Organic Letters
Letter
Table 1. Ratio of cis- and trans-Aziridines from
Photoreactions in Solution and in the Solid-State
In conclusion, the synthesis of substituted aziridines by a
stereospecific dipolar cycloaddition of activated alkenes and
azides followed by the photodenitrogenation of the resulting
triazolines in the crystalline phase presents some promise and
also some challenges. Although we confirmed a remarkably
high regioselectivity and stereospecificity for the hydrogen-
a
triazoline
MeCN-d3
Me CO-d
crystals
2
6
trans-5/cis-5
trans-5/cis-5
trans-5/cis-5
trans-4
cis-4
76:24
32:68
99:1
99:1
83:17
10:90
bond DMU-catalyzed dipolar cycloaddition of CF -activated
3
b
b
b
trans-8
86:14
99:1
99:1
acrylates, reaction yields are moderate to low. DFT calculations
suggest that dispersive π−π stacking interactions are respon-
sible for the regioselectivity of the (3 + 2) dipolar cycloaddition
and suggest that more active catalysts would be needed. By
a
Ratios were determined by 1H NMR. These entries pertain to
b
product ratios from aziridine 9.
2
contrast, we showed that solution photochemistry of Δ -1,2,3-
trans-8 yielded aziridine trans-9 in 86% yield in MeCN-d3.
Recognizing that high stereochemical retention values are
indicative of a short-lived 1,3-biradical singlet biradical where
bond formation must be competitive with conformational
triazolines gives good to excellent results. Direct photochemical
excitation generates the singlet 1,3-biradicals, which afford the
kinetically controlled trans- or cis-aziridine products with good
to excellent stereospecificities, as previously reported by
relaxation, we also carried out experiments using acetone-d as
6
2
16
Scheiner with different Δ -1,2,3-triazolines. We also found
that reactions carried out using acetone as a triplet sensitizer
proceed through the longer-lived triplet 1,3-birdical and give
the thermodynamically favored trans-product regardless of the
nature of the precursor. Finally, photochemical solid-to-solid
reactions occur with the highest stereochemical retention values
and in quantitative yields, suggesting that the reaction has
synthetic potential.
solvent and triplet sensitizer. In all three cases, the triplet
sensitized reaction resulted in the exclusive formation of the
less sterically encumbered trans-aziridine, suggesting that a
longer-lived triplet 1,3-biradical has an opportunity to relax and
give thermodynamically more stable product.
To establish the conditions required for a solid state
photochemical reaction, we determined the thermal stability
of the three triazoline crystals using differential scanning
calorimetric (DSC) and thermogravimetric analysis (TGA).
The DSC results showed a relatively sharp endothermic
transition which correlated with the melting temperature
determined visually at 133−134 °C for trans-4, and 165−166
ASSOCIATED CONTENT
Supporting Information
■
*
S
°
C for cis-4 (DSC for trans-8 does not show sharp endothermic
transition but only shows denitrogenation). In all three cases, a
melting endotherm was followed by a broad exothermic
transition corresponding to the thermal denitrogenation of
the corresponding triazoline (see SI section). The loss of mass
1
NMR; X-ray diffraction spectra (PDF)
Crystallographic data for trans-8 (CIF)
Crystallographic data for trans-4 (CIF)
corresponding to N was also documented by TGA. After
2
noting that the purified aziridines were crystalline, and with
melting points in the range of 84−125 °C, we recognized that
the triazoline reactant-to-aziridine product mixture could be a
good candidate for a solid-to-solid reaction at room temper-
ature. This was confirmed with solid-state photochemical
experiments carried out with ca. 5−10 mg of triazoline crystals
ground between two microscope slides and subsequently
exposed to Pyrex-filtered UV light. We also note that the
bulk powder triazolines used for solid-state photochemistry
were shown to be different polymorphs than those used for
single crystal X-ray diffractions. We were not able to replicate
the same polymorphic triazolines after numerous crystallization
attempts and we were not able to get good quality single
crystals of the new forms.
AUTHOR INFORMATION
■
*
*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by National Science Foundation
Grants CHE-1266405 and CHE-1361104. Calculations were
performed on the Hoffman2 cluster at UCLA and the Extreme
Science and Engineering Discovery Environment (XSEDE),
which is supported by National Science Foundation Grant
The solid-state photochemistry shown in the last column of
Table 1 was fully reacted to the aziridine product with
quantitative conversions. As expected, reactions in the solid-
state were more stereoselective than reactions in solution
17
Number OCI-10535. Figure 2 was generated using CYLview.
(
Table 1), suggesting a decrease in conformational relaxation
REFERENCES
for the postulated 1,3-biradical. Samples of trans-4 and cis-4
yielded trans-5 and cis-5 in 83% and 90% yield, respectively.
The highest level of retention was observed upon reaction of
the trisubstituted triazoline, trans-8, where the added methyl
group further hinders rotation of the 1,3-biradical intermediate.
The trans-aziridine was obtained in quantitative yield. A small
loss of stereochemical retention in the case of trans-4 and cis-4
indicates that a fraction of the 1,3-biradical is able to change the
■
(
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3
C
Org. Lett. XXXX, XXX, XXX−XXX