allylsilane of 16 might be harnessed for further C-C bond
formation after reaction of the stannane and aldehyde
functional groups. The modest and somewhat variable yields
are offset by the simplicity of the chemistry that begins with
cheap pyridines and uses tributyltin hydride as a relatively
nontoxic and inexpensive tin source. We have run the
stannylation reaction of 9 on 20 mmol scale in order to
demonstrate preparative scale utility; stannane 10 was
obtained in 58% yield (3.9 g), a result similar to that shown
in Table 1.
case, an aqueous quench suffices, presumably as a result of
the essentially irreversible nature of the reaction that gener-
ates an alkoxide leaving group, rather than an amide ion.
The mixture of geometrical isomers obtained from 21,
compared with the stereochemically homogeneous product
derived from vinylogous amide 17, might be explained by
the reversibility and potential for equilibration in the case
of 17 (thermodynamic control) and the lack of equilibration
with 21 (kinetic control).
Stannylenal 1812 and stannylenone 2013 were generated
from the corresponding commercially available vinylogous
amides 17 and 19 (Scheme 3). The formation of 20
One of many potential applications of the stannylation of
vinylogous amides is a two-step R-stannylmethylenation of
carbonyl compounds (eq 2). Readily accessible vinylogous
amides such as 23, which are derived in a high-yielding and
general thermal reaction with dimethylformamide dimethyl
acetal (DMFDA), serve as intermediates in this process.15,16
Stannylmethylenation of 23 afforded 2417 in 42% unopti-
mized yield (g10:1 E:Z).
Scheme 3. Stannylation of Simple Vinylogous Amides
demonstrates that the reaction is not limited to aldehydes;
this result, along with the formation of 12, demonstrates that
the presence of relatively acidic protons in the substrate does
not hamper this reaction. This is consistent with previous
reports suggesting a low basicity for trialkylstannyl an-
ion.11,14
Finally, since very few examples of the cross-coupling of
trialkyltin-substituted unsaturated aldehydes have been re-
ported,18 and only one of a stannyldienal (10),3j we were
compelled to demonstrate that this reaction could be readily
achieved. Scheme 4 shows that coupling of stannane 12 with
iodoalkene 25 under typical, unoptimized Stille conditions19
affords 26 with the expected conservation of alkene geom-
etries.20 Additionally, stannane 14 and iodobenzene undergo
Stille coupling under similar conditions to afford 27.
Though the yields of our stannane syntheses are modest,
the ready availability of the starting materials on large scale
from pyridines or from commercial sources and the simplicity
of the reaction conditions conspire to make this a very
Commercially available vinylogous ester 21 also leads to
the formation of stannane 18 in 70% yield (eq 1). In this
(8) The regioselectivity of addition of trimethylstannyllithium to enones
has been studied: Still, W. C.; Mitra, A. Tetrahedron Lett. 1978, 19, 2659–
2662.
(9) The conjugate addition of tin anions and stannylcopper reagents, in
particular, is well documented. For examples, some of which include
conjugate addition/elimination reactions to generate vinylstannanes from
acceptors that bear excellent ꢀ-leaving groups, see: (a) Piers, E.; Morton,
H. E. J. Chem. Soc., Chem. Commun. 1978, 1033–1034. (b) Piers, E.;
Morton, H. E. J. Org. Chem. 1980, 45, 4263–4264. (c) Piers, E.; Chong,
J. M.; Morton, H. E. Tetrahedron Lett. 1981, 22, 4905–4908. (d) Seitz,
D. E.; Lee, S.-H. Tetrahedron Lett. 1981, 22, 4909–4912. (e) Imanieh, H.;
MacLeod, D.; Quayle, P.; Zhao, Y.; Davies, G. M. Tetrahedron Lett. 1992,
33, 405–408.
(14) For discussions of the low pKa of trialkylstannanes, see: (a) Gilman,
H.; Marrs, O. L.; Trepka, W. J.; Diehl, J. W. J. Org. Chem. 1962, 27, 1260–
(10) A related reaction was recently disclosed by Fleming and co-
workers using PhMe2SiLi with simple vinylogous amides. In one particular
case, these authors found that the inclusion of an activated alkyl halide
was required for successful outcomes, but this observation was not attributed
to the reversibility of the process, nor was a satisfying explanation found.
See: Fleming, I.; Marangon, E.; Roni, C.; Russell, M. G.; Taliansky
Chamudis, S. Can. J. Chem. 2004, 82, 325–332.
1265. (b) Kuivila, H. G.; Lein, G. H., Jr J. Org. Chem. 1978, 43, 750–751
.
(15) Vinylogous amides from ketones and amide acetals: Meerwein, H.;
Florian, W.; Schon, G.; Stopp, G. Liebigs Ann. Chem. 1961, 641, 1–39
.
(16) Tendency of ketone-derived vinylogous amides related to 23 to
undergo conjugate addition/elimination with alkyllithium nucleophiles:
Abdullah, R. F.; Fuhr, K. H. J. Org. Chem. 1978, 43, 4248–4250
.
(11) For the reversibility of trialkylstannyl anion additions to unsaturated
electrophiles, see: Cox, S. D.; Wudl, F. Organometallics 1983, 2, 184–
185. See also ref 8.
(12) E-Vinylstannane 18 has only been made stereoselectively once, via
a multistep sequence: Asano, M.; Inoue, M.; Watanabe, K.; Abe, H.; Katoh,
T. J. Org. Chem. 2006, 71, 6942–6951.
(17) Stannane 24 has been prepared by conjugate addition/elimination
of the relevant ꢀ-iodoenone: Piers, E.; Morton, H. E.; Chong, J. M. Can.
J. Chem. 1987, 65, 78–87.
(18) (a) Han, Q.; Wiemer, D. F. J. Am. Chem. Soc. 1992, 114, 7692–
7697. (b) Bach, T.; Heuser, S. Chem.sEur. J. 2002, 8, 5585–5592.
(19) The conditions in Scheme 4 were derived from those detailed in
ref 18b.
(13) Stannane 20 is most frequently made by Lewis acid mediated
acetylation of trans-1,2-bis(tributylstannyl)ethylene: (a) Peel, M. R.;
Johnson, C. R. Tetrahedron Lett. 1986, 27, 5947–5950. It has been used in
synthesis several times; for representative examples, see: (b) Johnson, C. R.;
Kadow, J. F. J. Org. Chem. 1987, 52, 1493–1500. (c) Echavarren, A. M.;
Pe´rez, M.; Castan˜o, A. M.; Cuerva, J. M. J. Org. Chem. 1994, 59, 4179–
4185. (d) Winkler, J. D.; Holland, J. M.; Peters, D. A. J. Org. Chem. 1996,
61, 9074–9075.
(20) While stannyldienals with substituents R to the aldehyde such as
10 and 14 (and presumably 16) generally cross-couple with retention of
alkene geometries, stannane 12 readily isomerizes under Stille conditions,
affording a mixture of product geometrical isomers. The inclusion of
stoichiometric NEt3 suppressed isomerization in the synthesis of 26. A
similar isomerization of the Z-isomer of 18 to the E-isomer under Stille
conditions has been reported; see ref 18a.
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