Visible light photocatalysis of [2+2] styrene cycloadditions by energy transfer

Article abstract of DOI:10.1002/anie.201204835

Hip to be square: Styrenes participate in [2+2] cycloadditions upon irradiation with visible light in the presence of an iridium(III) polypyridyl complex. In contrast to previous reports of visible light photoredox catalysis, the mechanism of this process involves photosensitization by energy transfer and not electron transfer. Copyright

Full text of DOI:10.1002/anie.201204835

Angewandte
Chemie
DOI: 10.1002/anie.201204835
Photocatalysis
Visible Light Photocatalysis of [2+2] Styrene Cycloadditions by Energy
Transfer**
Zhan Lu and Tehshik P. Yoon*
The prospect of conducting synthetically useful organic
reactions with visible light has attracted significant recent
attention from a number of research groups[1] including our
own.[2] These efforts have focused on the utilization of the
remarkable photoredox properties of ruthenium[3] and iri-
dium[4] polypyridyl complexes, and a variety of photocatalytic
transformations have been shown to occur upon irradiation
with visible light in the presence of these complexes.[5] The
ability to use visible light rather than the ultraviolet light
generally required for traditional organic photochemistry has
numerous benefits,[6] including: (1) the lower cost and
decreased energy demand of visible light sources; (2) the
ability to conduct photoreactions without specialized photo-
reactors or quartz glassware; and (3) the ability to selectively
photoexcite the transition metal photocatalyst without induc-
ing undesired radical reactions of photochemically sensitive
organic functional groups.
by energy transfer has been documented with a number of
organic compounds,[7] to the best of our knowledge, there are
only two carbon-carbon bond-forming reactions using tran-
sition metal photocatalysts that have been demonstrated to
proceed via triplet sensitization of an organic substrate. The
first is the Ru(bpy)32+-mediated norbornadiene-to-quadricy-
clane valence isomerization studied by Kutal for solar energy
storage applications.[8] The second is the photocatalytic
dimerization of anthracene reported by Castellano to be
2+
sensitized by the related ruthenium photocatalyst Ru(dmb)3
(dmb = 4,4’-dimethyl-2,2’-bipyridine).[9] Thus, although the
utility of UV-absorbing organic chromophores as triplet
photosensitizers has been well established for decades,[10]
synthetic applications of triplet sensitization with transition
metal complexes that absorb in the visible range have not
been extensively explored.
We initiated our investigation by exploring the [2+2]
photocycloaddition of styrene 3, a substrate whose oxidation
potential (+ 1.42 V vs SCE)[11] has precluded its ability to
participate in radical cation cycloadditions previously
reported from our lab. Fluorinated iridium complex 2, first
reported by Malliaras and Bernhard[12] and subsequently
identified by Stephenson[13] as an optimal visible light photo-
catalyst for Kharasch-type radical additions, does not possess
an excited state oxidation potential (+ 0.89 V)[12] sufficient to
generate the radical cation of 1. On the other hand, its
reported emission maximum at 470 nm corresponds to an ET
of 61 kcalmolÀ1. In general, styrenes possess excited state
triplet energies (ET) of approximately 60 kcalmolÀ1.[14]
Together, these data suggested that 2 might be capable of
sensitizing triplet-state reactions of styrene 3 upon irradiation
with visible light.
Indeed, irradiation of 3 with a 23 W compact fluorescent
light bulb in the presence of 1 mol% of iridium complex 2·PF6
resulted in the formation of [2+2] cycloadduct 4 in a wide
range of solvents (Table 1, entries 1–7). Consistent with
a triplet sensitization mechanism, we observed no dramatic
dependence on solvent polarity, whereas we have observed
that radical cation processes benefit from the ability of polar
solvents to stabilize the charged intermediates. Slightly faster
conversion was observed in DMSO (entry 7), and upon
optimization we were able to obtain the cycloadduct in good
yield at lower reaction concentrations (entry 8). Also con-
sistent with a triplet sensitization mechanism was the
observation that metal complexes reported in other visible
light photocatalysis applications with triplet state energies
lower than that of styrene were ineffective in this trans-
formation (entries 9 and 10).[15] Finally, control reactions
confirmed that no reaction occurs either in the absence of
light or the absence of photocatalyst (entries 11 and 12).[16]
Our research group has been particularly interested in
visible light photocatalysis of cycloaddition reactions.[2] In our
investigations, we have been able to exploit both photo-
2+
reduction and photooxidation reactions of Ru(bpy)3 (1a)
and related ruthenium(II) chromophores to design [2+2],
[3+2], and [4+2] cycloaddition reactions involving radical
anion and radical cation intermediates. Collectively, the
diversity of products available using this strategy is quite
broad; however, the nature of the photoinduced electron-
transfer processes that generate the radical ion intermediates
necessarily limits the scope of these reactions to either
electron-deficient or electron-rich substrates that are ame-
nable to one-electron redox processes. The success of photo-
redox methods reported from other labs has likewise been
dictated by the redox properties of the organic substrates
involved.
Recognizing that such electrochemical constraints will be
important considerations in the design of any photoredox
process, we wondered whether similar transformations could
be initiated by energy transfer rather than by an electron-
2+
transfer mechanism. Although the quenching of Ru*(bpy)3
[*] Dr. Z. Lu, Prof. T. P. Yoon
Department of Chemistry, University of Wisconsin-Madison
1101 University Avenue, Madison, WI 53706 (USA)
E-mail: tyoon@chem.wisc.edu
Homepage: http://yoon.chem.wisc.edu
[**] This research was conducted using funds from the NIH
(GM095666) and the Sloan Foundation. The NMR facilities at UW-
Madison are funded by the NSF (CHE-9208463, CHE-9629688) and
NIH (RR08389-01, RR13866-01).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201204835.
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Table 1: Optimization and control studies for photocatalytic [2+2]
cycloaddition.
cycloaddition to 4 (see Supporting Information). Conversely,
cyclic styrenes that are incapable of undergoing this energy-
wasting isomerization react much more rapidly than acyclic
styrenes (30). The ability of the cyclic constraint to extend the
lifetime of the triplet is also presumably responsible for the
ability of indene to undergo intermolecular cycloaddition
(e.g., 31); acyclic styrenes simply undergo rapid (E) to (Z)
isomerization without productive intermolecular cycloaddi-
tion. We also observe that the reaction can be successfully
initiated with a variety of substituted styrenes regardless of
their electronic nature (8–12),[20] including both electron-rich
and electron-deficient heterostyrene compounds. On the
other hand, substrates containing only aliphatic, non-conju-
gated alkenes are recovered unchanged from these reaction
conditions (13), consistent with their significantly higher
triplet energies compared to styrenes.[21] The diversity of
coupling partners suitable for this cycloaddition is extensive
and includes aliphatic alkenes, styrenes, enones, enoates, enol
ethers, haloalkenes, and allenes (17–23). The functional group
compatibility of this process is also good; sulfonamides,
unprotected alcohols, carbonyl compounds, and halogens are
easily tolerated. Collectively, these data indicate that the
range of cyclobutane compounds accessible using this meth-
odology is quite broad and unconstrained by the redox
properties of the substrates.
The ability to use low-energy, operationally convenient,
and readily available visible light in the photosensitization
reactions makes these processes more attractive for synthetic
applications than UV irradiation. In order to demonstrate this
point, we compared the reaction of vinyl iodide 32 under our
optimized conditions to photoexcitation by direct irradiation
with UV (Scheme 1). We find that 32 is rapidly consumed
when irradiated in a Rayonet reactor outfitted with 254 nm
lamps; however, the mass recovery of the reaction is poor,
consistent with the propensity of high-energy UV radiation to
promote uncontrolled radical decomposition processes.
Indeed, resubjecting cyclobutane 23 to direct irradiation
with 254 nm UV light resulted in its complete decomposition
within 1 h. Thus, in addition to showing greater operational
convenience than traditional UV photolyses, these conditions
also increase the tolerance of photochemical reactions
towards photosensitive functional groups such as alkyl
iodides.
Entry[a]
Catalyst
Solvent
Conc. [m]
Yield[b] [%]
1
2
3
4
5
6
7
8
2·PF6
2·PF6
2·PF6
2·PF6
2·PF6
2·PF6
2·PF6
2·PF6
CHCl3
CH2Cl2
THF
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.01
0.01
0.01
0.01
0.01
22
26
21
24
21
13
acetone
MeOH
MeCN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
33
89 (83)[c]
9
1a·(PF6)2
1b·(PF6)2
none
0
0
0
0
10
11
12[d]
2·PF6
[a] Reactions irradiated using a 23 W compact fluorescent light bulb.
[b] Yields determined by 1H NMR analysis against a calibrated internal
standard unless noted. [c] Yield of the isolated product in parenthesis.
[d] Control reaction conducted in the dark.
To further differentiate this triplet sensitization mecha-
nism from radical cation cycloadditions, we investigated the
reaction of diene substrate 5 under two different sets of
conditions. First, Bauld has reported that the radical cation of
5 undergoes efficient intramolecular Diels–Alder cycloaddi-
tion,[17] and we recently reported photocatalytic conditions
that generate the same radical cation intermediate and
produce [4+2] cycloadduct 6 in good yields [Eq. (2)].[2h] On
the other hand, exposure of 5 to iridium catalyst 2 under
visible light affords a complex mixture of products that we
identified as diastereomeric [2+2] cycloadducts [Eq. (3)],[18]
with only a trace of the [4+2] cycloadduct. Similar prefer-
ences for [2+2] periselectivity in cycloadditions involving
dienes with a variety of triplet sensitizers have been pre-
viously reported.[19]
Studies exploring the scope of this process are summar-
ized in Table 2. Several themes emerge from an examination
of these data. First, as expected from the propensity of alkene
triplets to undergo geometric isomerization, the photo-
cycloaddition is stereoconvergent; the reaction of the (Z)
isomer of 3 gave results identical to the reaction of (E)-3
[Table 2, Eq. (4)]. A time course of the reaction confirms that
(E)/(Z) photoisomerization of 3 occurs faster than productive
2
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Table 2: Scope studies for photosensitized [2+2] cycloadditions under visible light.[a]
1
[a] Yields represent the averaged results of two reproducible experiments. Diastereomer ratios determined by H NMR analysis of the unpurified
reaction mixture. Reactions conducted using (E)-styrene isomer unless noted. PMP=p-methoxyphenyl. [b] Using (Z)-styrene isomer.
ester under typical ester hydrolysis conditions affords
(Æ)-cannabiorcicycloic acid in 97% yield.
The results of this study are significant for a variety of
reasons. First, they demonstrate that the class of transition
metal photocatalysts that have earned significant recent
interest for their ability to promote organic transformations
Scheme 1. Comparison of visible to UV conditions for cycloaddition of
32. [a] 1H NMR analysis against an internal standard revealed 100%
consumption of 32.
To demonstrate that these conditions are applicable to the
preparation of complex natural products, we undertook
a concise synthesis of cannabiorcicyclolic acid (37), one of
several
known
cyclobutane-containing
cannabinoids
(Scheme 2).[22] The chromene precursor 35 is easily obtainable
by base-catalyzed condensation between phenol 33 and citral
(34) in 54% yield. Photocycloaddition sensitized by 2·PF6
affords 86% yield of cyclobutane 36 after 8 h of irradiation
with a 23 W compact fluorescent light bulb. In contrast, the
direct irradiation of 35 with 254 nm UV light for 5 h gave only
19% yield of the desired cycloadduct with only 9% of the
starting chromene remaining. Finally, hydrolysis of the ethyl
Scheme 2. Synthesis of cannabiorcicycloic acid.
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maintains the same operational facility as previously reported
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in our laboratory.
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Published online: && &&, &&&&
Keywords: cycloaddition · cyclobutanes · energy transfer ·
.
photocatalysis · visible light
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4
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Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Photocatalysis
Hip to be square: Styrenes participate in
[2+2] cycloadditions upon irradiation
with visible light in the presence of an
iridium(III) polypyridyl complex. In con-
trast to previous reports of visible light
photoredox catalysis, the mechanism of
this process involves photosensitization
by energy transfer and not electron
transfer.
Z. Lu, T. P. Yoon*
&&&& — &&&&
Visible Light Photocatalysis of [2+2]
Styrene Cycloadditions by Energy Transfer
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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