over molecular sieves.
4
2
0. Reaction conditions: a) 1) 20 mol-% pTsOH, MeOH, H
8 h; 2) NEt (1 equiv.), Boc O (1 equiv.); b) Bu SnH (3 equiv.),
(CNtBu) (2 mol-%), THF,
5 °C, 16 h; c) 1) NaH, DMF, 0 °C, 30 min; 2) allyl bromide, room
2
O, ∆,
The products were purified by flash chromatography on silica gel.
4
3
2
3
Mixtures of EtOAc and hexanes were generally used as eluents.
hydroquinone (10 mol-%), Mo(CO)
5
3
3
TLC: commercially precoated Polygram® SIL-G/UV 254 plates. Vi-
sualization was accomplished with UV-light and KMnO
Melting points are uncorrected. NMR spectra were recorded in
CDCl using a Bruker DRX 500 NMR spectrometer. The forma-
4
solution.
3
temp., 3 h; (d) TsCl, NEt , THF, ∆, 3 h; d) allylamine, ∆, 5 h.
3
tion of rotamers causes broad signals in some cases and/or a second
set of signals. Selected signals in the NMR spectra for the minor
isomers are extracted from the spectra of the isomeric mixture. CI-
MS analyses were performed using a Finnigan MAT 95. Elemental
analyses were carried out at the department of chemistry, Univer-
sity of Saarbrücken.
and electron poor alkenes are generally unsuited substrates
[
15]
for RCM. But after reduction of the ketones under “Lu-
[
16]
che conditions”, and protection of the allylic alcohol ob-
tained, the cyclization products 33 and 34 were obtained in
acceptable to good yields.
N-(tert-Butyloxycarbonyl)-2,2-dimethyl-4-[(1-tributylstannyl)vinyl]-
oxazolidine (6): The alkyne 5 (450 mg, 2.0 mmol), hydroquinone
(
22.4 mg, 0.20 mmol) and Mo(CO)
3
(CNtBu)
3 3
(MoBI ) (17.2 mg,
0.04 mmol) were dissolved in THF (1.6 mL) in a Schlenk tube un-
3
der argon. Bu SnH (1.6 mL, 6.0 mmol) was added slowly and the
mixture was warmed to 60 °C until all starting material was con-
sumed (determined by TLC). After cooling to room temperature,
the reaction mixture was subjected to flash chromatography. Excess
Bu
3
SnH was removed using hexane as eluent. The two isomers were
separated by chromatography (hexane/ether, 100:1) giving rise to 6
1
(
879 mg, 1.7 mmol, 85 %) as a colorless oil. H NMR (500 Hz,
CDCl ): δ = 0.88 (t, J = 7.5 Hz, 9 H), 0.93 (t, J = 8.5 Hz, 6 H),
.31 (m, 6 H), 1.36–1.56 (m, 21 H), 3.58 (dd, J = 8.5, 1.5 Hz, 1 H),
.06 (dd, J = 6.5, 6.0 Hz, 1 H), 4.50 (m, 1 H), 5.24 (s, JSn-H
9.0 Hz, 1 H), 5.75 (s, JSn-H = 126.0 Hz, 1 H) ppm. 13C NMR
): δ = 9.7, 13.6, 23.2, 25.8, 27.4, 28.4, 29.0, 64.4,
8.4, 79.4, 94.4, 123.4, 152.4, 152.6 ppm. Selected signals of the
3
1
4
5
=
(500 Hz, CDCl
3
6
1
3
minor rotamer: C NMR (500 Hz, CDCl
5.8, 27.4, 28.4, 29.0, 65.2, 68.4, 79.9, 94.1, 123.5, 152.4, 152.6 ppm.
Sn (516.33): C 55.83, H 9.17, N 2.71; found C 55.03,
3
): δ = 9.7, 13.6, 23.2,
2
C
24
H
47NO
H 8.81, N 3.04. HRMS calcd. for C24
17.2578, found 517.2614.
3
+
H
3
48NO Sn [M + H] :
5
General Procedures for the Stille Coupling of Vinylstannanes 6: A
mixture of vinylstannane 6 (258 mg, 0.50 mmol) and RX
(
1.0 mmol) was solved in dry THF (2 mL) in a Schlenk tube under
argon. A solution of allyl palladium chloride dimer (3.7 mg,
.01 mmol) and PPh (5.3 mg, 0.02 mmol) was added in THF
2 mL) and the mixture was warmed to 60 °C overnight. After re-
0
(
3
Scheme 6. Synthesis of unsaturated heterocycles via ring closing
moval of the solvent, the residue was worked up using the “DBU
procedure” developed by Curran[ to remove the tin compound.
Therefore, the residue was dissolved in diethyl ether (5 mL) and an
metathesis. Reaction conditions: (a) BnBr, Pd(PPh
THF, 60 °C, overnight; (b) Grubbs II catalyst, (20 mol-%), CH
room temp., 2d; (c) acetyl chloride, [(allyl)PdCl] (2 mol-%), PPh
4 mol-%), THF, 60 °C, 16 h; (d) 1) NaBH , CeCl ·7H
0 min; 2) PhCH Br, Bu NI, NaH, THF, room temp., 16 h.
3
)
4
(2 mol-%),
17]
2
Cl ,
2
2
3
(
1
4
3
2
O, MeOH, excess of DBU was added, while some white solid precipitated. Af-
ter stirring for a few minutes, a solution of iodide in ether was
2
4
Eur. J. Org. Chem. 2007, 2839–2843
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2841

H. Lin, U. Kazmaier
J = 8.5 Hz, 2 H) ppm. 13C NMR (500 Hz, CDCl
): δ = 20.6, 23.5,
FULL PAPER
added until the iodine colour remains. The solution was transferred
3
to a short column (SiO
2
) and after elution of the product with
25.9, 28.3, 30.7, 44.3, 59.9, 63.8, 81.2, 94.2, 111.9, 128.8, 128.9,
134.4, 137.1, 153.0, 199.8 ppm. Selected signals of the minor rot-
diethyl ether (40 mL), the solvent was removed. The residue was
almost tin-free and the product was purified by flash chromatog-
raphy (silica gel, acetate/hexanes).
1
3
amer: C NMR (500 Hz, CDCl
3
): δ = 20.6, 22.3, 24.7, 28.3, 31.4,
44.3, 60.2, 63.8, 81.2, 94.2, 112.5, 128.8, 128.9, 134.4, 137.1, 153.0,
+
199.8 ppm. HRMS calcd. for C22
28 3 4
H N O [M + H] : 398.2080,
4
-[(2-Benzyl)vinyl]-N-(tert-butyloxycarbonyl)-2,2-dimethyloxazolid-
found 398.2063.
ine (8): According to the general procedure for Stille couplings, 8
was obtained from vinylstannane 6 (256 mg, 0.50 mmol) and ben-
zyl bromide (171 mg, 1.0 mmol) as a colourless oil (149 mg,
(2R)-2-(tert-Butyloxycarbonylamino)-3-methylene-4-phenyl-1-buta-
nol (17): A solution of 8 (137 mg, 0.43 mmol) and PTSA (17 mg,
1
0
1
(
0
2
.47 mmol, 94%). H NMR (500 Hz, CDCl
3
): δ = 1.30–1.76 (m,
0.10 mmol) in methanol (5 mL) and H
reflux for 48 h. After cooling to room temperature, Et
O (48 mg) was added and stirring was continued at room
.6 H), 5.08 (s, 0.4 H), 7.14–7.25 (m, 3 H), 7.28 (dd, J = 7.0, 7.5 Hz, temperature for additional 2 h. The solvent was evaporated and
2
O (1 mL) was heated at
5 H), 3.27–3.47 (m, 2 H), 3.66 (m, 0.4 H), 3.74 (m, 0.6 H), 4.00
m, 1 H), 4.27 (m, 0.6 H), 4.42 (m, 0.4 H), 4.75 (s, 1 H), 5.00 (s, and Boc
2
3
N (61 µL)
H) ppm. The major conformation: 13C NMR (500 Hz, CDCl
): the residue was purified by flash chromatography (silica, EtOAc/
3
δ = 23.2, 25.9, 28.4, 39.8, 61.3, 67.8, 79.6, 94.3, 111.9, 126.3, 128.4,
29.3, 138.7, 147.7, 152.1 ppm. Selected signals of the minor rot-
hexanes, 1:2) to give 17 (98 mg, 0.35 mmol, 82%) as white solid,
1
1
m.p. 73–75 °C. H NMR (500 Hz, CDCl
3
): δ = 1.43 (s, 9 H), 2.06
13
amer: C NMR (500 Hz, CDCl
3
): δ = 24.6, 26.6, 28.4, 39.4, 62.0, (br., OH), 3.42 (s, 2 H), 3.63 (m, 2 H), 4.16 (m, 1 H), 4.93 (br., 1
6
7.8, 80.2, 94.3, 112.4, 126.3, 128.4, 129.3, 138.7, 147.2, 152.1 ppm. H, NH), 4.94 (s, 1 H), 5.10 (s, 1 H), 7.18–7.24 (m, 3 H), 7.30 (ddd,
+
13
HRMS for C19
H27NO
3
[M ], 317.1991, found 317.2023.
J = 7.5, 5.5, 1.5 Hz, 2 H) ppm. C NMR (500 Hz, CDCl
3
): δ =
2
1
8.4, 41.0, 56.4, 64.3, 79.8, 113.7, 126.5, 128.6, 129.0, 138.5, 146.4,
56.0 ppm. HRMS calcd. for C16H24NO [M + H] : 278.1756,
3
4
-[(1-Benzoyl)vinyl]-N-(tert-butyloxycarbonyl)-2,2-dimethyloxazol-
idine (13): According to the general procedure for Stille couplings,
3 was obtained from vinylstannane 6 (256 mg, 0.50 mmol) and
benzoyl chloride (141 mg, 1.0 mmol) as a colorless solid (136 mg,
+
found 278.1767.
(2R)-2-(tert-Butyloxycarbonylamino)-3-tributylstannyl-3-buten-1-ol
): δ = (21): According to the synthesis of stannane 6, 21 was obtained by
hydrostannation of alcohol 20 (370 mg, 2.0 mmol) as a colourless oil
1
1
0
1
0
4
0
.41 mmol, 82%), m.p. 71–73 °C. H NMR (500 Hz, CDCl
3
.24–1.83 (m, 15 H), 3.86 (d, J = 9.0 Hz, 0.6 H), 3.91 (d, J = 8.5 Hz,
.4 H), 4.24 (dd, J = 8.5, 6.5 Hz, 1 H), 4.90 (d, J = 7.0 Hz, 0.6 H),
.96 (d, J = 5.5 Hz, 0.4 H), 5.78 (s, 0.4 H), 5.83 (s, 0.6 H), 5.95 (s,
1
(774 mg, 1.6 mmol, 81%). H NMR (500 Hz, CDCl
= 7.0 Hz, 9 H), 0.90–0.96 (m, 6 H), 1.27–1.35 (m, 6 H), 1.44 (s, 9 H),
.4 H), 6.06 (s, 0.6 H), 7.38–7.49 (m, 2 H), 7.55 (m, 1 H), 7.75 (d, 1.45–1.52 (m, 6 H), 2.17 (br., OH), 3.67 (m, 2 H), 4.33 (br., NH),
3
): δ = 0.89 (t, J
13
J = 7.5 Hz, 2 H) ppm. C NMR (500 Hz, CDCl
3
): δ = 22.9, 26.4,
8.4, 57.4, 68.9, 80.0, 94.4, 125.8, 128.3, 129.4, 132.5, 137.5, 147.5,
51.8, 197.3 ppm. Selected signals of the minor rotamer: 13C NMR
): δ = 24.4, 27.0, 28.4, 58.3, 68.4, 80.5, 93.9, 125.3,
28.2, 129.5, 132.2, 137.8, 146.2, 152.0, 197.6 ppm. HRMS calcd.
4.85 (d, J = 7.0 Hz, 1 H), 5.35 (s, JSn-H = 61.0 Hz, 1 H), 5.89 (s, JSn-
= 128.0 Hz, 1 H) ppm. 13C NMR (500 Hz, CDCl
): δ = 9.96, 13.6,
27.3, 28.4, 29.0, 60.2, 65.5, 79.7, 126.5, 152.5, 156.0 ppm. HRMS
2
1
H
3
+
(500 Hz, CDCl
3
calcd. for C21
2R)-2-(tert-Butyloxycarbonylamino)-3-tributylstannyl-3-butenyl To-
sylate (23): A solution of 21 (1.61 g, 3.38 mmol), p-toluenesulfonyl
chloride (0.77 g, 4.0 mmol) and Et N (0.41 g, 4.0 mmol) in CH Cl
3
H44NO Sn[M + 1] : 478.2343, found 478.2308.
1
(
+
4
for C19H25NO [M ]: 331.1784, found 331.1751.
The General Procedure for Micheal Additions Towards Vinyl
Ketones 12 and 13: A solution of 12 or 13 (0.2 mmol), diethyl ma-
lonate (0.4 mmol) or malononitrile (0.4 mmol) and lithium iodide
3
2
2
(15 mL) was heated to reflux for 4 h. After cooling, the solvent was
evaporated and the residue was purified by flash chromatography
(
2
0.4 mmol) in dimethoxyethane (5 mL) was stirred at reflux for
4 h. After cooling to room temperature, the solvent was evapo-
(silica gel, ether/hexanes, 1:80) to give 23 (1.95 g, 3.1 mmol, 92%)
1
as a colorless oil. H NMR (500 Hz, CDCl
3
): δ = 0.72–0.92 (m, 15
rated and the residue was purified by flash chromatography (silica,
EtOAc/hexanes) to give addition products.
H), 1.24–1.33 (m, 6 H), 1.36–1.50 (m, 15 H), 2.43 (s, 3 H), 3.98 (m,
1 H), 4.07 (m, 1 H), 4.42 (m, 1 H), 4.70 (m, 1 H), 5.31 (s, JSn-H
=
6
2
0.0 Hz, 1 H), 5.81 (s, JSn-H = 123.0 Hz, 1 H), 7.35 (d, J = 8.5 Hz,
H), 7.77 (d, J = 9.0 Hz, 2 H) ppm. C NMR (500 Hz, CDCl ):
3
4
-(1-Benzoyl-3,3-dicyanopropyl)-N-(tert-butyloxycarbonyl)-2,2-di-
1
3
methyloxazolidine (16): According to the general procedure for
Michael additions, 16 was obtained from vinyl ketone 13 (61 mg,
δ = 9.9, 13.6, 21.6, 27.3, 28.3, 28.9, 56.5, 70.7, 79.7, 127.1, 128.0,
29.9, 132.7, 144.9, 150.0, 154.8 ppm.
1
0
.20 mmol) and malononitrile (26 mg, 0.40 mmol) as a dia-
stereomeric mixture which could be separated by chromatography
EtOAc/hexanes, 10:1, 5:1). The anti-isomer was obtained as color-
(2S)-N-Allyl-N-(tert-butyloxycarbonyl)-2-(tert-butyloxycarbonyl-
amino)-3-tributylstannyl-3-butenyl-1-amine (24): A solution of
crude 23 (475 mg, 0.75 mmol) in allylamine (3 mL) was heated at
(
1
less crystals (27 mg, 0.068 mmol, 34%), m.p. 130–132 °C. H NMR
500 Hz, CDCl
H), 3.61–3.93 (m, 3 H), 4.34 (m, 0.4 H), 4.42 (m, 0.6 H), 4.51
m, 0.4 H), 4.57 (d, J = 10.0 Hz, 0.6 H), 7.41–7.58 (m, 2 H), 7.67
(
1
3
): δ = 1.34–1.75 (m, 15 H), 2.28 (m, 1 H), 2.76 (m, reflux for 5 h. The excess allylamine was removed by evaporation
in vacuo. The residue was dissolved in CH Cl (5 mL) and Boc
(329 mg, 1.5 mmol) and Et N (0.25 mL) was added. The resulting
m, 1 H), 8.06 (m, 1 H), 8.26 (d, J = 7.0 Hz, 1 H) ppm. C NMR solution was stirred at room temperature for 4 h. The solvent was
2
2
2
O
(
(
(
3
13
500 Hz, CDCl
3
): δ = 21.1, 23.4, 25.8, 26.8, 28.7, 45.4, 58.0, 62.5,
evaporated and the residue was purified by flash chromatography
8
1.5, 94.2, 112.0, 128.7, 129.1, 134.5, 135.1, 152.7, 199.1 ppm. Se-
(silica gel, ether/hexanes, 1:100) to give the product 24 (288 mg,
13
1
lected signals of the minor rotamer: C NMR (500 Hz, CDCl
3
): δ
0.46 mmol, 62%) as a colourless oil. H NMR (500 Hz, CDCl
3
): δ
=
21.1, 22.1, 25.8, 26.8, 28.3, 46.5, 56.8, 63.1, 82.0, 95.4, 112.6, = 0.83–0.98 (m, 15 H), 1.27–1.37 (m, 6 H), 1.38–1.55 (m, 24 H),
1
28.7, 129.1, 134.5, 135.1, 151.8, 199.1. The syn-isomer was ob-
2.75 (d, J = 13.5 Hz, 0.6 H), 2.88 (d, J = 14.0 Hz, 0.4 H), 3.43 (m,
0.4 H), 3.57–3.77 (m, 1.6 H), 3.98 (d, J = 15.0 Hz, 0.6 H), 4.14 (d,
1
tained as a colorless oil (38 mg, 0.096 mmol, 48%) ppm. H NMR
500 Hz, CDCl
H), 2.18 (m, 1 H), 2.59 (m, 1 H), 3.63 (m, 0.4 H), 3.85 (m, 0.6 H), 61.5 Hz, 1 H), 5.55 (br., NH), 5.74 (m, 1 H), 5.86 (s, JSn-H
(
3
): δ = 0.94 (s, 3 H), 1.33 (s, 3 H), 1.39–1.70 (m, 9 J = 14.0 Hz, 0.4 H), 4.34 (m, 1 H), 5.10 (m, 2 H), 5.26 (s, JSn-H
=
=
1
3
3
.91 (m, 2 H), 4.08 (m, 0.4 H), 4.25 (m, 0.6 H), 4.43 (m, 1 H), 7.48
128.0 Hz, 1 H) ppm. C NMR (500 Hz, CDCl
3
): δ = 10.0, 13.7,
(dd, J = 8.0, 7.5 Hz, 2 H), 7.62 (dd, J = 8.0, 7.0 Hz, 1 H), 7.99 (d, 27.4, 28.3, 28.4, 29.0, 49.5, 50.0, 58.8, 78.6, 80.0, 116.3, 125.7,
2842
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2839–2843

Regioselective Mo-Catalyzed Hydrostannation
FULL PAPER
1
33.9, 154.3, 155.0, 157.0 ppm. C29
H
56
N
2
O
4
Sn (615.46): C, 56.59;
thanks the Alexander von Humboldt-Foundation for a postdoc-
toral fellowship.
H, 9.17; N, 4.55, found C 56.84, H 8.84, N 4.57. HRMS calcd. for
+
C
29
H
56
N
2
O
4
Sn [M ]: 616.3262, found 616.3285.
2S)-N-Allyl-3-benzyl-N-(tert-butyloxycarbonyl)-2-(tert-butyloxy-
carbonylamino)-3-butenyl-1-amine (26): Stannane 24 (120 mg,
.195 mmol) and benzyl bromide (41 mg, 0.24 mmol) was solved in
dry THF (1 mL) in a Schlenk tube under argon. Pd(PPh (1.7 mg)
(
[1] a) J. K. Stille, Angew. Chem. 1986, 98, 504–519; Angew. Chem.
Int. Ed. Engl. 1986, 25, 508–523; b) J. E. Baldwin, R. M. Ad-
lington, S. H. Ramcharitar, J. Chem. Soc., Chem. Commun.
0
1
991, 940–942; c) A. G. Davies, Organotin Chemistry, VCH,
3 4
)
Weinheim 1997.
was added and the solution was warmed to 60 °C overnight. After
removal of the solvent, the residue was worked up with DBU pro-
cedure to remove the tin compounds. The crude product was puri-
fied by flash chromatography on silica gel with acetate-hexane in
[
[
2] A. G. Davies in Comprehensive Organometallic Chemistry II,
Pergamon, 1995, vol. 2, p. 217 ff.
3] a) H. X. Zhang, F. Guibé, G. Balavoine, J. Org. Chem. 1990,
55, 1857–1867; b) U. Kazmaier, D. Schauß, M. Pohlman, Org.
an appropriate ratio as the eluent to give the coupling products 25
Lett. 1999, 1, 1017–1019; c) S. Braune, U. Kazmaier, J. Or-
ganomet. Chem. 2002, 641, 26–29; d) S. Braune, M. Pohlman,
U. Kazmaier, J. Org. Chem. 2004, 69, 468–474; e) U. Kazmaier,
M. Klein, Chem. Commun. 2005, 501–503; f) U. Kazmaier, A.
Wesquet, Synlett 2005, 1271–1274.
1
(61 mg, 0.146 mmol, 74%) as a colourless oil. H NMR (500 Hz,
CDCl
3.0 Hz, 0.6 H), 2.94 (d, J = 13.0 Hz, 0.4 H), 3.35 (m, 0.4 H), 3.40
s, 2 H), 3.54 (m, 1 H), 3.64 (m, 0.6 H), 3.82 (d, J = 14.5 Hz, 0.6
H), 3.97 (d, J = 13.5 Hz, 0.4 H), 4.23 (m, 1 H), 4.80 (s, 0.6 H), 4.86
s, 0.4 H), 4.97–5.13 (m, 3 H), 5.58 (s, 1 H), 5.67 (m, 1 H), 7.15–
.23 (m, 3 H), 7.28 (dd, J = 8.5, 7.0 Hz, 2 H) ppm. 13C NMR
500 Hz, CDCl ): δ = 28.2, 28.3, 40.4, 49.0, 49.9, 54.8, 78.8, 80.1,
13.1, 116.4, 126.2, 128.3, 129.2, 133.6, 138.9, 147.6, 155.3, 155.7
3
): δ = 1.40 (s, 9 H), 1.44 (s, 6 H), 1.47 (s, 3 H), 2.78 (d, J =
1
(
[4] a) U. Kazmaier, M. Pohlman, D. Schauß, Eur. J. Org. Chem.
2
000, 2761–2766; b) A. O. Wesquet, S. Dörrenbächer, U. Kaz-
(
7
(
1
maier, Synlett 2006, 1105–1109.
[
5] a) G. T. Crisp, P. T. Glink, Tetrahedron Lett. 1992, 33, 4649–
3
4
652; b) G. T. Crisp, P. T. Glink, Tetrahedron 1994, 50, 3213–
3234; c) U. Kazmaier, D. Schauß, M. Pohlman, S. Raddatz,
Synthesis 2000, 914–917; d) U. Kazmaier, D. Schauß, S. Rad-
datz, M. Pohlman, Chem. Eur. J. 2001, 7, 456–464; e) S.
Dörrenbächer, U. Kazmaier, S. Ruf, Synlett 2006, 547–550.
13
ppm. Selected signals of the minor rotamer: C NMR (500 Hz,
CDCl ): δ = 28.2, 28.3, 40.2, 49.0, 49.4, 54.1, 79.3, 80.1, 113.1,
16.9, 126.3, 128.4, 129.1, 133.6, 138.7, 147.6, 154.9, 157.0 ppm.
3
1
+
[6] a) P. Garner, J. M. Park, Org. Synth. 1991, 70, 18–28; b) P.
Meffre, L. Gauzy, C. Perdigues, F. Desanges-Levecque, E.
Branquet, P. Durand, F. Goffic, Tetrahedron Lett. 1995, 36,
877–880.
HRMS calcd. for C24
The General Procedure of the RCM Reactions: The corresponding
25, 63 mg, 0.20 mmol) was solved in dry CH Cl (10 mL) in a
Schlenk tube under argon. Grubbs-II-type catalyst (34 mg,
.04 mmol, 20%mmol) was added and the solution was stirred 2 d
36 2 4
H N O [M ]: 416.2675, found 416.2644.
(
2
2
[7] G. Reginato, A. Mordini, M. Caracciolo, J. Org. Chem. 1997,
6
2, 6187–6192.
8] Bu
Therefore an excess of Bu
0
[
3
SnH is partly decomposing under the reaction conditions.
SnH is necessary to obtain good
at room temperature. After evaporation of the solvent, and the
crude product was purified by flash chromatography (silica gel,
ether/hexanes = 1:10, 1:4) to give the cyclization products.
3
yields. Alternatively, the tin hydride can be added slowly via
syringe pump. In this case the amount can be reduced to
1.1 equiv. (see ref.[ ).
4b]
(
3R)-4-Benzyl-3-(tert-butoxycarbonylamino)-1,2,3,6-tetrahydropy-
[
9] a) K. Kikukawa, H. Umekawa, T. Matsuda, J. Organomet.
Chem. 1986, 311, C44–46; b) G. Stork, R. C. A. Isaacs, J. Am.
Chem. Soc. 1990, 112, 7399–7400.
10] S. Ma, X. Lu, Z. Li, J. Org. Chem. 1992, 57, 709–713.
11] No isomerization of the acrylate double bond was observed
under the general reaction conditions. A coupling constant J
ran (27): Pyran 27 was obtained from diene 25 (63 mg, 0.20 mmol)
as a white solid (30 mg, 0.104 mmol, 52 %), m.p. 82–84 °C. H
NMR (500 Hz, CDCl
H), 3.39 (d, J = 15.5 Hz, 1 H), 3.57 (dd, J = 11.5, 2.5 Hz, 1 H),
3
4
1
3
): δ = 1.43 (s, 9 H), 3.33 (d, J = 15.5 Hz, 1
[
[
.87 (d, J = 7.0 Hz, 1 H), 3.94 (d, J = 9.0 Hz, 1 H), 4.05 (m, 1 H),
.13 (d, J = 16.5 Hz, 1 H), 4.86 (br., NH), 5.47 (m, 1 H), 7.16–7.24
=
7.5 Hz for the α-vinylic proton confirmed the (Z)-olefin ge-
13
(
m, 3 H), 7.30 (dd, J = 7.5, 6.0 Hz, 2 H) ppm. C NMR (500 Hz,
CDCl ): δ = 28.4, 40.4, 46.5, 65.5, 69.9, 79.4, 124.8, 126.3, 128.4,
29.2, 135.9, 138.6, 155.5 ppm. HRMS calcd. for C17 [M
ometry.
3
[12] R. Antonioletti, F. Bonadies, E. S. Monteagudo, A. Scettri,
Tetrahedron Lett. 1991, 39, 5370–5374.
1
+
H24NO
3
+
[13] Recent reviews on ring closing metathesis see: a) R. H. Grubbs,
S. Chang, Tetrahedron 1998, 54, 4413–4450; b) A. Fürstner,
Angew. Chem. 2000, 112, 3140–3172; Angew. Chem. Int. Ed.
2000, 39, 3012–3043; c) T. M. Trnka, R. H. Grubbs, Acc. Chem.
Res. 2001, 34, 18–29; d) S. J. Connon, S. Blechert, Angew.
Chem. 2003, 114, 1944–1968; Angew. Chem. Int. Ed. Engl. 2003,
1] : 290.1756, found 290.1775.
(
3R)-4-Benzyl-N-(tert-butoxycarbonyl)-3-(tert-butoxycarbonyl-
amino)-1,2,3,6-tetrahydropyridine (28): According to the general
procedure for RCM, 28 was obtained from diene 26 (56 mg,
0
1
.13 mmol) as a colourless oil (39 mg, 0.10 mmol, 78%). H NMR
4
2, 1900–1923, and references therein.
(500 Hz, CDCl
3
): δ = 1.44 (s, 9 H), 1.45 (s, 9 H), 2.95 (m, 1 H),
[
14] B. Schmidt, Eur. J. Org. Chem. 2003, 816–819.
3
.35 (m, 2 H), 3.52 (m, 1 H), 4.03 (m, 2 H), 4.28 (s, 1 H), 4.58 (br.,
13
[15] a) A. K. Chatterjee, J. P. Morgen, R. H. Grubbs, J. Am. Chem.
Soc. 2000, 122, 3783–3784; b) O. Brümmer, A. Rückert, S. Ble-
chert, Chem. Eur. J. 1997, 3, 441–446; c) H. E. Blackwell, D. J.
O’Leary, A. K. Chatterjee, R. A. Washenfelden, D. A.
Bussmann, R. H. Grubbs, J. Am. Chem. Soc. 2000, 122, 58–71.
NH), 5.43 (m, 1 H), 7.10–7.43 (m, 5 H) ppm. C NMR (500 Hz,
CDCl ): δ = 28.3, 28.4, 40.7, 42.8, 46.6, 47.4, 79.4, 79.9, 126.3,
28.3, 128.5, 129.2, 138.6, 142.5, 155.2, 155.3 ppm. HRMS calcd.
3
1
+
32 2 4
for C22H N O [M ]: 388.2362, found 388.2331.
[
16] L. A. Paquette, R. E. Hartung, J. E. Hofferberth, I. Vilotijevic,
J. Yang, J. Org. Chem. 2004, 69, 2454–2460.
17] D. P. Curran, C. T. Chang, J. Org. Chem. 1989, 54, 3140–3157.
Received: February 12, 2007
Supporting Information (see also the footnote on the first page of
this article): Analytical and NMR spectroscopic data of all new
compounds).
[
Published Online: April 19, 2007
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
(Ka 880/7-1) and by the Fonds der Chemischen Industrie. H. L.
Eur. J. Org. Chem. 2007, 2839–2843
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2843