Transition-metal-free conjugate stannyl transfer to α,β- unsaturated carbonyl and carboxyl compounds in basic aqueous media

Article abstract of DOI:10.1055/s-2008-1078493

An unpretentious procedure for the conjugate stannylation of several α,β-unsaturated acceptors using silyl stannanes is reported. Competing reaction pathways of conjugate addition and reduction are discussed. Thieme Stuttgart.

Full text of DOI:10.1055/s-2008-1078493

1690
LETTER
Transition-Metal-Free Conjugate Stannyl Transfer to a,b-Unsaturated
Carbonyl and Carboxyl Compounds in Basic Aqueous Media
T
ransition-Meta
l
u
t
a
te Sta
h
nnylation K. Schmidt, Martin Oestreich*
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstraße 40, 48149 Münster, Germany
Fax +49(251)8336501; E-mail: martin.oestreich@uni-muenster.de
Received 8 April 2008
R3SiSnR3 (B)
(2.5 equiv)
MX (1.0 equiv)
Abstract: An unpretentious procedure for the conjugate stannyla-
tion of several a,b-unsaturated acceptors using silyl stannanes is re-
ported. Competing reaction pathways of conjugate addition and
reduction are discussed.
O
SnR3
O
R1
R2
R1
R2
THF–H2O = 20:1
50 °C
A
C
(cyclic or acylic
ketones, ester or imides)
(R = aryl and/or alkyl)
Key words: aqueous media, conjugate addition, interelement link-
ages, silicon, tin
MX =
NaOAc or KOH
Scheme 1 Transition-metal-free conjugate stannyl transfer
The carbon–tin bond belongs to the most widely used car-
bon–element linkages in organic chemistry.1 A classic
way of installing a triorganostannyl group at saturated car-
bon is the indirect 1,4-addition of stannyl lithiums to a,b-
unsaturated acceptors,2 a reaction that is believed to fol-
low a 1,2-addition–1,3-allylic transposition pathway.3
These anions also provide an entry into tin-based cu-
prates,4 and there is a rich chemistry connected with that.5
In order to bypass stannyl lithium generation by reductive
metalation or deprotonation reactions,2 alternative ap-
proaches were later elaborated, which rely on cleavage of
tin–element bonds (element = hydrogen, silicon, and tin)
by metalates.6 Prior to this development, Chenard et al.8
had realized that interelement linkages, namely silyl stan-
nanes,7 are chemoselectively activated by cyanide8 or
halides9 thus enabling a (transition) metal-free stannyl
transfer onto a,b-unsaturated acceptors.10
lyl stannane Me3SiSnMe2Ph (1)14,15 in all transformations;
in principle, related known silyl stannanes6b,7–9 do also
work in these reactions. Cyclic a,b-unsaturated ketones
cleanly underwent the conjugate stannylation in high
chemical yields (Table 1).13 No conversion was seen
when the acceptor and 1 were reacted in aqueous THF
without NaOAc or KOH.
We next turned to acyclic a,b-unsaturated carbonyl and
carboxyl compounds (Table 2).13 Under reaction condi-
tions identical to those for cyclic enones (Table 1, entries
1–6), chemical yields were markedly decreased for acy-
clic enones due to competing conjugate reduction
(Table 2, entries 1–4). While only minor amounts (5–
10%) of the reduced acceptor were formed from a b-alkyl-
substituted acceptor (Table 2, entries 1 and 2), appreciable
quantities were isolated in the case of a b-arylated sub-
strate (Table 2, entries 3 and 4). A tentative mechanism of
this undesired side reaction is outlined further below.
Conversely, this 1,4-reduction was virtually not detected
In the course of our investigations towards catalytic asym-
metric conjugate carbon–element bond formation by acti-
vation of element–element bonds with chiral RhIOH
complexes,11,12 we also tested silyl stannanes as a source
of nucleophilic tin. These catalyses are usually performed
at elevated temperatures (45–60 °C) in basic aqueous me-
dia using 1,4-dioxane–H2O solvent mixtures and Et3N or
KOH as bases. From control experiments, we quickly
learned that, in fact, several acceptors A do undergo the
desired 1,4-addition with silyl stannanes B in the absence
of a rhodium catalyst (A → C, Scheme 1).13 In this com-
munication, we report an unpretentious conjugate stannyl
transfer requiring neither a transition metal nor exclusion
of water.
Table 1 Transition-Metal-Free Conjugate Stannylation of Cyclic
a,b-Unsaturated Carbonyl Acceptors13
Entry
Acceptor
Producta
Base
Yield
(%)
O
O
1
2
NaOAc
KOH
85
60
SnMe2Ph
O
O
3
4
NaOAc
KOH
92
72
For simplification, we replaced 1,4-dioxane by THF in
these reactions. In contrast to our previous work,11,12 Et3N
was not effective, which is why we employed NaOAc as
well as KOH as activators. We decided to use the novel si-
SnMe2Ph
O
O
5
6
NaOAc
KOH
90
93
SYNLETT 2008, No. 11, pp 1690–1692
Advanced online publication: 11.06.2008
x
x
.x
x
.2
0
0
8
SnMe2Ph
DOI: 10.1055/s-2008-1078493; Art ID: G08108ST
© Georg Thieme Verlag Stuttgart · New York
a Satisfactory elemental analyses were obtained.

LETTER
Transition-Metal-Free Conjugate Stannylation
1691
Table 2 Transition-Metal-Free Conjugate Stannylation of Acyclic a,b-Unsaturated Carbonyl and Carboxyl Acceptors13
Entry
Acceptor
Producta
Base
Conjugate
reduction
Conjugate
stannylation
Yield (%)
Yield (%)
O
Me2PhSn
O
O
O
O
1
2
NaOAc
KOH
~5
55
74
~10
Me
Ph
Me
Ph
Me2PhSn
O
O
3
4
NaOAc
KOH
19
30
59
54
Ph
Ph
Ph
Ph
Ph
Me2PhSn
5
6
NaOAc
KOH
<5
<5
57
41
Ph
OEt
OEt
OEt
Me2PhSn
Ph
O
O
7
8
NaOAc
KOH
<5
<5
22
50
Ph
OEt
O
Me2PhSn
O
O
9
10
NaOAc
KOH
0
0
95
54
Ph
Ph
O
O
CF3
Ph
O
CF3
O
O
Me2PhSn
O
11
12
NaOAc
KOH
<5
<5
77
83
N
Ph
N
a Satisfactory elemental analyses were obtained except for entries 11 and 12.
for a,b-unsaturated carboxyl compounds, esters and im-
ides (Table 2, entries 5–12). A standard ethyl ester afford-
ed the stannylated product independent of the double bond
geometry in modest yields (Table 2, entries 5–8); the
more reactive trifluoroethyl ester performed very well
(Table 2, entries 9 and 10). Imides are also possible pre-
cursors, which undergo the stannylation in high yields
(Table 2, entries 11 and 12).
1 followed
by hydrolysis
Me2PhSn
O
Ph
Ph
conjugate
addition
3
Me3SiSnMe2Ph (1)
(1.0 equiv)
MX (1.0 equiv)
+
O
O
THF–H2O = 20:1
50 °C
Ph
Ph
Ph
Ph
2
4
The origin of the aforementioned competition between
conjugate addition and reduction might be understood on
the basis of an interesting methodology developed by
Takeda et al., by which b-aryl (not b-alkyl) a,b-unsaturat-
ed carbonyl as well as carboxyl compounds are reduced
with the Me3SiCl–NaI–H2O reagent.16 The proposed
mechanism involves the 1,4-addition of Me3SiI forming a
b-iodo silyl enol ether with a substantially weakened al-
lylic and benzylic carbon–iodine bond. Nucleophilic at-
tack at iodine by iodide then breaks this bond
accompanied by formation of diiodine followed by protol-
ysis.
conjugate
reduction
1
H2O
M
XMe3Si−SnMe2Ph
H2O
M
OH
Me2PhSn
Ph
OSiMe3
Ph
OSiMe3
Ph
– (Me2PhSn)2 (7)
Ph
5
6
MX = NaOAc: 3 (57%), 4 (30%), 7 (30%)
MX = KOH:
3 (15%), 4 (54%), 7 (40%)
Scheme 2 Tentative ionic mechanism for conjugate reduction
The same reaction sequence might apply to our
Me3SiSnMe2Ph–MX–H2O system (2 → 3 and 4,
Scheme 2). An allylic and benzylic carbon–tin bond in the
initially formed b-stannyl silyl enol ether (2 → 5) is also
relatively labile and might be prone to nucleophilic attack
at tin accordingly (5 → 6). The nucleophile might be
Lewis base-activated 1 (= 1·MX), a hypervalent silicon in-
termediate.17 When exactly one equivalent of 1 was used,
almost equimolar amounts of (Me2PhSn)2 (7) and the re-
duced acceptor 4 with acetate as an activator were isolat-
ed; that further supports this assumption (MX = NaOAc).
As hydroxide is a good nucleophile itself (MX = KOH), it
might also attack at tin in intermediate 5 thus producing
more of 4 (54%) than expected on the basis of isolated 7
(40%).
We are also aware of a report by Oshima and Utimoto et
al., in which the Et3B-induced 1,4-reduction of a,b-unsat-
urated carbonyls using Ph3SnH is disclosed.10b The iden-
tical procedure yields b- and a-stannylated products for b-
alkyl and b-aryl a,b-unsaturated carboxyls, respectively.
We, however, currently rule out radical pathways in our
system.
Synlett 2008, No. 11, 1690–1692 © Thieme Stuttgart · New York

1692
R. K. Schmidt, M. Oestreich
LETTER
(9) (a) Bu4NX (X = F, Cl, or Br): Mori, M.; Kaneta, N.; Isono,
N.; Shibasaki, M. J. Organomet. Chem. 1993, 455, 255.
(b) Et3SMe3SiF2: Honda, T.; Mori, M. Chem. Lett. 1994, 23,
1013. (c) [HMIM]Cl (1-hexyl-3-methylimidazolium
chloride): Dickson, S.; Dean, D.; Singer, R. D. Chem.
Commun. 2005, 4474.
(10) For conjugate stannylation by radical reactions of R3SnH,
see: (a) Nishida, M.; Nishida, A.; Kawahara, N. J. Org.
Chem. 1996, 61, 3574. (b) Nozaki, K.; Oshima, K.;
Utimoto, K. Bull. Chem. Soc. Jpn. 1991, 64, 2585.
(11) For conjugate silyl transfer using silyl boronic esters, see:
(a) Walter, C.; Auer, G.; Oestreich, M. Angew. Chem. Int.
Ed. 2006, 45, 5675; Angew. Chem. 2006, 118, 5803.
(b) Walter, C.; Oestreich, M. Angew. Chem. Int. Ed. 2008,
47, 3818; Angew. Chem. 2008, 120, 3878.
The reaction mechanism of this conjugate stannylation it-
self is not completely understood. As the presence of a
Lewis base is essential, it might involve chemoselective
nucleophilic activation of the silyl stannane at the silicon
atom;17 the water tolerance makes the intermediacy of a
stannyl anion at least unlikely. Interaction of thus-activat-
ed silyl stannane with the carbonyl/carboxyl oxygen re-
sulting in 1,2-addition followed by 1,3-allylic trans-
position3 or direct 1,4-addition are conceivable scenarios.
In summary, we have elaborated a facile water-tolerant
protocol for the 1,4-addition of a triorganostannyl group
avoiding the generation of sophisticated tin-based organo-
metallic reagents. We believe that these reaction condi-
tions would be excellent for an asymmetric phase-transfer
catalysis.18
(12) For conjugate phosphination using silyl phosphines, see:
Trepohl, V. T.; Oestreich, M. Chem. Commun. 2007, 3300.
(13) General Procedure for Conjugate Stannylation: Under an
inert atmosphere, a flame-dried Schlenk tube was charged
with the indicated a,b-unsaturated acceptor A (0.10 mmol,
1.0 equiv) and the THF–H2O solvent mixture (20:1, 2.1 mL).
The base MX (0.1 mmol, 1.0 equiv) as well as B (1, 0.25
mmol, 2.5 equiv) were added, and the reaction mixture was
heated to 50 °C. Conversion was monitored by TLC. After
full consumption of A the reaction mixture was diluted with
tert-butylmethylether (10 mL) at r.t. A small portion of silica
gel was added and the solvents were removed in vacuo. The
crude product C on silica gel was then subjected to flash
chromatography on Et3N-deactivated silica gel using
cyclohexane–tert-butylmethylether solvent mixtures.
Stannanes C (22–95%) were isolated as colorless oils.
(14) Reagent 1 is not particularly volatile, stable towards GLC
measurements, and provides easy-to-interpret NMR spectra.
(15) Preparation of Dimethylphenyl(trimethylsilyl)stannane
(1): Neat dimethylphenylstannyl chloride19 (3.00 g, 11.5
mmol, 1.00 equiv) was added dropwise to Me3SiCl-activated
lithium (large excess) in THF (40 mL) at 0 °C under
ultrasonic irradiation, and the reaction mixture was then
maintained at these conditions for 2 h. The supernatant blue-
black-colored solution was subsequently transferred to
another flask and slowly treated with trimethylsilyl chloride
(3.10 mL, 24.3 mmol, 2.10 equiv) at 0 °C. After stirring at
ambient temperature for additional 3 h, the solvent was
removed under reduced pressure. Crude 1 was purified by
flash chromatography on silica gel using cyclohexane as
solvent. The title compound (3.22 g, 10.8 mmol, 94%) was
obtained as a colorless oil. IR (ATR): 3062 (w), 2950 (w),
2893 (w), 1427 (m) cm–1. 1H NMR (300 MHz, CDCl3):
d = 0.26 [t, 2JH,Sn = 24 Hz, 6 H, SnMe2], 0.29 [t, 3JH,Sn = 3.0
Hz, 9 H, SiMe3], 7.27–7.55 (m, 5 H, Ph). 13C NMR (75 MHz,
CDCl3): d = –11.3 [SnMe2], 1.3 [SiMe3], 128.2, 128.5,
137.1, 142.0 (Ph). 29Si NMR (60 MHz, CDCl3): d = –9.3.
119Sn NMR (112 MHz, CDCl3): d = –138.9. Anal. Calcd for
C11H20SiSn: C, 44.18; H, 6.74. Found: C, 44.30; H, 7.01.
(16) Sakai, T.; Miyata, K.; Utaka, M.; Takeda, A. Bull. Chem.
Soc. Jpn. 1987, 60, 1063.
Acknowledgment
This research was supported by the Universität Münster and the
Fonds der Chemischen Industrie. M.O. is indebted to the Aventis
Foundation for a scholarship (Karl-Winnacker-Stipendium, 2006–
2008). We thank Christian Walter for making available several a,b-
unsaturated acceptors and the Wacker Chemie AG (Burghausen,
Germany) for the donation of trimethylsilyl chloride.
References and Notes
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L. J. Org. Chem. 1989, 54, 4975. (c) R3SnSnR3 with
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Synlett 2008, No. 11, 1690–1692 © Thieme Stuttgart · New York