Letter
The resulting bis-Boc arylhydrazines proved to be challenging
substrates for a variety of alkynylation reactions, including
standard ynamide-forming cross-coupling reactions with silyl-
2
8
protected bromoalkynes and a recently reported CuCl -
2
29
catalyzed silyl-acetylene oxidative ynamide coupling. For-
tunately, we were able to access 4a−4d in good to excellent
yields through a very robust two-step sequence involving
dichlorovinylation followed by alkyl lithium-mediated elimi-
30
nation and lithium halogen exchange (Scheme 1).
The method used to synthesize 4a−4d was not amenable to
the synthesis of 4e, so we took an alternative approach. The
addition of lithiated silyl-acetylene to di-tert-butyl azodicarbox-
31
ylate produced 5 in 48% yield. Copper-catalyzed cross-
coupling of 5 with N-(4-iodophenyl) acetamide yielded 6 in
moderate yield, which was readily deprotected with TBAF
(
Scheme 1). We successfully employed this method with other
aryl halides, and thus, it seems to be general. However, we
favor the dichlorovinylation/elimination sequence in most
scenarios given its simplicity and robustness.
To access a series of model arylazotriazoles, we reacted
compounds 4a−4e with benzyl azide under CuAAC
conditions followed by Boc group removal and oxidation of
the hydrazine (Scheme 2). We opted to take the bis-protected
hydrazines into the cycloaddition reaction given that
unprotected ynamines are known to be relatively unstable
and readily tautomerize to reactive ketenimines that undergo
32,33
rapid hydration to form the corresponding hydrazides.
Cascade deprotection/oxidation strategies using acid were
unsuccessful given that the acid can catalyze the rearrangement
of hydrazo compounds to benzidenes, diphenylines, and
3
4
semidines. Thermal deprotection of the Boc groups
produced the desired azo compounds in low yields. Ultimately,
3
5,36
we found that Boc group deprotection with TMSI
followed by hydrolysis of the resulting trimethylsilyl
carbamates in an oxygenated atmosphere afforded the desired
benzyl-substituted arylazo-1,2,3-triazoles 8a−8e in good over-
all yields (Scheme 2).
Figure 3. Synthesis and properties of arylazotriazoles. PSSs at 365 nm
(
most Z-enriched) and 530 nm (most E-enriched) are shown.
Quantification of a photostationary state consisting of >95% of a
Next, we performed constant illumination NMR experi-
1
single isomer is challenging due to the signal-to-noise ratio of H
23,37
ments
to establish the PSSs of these electronically diverse
NMR. Therefore, a 95:5 ratio represents a maximally enriched
a
model arylazotriazoles at a variety of wavelengths (Figure 2B).
The electron-withdrawn photoswitch 8a underwent near-
quantitative conversion to the Z isomer when irradiated with
photostationary state. Photoswitch 15 achieves the most E-enriched
PSS (78%) at 470 nm, not 530 nm.
3
65 nm light but was unable to fully isomerize back to the E
1
7
described previously; however, the relative position of the
three nitrogen atoms excludes them from the modularity and
synthetic ease associated with CuAAC chemistry. We
envisioned constructing the photoswitch through reaction of
an arylazoalkyne-equivalent synthon with an azide preattached
to any structure of interest. The robustness of CuAAC click
chemistry and the associated wealth of methodology available
isomer at any wavelength tested. Unsubstituted photoswitch
8b also did not possess ideal photophysical properties as it was
unable to reach highly enriched E or Z PSSs at any wavelength
tested and displayed a diminished extinction coefficient in the
UV−vis spectrum, as compared to other arylazotriazole
photoswitches.
Fortunately, methoxy-substituted 8c can access a PSS
quantitatively enriched in the Z isomer under 365 nm light
with longer wavelengths achieving approximately 80% photo-
conversion to the E isomer (Figure 2B). Increasing the
electron donating ability of the para substituent further as in
8d appeared to be detrimental, likely due to rapid thermal
relaxation due to the strong push−pull effect. Compound 8e,
chosen for its electronic similarity to 8c, achieved near-
quantitative conversion to the Z isomer at 365 nm, and >85%
photoconversion to the E isomer at longer wavelengths.
Interestingly, unlike push−pull azobenzenes that typically
experience rapid thermal relaxation, compounds 8c and 8e
are exceptionally stable as their Z isomers. Their thermal
stabilities, defined as the percentage of Z to E relaxation in the
24−26
for accessing azide-functionalized molecules
made this
strategy quite attractive. Moreover, we anticipated that the
tethered group would be electronically decoupled from the
photoswitchable module due to a lack of π-conjugation
between the two components and, thus, would not impact
the photochemistry. Unlike previous modular photoswitchable
scaffolds, the tethered group of arylazotriazoles would be
directly attached to the photoswitch, which would reduce the
degrees of freedom and increase the likelihood that the two
isomers would possess differential functional properties.
To access arylazotriazoles with diverse electronic properties,
we first coupled di-tert-butyl hydrazodiformate (1) with a
27
variety of aryl iodides under copper catalysis (Scheme 1).
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307
Org. Lett. 2021, 23, 4305−4310