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Electrospray MS studies of C60 Diels-Alder chemistry: Characterization of a C60 Adduct with the Danishefsky Diene
oo404039193 $6.00+.00
Teulhedron Lums. Vol. 34. No. SO.pp. 80434046.1993 Rited iu Great Britain
Electrospray Characterization
FWgUMItRersL4d
MS Studies of CT,,,Diels-Alder
Chemistry:
of a C,, Adduct with the Danisbefsky Diene Stepheu R. Wilson* and wgyi
Lu
DepaTmEntof(BmisBy New York University, Washington Square New York, NY 10003
Abstract:
The Diels-Alderreactionof C,
with a cmwn-ether substituted diene as
well as l-methoxy-3-(siloxyl)-13-butadiene
(the Danishefsky Diene) is
repomzd Cm shows dienophile reactivity comparable to N-phenylmaleimide. Electrospmy MS is an exciting new technique for the mass spectral analysis of ions in solution.1 We have recently been adaptiug electrospray MS methods to the study of organic xeaction~.~ We showed that crown ethers are ideal substrates for e&rospray MS detectio~~.~ Crown ethers may also be used4 to design derivatization reagents for?isualization” of neutral molecules in solution. Such tagged molecules give very strong [M+K]+ signals by electrospray MS. The scope of the chemical reactivity of Cm is a topic
ofcurrent interest
and has been reviewed.5 We also
have xeported6 several new aspects of Cm chemistry including the use of electrospray MS to study nucleophilic addition, 1.3 dipolar addition and 2+2-photocycloaddition reaction reactions. An early report on the Diels-Alder reaction of C, witb anthracene, furan and cyclopentadiene suggested that cyclomversion of the initially fcnmed Diels-Alder adduct occurred.7 Mm Iecently, Diels-Alder cycloaddition of C, strategies wem designed to give stable products after the extrusion of COJJ or by the use of quinodimethane-type dienes9 or isobenzofuran .t 0 All of these reports suggest that that C&Xels-Alder
adducts
are unstable. in contrast to our own experience. vida &fia. We have been investigating the reactivity of Cm in Diels-Alder reactions and report our nsults on C, Diels-Alder reaction with a nlatively umractive crown ether diene 1. We show that (1) the electrospray MS method is ideal for following Diels-Alder nactions, (2) the Diels-Alder reaction of G
does not appear to be reversible
and (3) C, reacts with the well known “Danishefsky Diene” to produce an annelated ketone producb 11 and 12 that may he quite useful for preparation of functional&d fullerenes. The “electrospray -active” crowu ether diene 1 was prepared by a modification of the method for the preparation of I-phenyl-1,3-butadiene.11
The crown ether group makes 1 and all of its derivatives visible as their
K+ complexes using the solution technique of electmspray MS. We can dhectly monitor the Diels-Alder reaction
8043
mixture by dilution and injection of reaction aliquots (Figute 1.) Compound 1 reacts withC, (2)at mom tempemtum and a monoadduct 3 could be isolated in 34% yield.12 Reaction
ofcrownether diene 1 withother
common dienophiles, e.g. maleic anhydride 4 and N-phenyhualeimide 5 required tefhuting benzene to produce similaradducts6
and7 (‘l’hble 1).
2
1
3
While the Diels-Alder reaction of 1 withCa gives onlymonoadduct at room temperature, at higher temperatute (80 OC, 29 hrs.) compound 1 and C, yields a 1: 1 mixture of mono- and bis-adduct. The half life of the reaction of 1 and related diene 8 with C, places the reactivity of Cm close to that of N-phenyhnaleimide 5. All C, Diels-Alder adducts are stable. Compound 3, for example, does not undergo cycloreversion during 3 hours at -8BC @fluxing benzene.) I1+ K+l+
C
A
p + K+]+
4
;I; Figure1:
IfDiels-Alder reaction mixture of 1 with2 inbenzene at R.T. at time: A. 7 hrs. B. 31.5 hrs. C. 46 hrs. An aliquot was removed and diluted with toluene/MeOH/KOAc (to 10m5M KOAc) and electrosprayed as described in ref 3a or 4c. The electrospray response factor for compound 3 (0.5 relative to 1)indicates that thereaction half-life (T,,) is - 46 hrs, i.e. is 50% complete in spectrum C. M/z for [l+K]+= 403 and m/z for [3+K]+= 1124.
We have also prepared the adduct of l-methoxy-3-(trimethylsiloxyl)-13-butadiene
10 (Danishefsky
diene)13 with C60’ Since the data in Table I indicates that C, is a potent dienophile, it is not surprising that 10
~hocH,
1
10
-_
E&o+
11
12
mctsmclilywithC&at60“.
Adductll
IRwereconsiJtentwiththc~~.
wasisolatedin39%yieMbyflash~~~hy..eNMRand 14theFABMSshowsnomolecularionf6r11 hutonlyakagment
at 720 comspcnding to cleavage of the six-amnhered ring. This is the typical result of most MS techniquesfor Ca derivatives and probablyone of the masons that Diels-Alder cyclortversiaa was suspected for previously qorted c,
adducts. Jf compomd 11 was tagged with a dko+mwn
reagent B = N2C(Ph)(Ph-crown)]6b
electrosprayMS shows a single peak spectmm with a molecular ion at m/z = 1258 w+Kl+. Elimimionofll togiveenone12 15J7proce& with 50% TFA/benzene. Furthermansf~tions of ketones 11 and 12 as well as additionalcycloadditionchemistry C!, am in progress and will he qorted in the near future. ‘IBble 1. Reaction Conditions, Products and Yields for DiebAlder
diene
dienophile
1
Reaction
product
conditions
% yield
30 h, r.t. benzene
34a
8 h, 7580°C benzene
86
22 h, 75-8oOC benzene
100
25a
15 h, 58OC benzene 8
2 a Tbemetimwa3ca&daitto-SO%cmvemim.
References 1.
umeactedc6owaslecov~
and Notes
(a) Fenn, J.B.; Mann, M.; Meng, C.K.; Wang. S.F.; Whitehouse, C.M. Science 1989,2&j, Smith, R.D.; Loo, J.A.; Edmonds, C.G.; Barinage, C.J.; Udseth, H.R. Anal. Ckm. 1990,& Loo, J.A., Loo, R.R.O., Light, K.J., Edmonds. C.G., Smith, RD. Anal. Chem. 1992,s
64. (b) 882. (c) 81. (d) Few,
J.B. J. Am. Sot. MassSpectrom, 2.
1993,524.
(a) Wilson. S.R.; Yasmin, A.; Wu, Y. J. Org. Chem 1992, a. 6941. (b) W&m. S.R; Perez, J.; Wu. Y. Natumlpromccrrka.
1992.11
103. (c). Wilson, S.R.; WU. Y Orgmomdh
Wilson, S. R.; Fwcz, J.; Pastcmak, A J. Amer. Chem. Sot. 1993, m
3.
1478. (d)
(a) S. R. Wilson, Tulchinsky, M. J. Org. Chem. 1993, % 1407. (b) Wilson, S.R; Wu, Y , Supmuwk&arChcmisny,
4.
1993.12,
1994.
in press. (c) Wilson, S.R; Wu, Y, submiti.
(a) Wilson, S. R; Tttlchinsky, M.; Lu, Q.; Wu, Y Bioorg Med Ghan Lea, in pmss. (b) Wilson, S. R.; Tulchinsky, M.; Lu, Q.; Wu, Y J. Chem. Sot. Chemical Commutr. 1993, 664 (c) Wilson, S.R.; Wu, Y, J. Am. Sot. Mass Spectrom 1993,596.
5.
(a). Taylor, R; Walton, D.RM. Nature 1993, J& 685. (b) Miller, G. P. Chemisrtymd Zndusmy 1993, 226. (c) Olah, G. A.; Bucsi, I., Anisfeld, R.; FVakash,G. K. S. Curbon 1992, % 1203. (d)
Bniun, T. Angew. Chem. Znt Ed Engl 6.
1992,&
588.
(e) Wudl, F. Act% Chem Res 1992, &
157.
(a) Wilson, S.R.; Wu, Y J. Amer. Chem. Sot., in press (b) Wilson, S.R.; Wu, Y., J.C.S. Chem Commun.. 1993 784. (c) Wilson, S. R.; Wu, Y Organic Mass Spectrom., in press. (d) Wilson, S. R.; Kaprinidis, N.; Wu, Y; Schuster, D.I. J. Am. Chem.Soc., 1993. U
7.
8495.
Wudl, F.; Hirsch, A,; Khemani, K.C.; Suzuki, T.; Allemand, P.-M.; Koch, A.A.; Eckert, H; Srdanov,G.; Webb. H.M. In Fullerenes: Synthesis, Properties, and Chemistry of Large Carbon Clusters; Hammond, G.
8.
S.; Kuck, V.G., Rds.; Amrican Chemical Society: Washington, D.C., 1992; ~~161-175. 344-345. m
(a) Rubin, Y; Khan, S.; Feedberg, D. I.; Yeretxian, C. J. Am. Chem. Sot. 1993,
(b) Khan, S.; Oliver, A. M.; Paddon-Row, M. N.; Rubin, YJ . Am. Chem. Sot. 1993,
u
4919.
9.
B&k,
10.
Prato, M.; Suzzuki, T.; Foroudian, H.; I&K. K.; Wudl, F. J. Am. Chem. Sot. 1993,
11.
Wittig, G.; Schollkopf. U. Chem. Ber., 1954. P. 1318. Compound 1 showed ES-MS pi+K]+ = 403.
P.; Gugel, A.; Spickermann, J.; Mullen, K. Angew. Chem.. Znt. Ed. Engl. 1993,2,
78.
Il=i. 1594.
‘NMR (CDClj, 7.G6.2 (6H. m). 5.4-5.1 (2H, m). 4.2-3.7 (2OH. m). Calculated for Q,Hzs06: C 65.39, H 7.68 Found: 65.72, H 7.7. 12.
Compound 3: ES-MS [M+Kj+= 1124. FAB MS [M+HJ+= 1086 . ‘H-NMR (acetone-dg-CS$:
13.
Danlshefsky, S.; Kitahara, T. J. Am. Chem. Sot. 1974 96 7807.
14.
Compound 11: ES-MS (tagged with X as in nf 6b) [MX+Kl+= 1259. FAB MS: no M+, base peak m/z = 720 (Cm tiagment).‘H-NMR (CS$: 3.93 ( lH, J = 15 I-Ix ), 4.90 (1H. broad s), 4.80 (1H. broad s), 3.43
3.47-3.98
(20 H, m), 4.17-4.27 (1 H, m), 5.35 (lH, broads), 6.72 (lH, d, J=8 Hz), 6.94-7.11 (5H. m)
(W. dd, J=4, E18.3) 3.4 (3H. s). IR:1725 cm-t(C=G). 15.
Compound 11 and 12 show single peaks at Rf = 21 and 29 min respectively on Buckyclutche@
16.
Welch. C.J., Pirkle, W.H., J. Chromatogr, 1992 m,
17.
We proposethatDiels-Alderadditionoccursata 6-6 bondbasedon the literatum8 and CMR data for 12.
HPLC
(1:l toluene&exane, 1 mUmin, W detection at 300 nm). 89.
Compound 12 is almost symmetrical and shows only 14 lines in the fullemne region (141- 147 ppm) as well as 2 vinyl carbons (149.4.128.8 ppm), two sp3 fullerene carbons (61 and 64 ppm) and one sp3 carbon adjacent to the ketone (51 ppm). The C=G carbon cannot be observed with our instrument (300 MHz for proton). In addition, compounds 11 and 12 shown a distinctive band at -438 nm (red sbifted from a band in C, at 400 MI) indicative of tbe “66 dihydrofullerene” structure.
(Received in USA 2 August 1993: accepted 8 October 1993)
Teulhedron Lums. Vol. 34. No. SO.pp. 80434046.1993 Rited iu Great Britain
Electrospray Characterization
FWgUMItRersL4d
MS Studies of CT,,,Diels-Alder
Chemistry:
of a C,, Adduct with the Danisbefsky Diene Stepheu R. Wilson* and wgyi
Lu
DepaTmEntof(BmisBy New York University, Washington Square New York, NY 10003
Abstract:
The Diels-Alderreactionof C,
with a cmwn-ether substituted diene as
well as l-methoxy-3-(siloxyl)-13-butadiene
(the Danishefsky Diene) is
repomzd Cm shows dienophile reactivity comparable to N-phenylmaleimide. Electrospmy MS is an exciting new technique for the mass spectral analysis of ions in solution.1 We have recently been adaptiug electrospray MS methods to the study of organic xeaction~.~ We showed that crown ethers are ideal substrates for e&rospray MS detectio~~.~ Crown ethers may also be used4 to design derivatization reagents for?isualization” of neutral molecules in solution. Such tagged molecules give very strong [M+K]+ signals by electrospray MS. The scope of the chemical reactivity of Cm is a topic
ofcurrent interest
and has been reviewed.5 We also
have xeported6 several new aspects of Cm chemistry including the use of electrospray MS to study nucleophilic addition, 1.3 dipolar addition and 2+2-photocycloaddition reaction reactions. An early report on the Diels-Alder reaction of C, witb anthracene, furan and cyclopentadiene suggested that cyclomversion of the initially fcnmed Diels-Alder adduct occurred.7 Mm Iecently, Diels-Alder cycloaddition of C, strategies wem designed to give stable products after the extrusion of COJJ or by the use of quinodimethane-type dienes9 or isobenzofuran .t 0 All of these reports suggest that that C&Xels-Alder
adducts
are unstable. in contrast to our own experience. vida &fia. We have been investigating the reactivity of Cm in Diels-Alder reactions and report our nsults on C, Diels-Alder reaction with a nlatively umractive crown ether diene 1. We show that (1) the electrospray MS method is ideal for following Diels-Alder nactions, (2) the Diels-Alder reaction of G
does not appear to be reversible
and (3) C, reacts with the well known “Danishefsky Diene” to produce an annelated ketone producb 11 and 12 that may he quite useful for preparation of functional&d fullerenes. The “electrospray -active” crowu ether diene 1 was prepared by a modification of the method for the preparation of I-phenyl-1,3-butadiene.11
The crown ether group makes 1 and all of its derivatives visible as their
K+ complexes using the solution technique of electmspray MS. We can dhectly monitor the Diels-Alder reaction
8043
mixture by dilution and injection of reaction aliquots (Figute 1.) Compound 1 reacts withC, (2)at mom tempemtum and a monoadduct 3 could be isolated in 34% yield.12 Reaction
ofcrownether diene 1 withother
common dienophiles, e.g. maleic anhydride 4 and N-phenyhualeimide 5 required tefhuting benzene to produce similaradducts6
and7 (‘l’hble 1).
2
1
3
While the Diels-Alder reaction of 1 withCa gives onlymonoadduct at room temperature, at higher temperatute (80 OC, 29 hrs.) compound 1 and C, yields a 1: 1 mixture of mono- and bis-adduct. The half life of the reaction of 1 and related diene 8 with C, places the reactivity of Cm close to that of N-phenyhnaleimide 5. All C, Diels-Alder adducts are stable. Compound 3, for example, does not undergo cycloreversion during 3 hours at -8BC @fluxing benzene.) I1+ K+l+
C
A
p + K+]+
4
;I; Figure1:
IfDiels-Alder reaction mixture of 1 with2 inbenzene at R.T. at time: A. 7 hrs. B. 31.5 hrs. C. 46 hrs. An aliquot was removed and diluted with toluene/MeOH/KOAc (to 10m5M KOAc) and electrosprayed as described in ref 3a or 4c. The electrospray response factor for compound 3 (0.5 relative to 1)indicates that thereaction half-life (T,,) is - 46 hrs, i.e. is 50% complete in spectrum C. M/z for [l+K]+= 403 and m/z for [3+K]+= 1124.
We have also prepared the adduct of l-methoxy-3-(trimethylsiloxyl)-13-butadiene
10 (Danishefsky
diene)13 with C60’ Since the data in Table I indicates that C, is a potent dienophile, it is not surprising that 10
~hocH,
1
10
-_
E&o+
11
12
mctsmclilywithC&at60“.
Adductll
IRwereconsiJtentwiththc~~.
wasisolatedin39%yieMbyflash~~~hy..eNMRand 14theFABMSshowsnomolecularionf6r11 hutonlyakagment
at 720 comspcnding to cleavage of the six-amnhered ring. This is the typical result of most MS techniquesfor Ca derivatives and probablyone of the masons that Diels-Alder cyclortversiaa was suspected for previously qorted c,
adducts. Jf compomd 11 was tagged with a dko+mwn
reagent B = N2C(Ph)(Ph-crown)]6b
electrosprayMS shows a single peak spectmm with a molecular ion at m/z = 1258 w+Kl+. Elimimionofll togiveenone12 15J7proce& with 50% TFA/benzene. Furthermansf~tions of ketones 11 and 12 as well as additionalcycloadditionchemistry C!, am in progress and will he qorted in the near future. ‘IBble 1. Reaction Conditions, Products and Yields for DiebAlder
diene
dienophile
1
Reaction
product
conditions
% yield
30 h, r.t. benzene
34a
8 h, 7580°C benzene
86
22 h, 75-8oOC benzene
100
25a
15 h, 58OC benzene 8
2 a Tbemetimwa3ca&daitto-SO%cmvemim.
References 1.
umeactedc6owaslecov~
and Notes
(a) Fenn, J.B.; Mann, M.; Meng, C.K.; Wang. S.F.; Whitehouse, C.M. Science 1989,2&j, Smith, R.D.; Loo, J.A.; Edmonds, C.G.; Barinage, C.J.; Udseth, H.R. Anal. Ckm. 1990,& Loo, J.A., Loo, R.R.O., Light, K.J., Edmonds. C.G., Smith, RD. Anal. Chem. 1992,s
64. (b) 882. (c) 81. (d) Few,
J.B. J. Am. Sot. MassSpectrom, 2.
1993,524.
(a) Wilson. S.R.; Yasmin, A.; Wu, Y. J. Org. Chem 1992, a. 6941. (b) W&m. S.R; Perez, J.; Wu. Y. Natumlpromccrrka.
1992.11
103. (c). Wilson, S.R.; WU. Y Orgmomdh
Wilson, S. R.; Fwcz, J.; Pastcmak, A J. Amer. Chem. Sot. 1993, m
3.
1478. (d)
(a) S. R. Wilson, Tulchinsky, M. J. Org. Chem. 1993, % 1407. (b) Wilson, S.R; Wu, Y , Supmuwk&arChcmisny,
4.
1993.12,
1994.
in press. (c) Wilson, S.R; Wu, Y, submiti.
(a) Wilson, S. R; Tttlchinsky, M.; Lu, Q.; Wu, Y Bioorg Med Ghan Lea, in pmss. (b) Wilson, S. R.; Tulchinsky, M.; Lu, Q.; Wu, Y J. Chem. Sot. Chemical Commutr. 1993, 664 (c) Wilson, S.R.; Wu, Y, J. Am. Sot. Mass Spectrom 1993,596.
5.
(a). Taylor, R; Walton, D.RM. Nature 1993, J& 685. (b) Miller, G. P. Chemisrtymd Zndusmy 1993, 226. (c) Olah, G. A.; Bucsi, I., Anisfeld, R.; FVakash,G. K. S. Curbon 1992, % 1203. (d)
Bniun, T. Angew. Chem. Znt Ed Engl 6.
1992,&
588.
(e) Wudl, F. Act% Chem Res 1992, &
157.
(a) Wilson, S.R.; Wu, Y J. Amer. Chem. Sot., in press (b) Wilson, S.R.; Wu, Y., J.C.S. Chem Commun.. 1993 784. (c) Wilson, S. R.; Wu, Y Organic Mass Spectrom., in press. (d) Wilson, S. R.; Kaprinidis, N.; Wu, Y; Schuster, D.I. J. Am. Chem.Soc., 1993. U
7.
8495.
Wudl, F.; Hirsch, A,; Khemani, K.C.; Suzuki, T.; Allemand, P.-M.; Koch, A.A.; Eckert, H; Srdanov,G.; Webb. H.M. In Fullerenes: Synthesis, Properties, and Chemistry of Large Carbon Clusters; Hammond, G.
8.
S.; Kuck, V.G., Rds.; Amrican Chemical Society: Washington, D.C., 1992; ~~161-175. 344-345. m
(a) Rubin, Y; Khan, S.; Feedberg, D. I.; Yeretxian, C. J. Am. Chem. Sot. 1993,
(b) Khan, S.; Oliver, A. M.; Paddon-Row, M. N.; Rubin, YJ . Am. Chem. Sot. 1993,
u
4919.
9.
B&k,
10.
Prato, M.; Suzzuki, T.; Foroudian, H.; I&K. K.; Wudl, F. J. Am. Chem. Sot. 1993,
11.
Wittig, G.; Schollkopf. U. Chem. Ber., 1954. P. 1318. Compound 1 showed ES-MS pi+K]+ = 403.
P.; Gugel, A.; Spickermann, J.; Mullen, K. Angew. Chem.. Znt. Ed. Engl. 1993,2,
78.
Il=i. 1594.
‘NMR (CDClj, 7.G6.2 (6H. m). 5.4-5.1 (2H, m). 4.2-3.7 (2OH. m). Calculated for Q,Hzs06: C 65.39, H 7.68 Found: 65.72, H 7.7. 12.
Compound 3: ES-MS [M+Kj+= 1124. FAB MS [M+HJ+= 1086 . ‘H-NMR (acetone-dg-CS$:
13.
Danlshefsky, S.; Kitahara, T. J. Am. Chem. Sot. 1974 96 7807.
14.
Compound 11: ES-MS (tagged with X as in nf 6b) [MX+Kl+= 1259. FAB MS: no M+, base peak m/z = 720 (Cm tiagment).‘H-NMR (CS$: 3.93 ( lH, J = 15 I-Ix ), 4.90 (1H. broad s), 4.80 (1H. broad s), 3.43
3.47-3.98
(20 H, m), 4.17-4.27 (1 H, m), 5.35 (lH, broads), 6.72 (lH, d, J=8 Hz), 6.94-7.11 (5H. m)
(W. dd, J=4, E18.3) 3.4 (3H. s). IR:1725 cm-t(C=G). 15.
Compound 11 and 12 show single peaks at Rf = 21 and 29 min respectively on Buckyclutche@
16.
Welch. C.J., Pirkle, W.H., J. Chromatogr, 1992 m,
17.
We proposethatDiels-Alderadditionoccursata 6-6 bondbasedon the literatum8 and CMR data for 12.
HPLC
(1:l toluene&exane, 1 mUmin, W detection at 300 nm). 89.
Compound 12 is almost symmetrical and shows only 14 lines in the fullemne region (141- 147 ppm) as well as 2 vinyl carbons (149.4.128.8 ppm), two sp3 fullerene carbons (61 and 64 ppm) and one sp3 carbon adjacent to the ketone (51 ppm). The C=G carbon cannot be observed with our instrument (300 MHz for proton). In addition, compounds 11 and 12 shown a distinctive band at -438 nm (red sbifted from a band in C, at 400 MI) indicative of tbe “66 dihydrofullerene” structure.
(Received in USA 2 August 1993: accepted 8 October 1993)