Preparation and Diels-Alder Reactivity of 1-Amino-3-siloxy-1,3-butadienes

Full text of DOI:10.1021/jo970438q

5252
J . Org. Chem. 1997, 62, 5252-5253
Sch em e 1
P r ep a r a tion a n d Diels-Ald er Rea ctivity of
1-Am in o-3-siloxy-1,3-bu ta d ien es
Sergey A. Kozmin and Viresh H. Rawal*
Department of Chemistry, The University of Chicago,
Chicago, Illinois 60637
Received March 10, 1997 (Revised Manuscript Received J une
20, 1997 )
The synthetic potential of the Diels-Alder reaction has
been greatly expanded over the years through modifica-
tion of the diene and dienophile components.1 Lone pair-
containing heteroatom substituents on the diene, for
example, render it more reactive to dienophiles and lead
to improved regioselectivity in the cycloaddition.2 As an
added benefit, the heteroatom also serves as a handle
for further functionalization of the product. Among the
most extensively investigated heteroatom-substituted
dienes are mono- and dialkoxybutadienes,3 such as the
widely used 1-methoxy-3-(trimethylsiloxy)-1,3-butadiene,
known also as Danishefsky’s diene.4 Amino-substituted
dienes have also been synthesized and used in the Diels-
Alder reaction.5 By contrast, 1-amino-3-siloxy dienes
have received little attention.6,7 We report here the first
preparation of the parent 1-amino-3-siloxy-1,3-butadiene
and describe its usefulness in Diels-Alder reactions.
Amino siloxy diene 3 was prepared in high yield from
vinylogous amide 1, which is available via either a one-
pot Eschenmoser contraction procedure8 or an addition
elimination reaction of vinylogous ester 2 (Scheme 1).9
Deprotonation of 1 with potassium bis(trimethylsilyl)-
amide (KHMDS) and subsequent trapping of the result-
ing enolate with tert-butyldimethylsilyl chloride (TBS-
Cl) afforded essentially pure 1-(dimethylamino)-3-siloxy-
1,3-butadiene 3 in nearly quantitative yield.10 Diene 3
is quite stable to normal handling and, if desired, can be
Sch em e 2
further purified by vacuum distillation (85-90% yield).
Dienes protected with the bulkier TIPS and TBDPS
groups were prepared analogously and exhibit similar
reactivity, although offered no particular advantage.11
Having an enamine unit and an enol ether unit, both in
a synergystic arrangement, these dienes were expected
to be very reactive in Diels-Alder reactions.
(1) Oppolzer, W. Intermolecular Diels-Alder Reactions. In Com-
prehensive Organic Synthesis; Pergamon Press: New York, 1991; Vol
5, pp 315-400.
(2) (a) Petrzilka, M.; Grayson, J . I. Synthesis 1981, 753. (b)
Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction; Wiley:
New York, 1990.
The initial studies were designed to evaluate the
reactivity of 1-amino 3-siloxy dienes. Diene 3 reacts with
doubly-activated dienophiles at or below 0 °C. Indeed,
the reaction of 3 with N-phenylmaleimide was complete
in about 1 h at -78 °C and gave exclusively the endo-
adduct 6, in 96% yield after chromatography (Scheme 2).
The cycloaddition of 3 with diethyl acetylenedicarboxylate
proceeded efficiently at 5 °C and gave directly the
aromatized cycloadduct 7. Slightly higher temperatures
were required for cycloadditions with monoactivated
dienophiles, such as methacrolein and methyl methacry-
late. It is noteworthy that whereas the reaction with the
former was highly endo-selective, that with the latter
gave a significant amount of the exo diastereomer. These
results suggest that 1-amino-3-siloxybutadienes are con-
siderably more reactive than 1-methoxy-3-siloxy-1,3-
butadiene. For comparison, the Diels-Alder reaction
between Danishefsky’s diene and N-phenylmaleimide is
reported to require 0 °C to room temperature,12 and with
dimethyl acetylenedicarboxylate and methacrolein, re-
fluxing benzene.13
(3) (a) Shavrygina, O. A., Makin, S. M. Khim-Farm. Zh. 1969, 3,
17. (b) Cazeau, P., Frainnet, E. Bull. Soc. Chim. Fr. 1972, 1658-1659.
(c) J ung, M. E., McCombs, C. A. Tetrrahedron Lett. 1976, 2935-2938.
(d) Ibuka, T., Mori, Y., Inubushi, Y. Tetrrahedron Lett. 1976, 3169-
3172. (e) Obrecht, D. Helv. Chim. Acta 1991, 74, 27-46.
(4) Reviews: (a) Danishefsky, S. Acc. Chem. Res. 1981, 14, 400. (b)
Danishefsky, S. J .; DeNinno, M. P. Angew. Chem., Int. Ed. Engl. 1987,
26, 15. (c) Danishefsky, S. Chemtracts-Org. Chem. 1989, 2, 273.
(5) For a review on 2-amino dienes, see: (a) Enders, D.; Meyer, O.
Liebigs. Ann. 1996, 1023. For the preparation and use of 1-amino
dienes, see: (b) Oppolzer, W.; Frostl, W. Helv. Chim. Acta 1975, 58,
590. (c) Oppolzer, W.; Bieber, L.; Francotte, E. Tetrahedron Lett. 1979,
4537. (d) Overman, L. E.; Taylor, G. F.; J essup, P. J . Tetrahedron Lett.
1976, 3089. (e) Overman, L. E.; J essup, P. J . J . Am. Chem. Soc. 1978,
100, 5179. (f) Overman, L. E.; Freerks, R. L.; Petty, C. B.; Clizbe, L.
A.; Ono, R. K.; Taylor, G. F.; J essup, P. J . J . Am. Chem. Soc. 1981,
103, 2817. (g) Sustmann, R.; Rogge, M.; Nuchter, U.; Bandmann, H.
Chem. Ber. 1992, 125, 1647, and references cited therein.
(6) (a) Smith, A. B., III; Wexler, B. A.; Tu, C.-Y.; Konopelski, J . P.
J . Am. Chem. Soc. 1985, 107, 1308, and recerences cited therein. (b)
Comins, D. L.; Al-awar, R. S. J . Org. Chem. 1992, 57, 4098.
(7) 1-Amino-3-ethoxy-1,3-butadiene was previously prepared but
never used in a Diels-Alder reaction: Meerwein, H.; Florian, W.;
Schon, N.; Stopp, G. Liebigs Ann. 1961, 641, 1.
(8) For a recent review, see: (a) Shiosaki, K. Eschenmoser Coupling
Reaction. In Comprehensive Organic Synthesis; Pergamon Press: New
York, 1991; Vol 2, pp 865-892. Also, see: (b) Ireland, R. E.; Brown,
F. R. J . Org. Chem. 1980, 45, 1868.
(9) (a) Lienhard, U.; Fahrni, H.-P.; Neuenschwander, M. Helv. Chim.
Acta 1978, 61, 1609. (b) Markova, N. K.; Zaichenko, Y. A.; Tsil'ko, A.
E.; Maretina, I. A. J . Org. Chem. USSR 1984, 876.
(10) Other dialkylamino-substituted dienes were similarly prepared.
Details of their synthesis and reactivity will be reported in due course.
(11) Dienes 3-5 are slowly hydrolyzed in water and in the presence
of Lewis acids.
(12) Baldwin, S. W.; Greenspan, P.; Alaimo, C.; McPhail, A. T.
Tetrahedron Lett. 1991, 32, 5877.
S0022-3263(97)00438-6 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 16, 1997 5253
Ta ble 1. Diels-Ald er Rea ction s of Am in o Siloxy Dien e 3
w ith Va r iou s Dien op h iles
F igu r e 1. Competition experiment between dienes 3 and 10.
1H NMR spectra were recorded on a Bruker DRX-400 spec-
trometer at 400 MHz as solutions in CDCl3, using Me4Si (TMS)
as an internal standard.
Sch em e 3
regioselectivity. The cycloadducts are stable to flash
chromatography, which allowed the separation of the
endo and exo diastereomers. In contrast to the high endo-
selectivity observed for two of the examples shown above,
the reaction of 3 with methyl acrylate, methyl crotonate,
and acrylonitrile (entries 1-3) were less selective and
gave significant amounts of the exo isomers. Remarkably
high exo selectivity was observed for the cycloaddition
with dimethyl maleate (entry 5).
The products of these Diels-Alder reactions are po-
tentially versatile intermediates. As anticipated, the
â-amino enol silyl ether portion of the Diels-Alder
adducts can be converted to the corresponding enone
under acidic conditions, which promote hydrolysis of the
silyl enol ether as well as â-elimination of the amino
group. For example, subjection of the methacrolein
cycloadduct to aqueous HCl in THF afforded 4-formyl-
4-methylcyclohexenone 13 in 96% yield. The cycload-
ducts are sufficiently stable that certain chemical trans-
formations can be carried out on them prior to the
hydrolysis step. Thus, the carbonyl group of the meth-
acrolein adduct can either be reduced with lithium
aluminum hydride or subjected to Wittig olefination and
the resulting products hydrolyzed to afford the corre-
sponding alcohol 14 and alkene 15, respectively (Scheme
3).
Our studies have shown that 1-amino-3-siloxy-1,3-
butadienes can be prepared easily and in high yield and
are extremely reactive in Diels-Alder reactions. Diene
3 is appreciably more reactive than a 1-methoxy-3-siloxy-
1,3-butadiene and reacts readily with a wide range of
dienophiles to afford the cycloadducts in good yield.
Further applications of 1-amino 3-siloxy dienes, particu-
larly to the asymmetric Diels-Alder reaction, are in
progress and will be reported in due course.15
In order to better assess the relative reactivity of amino
siloxy diene 3 and Danishefsky’s diene 10, we carried out
an experiment which allowed the two dienes to compete
directly for a dienophile. A C6D6 solution containing 1
equiv each of dienes 3 and 10 (Figure 1, spectrum A) was
treated at room temperature with 1 equiv of methacrolein
(11). Two adducts, 8 and 12, can potentially form from
the competing Diels-Alder reactions. The NMR spec-
trum taken soon after addition of the dienophile (t ) 10
min, spectrum B) showed appreciable decrease in the
relative amount of diene 3, and the appearance of signals
from a single Diels-Alder adduct, independently con-
firmed to be adduct 8. After all the dienophile was
consumed (t ) 4 h, spectrum C), the reaction mixture
contained adduct 8 and unreacted diene 10, with no
discernible amount of adduct 12. On the basis of the
assumption that side-products present to the extent of
3-5% should be detectable by NMR, it may be safe to
conclude that amino siloxy diene 3 is over 25 times more
reactive than 1-methoxy 3-siloxy diene 10.
Amino siloxy diene 3 undergoes Diels-Alder reactions
with various dienophiles (Table I).14 The cycloaddition
reactions proceed under relatively mild conditions and
afford the cycloadducts in good yields, with complete
Ack n ow led gm en t. We thank the University of
Chicago for financial support of this work. Generous
financial support from Pfizer Inc. and Merck & Co. are
also gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data of all new compounds employed in
this study (48 pages).
(13) Danishefsky, S.; Kitahara, T.; Yan, C. F.; Morris, J . J . Am.
Chem. Soc. 1979, 101, 6996.
(14) Typical Diels-Alder procedure: To a solution of diene 3 (1.2-
1.5 mmol) in dry toluene (1-2 mL) was added the dienophile (1 mmol),
and the reaction mixture was stirred overnight at the temperature
indicated (see Table 1). Concentration in vacuo, followed by flash
chromotography on silica gel (the eluent contained 2-5% triethy-
lamine), afforded the cycloadducts shown.
J O970438Q
(15) Kozmin, S. A.; Rawal, V. H. J . Am. Chem. Soc. 1997, 119, 7165.