An intramolecular hetero Diels-Alder reaction of α- (alkynylsiloxy)aldimine derivatives

Article abstract of DOI:10.1016/S0040-4039(00)00936-9

Intramolecular hetero Diels-Alder reactions of α- (alkynylsiloxy)aldimine derivatives were developed. α- (Alkynylsiloxy)aldehydes, which were prepared from 1,2-alkanediols in two steps, were converted into the corresponding biscarbamates or N-arylimines. In the presence of BF₃·OEt₂, the biscarbamates afforded oxazine derivatives in high diastereoselectivity. On the other hand, quinoline derivatives were obtained in good yields by treating the N-arylimines with trifluoromethanesulfonic acid. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00936-9

Tetrahedron Letters 41 (2000) 5715±5718
An intramolecular hetero Diels±Alder reaction of
a-(alkynylsiloxy)aldimine derivatives
Tadashi Shimizu,a Keiji Taninoa,* and Isao Kuwajimab,*
aDivision of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan
bLaboratory for Natural Products Chemistry, Kitasato University, S-105 1-15-1, Kitasato,
Sagamihara 228-8555, Japan
Received 12 May 2000; revised 29 May 2000; accepted 2 June 2000
Abstract
Intramolecular hetero Diels±Alder reactions of a-(alkynylsiloxy)aldimine derivatives were developed.
a-(Alkynylsiloxy)aldehydes, which were prepared from 1,2-alkanediols in two steps, were converted into
.
the corresponding biscarbamates or N-arylimines. In the presence of BF3 OEt2, the biscarbamates a€orded
oxazine derivatives in high diastereoselectivity. On the other hand, quinoline derivatives were obtained in
good yields by treating the N-arylimines with tri¯uoromethanesulfonic acid. # 2000 Elsevier Science Ltd.
All rights reserved.
Keywords: Diels±Alder reactions; imines; carbamates; alkynes; oxazines; quinolines.
Hetero Diels±Alder reactions of aldimine derivatives with various dienes provide a powerful
methodology for the synthesis of nitrogen-containing compounds.1 From a synthetic viewpoint,
the intramolecular version of the cycloaddition reaction is particularly useful because of the high
regio- and stereoselectivity.2 On the other hand, we have recently reported a convenient method
for the synthesis of a-(alkynylsiloxy)aldehydes from 1,2-alkanediols in two steps.3 Under the
in¯uence of Me2AlCl, the aldehyde underwent an intramolecular alkynylation reaction to yield
an anti diol predominantly (Scheme 1).
Scheme 1.
* Corresponding author.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00936-9

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The high stereoselectivity of the above reaction led us to examine a similar transformation
using the corresponding aldimine derivatives; the method was found, however, to a€ord bicyclic
products through an intramolecular hetero Diels±Alder reaction.
At ®rst, biscarbamates 2a and 2b, which were chosen as a precursor of an N-acyliminium
intermediate,4 were prepared in high yield by treating a-(alkynylsiloxy)aldehydes 1a and 1b with
urethane and a catalytic amount of 10-camphorsulfonic acid (Scheme 2).5 Treatment of the
.
biscarbamates with BF3 OEt2 induced an intramolecular hetero Diels±Alder reaction to give
bicyclic oxazines 3a and 3b as a single isomer, respectively. The trans relationship between the
1
phenyl group and the nitrogen atom of 3b was determined by H NMR spectra, in which the
coupling constant between Ha and Hb has a fairly large (9.3 Hz) value. Since these oxazines proved
to easily undergo hydrolysis by silica gel column chromatography, the cycloadducts were isolated
as the corresponding ketocarbamates 4 after being treated with pridinium p-toluenesulfonate
(PPTS).6
Scheme 2.
The stereochemistry of the intramolecular hetero Diels±Alder reaction can be rationalized by
assuming transition state models TS-1 and TS-2, both of which have the substituent R on the
quasi equatorial position. Since TS-2 su€ers from gauche repulsion between the substituent R
and the iminium ion moiety, the reaction would proceed mainly through TS-1 to give the
anti-product (Fig. 1).
Figure 1.
Next, a-(alkynylsiloxy)aldehyde 1b was subjected to a condensation reaction with aniline in the
presence of MS4A to a€ord N-arylimine 5. Under the in¯uence of tri¯uoromethanesulfonic acid,
imine 5 gave dihydroquinoline derivative 6 along with a small amount of quinoline 7 via an

5717
intramolecular hetero Diels±Alder reaction (Scheme 3).7 In a similar manner, dihydroquinoline
derivative 8, having an angular methyl group was obtained from 1a and 2,6-xylidine as a single
1
diastereomer. The H NMR spectra of 6 and 8 indicated the anti-stereochemistry at the ®ve-
membered ring, which would be explained by a transition state model similar to TS-1 in Fig. 1.
Scheme 3.
The use of o- or p-substituted anilines resulted in the formation of quinoline derivatives having
a functional group at the 6- or the 8-position, respectively. In these cases, the crude product of the
Diels±Alder reaction was treated with DDQ to give the corresponding quinoline derivative, since
some of the dihydroquinoline derivatives were fairly labile (Scheme 4).8
Scheme 4.
In conclusion, biscarbamates and N-aryl imine derivatives, which were prepared from a-(alky-
nylsiloxy)aldehydes, underwent intramolecular hetero Diels±Alder reactions under acidic
conditions to give bicyclic compounds in good yield. Since a-(alkynylsiloxy)aldehydes, including
optically active ones, can be easily prepared from the corresponding 1,2-alkanediols, the present
reactions would provide a useful pathway for the synthesis of naturally occurring, nitrogen-containing
compounds.
Acknowledgements
This work was partially supported by Grants from the Ministry of Education, Science, Sports,
and Culture of the Japanese Government.

5718
References
1. (a) Boger, D. L.; Weinreb, S. M. Hetero Diels±Alder Methodology in Organic Synthesis; Academic Press: San
Diego, 1987; pp. 34±70. (b) Weinreb, S. M. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I. Eds.
Pergamon: Oxford, 1991; Vol. 5, pp. 401±449. (c) Boger, D. L. In Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I. Eds. Pergamon: Oxford, 1991; Vol. 5, pp. 451±512. (d) Weinreb, S. M.; Scola, P. M. Chem. Rev. 1989,
89, 1525±1534.
2. Roush, W. R. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I. Eds. Pergamon: Oxford, 1991; Vol. 5,
pp. 513±550.
3. Tanino, K.; Shimizu, T.; Kuwahara, M.; Kuwajima, I. J. Org. Chem. 1998, 63, 2422±2423.
4. (a) Merten, R.; Muller, G. Angew. Chem. 1962, 74, 866±867. (b) Tohyama, Y.; Tanino, K.; Kuwajima, I. J. Org.
Chem. 1994, 59, 518±519.
5. Preparation of 2a: A mixture of aldehyde 1a (0.60 g, 1.7 mmol), urethane (0.45 g, 5.1 mmol), and camphorsulfonic
acid (78 mg, 0.34 mmol) in benzene (3.4 mL) was stirred at room temperature for 24 h. A saturated aqueous
solution of NaHCO3 was added, and the mixture was separated. The aqueous layer was extracted with ether, and
the combined organic layer was dried over MgSO4. Concentration under reduced pressure followed by puri®cation
by ¯ash chromatography a€orded 0.82 g (92%) of biscarbamate 2a. IR (neat) 3350, 1739, 1558, 1471, 1224, 1060
cm^1; 1H NMR (270 MHz, CDCl3) ꢀ 0.88 (t, J=7.1 Hz, 3 H), 0.90 (t, J=7.1 Hz, 3 H), 1.04 (s, 18 H), 1.16±1.80 (m,
14 H), 2.29 (t, J=7.0 Hz, 2 H), 3.92±4.32 (m, 5 H), 5.20±5.50 (m, 2 H), 5.84 (bs, 1 H); 13C NMR (75 MHz, CDCl3)
ꢀ 13.93, 14.05, 19.64, 20.61, 20.69, 22.49, 22.61, 22.71, 27.56 (6C), 28.29, 28.44, 31.19, 31.54, 60.58, 60.83, 61.13,
76.36, 79.34, 111.19, 155.02, 155.42.
.
6. Synthesis of ketocarbamate 4a: A mixture of biscarbamate 2a (0.23 g, 0.46 mmol) and BF3 OEt2 (0.23 mL, 1.8
mmol) in dichloroethane (1.2 mL) was stirred at room temperature for 5 h. Usual work-up (see above) a€orded
cycloadduct 3a, which was treated with PPTS (12 mg, 0.05 mmol) in dichloroethane (2.3 mL) at room temperature
for 10 h. Usual work-up followed by puri®cation by ¯ash chromatography a€orded 153 mg (84% from 2a) of
biscarbamate 4a. IR (CDCl3) 3440, 1720, 1510, 1420, 1270 cm^1; 1H NMR (270 MHz, CDCl3) ꢀ 0.87 (t, J=7.1 Hz,
3 H), 0.91 (t, J=7.3 Hz, 3 H), 0.97 (s, 9 H), 1.18 (s, 9 H), 1.20±1.78 (m, 14 H), 2.45 (dt, J=1.6, 7.0 Hz, 2 H), 3.72±
4.24 (m, 5 H), 4.92 (bs, 1 H).
7. (a) Linkart, F.; Laschat, S. Synlett 1994, 125±126. (b) Linkart, F.; Laschat, S.; Knickmeier, M. Liebigs Ann. Chem.
1995, 985±983. (c) Linkart, F.; Laschat, S.; Kotila, S.; Fox, T. Tetrahedron 1996, 52, 955±970.
8. Synthesis of quinoline derivative 9: A mixture of aldehyde 1a (33 mg, 0.09 mmol), p-anisidine (13 mL, 0.11 mmol),
and MS4A (65 mg) in benzene (0.45 mL) was stirred at room temperature for 3 h. The mixture was ®ltered, and
the ®ltrate was concentrated under reduced pressure. The crude imine was treated with tri¯uoromethanesulfonic
acid (10 mL, 0.11 mmol) in dichlolomethane (0.45 mL) at ^78ꢀC for 30 min. Usual work-up a€orded the
corresponding dihydroquinoline derivative, which was treated with DDQ (25 mg, 0.11 mmol) in dichloroethane
(0.45 mL) at room temprature for 1 min. Concentration under reduced pressure followed by puri®cation by ¯ash
chromatography a€orded 39 mg (91% from 1a) of 9: IR (neat) 1575, 1560, 1495, 1470, 1390, 1360, 1330, 1225,
1
1090, 1050 cm^1; H NMR (270 MHz, CDCl3) ꢀ 0.92 (t, J=7.3 Hz, 3 H), 0.95 (t, J=7.3 Hz, 3 H), 1.02 (s, 9 H),
1.13 (s, 9 H), 1.20±1.90 (m, 14 H), 2.10±2.40 (m, 1 H), 2.94±3.29 (m, 2 H), 3.94 (s, 3H), 5.10 (dd, J=3.6, 10.2 Hz, 1
H), 7.28 (d, J=3.3 Hz, 1 H), 7.37 (dd, J=3.3, 10.5 Hz, 1 H), 7.96 (d, J=10.5 Hz, 1 H), 13C NMR (75 MHz,
CDCl3) ꢀ 14.12, 14.32, 20.56, 22.49, 22.65, 22.86, 27.87 (3C), 28.32 (3C), 28.66, 30.16, 30.74, 31.63, 37.77, 38.22,
55.48, 82.05, 102.79, 121.51, 125.58, 126.72, 131.05, 145.08, 152.68, 156.74, 169.47.