Diastereoselective synthesis of 4-sila-3,4,4a,5-tetrahydro-2H-isoquinolin-1-ones through intramolecular Diels-Alder reaction of chiral silatrienes

Article abstract of DOI:10.1055/s-2001-16784

New Si-chiral N-2-silabut-3-enylpyran-2-one-6carboxamides were prepared in four steps from dichloro(chloro-methyl)methylsilane. The thermal inverse electron demand intra-molecular Diels-Alder reaction of these compounds gave 4-sila3,4,4a,5-tetrahydro-2H-isoquinolin-1-ones. Moderate diastereoselectivity was observed for a silatriene bearing a methyl and a cyclohexyl substituent on the chiral silicon atom. The intermediate tricyclic adduct of this reaction was also isolated.

Full text of DOI:10.1055/s-2001-16784

LETTER
1455
Diastereoselective Synthesis of 4-Sila-3,4,4a,5-tetrahydro-2H-isoquinolin-1-
ones through Intramolecular Diels-Alder Reaction of Chiral Silatrienes
Paulo J. Coelho,*1 Luis Blanco
Laboratoire des Carbocyles (Associé au CNRS), Institut de Chimie Moléculaire d'Orsay, Bât 420, Université de Paris-Sud, 91405 Orsay,
France
Fax +351-259-350480; E-mail: Pcoelho@marao.utad.pt
Received 14 May 2001
magnesium bromide. Heating chloromethylsilanes 3a,b in
Abstract:
New
Si-chiral N-2-silabut-3-enylpyran-2-one-6-
benzylamine at 100 °C for 2 hours provided N-benzyl-
amines 4a,b which were acylated with pyran-2-one-6-car-
bonyl chloride,6 to afford the requisite carboxamides 5a,b,
carboxamides were prepared in four steps from dichloro(chloro-me-
thyl)methylsilane. The thermal inverse electron demand intra-mo-
lecular Diels-Alder reaction of these compounds gave 4-sila-
3,4,4a,5-tetrahydro-2H-isoquinolin-1-ones. Moderate diastereo- in good yield.7 The structure of silanes 2-5 were assigned
selectivity was observed for a silatriene bearing a methyl and a
on the basis of their spectral data.
cyclohexyl substituent on the chiral silicon atom. The intermediate
tricyclic adduct of this reaction was also isolated.
Key words: Diels-Alder reactions, stereoselectivity, chiral
silatrienes, 4-silatetrahydro-2H-isoquinolin-1-ones
Cl
Cl
R
Cl
R
Cl
i
ii
Si
Si
Si
Me
Cl
Me
Me
Cl
1
3a 63 %
3b 71 %
a R= Ph
b R= c-C6H11
2a 67%
2b 41%
Asymmetric synthesis is one of the major goals in organic
chemistry. Highly diastereoselective chemical transfor-
mations have been achieved based on a carbon chiral cen-
tre. Although silicon is, in several aspects, comparable to
carbon, rather few examples have been reported on the use
of chiral silicon compounds as chiral inductors. The initial
studies were undertaken using mainly methyl(1-naphth-
yl)phenylsilyl derivatives in intermolecular reactions.2
The difficulty of the synthesis of such compounds and the
low diastereoselectivities frequently observed, have
somehow discouraged further studies. Recently, very high
diastereomeric excesses (d.e.) have been achieved in the
addition, at very low temperatures, of organometallic
compounds to chiral acylsilanes bearing an alkoxymeth-
ylgroup on the silicon atom.3 Since intramolecular reac-
tions could be more selective than intermolecular ones,
we have focused our attention on the study of the
selectivity of intramolecular reactions of chiral silicon
compounds.4
Ph
Ph
iv
N
O
R
NH
iii
Si
R
Si
Me
O
Me
O
4a 67 %
4b 85 %
5a 80 %
5b 73 %
Scheme 1 i) PhMgBr, reflux, Et2O; c-C6H11MgBr, CuCN (5%), re-
flux Et2O. ii) CH2 = CHMgBr, CuCN (5%), THF, r.t. iii) PhCH2NH2,
Et3N, 100 ºC. iv) Pyran-2-one-6-carbonyl chloride, Et3N, CH2Cl2, 0
ºC.
Heating a dilute xylene solution of carboxamide 5a (1 h)
and a toluene solution of carboxamide 5b (3 h) under re-
flux, yielded 4-sila-3,4,4a,5-tetrahydro-2H-isoquinolin-1-
ones 7a (85%) and 7b (76%) respectively, as a mixture of
two diastereomers, which could not be separated by chro-
matography on silica gel (Scheme 2).8
In this work we describe the thermal inverse electron de-
mand intramolecular Diels-Alder reaction of pyran-2-
one-6-carboxamides linked to a vinyl dienophile by a
chiral silicon atom possessing methyl and phenyl or cy-
clohexyl groups, followed by elimination through a retro
Diels-Alder reaction, which gave new 4-sila-3,4,4a,5-
tetrahydro-2H-isoquinolin-1-ones.5
Ph
Ph
N
N
O
O
R
∆
R
Si
Si
Pyran-2-one-6-carboxamides 5a,b were prepared in 4
steps, starting from dichloro(chloromethyl)methylsilane 1
(Scheme 1).
O
Me
Me
O
7a,b
5a,b
Treatment of dichloro(chloromethyl)methyl silane 1 with
the Grignard reagents derived from bromobenzene and
bromocyclohexane afforded, respectively, chlorosilanes
2a and 2b, which were converted into the corresponding
vinylsilanes 3a,b by CuCN-catalyzed reaction with vinyl-
Scheme 2
Synlett 2001, No. 9, 1455–1457 ISSN 0936-5214 © Thieme Stuttgart · New York

1456
P. J. Coelho, L. Blanco
LETTER
The diastereomeric ratio was determined by 1H NMR by Thus, both compounds should be formed via an exo tran-
integration of the CH3Si singlets. Formation of silalactam sition state, and the observed diastereomeric ratio 80 / 20
7b bearing methyl and cyclohexyl groups on the silicon represents the diastereoselectivity imposed by the chiral
chiral atom occurred with moderate diastereoselectivity silicon atom.
(d.e. = 58%), while the cyclisation of silatriene 5a pre-
In conclusion, the intramolecular Diels-Alder reaction
of N-(vinylsilylmethyl)pyran-2-one-6-carboxamides fol-
lowed by CO2 elimination through a retro Diels-Alder
senting methyl and phenyl groups on the silicon chiral at-
om, showed very poor selectivity (d.e. = 12%).9
It is known that the inverse electron demand DA reaction reaction allows the preparation of 4-silatetrahydro-
of pyran-2-ones with alkenes affords 2-oxabicyclo- 2H-isoquinolin-1-ones in good yield. When performed
[2.2.2]oct-5en-3-ones.5 These highly functionalized com- at 80 ºC the reaction gave a tricyclolactam which is an
pounds bearing several chiral centres are of great interest interesting intermediate since it has 4 chiral centers and
as intermediates in the synthesis of natural products, but could be used to prepare highly functionalized cyclohex-
are rarely isolated since they easily lose CO2 to produce ene derivatives. We have shown that even at relatively
dihydrobenzenes. Cycloaddition reaction of carboxamide high temperature a diastereoselective intramolecular DA
5b, performed in a toluene solution at 80 °C (2 h) instead reactions of Si-chiral silatrienes can be obtained. The
of 110 ºC, led to the tricyclolactam 6 presenting the CO2 diastereoselectivity of this reaction can be enhanced when
bridge, isolated in 90% yield, after chromatography on sil- the silicon atom possesses bulky substituents such as the
ica gel. 1H NMR analysis showed the presence of a mix- cyclohexyl group.
ture of two diastereomers in a 80 / 20 ratio. Heating a
xylene solution of this compound for 2 h, resulted in
silactam 7b, isolated in 56% yield with a d.e. of 60%,
Acknowledgement
We thank JNICT for awarding a PhD grant to P. Coelho.
similar to the one obtained after heating the carboxamide
5b at 110 °C (58%) (Scheme 3).
References and Notes
O
(1) Departamento de Química, Universidade de Trás-os-Montes e
Alto Douro, 5000 Vila Real, Portugal.
H6
O
H5exo
(2) a) Brook, A.G.; Duff, J. M.; Anderson, D. G. J. Am. Chem.
Soc. 1970, 92, 7567. b) Daniels, R.G.; Paquette, L.A.
Organometallics 1982, 1, 1449. c) Larson, G.L.; Sandoval, S.;
Cartledge, F.; Froonczec, F.R. Organometallics 1983, 2, 810.
d) Hathaway, S.J.; Paquette, L.A. J. Org. Chem. 1983, 48,
3351. e) Fry, J.L.; McAdam, M.A. Tetrahedron Lett. 1984, 25,
5859. f) Larson, G.L.; Torres, E. J. Organomet. Chem. 1985,
19, 293. g) B. F. Bonini; G. Maccagnani; S. Masiero; G.
Mazzanti; P. Zani, Tetrahedron Lett. 1989, 30, 2677.
(3) a) Bienz, S.; Chapeaurouge, A. Helv. Chim. Acta 1991, 74,
1477. b) Chapeaurouge, A.; S. Bienz, S. Helv. Chim. Acta
1993, 76, 1876.
Si(CH3)(c-C6H11
)
Ph
N
H5endo
O
6
80 °C
H4a
N
Ph
O
Me
Si
O
140 °C
O
c-C6H11
Ph
O
110 °C
N
5b
-CO2
Me
Si
c-C6H11
7b
(4) a) Coelho, P.; Blanco, L. Tetrahedron Lett. 1998, 39, 4261.
b) Coelho, P.; Blanco, L. Eur. J. Org. Chem. 2000, 3039. For
current reviews on Si-tethered Diels-Alder reactions see:
c) Gauthier, J.; Zandi, K; Shea, K. Tetrahedron 1998, 54,
2289. d) Fensterbank, L.; Malacria, M.; Sieburth, S. Synthesis
1997, 813-854. e) Bols, M.; Skrydstrup, T. Chem. Rev. 1995,
95, 1253-1277.
(5) For a review on the inverse DA of pyran-2-ones see:
Afarinkia, K; Vinader, V.; Nelson, T.D.; Posner, G. H.
Tetrahedron 1992, 48, 9111
Scheme 3
Assignment of the configuration of the two diastereomers
of tricyclolactam 6 was done by comparison of the chem-
ical shifts and the coupling constants between the protons
H5 and H6 with the 1H NMR data for this type of bicyclic
compounds.10 In general, H5endo appears at higher field
than H5exo and the coupling constant between H6 and H5exo
is slightly higher than the one observed between H6 and
(6) Dunhelblum, M.R.; Allain, R.; Dreiding, A.S. Helv. Chim.
Acta 1970, 53, 2159.
(7) Procedure for the synthesis of 5: Pyran-2-one-6-carbonyl
chloride (0.75 mmol) was added dropwise to a solution of
N-benzyl-N-silylmethylamines 4 (0.5 mmol), 20 mL of
CH2Cl2 and 150 L of triethylamine (1.0 mmol) under argon
atmosphere at 0 ºC. After stirring for 30 min, the mixture was
hydrolyzed with NH4Cl and extracted three times with
CH2Cl2. The combined organic extracts were dried over
anhydrous Na2SO4 and concentrated under reduced pressure.
The crude product was purified by column chromatography
(n-hexane/Et2O, 60/40).
H
5endo. For the major isomer of lactam 6 and using this
chemical shift order rule, the signal at 1.99 ppm should be
attributed to H5exo and the one at 1.72 to H5endo. These at-
tributions are in agreement with the respective coupling
constants of 3 Hz and 2 Hz with the H6 proton (3.48 ppm).
Since H5endo has a coupling constant of 12 Hz with H4a, the
C-Si bond on C4 must be exo. The same deduction al-
lowed the attribution of an exo C-Si bond to the minor iso-
mer (H5exo at 2.05 ppm, JH5exoH6 = 2.5 Hz; H5endo at 1.75
ppm, JH5exoH6 = 2 Hz, JH5endoH4a = 12 Hz).
5a : 80% yield; IR (neat) 1750 (C=O) 1650 (C=C), 1260
(Si-CH3); 1H NMR (200 MHz, CDCl3) 7.75-7.6 (m, 2H),
Synlett 2001, No. 9, 1455–1457 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Diastereoselective Synthesis of 4-Sila-3,4,4a,5-tetrahydro-2H-isoquinolin-1-ones
1457
7.5-7.2 (m, 7H), 7.2-7.1 (m, 2H), 6.6-6.1 (m, 4H), 5.9-5.75 (m,
J = 15 Hz, major isomer) and 2.48 (d, J = 14.7 Hz, minor
isomer) and 2.69 (d, J = 15 Hz, major isomer) (2H), 2.60-2.10
(m, 3H), 0.42 (s, 1.7H), 0.40 (s, 1.3H); 13C NMR 168.67,
167.84, 137.28, 137.20, 134.65, 133.84, 132.83, 132.62,
131.46, 131.20, 130.20, 130.05, 129.94, 129.86, 129.21,
128.61, 128.43, 128.36, 128.27, 128.17, 127.80, 127.21,
127.19, 124.52, 124.44, 54.51, 53.95, 35.72, 23.67, 23.05,
21.19, 21.09, -6.73, -8.59; MS-EI m/z 345 (53, M+), 344 (59),
254 (24), 151 (48), 148 (22), 105 (38), 91 (100).
1H), 4.48 (s, 2H), 3.21 (s, 2H), 0.49 (s, 3H); 13C NMR 159.46,
155.66, 142.66, 135.32, 134.92, 134.78, 134.07, 129.46,
128.66, 127.82, 127.28, 117.07, 106.21, 53.89, 36.36, -5.08;
MS-EI m/z 346 (11), 345 (36), 344 (36), 330 (2), 354 (21), 151
(28), 148 (17), 121 (19), 105 (17), 91 (100), 77 (15). MS-CI
(NH3) m/z 390 (100, M++1), 389 (M+), 346 (33), 345 (30), 344
(53).
5b : 73% yield; IR (neat) 1750 (C=O), 1650 (C=C), 1260
(Si-CH3); 1H NMR (200 MHz, CDCl3) 7.4-7.15 (m, 6H),
6.59 (d, J = 7.1 Hz, 1H), 6.35 (d, J = 9.4 Hz, 1H), 6.15-6.05
(m, 2H), 5.85-5.65 (m, 1H), 4.67 (d, J = 16.0 Hz, 1H), 4.54 (d,
J = 16.2 Hz, 1H), 3.11 (d, J = 14.7 Hz, 1H), 2.95 (d, J = 14.9
Hz, 1H), 1.8-0.7 (m, 11H), 0.14 (s, 3H); 13C NMR 160.78,
159.56, 155.90, 142.76, 135.60, 135.04, 133.96, 128.68,
127.79, 127.17, 117.04, 106.30, 53.93, 34.61, 27.64, 27.10,
26.58, 26.96, 24.26, -7.86; MS-EI m/z 352 (16), 351 (54), 268
(45), 260 (22), 178 (66), 91 (100).
7b: 76% yield; 1H NMR (200 MHz, CDCl3) 7.40-7.15 (m,
5H), 7.12-7.06 (m, minor isomer) and 6.96-6.88 (m,major
isomer)(1H), 6.15-5.80 (m, 2H), 4.78 (d, J = 14.7 Hz, minor
isomer) and 4.72 (d, J = 15 Hz, major isomer) and 4.62 (d,
J = 15 Hz, major isomer) and 4.60 (d, J = 14.7 Hz, minor
isomer) (2H), 2.69 (d, J = 15.1 Hz, minor isomer) and 2.65 (d,
J = 14.6 Hz, major isomer) and 2.54 (d, J = 15.1 Hz, minor
isomer) and 2.65-2.47 (m) and 2.45 (d, J = 14.7 Hz, major
isomer) (3H), 2.35- 2.24 (m, 0.8H), 2.21-1.95 (m, 1.2H), 1.70-
1.50 (m, 5H),1.30-0.90 (m, 5H), 0.90-0.70 (m, 1H), 0.07 (s,
2.4H), 0.01 (s, 0.6H); 13C NMR 169.12, 168.04, 137.51,
137.45, 131.92, 131.36, 130.23, 128.90, 128.69, 128.62,
128.46, 128.25, 127.29, 127.20, 126.93, 124.88, 124.54,
129.36, 54.43, 53.99, 33.95, 33.54, 27.84, 27.69, 27.41, 27.35,
27.28, 26.53, 23.89, 23.60, 23.50, 22.18, 21.67, 18.99, -8.08,
-9.44; MS-EI m/z 351 (26.6, M+), 350 (22.9), 268 (11), 260
(15), 178 (21), 176 (27), 91 (100).
(8) Diels-Alder reaction of 5: A solution of pyran-2-one-6-
carboxamide 5 (0.25 mmol), 10 mg of phenothiazine and 20
mL of toluene or xylene were heated at 80 °C, 110 °C or
140 ºC under argon atmosphere. The reaction evolution was
followed by thin layer chromatography. After the complete
disappearance of the silatriene, the solvent was removed under
reduced pressure and the crude product was purified by
column chromatography (n-hexane/Et2O, 60/40).
6: 90% yield; IR (neat): 1760 (C=O), 1670, 1650, 1260 (Si-
CH3);1H NMR (200 MHz, CDCl3) 7.40-7.15 (m, 6H), 6.49
(dd, J = 7.4, 8.2 Hz, 0.8 H), 6.43 (dd, J = 7.4, 8.2 Hz, 0.2H),
4.79 (d, J = 14.7 Hz, 0.8H), 4.72-4.53 (m, 0.4H), 4.47 (d,
J = 14.7 Hz, 0.8H), 3.58-3.53 (m, minor isomer) and 3.53-
3.43 (m, major isomer) (1H), 3.22 (d, J = 15.2 Hz, 0.2H), 3.00
(d, J = 15 Hz, 0.8H), 2.64 (d, J = 15 Hz, 0.8H), 2.43 (d,
J = 15.2 Hz, 0.2H), 2.05 (ddd, J = 2.5, 4, 13 Hz, minor isomer)
and 1.99 (ddd, J = 3, 3.5, 12 Hz, major isomer) (1H), 1.75
(ddd, J = 2, 12, 12 Hz, minor isomer) and 1.72 (ddd, J = 2, 12,
12 Hz, major isomer)(1H), 1.70-1.42 (m, 4H), 1.42-0.60 (m
with dd at 1.32, J = 3.5, 12 Hz, 7H), 0.52-0.33 (m, 1H), -0.01
(s, 2.4H), -0.20 (s, 0.6H); 13C NMR 173.42, 165.95, 137.33,
136.47, 133.83, 133.29, 129.23, 128.51, 128.31, 128.13,
127.59, 127.53, 127.07, 124.38, 84.31, 84.06, 54.14, 54.02,
40.91, 40.79, 34.99, 33.81, 27.56, 27.41, 27.33, 27.15, 26.65,
26.47, 26.40, 26.35, 25.05, 24.64, 23.77, 23.34, 23.28, 22.51,
21.95, -6.52, -7.86.
(9) For examples of the stereochemical influence of a stereogenic
center at the position of the silicon see: a) Roush, W. R.;
Peseckis, S. M. J. Am. Chem. Soc. 1981, 103, 6696-6704.
b) Taber, D. F.; Campbell, C.; Gunn, B. P.; Chiu, I. -C.
Tetrahedron Lett. 1981, 22, 5141-5144. c) Funk, R. L.; Zeller,
W. E. J. Org. Chem. 1982, 47, 180-182. d) Cauwberghs, S.;
De Clercq, P. J.; Tinant, B.; De Clercq, J. P. Tetrahedron Lett.
1988, 29, 2493-2496. e) Kametani, T.; Kato Y.; Honda T.;
Fukumoto K. J. Am. Chem. Soc. 1976, 98, 8185-8190.
(10) a) Markó J. E.; Seres P.; Swarbrick, T. M.; Staton, J.; Adams
H.; Tetrahedron Lett. 1992, 33, 5649-5652. b) Tomisawa, H.;
Hongo, H.; Kato, H.; Fujita, R.; Sato A. Chem. Pharm. Bull.
1978, 26, 2312-2315. c) Harano, K.; Aoki, T.; Eto, M.;
Hisano, T. Chem. Pharm. Bull. 1990, 38, 1182-1191.
d) Martin, P.; Steiner, E.; Streith, J.; Winkler, T.; Bellus, O.,
Tetrahedron 1985, 41, 4057-4078. e) Somekawa, K.; Shimo,
T., Yoshimura, H.; Suishu, T. Bull. Chem. Soc. Jpn. 1990, 63,
3456-3461.
7a: 85% yield; IR (neat) 1770 (C=O), 1640, 1610, 1260
(Si-CH3); 1H NMR (200 MHz, CDCl3) 7.50-7.20 (m, 10H),
7.22-7.14 (m, 0.45H), 7.08-7.01 (m, 0.55H), 6.15-5.80 (m,
2H), 4.81 (d, J = 14.3 Hz) and 4.77 (s) and 4.65 (d, J = 14.3
Hz) (2H), 2.93 (d, J = 14.7 Hz, minor isomer) and 2.90 (d,
Article Identifier:
1437-2096,E;2001,0,09,1455,1457,ftx,en;G08601ST.pdf
Synlett 2001, No. 9, 1455–1457 ISSN 0936-5214 © Thieme Stuttgart · New York