M. S. Morales-Ríos et al.
height of 6, 12 and 15 s, respectively. As expected, variation REFERENCES
of the injection port temperature changes the peak shape, with
[1] For a review of applications of ketene acetal rearrangements in
synthesis, see K. Tadano. In Studies in Natural Products Chemistry,
A.-U. Rahman (Ed). Elsevier: Amsterdam, 1992, 405.
[2] R. T. Arnold,S. T. Kulenovic.Competitive[1,3]-and[3,3]-sigmatropic
rearrangements. J. Org. Chem. 1980, 45, 891.
[3] I. Shiina, H. Nagasue. 1,3] Sigmatropic rearrangement of ketene
silyl acetals derived from benzyl α-substituted propanoates.
Tetrahedron Lett. 2002, 43, 5837.
higher temperatures narrowing the peaks. It is relevant to mention
that, regardless the broadness of the MC traces, the corresponding
fragmentation patterns in the MS of isomers a (1, 2 and 4) acquired
at different scans remain identical between them. However, the
relative abundances of the most prominent peaks arising from 1a
or 2a at m/z 281, 272 and 240 differ significantly from those of 4a
(Table 1). Concerning the MC of series b (Fig. 4), all isomers (1, 2
and 4) show sharp peaks with 2 s line widths and the same 8.5-
min retention time. The only difference between the peaks is an
emerging shoulder in 1b and 2b. These findings are in agreement
with skeletal rearrangements occurring before ionization in the
EI source, with 1b and 2b rearranged more easily than 1a and
2a.
[4] K. Burger, K. Gaa, K. Geith, C. Schierlinger.
A new general
access to α-trifluoro-methyl-substituted aromatic and heteroaro-
matic α-amino acids. Synthesis 1989, 850.
[5] K. Shishido, E. Shitara, K. Fukumoto. Tandem electrocyclic-
sigmatropic reaction of benzocyclobutenes. An expedient route
to 4,4-disubstituted isochromanones. J. Am. Chem. Soc. 1985, 107,
5810.
[6] T. Susuki, M. Inui, S. Hosokawa, S. Kobayashi. 1,3-Rearrangement of
ketene-N, O-acetals. Tetrahedron Lett. 2003, 44, 3713.
[7] For a review including the [1,3]-sigmatropic rearrangement of
ketene-acetals, see C. G. Nasveschuk, T. Rovis. The [1,3] O-to-C
rearrangement: opportunities for stereoselective synthesis. Org.
Biomol. Chem. 2008, 6, 242.
[8] P. Y. Lo´pez-Camacho, P. Joseph-Nathan, B. Gordillo-Roma´n, O. R.
Sua´rez-Castillo, M. S. Morales-Ríos. Cascade [1,3]-sigmatropic
rearrangements of ketene O,O-acetals: kinetic and DFT level
mechanistic studies. J. Org. Chem. 2010, 75, 1898.
Other thermal reactions via GC-MS analysis
As stated before, elution of a low-intensity peak, 6a, was also
detected at retention time of 7.8 min during gas chromatogra∗phic
analysis of ketene-O,O-acetals 1a or 2a (indicated by
in
Fig. 4). As expected, 6a was also produced during GC-MS
chromatogram of indole 4a, albeit in an increased abundance
(4a:6a ratio ca 10 : 1). An analogous eluted peak was also
observed in the GC-MS chromatograms of 1b, 2b and 4b at
retention time of 7.3 min (Fig. 4). The resulting product ion profile
of 6a and 6b were consistent with an N-carbomethoxylated
indole structure formed via the liability of the C–CO2Me bond
towards thermal breakage (Scheme 3). The peak assignment
was firmly established with an authentic standard, prepared
by decarbomethoxylation of 4a under condensed phase. The
accurate mass measurements of the low-intensity fragment
at m/z 211.1235 (C14H15N2+, −1.4 ppm) in the EI-MS of 6a
provided evidence for loss of CO2Me from the molecular ion. The
systematic presence of thermal degradation products 6c–6d in
the corresponding ion chromatograms of 4c–4e is worth nothing.
The possible mechanistic pathway by which these gas-phase
decarboalkoxylation reactions proceed could involve two steps,
namely deesterification of the methyl esters and decarboxylation
events.[28,29]
In conclusion, ketene-O,O-acetals 1a,b and 2a,b undergo
rearrangements in the gas phase. Such rearrangement processes
occur in the ion source and in the flight path preceding
fragmentation processes. The EI-MS of 4a–e contain common
and in some cases individual fragment ions, whose generation
is dominantly influenced by the C-2-linked side chain in the first
case and by the alkyl group at C-3 in the last case. The structures
of 4a–e, bearing N- and C-carbomethoxyl groups, were assigned
on the basis of characteristic loss of methanol from the molecular
ion involving the methyl ester group of the cyanomalonate side
chain, and by the production of [M−59]+ ion species through the
cleavage of the N–C carbamate bond. The mechanism for the
diagnostic loss of methanol from 4a–e was supported by isotopic
labeling studies. Thermal gas-phase reaction products during gas
chromatographic analysis of indoles 4a–e were confirmed with
an authentic standard.
[9] M. S. Morales-Ríos, P. Y. Lo´pez-Camacho, O. R. Sua´rez-Castillo,
P. Joseph-Nathan. Trapping enols of esters and lactones with
diazomethane. Tetrahedron Lett. 2007, 48, 2245.
[10] J. E. Baldwin, A. S. Raghavan, B. A. Hess Jr., L. Smentek. Thermal
[1,5] hydrogen sigmatropic shifts in cis,cis-1,3-cyclononadienes
probed by gas-phase kinetic studies and density functional theory
calculations. J. Am. Chem. Soc. 2006, 128, 14854.
[11] M. R. Ahmad, S. R. Kass. Unimolecular rearrangements and frag-
mentations in the gas phase: [1,3] sigmatropic isomerizations and
[2 + 2] cycloreversions. Aust. J. Chem. 2003, 56, 453.
[12] J. D. Bender, P. A. Leber, R. R. Lirio, R. S. Smith. Thermal rearrange-
ment of 7-methylbicyclo[3.2.0]hept-2-ene: an experimental probe
of the extent of orbital symmetry control in the [1,3] sigmatropic
rearrangement. J. Org. Chem. 2000, 65, 5396.
[13] M. A. Forman, P. A. Leber. The thermal rearrangement of endo-7-
methyl-exo-7-vinylbicyclo[3.2.0]hept-2-ene.TetrahedronLett.1986,
27, 4107.
[14] J. M. Janusz, L. J. Gardiner, J. A. Berson. A thermal[1,3]sigmatropic
acyl shift in the degenerate rearrangement of bicyclo[3.2.1]oct-2-
en-7-one. J. Am. Chem. Soc. 1977, 99, 8509.
[15] G. Sarodnick, T. Linker, M. Heydenreich, A. Koch, I. Starke, S.
Fu¨rstenberg, E. Kleinpeter. Quinoxalines XV. Convenient synthesis
and structural study of pyrazolo[1,5-a]quinoxalines. J. Org. Chem.
2009, 74, 1282.
[16] D. V. Ramana, M. S. Sudha. Claisen rearrangements and cyclizations
in phenyl propargyl ethers under electron impact conditions.
J. Chem. Soc. Perkin Trans. 1993, 2, 675.
[17] E. E. Kingston, J. H. Beynon, J. G. Liehr, P. Meyrant, R. Flammang,
A. Maquestiau. The Claisen rearrangement of protonated allyl
phenyl ether. Org. Mass Spectrom. 1985, 20, 351.
[18] P. C. H. Eichinger, J. H. Bowie, R. N. Hayes. Sigmatropic rearrange-
ments of deprotonated allyl phenyl acetates in the gas phase.
J. Org. Chem. 1987, 52, 5224.
[19] M. S. Morales-Ríos, C. García-Martínez, M. A. Bucio, P. Joseph-
Nathan. Stereocontrolled synthesis of 3-alkylindolines from (Z)-
2-hydroxyindolenines. Monatsh. Chem. 1996, 127, 691.
[20] O. R. Sua´rez-Castillo, M. García-Velgara, M. S. Morales-Ríos, P.
Joseph-Nathan. Chemoselective intramolecular annulation of 3-
alkylindolines into dihydro or tetrahydrofuro[2,3-b]indoles. Can. J.
Chem. 1997, 75, 959.
[21] F. Arndt. Nitrosomethylurea from methylamine hydrochloride. In
Organic Syntheses, Vol. 2. Wiley: New York, 1943, 165.
[22] J. H. Gross, A. Eckert, W. Siebert. Negative-ion electropray mass
spectra of carbon dioxide-protected N-heterocyclic anions. J. Mass
Spectrom. 2002, 37, 541.
[23] M. S. Morales-Ríos, L. Velasco, N. A. Pe´rez-Rojas, P. Joseph-Nathan.
Electron ionization mass spectra of indolenines obtained using
sector and ion trap mass spectrometers. Rapid Commun. Mass
Spectrom. 2005, 19, 1296.
Acknowledgement
Financial support by CONACYT Grant No. 81810 is gratefully
acknowledged.
c
wileyonlinelibrary.com/journal/jms
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
J. Mass. Spectrom. 2011, 46, 489–495