Chromium photocatalysis: accessing structural complements to Diels-Alder adducts with electron-deficient dienophiles

Article abstract of DOI:10.1039/c6sc03303b

A chromium-catalyzed, visible light-activated net [4 + 2] cycloaddition between dienes and electron-deficient alkenes is described. Gathered evidence, via control experiments, isolated intermediates, and measured redox potentials, points to several converging reaction pathways that afford the cyclohexene adducts, including a photochemical [2 + 2] cycloaddition/vinylcyclobutane rearrangement cascade and a substrate excitation/oxidation sequence to a radical cation intermediate. Notably, the accompanying mechanistic stipulations result in a process that yields regioisomeric compounds from those generated by traditional Diels-Alder cycloadditions.

Full text of DOI:10.1039/c6sc03303b

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R. F. Higgins, M. P. Shores and E. M. Ferreira, Chem. Sci., 2016, DOI: 10.1039/C6SC03303B.
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DOI: 10.1039/C6SC03303B
Journal Name
ARTICLE
Chromium Photocatalysis: Accessing Structural Complements to
Diels-Alder Adducts with Electron-Deficient Dienophiles
Susan M. Stevenson,a Robert F. Higgins,b Matthew P . Shoresb and Eric M. Ferreira*a
Received 00th January 20xx,
Accepted 00th January 20xx
A chromium-catalyzed, visible light-activated net [4+2] cycloaddition between dienes and electron-deficient alkenes is
described. Gathered evidence, via control experiments, isolated intermediates, and measured redox potentials, points to
DOI: 10.1039/x0xx00000x
www.rsc.org/
several converging reaction pathways that afford the cyclohexene adducts, including
a photochemical [2+2]
cycloaddition/vinylcyclobutane rearrangement cascade and a substrate excitation/oxidation sequence to a radical cation
intermediate. Notably, the accompanying mechanistic stipulations result in a process that yields regioisomeric compounds
from
those
generated
by
traditional
Diels-Alder
cycloadditions.
bonds via novel reaction manifolds,14 we wondered whether
electron-poor dienophiles outside of the oxidizable realm
could also yield cycloaddition products. Though electron-poor
olefins would typically be expected to participate in [4+2]
cycloadditions through more conventional, LUMO-lowering
activation modes (e.g., thermal, Lewis acid), a photochemical
strategy could broaden the range of Diels-Alder cycloadducts
attainable, and perhaps offer orthogonal selectivity profiles
(e.g., regio-, diastereo-). Herein, we report the Cr-
photocatalyzed cycloaddition of electron-poor olefins with
dienes (Figure 1). Experiments implicate multiple operative
mechanistic pathways that converge to form the same
cycloadducts. Importantly, the described transformation
results in Diels-Alder products of reversed regioselectivity,
yielding “meta” adducts as opposed to the “ortho” and ”para”
adducts generated under conventional activation.
Introduction
In the past decade, the renaissance of photoredox catalysis
has generated renewed interest in radical cation accelerated
reactions initiated through photoinduced electron transfer
(PET).1 Notable examples in the area of radical cation [2+2]
and [4+2] cycloadditions2 have utilized metal photoredox
catalysts containing Ru3 and Ir4 ions, as well as triarylpyrylium
salts,5 as light-activated single-electron oxidants. In the
interest of advancing sustainable chemical transformations,6
there has recently been
a
shift toward developing
photocatalysts based on more earth-abundant metals, with
particular achievements reported using Cu-7 and Fe-
containing8 systems. Our groups have investigated strongly
oxidizing poly-pyridyl and -phenanthrolinyl Cr photocatalysts.9
We reported that these light-activated Cr(III) complexes (Ered
=
+1.33-1.84 V vs. SCE10) are capable of initiating radical cation
Diels-Alder cycloadditions of electron-rich alkenes,9b akin to
the Ru-catalyzed examples from Yoon in 2011.11
Mechanistically, however, the Cr-photocatalyzed cycloaddition
differs from the Ru version12 in that the reaction catalyzed by
[Cr(Ph2phen)3](BF4)3 favored an oxygen-mediated catalytic
cycle over radical chain propagation.9c This unique behavior
encouraged us to investigate the synthetic utility of the Cr
photocatalysts further.
Previous Work
electron rich
alkene
EDG
EDG
EDG
R
Photocatalysis
Cycloaddition
R
Direct
single electron
oxidation
R
R
R
This Work
1,3
electron poor
alkene
R
EWG
EWG
R
Cr Photocatalysis
R
Direct single electron
oxidation/cycloaddition DISALLOWED
R
"Meta" Diels-Alder
Adducts
The radical cation [4+2] cycloaddition using Ru or Cr with
light was relatively constrained by the requirement of
sufficiently oxidizable alkenes, a common stipulation in these
reactions.13 Being mindful that photocatalysis has often
provided an entry point for the construction of nonintuitive
Cr Photocatalysis
Three separate, converging pathways
Fig. 1. Photocatalyzed [4+2] cycloadditions with electron deficient alkenes.
Results and discussion
Reaction Development. The reactivity of 4-methoxychalcone is
illustrative (1, Figure 2). In intermolecular Diels-Alder
cycloadditions using conventional activation, enones of this
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Standard conditions
O
View OArticle OnMlinee
type routinely require rather forcing conditions and yield
predominantly adduct 4.15 Based on our previous efforts, we
reasoned that the cycloaddition of 4-methoxychalcone
through a photocatalytic oxidation pathway would be out of
the question, as the oxidation potential of enone 1 (+2.00 V, in
CH3NO2) is too positive to be oxidized by the [Cr(Ph2phen)3]3+
catalyst (E1/2* = +1.33 V, in CH3NO2) in the pathway as
described for the electron-rich dienophiles.9b,16 Thus, under Cr-
photocatalysis conditions, no cycloaddition between 4-
methoxychalcone (1) and isoprene (2) should occur.
[Cr(Ph2phen)3](BF4)3
(0.5 mol %)
Me
Ph
Ph
DOI: 10.1039/C6SC03303B
CH3NO2
23 W CFL, air
6 h
85% yielda (80%)b
2
(3 equiv)
MeO
MeO
1
5
13:1 5 / 4
Resulta
Deviation from standard conditions
1 mol % cat., 10 equiv diene
1 mol % cat., 10 equiv diene, NUVc
1 mol % cat., 10 equiv diene, blue LEDs
1 mol % cat., 10 equiv diene, sunlight
other photocatalytic systemsd
no light
81% yield
70% yield
75% yield
54% yield
3-53% yield
no reaction
O
Ph
Me
no [Cr(Ph2phen)3](BF4)3, 10 equiv diene
under Ar, 10 equiv diene, 19 h
0% yield, 20% yield 6
31% yield, 26% yield 6
MeO
6
a Yields determined by 1H NMR with dodecyl acetate as an internal standard.
b Isolated yield. Irradiation time was 16 h.
c NUV = 419, 350, 300 nm light.
O
E1/2 = +2.00 V
E1/2 = +1.98 V
[Cr]3+
*
d See the Supporting Information for individual experiments.
conventional Diels-Alder
conditions
Ph
Me
E1/2* = +1.33 V
Scheme 1. Selected optimization experiments.
MeO
1
2
O
major TS
• Effect of
cycloaddition mode
on regioselectivity?
Substrate Scope. Encouraged by the success of this reaction,
we set out to test the limits of these cycloadditions by
examining other electron-poor olefins (Scheme 2). We were
delighted to find this process was successful for a range of
cycloaddition partners. Several differentially substituted
chalcone derivatives were found to be viable substrates for
this transformation (5, 7-9). Other α,β-unsaturated carbonyl
compounds reacted in moderate to high yields (10-13). A
[4+2]
cycloaddition
O
Ph
Ph
Me
O
MeO
Ar
1•+
3
Ph
Me
O
Me
Me
MeO
Ph
4
conventional
Diels-Alder
adduct
MeO
5
reversed Diels-Alder
adduct
nitroolefin was also
a
competent substrate, forming
cyclohexene 14 in 74% yield. Consistent with the 4-
methoxychalcone case, the transformations with isoprene all
proceeded with high levels of regioselectivity (8:1 to 19:1).
Symmetrical 2,3-dimethyl-1,3-butadiene could be used with
several of these dienophiles, affording cyclohexenes 15-17 in
good yields. Regioselectivity considerations are not applicable
for this diene, but it is still remarkable that this method
circumvents the forcing conditions generally required to obtain
these adducts.19 Differentially substituted dienes were also
proficient in this reaction. The cycloaddition conditions were
tolerant of a variety of functional groups on the diene (18-21,
24, 26). In addition, terminally substituted dienes gave
cyclohexenes 22-26 in high yields. Somewhat lower
regioselectivity ratios were observed, but stereoselectivity was
excellent in these processes, as the major constitutional
isomer was observed as a single diastereomer.20 Lastly, enones
containing different electron-rich aryl groups at the β-position
also participated in the reaction (27, 28), although we note
here the scope was more limited.21 For example, an enone
with an electron-neutral arene was not productive in this
transformation (29).
Fig. 2. Cycloaddition reactivity of 4-methoxychalcone.
Surprisingly, however, when enone 1 was exposed to
[Cr(Ph2phen)3](BF4)3 in the presence of isoprene (2) and
irradiation with a 23 W compact fluorescent light bulb,
cycloadduct 5 was formed in 85% yield (80% isolated yield,
Scheme 1). Remarkably, the regioselectivity of this
cycloaddition was 13:1 favoring the reversed Diels-Alder
adduct (5). We found that increased catalyst loading and
equivalents of diene did not increase the yield. Near-UV (NUV),
blue LEDs, and sunlight also effected this transformation, but
optimal results were achieved with the 23 W CFL. Other
photoredox catalysts were less effective (vide infra). A control
experiment confirmed that no reaction occurred without light.
Notably, with light but in the absence of catalyst,
vinylcyclobutane 6 was formed in 20% yield, presumably via
photochemical [2+2] cycloaddition between enone 1 and
isoprene,17 but no [4+2] products were detected. Lastly,
performing the reaction in the absence of air significantly
decelerated the formation of cyclohexene 5, while
vinylcyclobutane 6 also formed. We had previously found
oxygen to be important for Cr-mediated photocatalysis with
electron-rich substrates (vide infra).9b,c,18
2 | J. Name., 2012, 00, 1-3
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EWG
EWG
[Cr(Ph2phen)3](BF4)3 (0.5 mol %)
cross-adduct between 4-methoxychalcone and the added
View Article Online
R
R
CH3NO2, air
23 W CFL
diene, confirming that cyclohexene 5 is fDoOrmI: i1n0g.10t3h9r/oCu6gShC0d3i3r0e3cBt
Ar
Ar
(3 equiv)
O
rearrangement of vinylcyclobutane
6 and not through
O
O
Me
O
OMe
cycloreversion/recombination.28,29 Thus, we believe that a
cascade pathway involving photochemical [2+2] cycloaddition
(λmax1 = 340 nm) followed by single-electron oxidative
vinylcyclobutane rearrangement30 is viable and occurring. We
note, however, that cyclobutane 6 was formed in only 20%
yield without catalyst, while 85% yield of cyclohexene 5 was
formed with catalyst in the same duration, suggesting that this
[2+2]/rearrangement may not be the only mechanistic
pathway.
R =
Br
R
Me
5
7
78% yield
(13:1)
8
64% yield
(8:1)
9
74% yield
(10:1)
88% yieldb
(11:1)
O
O
O
O
MeO
NO2
Me
OEt
11
75% yield
(19:1)
OH
H
13
53% yieldd
(11:1)
14
74% yieldc
(17:1)
10
83% yield
(12:1)
12
57% yieldc
(17:1)
R = CHO,18
54% yield (6:1)
R = Ph, 15
73% yielde
O
O
R = CH2OAc,19
61% yield (7:1)
Me
Me
R
R
Ph
R = Me, 16
56% yield
R = CH2OH, 20
55% yield (8:1)
O
R = OEt,17
58% yield
O
O
O
A
Me
R =
, 21
MeO
MeO
Me
72% yield (7:1)
Me
Ph
Ph
Ph
[Cr]
Me
O
O
R = n-Hex, 22
89% yield (5:1)
hν
hν
Me
Me
R = n-Pent, 25
61% yield (3:1)
EtO
EtO
MeO
MeO
MeO
R = (CH2)2Ph, 23
85% yield (4:1)
1
E1/2 = +2.00 V
6
E1/2 = +1.68 V
5
R = CH2OAc, 26
78% yield (6:1)
O
O
R = CH2OTBS, 24
77% yield (4:1)
R
R
hν
MeO
MeO
Ph
Ph
B
O
O
O
Me
Me
Me
R = OMOM, 28
54% yield (12:1)
Me
Ph
30
E1/2 = +1.40 V
27
68% yield (15:1)
MeO
OMe
Ph
[Cr]
R = H, 29
0% yieldf
O
hν
*
[4+2] or
[2+2]/rearr.
hν
BnO
R
excited state
species
Ph
MeO
C
a Isomeric ratio in parenthesis, major isomer is drawn. b Gram scale. c 1 mol % cat. d 9 equiv diene.
e NUV irradiation was used. f A vinylcyclobutane analogous to 6 was formed in 11% yield.
1•+
MeO
Scheme 2. The Cr-photocatalyzed [4+2] cycloaddition between dienes and electron-
1*
deficient alkenes - scope.
Fig. 3. Possible mechanistic pathways.
Mechanistic Pathways. We have found in our initial
mechanism studies the potentially operative pathways deviate
significantly from the direct oxidation route. As mentioned
previously, accounting for reduction potentials it is unlikely
that the photoexcited Cr catalyst (Cr3+*/2+ E1/2 = +1.33 V in
O
O
[Cr(Ph2phen)3](BF4)3
(0.5 mol %)
Me
Ph
Ph
23 W CFL, air
CH3NO2, 10 h
67% yield
Me
CH3NO2) could be directly oxidizing 4-methoxychalcone (1+/0
,
MeO
Me
MeO
O
6
5
+2.00 V) or isoprene (2+/0, +1.98 V22) to initiate the
cycloaddition.23 Furthermore, all attempts to catalyze the
cycloaddition using photocatalysts with more positive excited
Me
Me
Ph
[Cr(Ph2phen)3](BF4)3
(0.5 mol %)
Me
23 W CFL, air
CH3NO2, 6 h
MeO
31
(10 equiv)
15
not formed
state
reduction
potentials,
such
as
[Ru(bpz)3]2+,
triphenylpyrilium, Mes-Acr, or a variety of cyanoarenes and
chloranil,24 provided lower yields than [Cr(Ph2phen)3](BF4)3
(see the Supporting Information), indicating that this
transformation is likely not proceeding via simple direct
oxidation of the electron deficient alkene. An energy transfer
pathway could also be ruled out since the long-lived excited
state of [Cr(Ph2phen)3](BF4)3* (38 kcal/mol) is considerably
lower than the transfer energies of either the 4-
methoxychalcone (1) or isoprene (the triplet excited state
energies are both ~60 kcal/mol).25
We thus considered other mechanistic pathways (Figure 3).
One possibility is that the reaction is proceeding through
intermediate vinylcyclobutane 6 (Pathway A), which we
observed when the reaction was performed without catalyst.26
Indeed, when vinylcyclobutane 6 (E1/2 = +1.68 V in CH3NO2)
was exposed to the Cr conditions, product 5 was formed in
67% yield as a single isomer (Scheme 3).27 When this
rearrangement was performed in the presence of excess diene
31, only the rearrangement product was observed and not the
Scheme 3. Rearrangement of vinylcyclobutane 6.
A different route, Pathway B offers a means of accessing a
reactive enone radical cation (1•+, Figure 3). If in situ
dimerization of enone 1 occurs,31 the resulting dimer (30) has a
significantly lower reduction potential (E1/2 = +1.40 V, in
CH3NO2) than the starting enone. Oxidation could then induce
cycloreversion to the radical cation, and interception of this
putative radical cation with the diene could afford the
cycloaddition
product
(via
direct
[4+2]
and/or
[2+2]/rearrangement32). Control experiments suggest this
pathway is a minor contributor at most. First, enone dimer 30
was found to form in only trace amounts under the standard
Cr conditions in the absence of diene. Furthermore,
independently synthesized enone dimer 30 subjected to
irradiation affords retrocyclobutanation with and without
catalyst, but in low yields (Scheme 4). When dimer 30 was
exposed to the cycloaddition conditions in place of enone 1,
cyclohexene 5 formed in 20% yield, at least implicating the
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feasibility of this pathway. Notwithstanding, the low
Journal Name
In an effort to probe the termination step(s) concerning all
View Article Online
production of dimer 30 and the relatively sluggish possible pathways, quantum yield DOeI:x1p0e.1r0im39e/Cn6tSsC03w30e3rBe
cycloreversion suggests a lesser role in the formation of performed. Since compounds 1, 6, and 30 can all be invoked as
cyclohexene 5.
starting materials or intermediates in the mechanism, each
was tested for their photochemical efficiency. At 350 nm
excitation, maximum quantum yield values for species 1, 6,
and 30 were Φ = 0.013, 0.45, and 0.013, respectively.
Compounds 1, 6, and 30 do absorb light at 350 nm (as does
nitromethane), and their equilibria in solution complicate the
calculation of an accurate quenching factor. Therefore
compound 6, which showed the largest quantum yield, was
excited at 400 nm in the presence of [Cr(Ph2phen)3]3+ in
CD3NO2 where the maximum quantum yield was Φ = 0.93.
Since only [Cr(Ph2phen)3]3+ absorbs light at this wavelength,
the quenching factor is assumed to be ~1, giving a chain length
value of <1. These data corroborate the lack of a radical chain
mechanism12 in the reaction manifold. Moreover, when a
deoxygenated sample containing 6 and [Cr(Ph2phen)3]3+ was
irradiated at 400 nm in nitromethane, the quantum yield
decreased to a maximum value of Φ = 0.21, further implicating
this reactivity as photocatalytic instead of photoinitiated, akin
to our previous report.9c
O
Ph
[Cr(Ph2phen)3](BF4)3 (0.5 mol %)
23 W CFL, air
CH3NO2, 6 h
O
O
1
16% yielda
(4% yield)b
Ph
Ph
MeO
2
(3 equiv)
O
Me
Me
[Cr(Ph2phen)3](BF4)3 (0.5 mol %)
Ph
MeO
OMe
30
23 W CFL, air
CH3NO2, 6 h
5
20% yielda
MeO
a NMR yield with dodecyl acetate as internal standard. The remainder is recovered 30.
b Yield when reaction was performed without catalyst.
Scheme 4. Cycloreversion of enone dimer 30.
An alternative pathway for the generation of 1•+ recognizes
that the photoexcited enone (1*) will be easier to oxidize than
its ground state form (Figure 3, Pathway C). Select reports
indicate that the excitation of chalcone derivatives and related
α,β-unsaturated carbonyl species lead to excimers33 and/or
charge-transfer complexes,34 which enable single-electron
oxidation.35 The oxidation of enone 1* in this manner would
generate radical cation 1•+, which would proceed to product 5
as described earlier. Here, we note that enone 1 shows weak
emission at 443 nm when excited at 340 nm in acetonitrile,
from which we estimate an excited state reduction potential
(1•+/0*) of -0.80 V, which suggests thermodynamic competency
for oxidation of 1* by the photoexcited Cr catalyst. The triplet
excited state lifetime of enone 1 was reported to be 23 and 29
ns in heptane and methanol, respectively,25a suggesting this is
well within the range of feasibility for oxidation by the long-
lived excited state of the Cr catalyst.
Bauld and coworkers have discussed the inhibitory effect of
trans-anethole on competing radical cation cycloadditions and
vinylcyclobutane rearrangements due to its highly oxidizable
nature (E1/2 = +1.35 V9c).22,36 Thus, if the cycloaddition of enone
1 and isoprene (2) is proceeding through a radical cation (e.g.,
1•+), we would expect the addition of trans-anethole to
considerably impede the formation of cycloadduct 5. In
accordance with this hypothesis, in a competition experiment
using a 1:1 mixture of trans-anethole (32) and enone 1 with
excess isoprene, the cycloaddition with enone 1 proceeded
only after the majority of 32 was consumed (Scheme 5). The
inhibitory effect of alkene 32 may implicate the intermediacy
of the enone radical cation (1•+) in the overall process.
The presence of oxygen in this transformation also
deserves mention. In our earlier study, we had discussed the
roles of O2 in the cycloaddition using electron-rich alkenes. O2
was essential, and the absence of it shut down catalysis
altogether. Singlet oxygen was formed in these cycloadditions
via a quench of the long-lived Cr(III) excited state. The singlet
oxygen is then reduced to superoxide by Cr(II), and the
superoxide then reduces the cycloadduct radical cation. In this
specific reaction with electron-deficient alkenes, the effect of
O2 is still beneficial to the overall reaction progress, but not
nearly to the same extent as the earlier transformation (i.e.,
reaction rates are slower, but the cyclohexene product is still
formed via catalytic turnover). We believe singlet oxygen is
formed in these cycloadditions as well. In the analysis of the
reaction and the substrate scope, in several cases we noted
the formation of a minor byproduct (average <5% yield). We
determined this byproduct to be an allylic hydroperoxide,
presumably arising from the oxidation of the cyclohexene
1
product by O2.37 It is possible that we may be amplifying or
diminishing specific reaction pathways in the presence of O2;
future studies may elucidate its multifaceted effects.
From the evidence amassed thus far we conclude that this
Cr-photocatalyzed cycloaddition using an electron deficient
dienophile can occur through several reaction pathways
involving photochemical and radical cation processes, all
outside of the direct electron transfer or energy transfer
pathways. Coincidentally, the operative pathways all converge
to the same cyclohexene adducts. Further mechanistic studies
are underway.38
Diels-Alder Regioselectivity Analysis. A hallmark characteristic
of the Diels-Alder reaction is its highly predictive regioselective
outcomes. An electron-withdrawing group on the dienophile
and an electron-donating group on the diene will impact the
coefficients of the FMOs so as to dictate the overall
regioselectivity of the cycloaddition (i.e., the “ortho-para
Me
Me
Me
% Yielda
2
(10 equiv)
Time (h) 33
5
Me
PMP
[Cr(Ph2phen)3](BF4)3
(0.5 mol %)
PMP
2
6
17
0 (3)
32
O
33
O
64 < 5 (5)
74 18 (0)
75 62 (0)
Me
CH3NO2, air
23 W CFL
Ph
10
Ph
24
PMP
PMP
1
5
a
1H NMR yields with dodecyl acetate as internal standard. Yields in parentheses are of vinylcyclobutane 6.
PMP = 4-MeOC6H4
Scheme 5. Competition experiment with trans-anethole.
4 | J. Name., 2012, 00, 1-3
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Me
rule”). Efforts to reverse this natural regioselectivity of Diels-
Alder cycloadditions have been reported, but only a handful of
strategies have been successful.39,40 These include the
incorporation of electronically steering substituents that can
*
View Article Online
DOI: 10.1039/C6SC03303B
[2+2]/rearr.
COPh
2
PhOC
PMP
Me
Me
Pathway A
PMP
PMP
PhOC
Me
1*
37
38
Me
PMP
COPh
PhOC
PMP
or [4+2]
2
5
be
subsequently
removed,41
and
catalyzed
vs.
Pathway B or C
1•+
thermal/noncatalyzed cycloadditions that adjust the molecular
orbital coefficients of the reactants (e.g., selective
coordination of a sterically unhindered carbonyl).42 Table 1
depicts an alternative strategy to achieve this unnatural
Fig. 4. General regiochemical explanation.
regioselectivity.
Example
dienes
and
β-(para-
Conclusions
methoxyphenyl)nitroethylene were combined using both
previously described LiClO4/CH3NO2 conditions43 and our
chromium photocatalyzed conditions. As can be seen, these
transformations each proceed to afford complementary
regiochemistries, where the photocatalyzed reactions occur
with high selectivity for the unconventional Diels-Alder
adducts. This unconventional regioselectivity tracks
consistently with all of the selectivities observed in the cases in
The deliberate investigations of photocatalytic manifolds with
various components have unlocked new transformations that
possess tremendous potential for the chemistry community.
We have shown that that the Cr-catalyzed [4+2] cycloaddition
of dienes with electron-poor alkenes (i.e., outside of the
oxidizable realm) can yield cyclohexene adducts, and, perhaps
most pertinently, with opposite regioselectivities to those
provided via the traditional Diels-Alder cycloaddition.
Inasmuch as the previous Cr-catalyzed [4+2] cycloaddition is a
chemoselective complement to the Diels-Alder reaction, this
example represents a regioselective complement to the
transformation. This process is optimally effective using Cr
photocatalysis. Mechanistic investigations elucidating the
unique impact of Cr, and efforts to expand this chemistry, will
be reported in due course.
Scheme 2. These transformations represent
conditions-based approach to invert the Diels-Alder
regioselectivity with reactive diene/dienophile partners.
a novel,
Table 1. Reversed regioselectivity under Cr-photocatalysis conditions.
NO2
O2N
R
R
MeO
MeO
Conventional
Diels-Alder
5 equiv diene
4 M LiClO4
Cr Photocatalysis
3 equiv diene
0.5 mol % 2
CH3NO2, light, air
Cycloadducts
O2N
Acknowledgements
CH3NO2, 100 °C
O2N
Me
This research was carried out by the Catalysis Collaboratory for
Light-activated Earth Abundant Reagents (C-CLEAR), which is
supported by the NSF and EPA through the Network for
Sustainable Molecular Design and Synthesis program (NSF-
CHE-1339674). We acknowledge collaborators Niels Damrauer
and Anthony Rappé and their groups for enriching discussions.
Sang Lee is acknowledged for experimental assistance.
46% yield
18 : 1
74% yield
1 : 17
PMP
Me
PMP
34
35
14
O2N
OAc
62% yield
17 : 1
74% yield
1 : 11
PMP
O2N
PMP
OAc
36
Notes and references
Our hypothesis for the observed regioselectivity is
illustrated in Figure 4, using chalcone 1 and isoprene as an
example. Notably, whether the cycloaddition is proceeding
through a photochemical “head-to-tail” [2+2] cycloaddition44
followed by a radical cation vinylcyclobutane rearrangement,
or an enone radical cation pathway, the net reversed Diels-
Alder regioselectivity should be favored. With isoprene (2), the
methyl substituent allows selective generation of the more
stable diradical or radical cation intermediate. Presumably, the
aryl group also stabilizes this intermediate species to some
extent.
1
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8
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2
4
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A
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guide. Reduction potentials cited from the literature are
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also observed in very minor quantities (average <5% yield)
the formation of an allylic hydroperoxide byproduct.
19 In sample cases (e.g., 16, 17), this method provided
noticeably enhanced dienophile reactivity over conventional
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analysis.
20 Relative stereochemistry confirmed by NMR analysis.
21 In the interest of synthetic utility, the PMP group can be 37 For a review discussing allylic oxidation by O2, see: H. H.
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Cr3+*/2+ E1/2 = +1.42 V in CH3NO2, still well below the
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