On the reactivity of (7-oxabicyclo[2.2.1]hept-5-en-2-ylidene)amines. Different reaction paths leading to the same final products

Article abstract of DOI:10.1002/1522-2675(20011219)84:12<3667::AID-HLCA3667>3.0.CO;2-Z

The reaction of amines, N-substituted by a 7-oxabicycIo[2.2.1]hept-5-en-2-ylidene moiety, either with PhSCl or mCPBA (meta-chloroperbenzoic acid) unexpectedly afforded the same type of furan derivatives by two different reaction paths. The results confirm the intervention of a homoconjugative, electron-releasing effect of the oxabicycloalkenylideneamine moieties, as predicted theoretically.

Full text of DOI:10.1002/1522-2675(20011219)84:12<3667::AID-HLCA3667>3.0.CO;2-Z

Helvetica Chimica Acta Vol. 84 (2001)
3667
On the Reactivity of (7-Oxabicyclo[2.2.1]hept-5-en-2-ylidene)amines.
Different Reaction Paths Leading to the Same Final Products
by Odo¬n Arjona, Aurelio G. Csa¬ky, M. Carmen Murcia, and JoaquÌn Plumet*
»
¬
Universidad Complutense de Madrid. Facultad de QuÌmica. Departamento de QuÌmica Organica. E-28040
Madrid (e-mail: plumety@quim.ucm.es)
¬
Dedicated to Prof. Andre M. Braun on the occasion of his 60th birthday
The reaction of amines, N-substituted by a 7-oxabicyclo[2.2.1]hept-5-en-2-ylidene moiety, either with
PhSCl or mCPBA (meta-chloroperbenzoic acid) unexpectedly afforded the same type of furan derivatives by
two different reaction paths. The results confirm the intervention of a homoconjugative, electron-releasing
effect of the oxabicycloalkenylideneamine moieties, as predicted theoretically.
1. Introduction. Substituted 7-oxabicyclo[2.2.1]heptane derivatives 1 are impor-
tant synthetic intermediates because these compounds show a broad spectrum of
reactivity generally in a predictable regio- and stereocontrolled fashion [1]. In
particular, remote controlled electrophilic addition to the endocyclic CˆC bond of the
unsaturated derivatives 21) [2][3] and nucleophilic addition to the carbonyl group of
compounds 32) [4] have been considered in depth.
To the best of our knowledge, the reactivity of alkylideneamines (ˆ formal N-
substituted imines) derived from 7-oxatrinorbornene 4 [5] has not been previously
reported, perhaps because the a priori expected pattern of reactivity for these
compounds should not be very different that observed for their precursor 2b. However,
the very different behavior shown by compounds 4 as compared with ketone 2b in two
well-known and synthetically useful reactions constitutes a not-yet-reported aspect of
the chemistry of these bicyclic systems, which is the object of the present report.
1
)
)
For studies on remote substituent effects in bicyclic systems, see e.g. [2]; for synthetic applications, see e.g.
[3].
For the stereochemical control of nucleophilic additions to bicyclic ketone 3, see e.g. [4].
2

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Helvetica Chimica Acta Vol. 84 (2001)
Quantum calculations by Carrupt and Vogel [6] have predicted that homoconjugated
imino substituents can be electron-releasing-like carbonyl moieties.
2. Results and Discussion. 2.1. Reaction of N-(7-Oxabicyclo[2.2.1]hept-5-en-2-
ylidene)benzylamine (5) with Phenylsulfonyl Chloride. The 7-oxatrinorbornenone 2b
reacts with PhSCl to give the 5-exo-(phenylsulfenyl)-6-endo-chloro derivative 6 in a
reaction in which the remote carbonyl group behaves as a homoconjugated electron-
donating group [7] (Scheme 1). Under the same reaction conditions, alkylideneamine 5
gave the furan derivative 7. No traces of the expected addition product to the endocyclic
CˆC bond were observed.
Scheme 1
To account for this result, a Grob fragmentation [8] with C(1)ÀC(2) s-bond
cleavage of the bicyclic system can be proposed3) [9][10] (Scheme 2). Thus, the
expected episulfonium ion intermediate 8 undergoes s(C(1)ÀC(2)) bond fragmenta-
tion to give nitrilium ion 9, which, after being captured by the ClÀ counterion, affords
the imidoyl chloride 10. Hydrolysis of 10 [11] followed by aromatization under workup
of the reaction crude yields amide 7.
Scheme 2
3
)
For synthetic applications of the Grob fragmentation, see [9]; for a discussion on the aza-Grob
fragmentation, see [10].

Helvetica Chimica Acta Vol. 84 (2001)
3669
Two aspects should be pointed out regarding the proposed reaction path: first,
oxatrinorbornenone-derived ketals such as 11 have been found to be transformed into
furan derivatives by treatment with fluorosulfonic acid (transformation of 11 into 12)
[12] or Hg(NO3)2 in MeCN (transformation of 11 into 13) [13][14] (Scheme 3)4).
Second, the alignment of the n(N) orbital with the s(C(1)ÀC(2)) bond (case of the
(Z)-isomer of 5) is probably the reason for the ease of the fragmentation as predicted
by Carrupt and Vogel [6]. The MM2[5] and PM3 calculations performed on ( Z)-5
indicate an almost perfect alignment of the s(C(1)ÀC(2)) and n(N) orbitals. Thus, the
(Z)-diastereoisomer should be the reactive one, according to the stereoelectronic
requirements of the Grob fragmentation [8]. The equilibrium (E)-5>(Z)-5 (15 :1 in
the starting material) is shifted with the consumption of the more reactive (Z)-5
diastereoisomer.
2.2. Reactions of N-(7-Oxabicyclo[2.2.1]hept-5-en-2-ylidene)amines 4 and 5 with
meta-Chloroperbenzoic Acid (mCPBA). Amines 4 and 5 react with mCPBA (CH2Cl2,
À788, 10 min) to give the amides 14 and 7, respectively (Scheme 4).
Scheme 3
Scheme 4
R
R1
R2
Product (%)a)
(90)
14a (90)
b (85)
c (70)
d (75)
5
4a
b
c
d
PhCH2
H
H
H
H
H
H
H
Br
H
7
PhCH(Me)
CH2ˆCHÀCH2
PhCH2
CH2ˆCHÀCH2
Me
a) Isolated yield
4
)
For other examples of Grob fragmentations involving 7-oxabicyclo[2.2.1]heptane systems, see [1a][14].

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Helvetica Chimica Acta Vol. 84 (2001)
Scheme 5
It should be noted that the reaction of the alkylideneamines derived from
trinorcamphor 15 with mCPBA has been previously reported to afford the expected
oxaziridines 16 as a mixture of diastereoisomers [15]. On the other hand, 7-
oxatrinorbornanones such as 17 react with mCPBA to give the products of the
Baeyer-Villiger lactonization 18 or 19 [16] (Scheme 5). In our hands, 7-oxatrinorbor-
nenone 2b did not react with mCPBA under the conditions indicated for the reactions
in Scheme 5. Thus, the simultaneous presence of the endocyclic double bond and of the
alkylideneamino functionality appears to be responsible for the observed trans-
formation.
A probable reaction path for the transformation depicted in Scheme 4 is outlined in
Scheme 6. Thus, in this case, the endocyclic CˆC bond in 4 and 5 seems to induce the
generation of an allylic cation 20 via s(C(1)ÀC(2)) fragmentation. Proton abstraction
(probably by reaction with the carboxylate anion) yields the observed products 14a d
and 7. It is worth mentioning that this reaction path reminds that proposed for the
Beckmann fragmentation in dehydrotrinorcamphor oximes [17].
The trapping of the cationic intermediate 20 was achieved by reaction of 5 with
mCPBA in CH2Cl2/MeOH 1:1. Under these conditions, a ca. 1:1 mixture of the
dihydrofuranacetamides 21 and 22 was observed and characterized (1H-NMR). This
mixture evolved smoothly to the furan derivative 7 (Scheme 7).
Conclusion. We described the unexpected behavior of alkylideneamines derived
from 7-oxatrinorbornenone in two different reactions giving rise, through two different
reaction paths, to the same type of furan derivatives. The results reported herein open
the way for further research in the almost unexplored chemistry of the oxatrinorbor-
nenylideneamines and related N-derivatives.

Helvetica Chimica Acta Vol. 84 (2001)
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Scheme 6
Scheme 7
Experimental Part
General. TLC: silica gel 60 F254; detection by UV light and vainilline soln. Flash column chromatography
(FC): silica gel 60. [a]D: CHCl3 soln. at 258. IR Spectra: CHCl3 solns. in cmÀ1. 1H- and 13C-NMR Spectra: at 300
and 75.5 MHz, resp.; CDCl3 solns. d in ppm rel. to SiMe4 (ˆ0 ppm), J in Hz.
Reaction of N-(7-Oxabicyclo[2.2.1]hept-5-en-2-ylidene)benzylamine (5) with Phenylsulfonyl Chloride. To a
soln. of N-chlorosuccinimide (66 mg, 0.50 mmol) in CHCl3 (0.5 ml) at 08, PhSH (0.05 ml, 0.50 mmol) was added,
and the mixture was stirred for 30 min. Amine 5 (50 mg, 0.25 mmol) in CHCl3 (1.25 ml) was added and the
mixture stirred at 08 for 1 h and at r.t. for 18 h. The mixture was quenched with 5% NaHCO3 soln. (1 ml) and
extracted with CH2Cl2 (3 Â 2ml). The combined org. extracts were washed with brine (1 Â 2ml), dried
(MgSO4), and evaporated: pale yellow oil, which was purified by FC (AcOEt/hexane 1:1).
Reactions of N-(7-Oxabicyclo[2.2.1]hept-5-en-2-ylidene)amines 4 and 5 with meta-Chloroperbenzoic Acid:
General Procedure. A soln. of 4 or 5 (0.5 mmol) in CH2Cl2 (1.25 ml) was added dropwise to a suspension of
mCPBA (0.6 mmol) in CH2Cl2 (3.6 ml) at À788. After 10 min, sat. Na2S2O3 soln. (2ml) was added, and the
mixture was allowed to warm to r.t. The org. phase was washed with brine (2ml), dried (MgSO 4), and
evaporated: pale yellow oil, which was purified by CC (AcOEt/hexane 1:1).
N-Benzylfuran-2-acetamide (7). White solid. M.p. 55 588 (hexane/AcOEt). IR: 3490, 1715, 1680.
1H-NMR: 7.50 (d, 3J ˆ 1.8, 1 H); 7.40 7.20 (m, 5 H); 6.38 (dd, 3J ˆ 3.0, 1.8, 1 H); 6.25 (d, 3J ˆ 3.2, 1 H); 6.00
(s, NH); 4.70 (d, 3J ˆ 5.6, 2H); 3.68 ( s, 2 H). 13C-NMR: 168.4; 148.4; 142.4; 137.8; 128.5; 127.3; 110.7; 108.5; 43.5;
36.1. Anal. calc. for C13H13NO2: C 72.54, H 6.09, N 6.51; found: C 72.63, H 6.12, N 6.60.
N-[(1R)-1-Phenylethyl]furan-2-acetamide (14a). Colorless oil. [a]2D5 ˆ 8.9 (CHCl3, c ˆ 2). IR: 3495, 1710,
1
1680. H-NMR: 7.35 (d, 3J ˆ 1.2, 1 H); 7.25 7.10 (m, 5 H); 6.30 (dd, 3 J ˆ 3.1, 1.9, 1 H); 6.15 (d, 3J ˆ 3.2, 1 H);
5.90 (br. s, NH); 5.05 (m, 1 H); 3.55 (s, 2H); 1.40 ( d, 3J ˆ 7.0, 3 H). 13C-NMR: 167.7; 148.8; 143.0; 142.5; 128.7;
127.4; 126.1; 110.9; 108.6; 48.9; 36.4; 21.9. Anal. calc. for C14H15NO2: C 73.34, H 6.59, N 6.11; found: C 73.42,
H 6.60, N 6.25.
N-(Prop-2-enyl)furan-2-acetamide (14b). Colorless oil. IR: 3490, 1715. 1H-NMR: 7.35 (d, 3J ˆ 1.6, 1 H);
6.30 (dd, 3J ˆ 3.2, 1.6, 1 H); 6.15 (d, 3J ˆ 3.2, 1 H); 5.85 5.55 (m, ˆCH, NH); 5.05 (dd, 3J ˆ 19.1, 10.3, 2H); 3.80

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Helvetica Chimica Acta Vol. 84 (2001)
(t, 3J ˆ 5.6, 2H); 3.55 ( s, 2 H). 13C-NMR: 168.6; 148.6; 142.5; 133.8; 116.2; 110.8; 108.7; 41.9, 36.2. Anal. calc. for
C9H11NO2: C 65.44, H 6.71, N 8.48; found: C 65.59, H 6.83, N 8.66.
N-Benzyl-3-bromofuran-2-acetamide (14c). White solid. M.p. 115 1178 (hexane/AcOEt). IR: 3490, 1710,
1685. 1H-NMR: 7.30 (d, 3J ˆ 2.1, 1 H); 7.25 7.10 (m, 5 H); 6.38 (d, 3J ˆ 2.1, 1 H); 5.75 (br. s, NH); 4.40 (d, 3J ˆ
5.7, 2H); 3.65 ( s, 2 H). 13C-NMR: 167.6; 146.6; 143.3; 138.2; 128.0; 127.9; 114.6; 99.8; 44.1; 34.8. Anal. calc. for
C13H12BrNO2: C 53.08, H 4.11, N 4.76; found: C 53.19, H 4.30, N 4.90.
5-Methyl-N-(prop-2-enyl)furan-2-acetamide (14d). Colorless oil. IR: 3495, 1710. 1H-NMR: 6.05 (d, 3J ˆ 3.0,
1 H); 5.90 (d, 3J ˆ 2.5, 2 H); 5.85 5.60 (m, ˆCH, NH); 5.05 (dd, 3J ˆ 19.2, 10.0, 2 H); 3.80 (t, 3J ˆ 5.6, 2H); 3.55
(s, 2H); 2.15 ( s, 3 H). 13C-NMR: 166.8; 152.2; 146.7; 133.9; 115.9; 109.4; 106.5; 41.8; 36.3; 13.4. Anal. calc. for
C10H13NO2: C 67.02, H 7.31, N 7.82; found: C 67.15, H 7.11, N 7.61.
The Ministerio de Ciencia y TecnologÌa (Project BQU2000-0653) is thanked for financial support. One of
¬
us (M. C. M.) thanks the Ministerio de Educacion y Cultura, Spain, for a predoctoral grant.
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Received June 1, 2001