Remarkable enhancement of nucleophilicity of tin enolates toward nitro-or cyanoalkenes by tetrabutylammonium halides

Article abstract of DOI:10.1246/cl.2000.1266

The reaction of tin enolates with nitroalkenes was effectively catalyzed by tetrabutylammonium bromide (Bu₄NBr) to give γ-nitroketones. When the substituted tin enolates at the β-carbon in the olefinic moiety were used, the diastereoselective a

Full text of DOI:10.1246/cl.2000.1266

1266
Chemistry Letters 2000
Remarkable Enhancement of Nucleophilicity of Tin Enolates toward Nitro- or Cyanoalkenes by
Tetrabutylammonium Halides
Makoto Yasuda, Noriyuki Ohigashi, and Akio Baba*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871
(Received August 7, 2000; CL-000754)
The reaction of tin enolates with nitroalkenes was effec-
tively catalyzed by tetrabutylammonium bromide (Bu4NBr) to
give γ-nitroketones. When the substituted tin enolates at the β-
carbon in the olefinic moiety were used, the diastereoselective
addition proceeded through the acyclic transition state.
Tetrabutylammonium chloride (Bu4NCl) strongly accelerated
the reaction with the cyanoalkene to give the γ-cyanoketone.
The reaction of tin enolate 1 with β-nitrostylene 2a at room
temperature gave the γ-nitroketone 3a in 66% yield although
accompanied with unidentified complicated products (Table 1,
entry 1).5 To avoid the formation of side products, the reaction
was performed at low temperature (–45 °C), but gave no prod-
ucts at all (entry 2). The loading of a catalytic amount of
Bu4NBr significantly accelerated the Michael addition to give
3a in 94% yield even at –45 °C (entry 3).6 Lower yield was
observed in the reaction with catalytic Bu4NBr at room temper-
ature owing to the complicated side products which probably
came from the over-reactions (entry 4). The conditions at low
temperature with a catalytic amount of Bu4NBr was also
applied to the cyclic nitroalkene 2b to afford 71% yield of 3b
(entry 6).
A plausible reaction mechanism is shown in Scheme 1.
The high coordination by the bromide anion causes increase of
nucleophilicity in the tin enolate.3,4 The generated active
species A attacks the β-carbon of nitro-substituted olefin to
form B. The tautomeric isomerization to the stable species C
takes place with releasing the ligand L as already reported in
the reaction with unsaturated esters.4 In this step, the ligand L
is readily dissociated from C and coordinates to the tin enolate
because the tendency of coordination clearly depends on the
Lewis acidity of the tin center; oxo-substituted stannane A has
higher Lewis acidity than tetra C-substituted stannane C.3a,c
The substituted tin enolates at the β-carbon in the olefinic
moiety could provide the diastereoselective reaction course
Organotin compounds have been used as versatile reagents
for organic syntheses.1 They usually require an activator to
accomplish the reactions because of their moderate reactivity.
Therefore, the activation methodology of the reaction using tin
reagents is significantly important and could lead to selective
reaction courses. The organotin(IV) has ability to accept lig-
ands to form a highly coordinated species owing to their vacant
d-orbitals.2 Our recent research disclosed that some appropriate
ligands form five-coordinated organotin(IV) enolates, which
have totally different reactivity from that of noncoordinated
enolates.3 In particular, we have previously reported the
Michael addition of organotin(IV) enolates to α,β-unsaturated
esters, ketones, and amides in the presence of a catalytic
amount of tetrabutylammonium bromide which donates the bro-
mide anion to the tin center.4 In this reaction course, five-coor-
dinated tin enolate, which is catalytically generated, is a key
species. We, then have been interested in other Michael accep-
tors for the reaction using tin enolates. In this paper, the dra-
matic enhancement of nucleophilicity of tin enolate by tetra-
butylammonium halides toward nitro- and cyanoalkenes to
afford γ-nitro- and cyanoketones, respectively, is reported.
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
1267
with the substituted nitroalkene. In fact, the reaction of 4 with
2a gave the product 5 quantitatively with 86/14 diastereomeric
ratio in the presence of Bu4NBr (eq 1).7 On the contrary, non-
catalyzed reaction gave lower yield and selectivity.8
Bu4NBr to give 10 in 44%. We have reported that the coordi-
nation ability of chloride to tin enolates is too high to be uti-
lized for the reaction probably because of their decomposi-
tion.3b However, the result in eq 3 suggests the potential of the
chloride anion as an accelerator of tin enolates in the case of
catalytic use.
The high selectivity using Bu4NBr can be explained by
Scheme 2, although the exact mechanism is unclear at this
stage.9 Since the highly coordinated trialkyltin is not likely to
accept another ligand,3a the acyclic transition states are reason-
ably assumed for the reaction between 4 and 2a in the presence
of Bu4NBr. The transition state TS1, which leads to syn-prod-
uct, is preferred to TS2 because of the steric hindrance between
phenyl and the bulky highly coordinated tin in TS2.
We are currently developing this methodology for other
substrates and reagents.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports, and
Culture, of the Japanese Government. Thanks are due to Mr. H.
Moriguchi, Faculty of Engineering, Osaka University, for assis-
tance in obtaining MS spectra.
References and Notes
1
a) P. J. Smith, Chemistry of Tin, Blackie Academic &
Professional, London (1998). b) M. Pereyre, J.-P. Quintard, and
A. Rahm, Tin in Organic Synthesis, Butterworth, London (1987).
c) A. G. Davies, Organotin Chemistry, VCH (1997).
2
3
R. Hulme, J. Chem. Soc., 1963, 1524.
a) M. Yasuda, K. Chiba, and A. Baba, J. Am. Chem. Soc., 122,
7549 (2000). b) M. Yasuda, K. Hayashi, Y. Katoh, I. Shibata, and
A. Baba, J. Am. Chem. Soc., 120, 715 (1998). c) M. Yasuda, Y.
Katoh, I. Shibata, A. Baba, H. Matsuda, and N. Sonoda, J. Org.
Chem., 59, 4386 (1994). d) M. Yasuda, T. Oh-hata, I. Shibata, A.
Baba, and H. Matsuda, J. Chem. Soc., Perkin Trans. 1, 1993, 859.
M. Yasuda, N. Ohigashi, I. Shibata, and A. Baba, J. Org. Chem.,
64, 2180 (1999).
Organotin enolates exist as equilibrium mixtures of keto- and/or
enol-forms, the ratio of which largely depends on their sub-
stituents and conditions. M. Pereyre, B. Bellegarde, J.
Mendelsohn, and J. Valade, J. Organometal. Chem., 11, 97
(1968). Since higher reactivity is generally shown by enol-types
than keto-ones (K. Kobayashi, M. Kawanisi, T. Hitomi, and S.
Kozima, Chem. Lett., 1983, 851), all structures of tin enolates in
this paper are drawn in enol-forms.
Typical experimental procedure for the synthesis of 3a: To a mix-
ture of tin enolate 1 (3.0 mmol) and Bu4NBr (0.1 mmol) in dry
THF (5 mL) at 45 °C was added β-nitrostylene 2a (1.0 mmol)
under nitrogen. The reaction mixture was stirred for 4 h at the
same temperature. Diethyl ether (30 mL) and aqueous NH4F
(15%; 15 mL) were then added to the solution and the homoge-
neous mixture was vigorously stirred for 15 min and the insoluble
solids were filtered off. The filtrates were extracted with diethyl
ether and the organic layer was dried over MgSO4 and evaporat-
ed. Column chromatography (hexane/Et2O, 5/2) of the resultant
residue on silica gel gave 3a as a pure form.
4
5
6
The acyclic tin enolate 6 showed high yield and selectivity
in the presence of Bu4NBr-catalyst (eq 2).10 This result proba-
bly means that the geometry of 6 in the transition state is E-
form in this reaction.
7
8
9
The spectral data of 5 were reported. E. Juaristi, A. K. Bech, J.
Hansen, T. Matt, T. Mukhopadhyay, M. Simson, and D. Seebach,
Synthesis, 1993, 1271.
In this case, the Michael adduct was obtained although the yield
was very low. The tin enolate 4 has higher reactivity than 1
because the enol ratio in tautomerism is highly favorable (ref 5).
Either an acyclic or a cyclic transition state is proposed for the
reaction of metal enolates with unsaturated carbonyls. a) C. H.
Heathcock, M. H. Norman, and D. E. Uehling, J. Am. Chem.
Soc., 107, 2797 (1985). b) D. A. Oare and C. H. Heathcock, J.
Org. Chem., 55, 157 (1990).
Finally, we examined cyanoalkene as the Michael acceptor.
The non-catalyzed reaction of 1 with 9 at room temperature or
higher temperature (63 °C) gave no product, and the starting
materials were recovered (eq 3). The addition of a catalytic
amount of Bu4NBr gave only 27% of the product 10 even at 63
°C. The yield was improved by use of Bu4NCl instead of
10 The spectral data of 8 were reported. F. Felluga, P. Nitti, G.
Pitacco, and E. Valentin, Tetrahedron, 45, 2099 (1989).