Allenylmethylsilanes as nucleophiles in N-acyliminium ion chemistry

Article abstract of DOI:10.1021/ol026615d

(matrix presented) Treatment of a variety of N-acyliminium ion precursors with 2,3-butadienyl(trimethyl)silane and related allenes in the presence of BF₃·OEt₂ provides good yields of N-protected 2-(aminomethyl)-substituted 1,3-dienes

Full text of DOI:10.1021/ol026615d

ORGANIC
LETTERS
2002
Vol. 4, No. 20
3497-3500
Allenylmethylsilanes as Nucleophiles in
N-Acyliminium Ion Chemistry
Gertjan Mentink, Jan H. van Maarseveen, and Henk Hiemstra*
Institute of Molecular Chemistry, UniVersity of Amsterdam, Nieuwe Achtergracht 129,
1018 WS Amsterdam, The Netherlands
hiemstra@science.uVa.nl
Received July 26, 2002
ABSTRACT
Treatment of a variety of N-acyliminium ion precursors with 2,3-butadienyl(trimethyl)silane and related allenes in the presence of BF3‚OEt2
provides good yields of N-protected 2-(aminomethyl)-substituted 1,3-dienes, which prove to be useful substrates for subsequent Diels−Alder
and alkene metathesis reactions.
An important C-C bond forming reaction for the construc-
tion of nitrogen-containing molecules is the addition of
carbon nucleophiles to N-acyliminium intermediates.1 Silicon-
containing π-nucleophiles have proven particularly useful
in this process, as the silyl function both enhances the
reactivity and controls the regioselectivity of the π-nucleo-
phile.2 Thus, the employment of allylsilanes, allenylsilanes,
and silyl enol ethers leads to the introduction of allyl,
propargyl, and 2-oxoalkyl groups, respectively, onto the
iminium carbon atom.1
with aldehydes and acetals4 and also in [2 + 2]-cycloaddi-
tions.5 To the best of our knowledge, 2,3-butadienyl-
(trimethyl)silane and analogues thereof have not been used
as nucleophiles with N-acyliminium ions.6
In this communication we report the reaction of allenyl-
methylsilanes 3 and analogous structures with a range of
N,O-(hemi)acetals 1 via the N-acyliminium ion intermediate
2 to form the 2-substituted dienes 4 (Scheme 1).7 We also
report on the versatility of the products 4 by showing
preliminary results of Diels-Alder and alkene metathesis
reactions.
Yet another type of silicon-containing nucleophiles are the
(allenylmethyl)silanes,3 which have been used in reactions
Our preparation of allenylmethylsilane 3a is a modification
of the procedure described by Gore´.3a On treatment of
propargyl tosylate (5a) with trimethylsilyl-methylmagnesium
chloride in diethyl ether in the presence of CuCN and LiCl
(1) For a recent reviews, see: (a) Speckamp, W. N.; Moolenaar, M. J.
Tetrahedron 2000, 56, 3817-3856. (b) Hiemstra, H.; Speckamp, W. N. In
ComprehensiVe Organic Synthesis, Trost, B. M., Fleming, I., Eds; Perga-
mon: Oxford, 1991; Vol. 2, pp 1047-1082.
(2) Review: Fleming, I.; Dunogue`s, J.; Smithers, R. Org. React. 1989,
37, 57-575.
(3) For syntheses of allenylmethylsilanes, see: (a) Montury, M.; Psaume,
B.; Gore´, J. Tetrahedron Lett. 1980, 21, 163-166. (b) Kleijn, H.; Vermeer,
P. J. Org. Chem. 1985, 50, 5143-5148. (c) Pornet, J. J. Organomet. Chem.
1988, 340, 273-282. (d) Harada, T.; Osada, A.; Oku, A. Tetrahedron Lett.
1995, 36, 723-724. (e) Creary, X.; Jiang, Z.; Butchko, M.; McLean, K.
Tetrahedron Lett. 1996, 37, 579-582. (f) Harada, T.; Katsuhira, T.; Osada,
A.; Iwazaki, K.; Maejima, K.; Oku, A. J. Am. Chem. Soc. 1996, 118,
11377-11390. (g) Lahrech, M.; Hacini, S.; Parrain, J.-L.; Santelli, M.
Tetrahedron Lett. 1997, 38, 3395-3398. (h) Tseng, H.-R.; Lee, C.-F.; Yang,
L.-M.; Luh, T.-Y. J. Org. Chem. 1999, 64, 8582-8587. (i) Maruyama, Y.;
Yoshiuchi, K.; Ozawa, F. J. Organomet. Chem. 2000, 609, 130-136.
(4) (a) For a recent review, see: Hatakeyama, S. J. Synth. Org. Chem.
Jpn 1997, 55, 793-802. (b) Luo, M.; Matsui, A.; Esumi, T.; Iwabuchi, Y.;
Hatakeyama, S. Tetrahedron Lett. 2000, 41, 4401-4402.
(5) (a) Colvin, E. W.; Ko¨nig, W. A.; Loreto, M. A.; Rowden, J. Y.;
Tommasini, I. Bioorg. Med. Chem. Lett. 1993, 3, 2405-2408. (b) Hojo,
M.; Murakami, C.; Nakamura, S.; Hosomi, A. Chem. Lett. 1998, 331-
332.
(6) For reactions of allenes with N-acyliminium ions, see: Beyersbergen
van Henegouwen, W. G.; Fieseler, R. M.; Rutjes, F. P. J. T.; Hiemstra, H.
J. Org. Chem. 2000, 65, 8317-8325 and references therein.
(7) For a comparable synthesis of 1,3-dienes with an amide substituent
at the 1-position of the diene, see: Takacs, J. M.; Weidner, J. J. J. Org.
Chem. 1994, 59, 6480-6483.
10.1021/ol026615d CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/11/2002

Scheme 1
Table 1.
the product was obtained in 65% yield on a 16 g scale
(Scheme 2). Three substituted analogues 3b-d8 were
Scheme 2
synthesized in a similar manner starting from the corre-
sponding substituted propargyl tosylates (synthesized by
tosylation of the corresponding alcohols) in 61-77% yield.
As allenylmethylsilane 3b is a chiral allene, we were
interested to know whether its axial chirality would be
transferred in the N-acyliminium ion reaction. Optically
active allene 3b ([R]D ) -11.1, c 1.31, CHCl3) was
synthesized in the usual way (see Scheme 2) from the tosylate
of commercially available enantiopure (S)-but-3-yn-2-ol.9
The ee of the product appeared to be only ca. 70% as
determined by a well-known NMR method.10
Allene 3a was then used as π-nucleophile in the reaction
with a range of different N-acyliminium ion precursors (see
Table 1). Precursors 6a-f and 7a,b were obtained from the
corresponding imides by successive N-alkylation, NaBH4
reduction, and acidic ethanolysis, according to well-known
procedures.11 Likewise, 812 and 913 were prepared via
reduction of N-substituted lactams. The methoxyglycine
derivatives 10a,b were synthesized via coupling of the
appropriate carbamate with methyl glyoxylate methyl hemi-
acetal followed by methanolysis.14
Initially CH2Cl2 was chosen as solvent to effect the
N-acyliminium ion reaction between allene 3a (4 equiv) and
precursor 6b in the presence of BF3‚OEt2 (2 equiv) as the
Lewis acid. This reaction did not go to completion even after
17 h, and only 16% of the expected dienelactam 11b was
isolated. However, when carried out in acetonitrile the
reaction was finished in 4 h in a satisfactory yield of 69%.
a Isolated yields after column chromatography. b Using 10 equiv of
nucleophile and 5 equiv of BF3‚OEt2 in CH2Cl2. c Using 10 equiv of
nucleophile and 5 equiv of BF3‚OEt2.
Similar conditions appeared successful for the other
N-acyliminium precursors 6-10 to provide the expected
dienelactam products in yields ranging from 42% to 88%
(Table 1). The products were somewhat air-sensitive oils that
should be kept under nitrogen. In two cases a slightly
different procedure was applied. For precursor 7b (entry 11)
the standard conditions resulted in only 34% yield of the
diene product 15b, together with 14% of the piperinone
resulting from ethanol elimination from 7b. On using a larger
excess of both the nucleophile (10 equiv) and the Lewis acid
(5 equiv) the yield was doubled to 68%, without observing
the elimination product. In the case of precursor 6d (entry
7) the standard conditions furnished none of the desired
diene, but instead the unsaturated N-substituent caused
N-acyliminium cyclization with incorporation of acetonitrile
furnishing bicyclic imidate 19 (Figure 1). When this reaction
(8) Colvin, E. W.; Monteith, M. J. Chem. Soc., Chem. Commun. 1990,
1230-1232.
(9) Elsevier, C. J.; Vermeer, P. J. Org. Chem. 1989, 54, 3726-3730.
(10) Mannschreck, A.; Munninger, W.; Burgemeister, T.; Gore´, J.; Cazes,
B. Tetrahedron 1986, 42, 399-408.
3498
Org. Lett., Vol. 4, No. 20, 2002

tems with a terminal alkene in the N-substituent was first
investigated.
The trienes 11c,d and 15b were subjected to Grubbs’
catalyst 22, resulting in the formation of the six-membered
ring products 24 and 27 in moderate to high yields. For
successful closure of the compounds 11d,e the 2nd generation
Grubbs’ catalyst (23) was required, giving the seven- and
eight-membered ring products 25 and 26, respectively, in
high yields (Scheme 3, entries 3 and 4). As could be expected
Figure 1. Bicyclic imidate from 6d.
was carried out in CH2Cl2 with a larger excess of both
nucleophile (10 equiv) and Lewis acid (5 equiv) the
cyclization was prevented and the diene 11d was formed in
a moderate yield (42%). The protected methoxyglycines 10
showed excellent reactivity to allene 3a, providing protected
butadienylglycines 18 in good yields. To the best of our
knowledge this special R-amino acid has not been synthe-
sized before. It was reported to occur in a natural γ-glutamyl-
dipeptide.15
Scheme 3a
The reactions of the substituted nucleophiles 3b-d with
N-acyliminium ion precursor 6a resulted in formation of the
1,2-disubstituted dienyllactams 12-14 in 65-85% yield.
Diene 12 was formed as the pure E-isomer as shown by a
1H NMR NOE experiment, whereas 14 was a 1:1 mixture
of geometric isomers.
Subjection of the N-acyliminium ion precursors 6a,b and
10a to the optically active allene 3b resulted in ee’s up to
21% for the products (Figure 2). Although the extent of
a Isolated yields after column chromatography.
from a literature precedent,18 only the least substituted double
bond of the 1,3-diene system reacted to produce compounds
24-27, which possess an exocyclic methylene.
Figure 2. Enantioenriched products from reactions of optically
active allene 3b (ee 70%). The ee’s were determined by using the
chiral shift reagent Eu(hfc)3 in H NMR.
1
The usefulness of the 1,3-dienylamides for further chem-
istry was also apparent from their reactivity in the Diels-
Alder reaction. We selected product 11b as an example
substrate and performed intermolecular Diels-Alder reac-
tions of this diene with maleic anhydride (28) and N-
methylmaleimide (29). As expected, these reactions pro-
ceeded smoothly at 120 °C in xylene to furnish the
cycloaddition products 30 and 31 as a 1:1 mixture of
diastereomers (Scheme 4).
transmission of axial chirality to the new stereocenter is rather
poor (30% at the most, corrected for the ee of starting allene),
the present work is the first demonstration of this phenom-
enon in a SE2′ reaction of a chiral allene.
After successful formation of a range of 1,3-dienylamides
we briefly explored the potential applications of these
molecules. The ring-closing metathesis reaction16,17 of sys-
We then turned our attention to the more interesting
intramolecular variant, which would be a type 2 Diels-Alder
(11) (a) Schoemaker, H. E.; Dijkink, J.; Speckamp, W. N. Tetrahedron
1978, 34, 163-172. (b) See also: Hiemstra, H.; Speckamp, W. N.
Tetrahedron 1985, 41, 4367-4416 and references therein.
(12) Nagasaka, T.; Tamano, H.; Hamaguchi, F. Heterocycles 1986, 24,
1231-1232.
(13) Åhman, J.; Somfai, P. Tetrahedron 1992, 48, 9537-9544.
(14) Zoller, U.; Ben-Ishai, D. Tetrahedron 1975, 31, 863-866. An
optimized procedure was used according to: Van Benthem, R. A. T. M.;
Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1992, 57, 6083-6085.
(15) Campos, L.; Marlier, M.; Dardenne, G.; Casimir, J. Phytochemistry
1983, 22, 2507-2508.
(16) For recent reviews, see: (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem.
Res. 2001, 34, 18-29. (b) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39,
3012-3043. (c) Fu¨rstner, A.; Ackermann, L.; Gabor, B.; Goddard, R.;
Lehmann, C. W.; Mynott, R.; Stelzer, F.; Thiel, O. R. Chem. Eur. J. 2001,
7, 3236-3253.
(17) Tarling, C. A.; Holmes, A. B.; Markwell, R. E.; Pearson, N. D. J.
Chem. Soc., Perkin Trans. 1 1999, 1695-1701.
(18) Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62, 7310-
7318.
Org. Lett., Vol. 4, No. 20, 2002
3499

Scheme 4
Scheme 5
process leading to bridged systems.19 For the synthesis of
the appropriate Diels-Alder precursors, the N,O-acetals
6d-f were subjected to a cross-metathesis reaction with
methyl acrylate (10 equiv) in the presence of catalyst 23. In
this way the activated alkenes 32a-c were obtained in high
yields. Subjection of 32a-c to the standard N-acyliminium
ion conditions provided the Diels Alder precursors 33a-c
in good yield. Heating of these compounds in xylene in a
sealed tube at 200 °C induced the cycloaddition reaction to
give the bridged systems 34a and 34b as single diastereomers
(Scheme 5). The assignment of the stereochemistry is
suggested by a computational comparison20 with the alterna-
tive diastereomer, which appeared higher in energy (4.5 kcal/
mol for 34a and 12.9 kcal/mol for 34b). Precursor 33c failed
to give cycloaddition.
In conclusion, we have shown that the use of allenyl-
methylsilane (3a) as nucleophile in N-acyliminium ion
reactions leads to amides containing the 1,3-diene moiety
in moderate to high yields. Substituted allenylmethylsilanes
(3b-d) react equally well and are able to transfer axial
chirality, although the levels of asymmetric induction are
poor. The products are versatile substrates, not only for
subsequent ring-closing metathesis and Diels-Alder reac-
tions, but conceivably for several other useful synthetic
processes.
Acknowledgment. This research has been financially
supported by the Council for Chemical Sciences of the
Netherlands Organization for Scientific Research (CW-
NWO).
Supporting Information Available: General procedures
for the N-acyliminium ion, metathesis, and Diels-Alder
reactions and full characterization data for compounds 3a-
d, 11-21, 24-27, and 30-34. This material is available free
of charge via the Internet at http://pubs.acs.org.
(19) For a recent review, see: Bear, B. R.; Sparks, S. M.; Shea, K. J.
Angew. Chem., Int. Ed. 2001, 40, 820-849.
(20) Spartan was used for the computation, employing the Single Point
Energy, Molecular Mechanics, MMFF method.
OL026615D
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Org. Lett., Vol. 4, No. 20, 2002