Z. Syrgiannis et al. / Tetrahedron Letters 50 (2009) 277–280
279
Table 2
of PhTAD to alkenes in aqueous environments, the potential forma-
tion of water addition products should always be borne in mind.
Further work with different alkenes is in progress to clarify the
nature of the transition state of the reaction.
Thermodynamic parameters calculated for the reaction of PhTAD with alkenes in
MeOH and mixtures of acetone/water as solvents
Alkene
MeOH
DDY# (kcal/mol)
Acetone/H2O
DDY# (kcal/mol) DDS# (e.u.)
DDS# (e.u.)
Acknowledgements
TriME
TetraME
6.8 0.1
5.3 0.1
22
18
1
1
4.3 0.1
4.5 0.1
16
18
1
1
We thank the NMR and MS Centres of the University of Ioann-
ina, Greece and SERC (UK) and the University of Glasgow for their
support. We thank Prof. Orfanopoulos for a preprint of their work,
prior to publication.
results may be taken as qualitative evidence for a similar ‘SN2-like’
transition state for the solvent addition process. The latter conclu-
sion, though qualitative in nature, witnesses, in our opinion, for the
intervention of the AI intermediate in water and alcohol environ-
ments, when used as protic nucleophilic solvents.
Supplementary data
As discussed above, the solvated AI intermediate may reach a
transition state by adding one water molecule to the tertiary car-
bon atom (in the case of TriME reaction, see Scheme 2), and a sec-
ond one approaching the negatively charged nitrogen atom of the
PhTAD moiety, in analogy with the reports on anti-addition of
nucleophilic solvents to AI intermediates.7,8 Alternatively, a single
water molecule could be added in a concerted fashion, donating a
proton to the negatively charged nitrogen atom and a hydroxide
anion to the tertiary carbon in a syn addition, Scheme 2.
This alternative has the advantage that the reactive nucleophile
(a partially formed hydroxide anion) is formed in situ, thereby
explaining the very low yields of iso-propanol, and TFE solvent ad-
ducts. Moreover, this transition state is consistent with the solid-
state structure of alcohol 2, which is stabilized by an intramolecu-
lar N–HÁÁÁO hydrogen bond (see Fig. 1). Further stereochemical
studies are needed to clarify the nature of this reaction and, in par-
ticular, to discriminate between syn and anti water addition to the
AI intermediate. Syn addition, though, of MeOH or EtOH as nucle-
ophilic solvent to a ‘closed’ AI intermediate has been ruled out.7
In summary, we have reported here for the first time the forma-
tion of a product derived from hydration of the AI intermediate in
the reaction of PhTAD with simple alkenes, such as trimethylethyl-
ene. This new aspect of the reactivity of TADs opens the way for
reactions in aqueous environments, for example, with lipid sub-
strates, which may model biological processes. It may also serve
as a useful, new, synthetic transformation of unfunctionalized
alkenes: for example, it could be used to synthesize amino alcohols
since it is known that the PhTAD moiety can be transformed into
an amino functionality,2b,18 and also to form enamines by dehydra-
tion. In addition, the present work emphasizes that, in the reaction
Supplementary data associated with this article can be found, in
References and notes
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R.; Mallakpour, S. E.; Adibi, H. J. Org. Chem. 2002, 67, 8666–8668; (h) Hajipour,
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E., ; Ternay, A. L., Jr. J. Org. Chem. 1994, 59, 8239–8244.
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12. 1H NMR (250 MHz, CDCl3) of alcohol 2: d (ppm) 7.87 (br s, 1H, –NH), 7.33–7.55
(m, 5H, aromatic), 4.18 (q, 1H, methine, J = 7.0 Hz), 1.93 (br s, 1H, –OH), 1.38 (s,
3H), 1.35 (d, 3H, J = 7.0 Hz), 1.32 (s, 3H). 13C NMR (60 MHz, CDCl3): d (ppm)
152.7 (carbonyl), 151.9 (carbonyl), 131.4 (aromatic), 129.1 (aromatic), 128.1
(aromatic), 125.6 (aromatic), 74.1 (C–N), 58.2 (C–O), 28.4 (Me2C–OH), 27.5
(Me2C–OH), 12.2 (Me–C–N). ESI MS spectra showed the [M+H]+ signal at 264.36
m/z (100% intensity), and also the [M+HÀH2O]+ signal at 246.36 m/z (50%
intensity). FT IR spectra (KBr) showed strong absorptions at 3417 (coupled
NH + OH), 3306 (shoulder), 2980 (C–H), 1763 (carbonyl), 1704 (carbonyl),
1435, 1127, 768, 704 cmÀ1. Elemental Anal. Calcd for C13H17N3O3: C, 59.30; H,
6.51; N, 15.96. Found: C, 59.53; H, 6.53; N, 16.02.
13. Triazolinediones were reported to react with alcohols by decomposition to
afford a variety of characterized products depending on the reaction media.14
We also noticed that a stirred PhTAD/water mixture lost the red colour at room
temperature after 15 min, and gave products that are unidentified for the
moment. For the above-mentioned reasons, the isolated yield of alcohol 2 is
expected to be lower than that estimated from the 1H NMR spectra of the crude
reaction mixture.
O
Ph
N
H
O
N
H
N
O
Solvated
AI Intermediate
O
N
O
N
Ph
O
Ph
O
N
H
O
N
H
H
H
N
O
N
O
H
H
14. (a) Izydore, R.; Johnson, H.; Horton, R. J. Org. Chem. 1985, 50, 4589–4595; (b)
Borhani, D.; Greene, F. J. Org. Chem. 1986, 51, 1563–1570; (c) Mackay, D.;
Taylor, N.; Wigle, I. J. Org. Chem. 1987, 52, 1288–1290.
Transition state
of water anti addition
to the AI Intermediate
Transition state
of water syn addition
to the AI Intermediate
15. Crystal data for 2: C13H17N3O3, M = 263.30, monoclinic, a = 9.1677(7),
b = 13.7222(13), c = 11.3050(11) Å, b = 109.50(1)°, U = 1340.6(2) Å3, T = 120 K,
space group P21/c, Z = 4,
1995 unique (Rint = 0.11). The final R(F) and wR(F2) values were 0.063 [I > 2(I)]
l(Mo Ka
) = 0.094 mmÀ1, 8117 reflections measured,
Scheme 2. Solvated AI intermediate and transition states for the syn and anti
addition of water to the AI intermediate.