Enantioselective intramolecular [2+2] photocycloaddition reactions of 4-substituted coumarins catalyzed by a chiral Lewis acid

Article abstract of DOI:10.1002/chem.201104032

Eight coumarins, which carry a terminal alkene tethered by a CH ₂XCH₂ group to their 4-position (X=CH₂, CMe₂, O, S, NBoc, NZ, NTs, NBn), were synthesized in overall yields of 51-80 %. Starting materials for the syntheses were either commercially available 4-hydroxycoumarin or 4-formylcoumarin. The intramolecular [2+2] photocycloaddition of these coumarins gave diastereoselectively products with a tetracyclic 3,3a,4,4a-tetrahydro-1H-cyclopenta[2,3]cyclobuta[1,2-c]chromen-5(2H) -one skeleton. Direct irradiation at λ=300 nm in dichloromethane (c=10 mM) led to product formation in good yields for most substrates, presumably via a singlet excited state intermediate. Due to the low coumarin absorption at λ >350 nm the photocycloaddition was slow upon irradiation at λ=366 nm. Addition of a chiral oxazaborolidine-based Lewis acid (50 mol %) increased the reaction rate at λ=366 nm and induced a significant enantioselectivity in the [2+2] photocycloaddition. Six out of eight coumarin substrates (X=CH₂, CMe₂, O, NBoc, NZ, NTs) gave the respective products in yields of 72-96 % and with 74-90 % enantiomeric excess (ee) upon irradiation in dichloromethane (c=20 mM) at -75 °C. The Lewis acid presumably acts by coordination to the coumarin carbonyl oxygen atom, which leads to a bathochromic shift (redshift) of the UV absorption and which increases the singlet state lifetime. A second electrostatic interaction of the hydrogen atom at C3 with the oxygen atom of the oxazaborolidine is likely. Copyright

Full text of DOI:10.1002/chem.201104032

FULL PAPER
DOI: 10.1002/chem.201104032
Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of
4-Substituted Coumarins Catalyzed by a Chiral Lewis Acid
Richard Brimioulle,[a] Hao Guo,[a, b] and Thorsten Bach*[a]
Abstract: Eight coumarins, which carry
terminal alkene tethered by
formation in good yields for most sub-
strates, presumably via a singlet excited
state intermediate. Due to the low cou-
marin absorption at l >350 nm the
photocycloaddition was slow upon irra-
diation at l=366 nm. Addition of
a chiral oxazaborolidine-based Lewis
acid (50 mol%) increased the reaction
rate at l=366 nm and induced a signifi-
cant enantioselectivity in the [2+2]
photocycloaddition. Six out of eight
coumarin substrates (X=CH2, CMe2,
O, NBoc, NZ, NTs) gave the respective
products in yields of 72–96% and with
74–90% enantiomeric excess (ee) upon
irradiation in dichloromethane (c=
20 mm) at ꢀ758C. The Lewis acid pre-
sumably acts by coordination to the
coumarin carbonyl oxygen atom, which
leads to a bathochromic shift (redshift)
of the UV absorption and which in-
creases the singlet state lifetime. A
second electrostatic interaction of the
hydrogen atom at C3 with the oxygen
atom of the oxazaborolidine is likely.
a
a CH2XCH2 group to their 4-position
(X=CH2, CMe2, O, S, NBoc, NZ, NTs,
NBn), were synthesized in overall
yields of 51–80%. Starting materials
for the syntheses were either commer-
cially available 4-hydroxycoumarin or
4-formylcoumarin. The intramolecular
[2+2] photocycloaddition of these cou-
marins gave diastereoselectively prod-
ucts with a tetracyclic 3,3a,4,4a-tetrahy-
dro-1H-cyclopentaACHTUNGTRENNUNG[2,3]cyclobutaACHUTNGTREN[NUGN 1,2-
Keywords: chirality · cycloaddition
reaction · enantioselectivity · Lewis
acids · photochemistry
c]chromen-5(2H)-one skeleton. Direct
irradiation at l=300 nm in dichloro-
methane (c=10 mm) led to product
Introduction
proach[3]—some recent developments, which enable a direct
access to enantiomerically pure cyclobutanes in solution.
One notable strategy is the immediate conversion of axial
chirality in the substrate into point chirality in the respective
cyclobutane.[4] It requires, however, the presence of a chirali-
ty axis, which in turn needs to be constructed enantioselec-
tively or which needs to be induced by recrystallization of
homochiral crystals. A second strategy makes use of chiral
entities, to which [2+2] photocycloaddition substrates bind
via non-covalent interactions and which are capable of in-
ducing asymmetry in the subsequent photochemical trans-
formation.[5] Several entities of this type have been devel-
oped, including cyclodextrins[6] and hydrogen-bonding tem-
plates,[7] with the latter compounds enabling catalytic enan-
tioselective transformations if the template was combined
with a suitable sensitizing unit.[8] In search for new ways to
induce enantioselectivity we have recently started to look
into Lewis acid catalysts as potential chiral templates for
[2+2] photocycloaddition reactions. This idea was inspired
by the discovery of Lewis et al. that a catalysis by BF3 and
EtAlCl2 can be observed in the photodimerization of cou-
marin and in its [2+2] photocycloaddition to other olefins.[9]
A typical example for such a [2+2] photocycloaddition is
the reaction of 2,3-dimethyl-2-butene with coumarin, which
exhibited a significant rate enhancement if conducted in the
presence of BF3·OEt2 (Scheme 1). As a reason for this rate
enhancement the ability of a Lewis acid to increase the sin-
glet state lifetime of coumarin was invoked. Upon coordina-
tion of the Lewis acid to the carbonyl group of coumarin,
ACHTUNGTRENNUNG[2+2] Photocycloaddition reactions belong to the most ver-
satile and most frequently used photochemical reactions.[1]
In particular, the light-induced addition reaction of olefins
to a,b-unsaturated enones has been extensively applied in
natural product total syntheses.[2] The resulting cyclobutanes
can be employed either as key building blocks for the syn-
thesis of cyclobutane-containing molecules or upon ring
opening for the generation of strategic bonds. In any case, it
is desirable to obtain cyclobutanes with high stereoselectiv-
ity, which poses a significant challenge both regarding the
development of diastereoselective and of enantioselective
[2+2] photocycloaddition reactions. In the latter case, there
have been—apart from the conventional chiral auxiliary ap-
[a] R. Brimioulle, Dr. H. Guo, Prof. Dr. T. Bach
Lehrstuhl fꢀr Organische Chemie 1 and Catalysis Research Center
(CRC)
Technische Universitꢁt Mꢀnchen
Lichtenbergstrasse 4, 85747 Garching (Germany)
Fax : (+49)89-289-13315
E-mail: thorsten.bach@ch.tum.de
[b] Dr. H. Guo
New address:
Fudan University, Department of Chemistry
220 Handan Road
200433 Shanghai (P. R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201104032.
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of Lewis acids led to a significant rate increase and AlBr3-
activated oxazaborolidines were found to induce promising
enantioselectivity in the photocycloaddition. Lewis acid 2
evolved from further optimization work, in which the sub-
stituents at position 2 (boron atom) and position 5 of the
heterocyclic core were varied. With this catalyst (50 mol%),
an enantioselectivity of 82% ee (84% yield) was realized in
the intramolecular [2+2] photocycloaddition of substrate 1a
at ꢀ758C and at l=366 nm in dichloromethane (c=20 mm).
We have now expanded the substrate scope of this enan-
tioselective [2+2] photocycloaddition and have obtained fur-
ther data regarding the absorption properties of coumarin
1a in the presence of Lewis acids. Enantioselectivities close
to 90% ee have been achieved with certain coumarin sub-
strates. Photophysical data of coumarins 1 in the presence of
Lewis acids were obtained, which provide further support of
the previously suggested mode of action. In this Full Paper
we summarize the results of our work in this area.
Scheme 1. Lewis acid catalysis in the [2+2] photocycloaddition of 2,3-di-
methyl-2-butene to coumarin as observed by Lewis and Barancyk.[9b]
the energy of the np* state was supposed to increase rela-
tive to the fluorescent pp* singlet state. The increased
energy difference avoids the—from a photochemical point—
disfavorable vibronic coupling of these states,[9–11] which is
the reason for a rapid, irradiationless decay from the singlet
state. In accordance with this hypothesis, it was observed
that coumarin, which is nonfluorescent at room temperature
in aprotic solvents, shows a strong fluorescence in dichloro-
methane solution upon addition of BF3·OEt2.[9b] The longer
lifetime of the first excited singlet state is a prerequisite for
the population of triplet states by intersystem crossing.
When revisiting the above-mentioned studies by Lewis
and Barancyk,[9b] we were able to fully confirm their syn-
thetic results and we could also identify other Lewis acids,
which raised the reaction rate in the [2+2] photocycloaddi-
tion at l=366 nm even further.[12] We suspected, however,
that an intermolecular [2+2] photocycloaddition would be
not an ideal system to be used for an enantioselectivity
study. The relative weak Lewis acid coordination to coumar-
in was expected to result in a rapid dissociation of the pho-
toexcited species and in an insufficient asymmetric induction
if chiral Lewis acids were to be used. Indeed, we have re-
cently noted in catalytic enantioselective reactions mediated
by a hydrogen-bonding sensitizer that a fast intramolecular
[2+2] photocycloaddition is crucial for effective enantioface
differentiation.[8] In order to minimize any distracting inter-
actions between the Lewis acid and the coumarin carbonyl
group we planned to attach the alkenyl chain for an intra-
molecular attack at the 4-position of the coumarin expecting
that linkage via a methylene group—as opposed to linkage
via a heteroatom—would lead to the least electronic dis-
turbance of the chromophore. Compounds of this type are
represented by structure 1 as depicted in Figure 1.
Results and Discussion
Preparation of the starting materials 1 and of Lewis acid 2:
The synthesis of substrate 1a was performed by Negishi
cross-coupling from triflate 3 and has been previously de-
scribed.[12,13] In an analogous fashion, the gem-dimethylated
substrate 1b was prepared. The direct zincation of 1-bromo-
2,2-dimethyl-4-pentene[14] was unsuccessful but the required
zinc compound could be prepared in situ by halogen-lithium
exchange and transmetalation to zinc chloride. Best condi-
tions for the cross-coupling included the use of [Pd CHTUNGTRENNUNG(dba)3]
2A
(dba=dibenzylidenacetone) as the catalyst and triACHTUNGTRENNUNG(2-furyl)-
phosphane (tfp) as the ligand (Scheme 2).
Scheme 2. Preparation of coumarin 1b by Negishi cross-coupling reaction
of triflate 3.
The oxygen (X=O, 1c) and sulfur (X=S, 1d) analogues
of 4-(pent-4-enyl)coumarin (1a) were accessible (Scheme 3)
from known 4-hydroxymethylcoumarin (4).[15]
An alkylation of substrate 4 was attempted with several
electrophiles. With allylic bromide, there was no reaction or
the attempted reaction led to unidentified side products. Ex-
perimental conditions included the use of a variety of bases
(NaH, K2CO3, NEt3) and the absence or presence of activa-
tion reagents (NBu4I, KI) in various solvents (THF, DMF,
MeCN, CH2Cl2). Only the use of KF on neutral alumina[16]
led to a noticeable conversion at 608C in MeCN. The yield
(32%), however, was not satisfactory. A significant improve-
ment was achieved by employing the respective allyl tri-
Figure 1. Coumarins 1 employed in intramolecular [2+2] photocycloaddi-
tion reactions catalyzed by chiral Lewis acid 2.
Preliminary studies were performed with 4-(pent-4-enyl)-
coumarin (1a), which is capable of intramolecular [2+2]
photocycloaddition. The reaction proceeded slowly at l=
366 nm in dichloromethane at room temperature. Addition
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Photocycloaddition Reactions of 4-Substituted Coumarins
FULL PAPER
Scheme 5. Preparation of oxazaborolidine 10 from triarylboroxine 8 and
enantiomerically pure aminoalcohol 9.
AHCTUNGTREG[NNNU 2+2] Photocycloaddition reactions in the absence of Lewis
Scheme 3. Preparation of coumarins 1c and 1d from 4-hydroxymethyl-
coumarin (4).
acids at l=300 nm: The UV/Vis spectra recorded for cou-
marins 1 are very similar indicating that the effect of the
substituent X in b-position to the coumarin core has little in-
fluence on the spectroscopic properties of the chromophore.
Representative spectra are depicted in Figure 2 for coumar-
flate[17] (Tf=trifluoromethanesulfonyl). With K2CO3 as aux-
iliary base a clean conversion of alcohol 4 to the desired al-
lylic ether 1c was observed in 93% yield. While the mesy-
late 5 (Ms=methanesulfonyl) or bromide 6 derived from al-
cohol 4 were not reactive in attempted conversions with
allyl alcohol,[18] the respective sulfur nucleophile, allyl mer-
captane, underwent a smooth reaction with bromide 6 to
provide the desired thioether 1d in 87% yield.[19]
The key intermediate for the preparation of the protected
amines 1e–h was secondary amine 1i, which was readily
available by reductive amination of known 4-formylcoumar-
in (7)[20] (Scheme 4). Preformation of the imine was followed
by reduction with sodium triacetoxyborohydride to provide
the desired intermediate 1i in 81% yield.[21] Subsequent N-
protection was straightforward following known proce-
dures[22–25] (see Experimental Section) and delivered the re-
spective amines with tert-butyloxycarbonyl (Boc) (1e, 97%),
benzyloxycarbonyl (Z) (1 f, 99%), tosyl (1g, 95%), and
benzyl protection (1h, 82%) in high yields.
Figure 2. UV/Vis spectra of representative coumarins 1a (—), 1b (- - -),
and 1c (· · ·) in dichloromethane solution (c=0.8 mm). The normalized
emission spectrum of the light source with lmax =366 nm (—) is superim-
posed.
ins 1a, 1b, and 1c in dichloromethane solution (c=0.8 mm).
As for the parent coumarin, two strong absorptions are ob-
served. A stronger absorption (e ffi 11000 Lmolꢀ1 cmꢀ1) ap-
pears at l=270–280 nm, to which previously a pp* transi-
tion was assigned,[8,11] and a slightly weaker absorption (e
ffi 6300 Lmolꢀ1 cmꢀ1) is observed at l=310–320 nm, which
in the parent compound was assigned to an np* transi-
tion.[8,11]
Despite the fact, that coumarin decay from the excited
state to the ground state is rapid, it was observed that the in-
tramolecular [2+2] photocycloaddition of substrates
1 occurs at l=300 nm (Table 1). Indeed, the reaction rate of
a five-membered ring closure[28] in intramolecular [2+2]
photocycloaddition reactions is high and it may effectively
compete with internal conversion to the ground state.
Except for substrates 1d (entry 4) and 1h (entry 8), all other
coumarins reacted cleanly to form the respective straight
photocycloaddition products rac-11 (entries 1–3, 5–7). The
reactions were regio- and stereoselective. Other photoprod-
ucts were not observed. For thioether 1d the [2+2] photocy-
cloaddition proceeded in low yields at room temperature
and severe decomposition was observed, which is likely due
to a photoinduced homolytic bond cleavage.[11,18,19] At lower
Scheme 4. Reductive amination of aldehyde 7 to amine 1i, the precursor
for the synthesis of N-protected coumarins 1e–h (see text).
Oxazaborolidine 10 was prepared from known aminoalco-
hol 9[26] and the respective tris(ortho-trifluoromethylphenyl)-
boroxine (8) upon heating in toluene (Scheme 5). The latter
compound can be readily prepared from the corresponding
commercially available boronic acid by azeotropic water re-
moval in refluxing benzene.[27] Lewis acid 2 was prepared
from precursor 10 in situ by dissolving the oxazaborolidine
together with a stoichiometric amount of AlBr3 in CH2Cl2
under complete exclusion of moisture and air (glove box).
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T. Bach et al.
Table 1. Intramolecular [2+2] photocycloaddition of coumarins 1 at l=
300 nm to provide racemic products rac-11.
Further evidence for a predominant singlet reaction path-
way was obtained by an attempted quenching of the puta-
tive triplet state with oxygen. An oxygen-saturated[32,33] solu-
tion of substrate 1c showed under conditions, which were
otherwise identical to those provided in Table 1 (entry 3),
complete conversion after six hours and gave a photocy-
cloaddition yield of 79%. The reaction rate was not changed
by the addition of a triplet quencher.
Entry[a]
X
T [8C]
t [h][b]
Product
Yield [%][c]
1
2
3
4
5
6
7
8
CH2
CMe2
O
30
30
30
ꢀ75
30
30
30
30
4.5
3.5
6.0
5.0
6.0
8.5
5.0
5.0
rac-11a
rac-11b
rac-11c
rac-11d
rac-11e
rac-11 f
rac-11g
rac-11h
89
78
73
52
69
82
74
30
AHCTUNGTREG[NNUN 2+2] Photocycloaddition reactions in the presence of Lewis
acid 2 at l=366 nm: As evidenced by their UV/Vis spectra
(Figure 2) an excitation of coumarins 1 at l=366 nm is not
expected to lead to an effective [2+2] photocycloaddition,
because the absorption at this wavelength is very low.
Indeed, none of the substrates depicted in Figure 1 showed
a high conversion if irradiated at l=366 nm (room tempera-
ture or ꢀ758C) in dichloromethane solution. Product yields
remained below 25% after five hours but it must be stressed
that a [2+2] photocycloaddition was still notable even at
this wavelength.
S
NBoc
NZ
NTs
NBn
[a] All reactions were conducted using a RPR-100 reactor with sixteen
Rayonet RPR-3000 ꢃ lamps as the irradiation source in deaerated di-
chloromethane (c=10 mm) as solvent. [b] Elapsed reaction time to ach-
ieve 100% conversion of the starting material. [c] Yield of isolated prod-
uct.
The situation changed dramatically when Lewis acid 2
was added to the reaction mixture. Reaction rates increased
and product formation was in most cases complete after five
hours. A substrate concentration of 20 mm was found to be
a good compromise between the limits of a sufficient reac-
tion rate and a high concentration neccessary to favor Lewis
acid association. Apart from the known product 11a
(Table 2, entry 1), seven additional products 11b–h were
formed successfully, five of which exhibited high enantio-
meric excesses (entries 2, 3, 5, 6, 7). Favored by the Thorpe–
Ingold effect,[34] ring closure of gem-dimethylated substrate
1b was fastest and the reaction was complete after only
temperature the homolytic bond dissociation could be sur-
pressed and product rac-11d could be isolated in higher
yields (entry 4).
The bond dissociation in thioethers such as 1d has been
reported to be possible from the lowest excited singlet
state.[11] In order to support the suspicion that also the intra-
molecular [2+2] photocycloaddition at l=300 nm occurs
from the singlet state, we used the known substrate (Z)-
12[12] as a stereochemical probe (Scheme 6). Reactions of
this substrate in the singlet manifold should be stereospecif-
ic. Reactions in the triplet manifold should be non-stereo-
specific, because an intermediate 1,4-biradical is expected to
undergo free rotation.[29,30] It has been shown in preliminary
work[12] that the photocycloaddition of (Z)-12 via triplet in-
termediates leads to a mixture of products, in which the
trans-product trans-13 prevails (d.r. cis/trans 30:70). In the
present case, however, cis-product cis-13 was the major
product under the conditions previously employed for sub-
strates 1 (Table 1). Although the reaction was not perfectly
stereospecific the relative configuration was retained to a sig-
nificant degree, which in turn supports a mechanistic path-
way at l=300 nm via the respective singlet excited state.
Indeed, it is—based on previous data[31]—unlikely that a sig-
nificant percentage of photoexcited coumarin can reach the
triplet state in the absence of a sensitizer.
Table 2. Enantioselective intramolecular [2+2] photocycloaddition of
coumarins 1 at l=366 nm to provide enantiomerically enriched products
11.
Entry[a]
X
t [h][b]
Product
e.r.[c]
ee [%]
Yield [%][d]
1
2
3
4
5
6
7
8
CH2
CMe2
O
5.0
3.5
5.0
5.0
7.0
9.0
5.0
5.0
11a
11b
11c
11d[e]
11e
11 f
91:9
82
74
88
42
90
74
76
0
84
96
72
22
81
93
91
71
87:13
94:6
S
71:29[f]
95:5
NBoc
NZ
NTs
NBn
87:13
88:12
50:50
11g
11h
[a] All reactions were conducted at ꢀ758C using a RPR-100 reactor with
sixteen 366 nm, 8 W fluorescent lamps (see Figure 2) as the irradiation
source in dry, deaerated dichloromethane (c=20 mm) as solvent.
[b] Elapsed reaction time to achieve 100% conversion of the starting ma-
terial. [c] The enantiomeric ratio (e.r.) was determined by chiral GC or
chiral HPLC. [d] Yield of isolated product. [e] 4-Methylcoumarin was iso-
lated as a by-product (26% yield). [f] The enantiomeric ratio was deter-
mined after reduction of the lactone to the respective primary alcohol.
Scheme 6. Intramolecular [2+2] photocycloaddition of coumarin (Z)-12
at l=300 nm to racemic products cis- and trans-13.
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Photocycloaddition Reactions of 4-Substituted Coumarins
FULL PAPER
three and a half hours (entry 2). With 74% ee, the enantio-
selectivity is lower than recorded for the unsubstituted sub-
strate 1a, which is most likely due to a significant contribu-
tion of the uncatalyzed pathway to the reaction yield. The
absorption wavelength of 1b is shifted slightly bathochromic
(redshifted) relative to 1a (Figure 2).
The oxygen analogue 1c (entry 3) of 4-(pent-4-enyl)-cou-
marin (1a) turned out to be a substrate, which showed high
enantioselectivity (88% ee). The only obvious reason for the
better performance compared to 1a is a lower background
reaction due to a decreased absorption in the employed
wavelength region. Indeed, the absorption maximum of 1c
is blueshifted relative to 1a (Figure 2). Similar arguments
are valid for compound 1e, which showed the best enantio-
selectivity so far observed in these reactions (entry 5). Still,
the subtle differences between the differently protected
amines 1e–g regarding their enantioselectivity are difficult
to explain. In the case of amine 1h, however, the lack of
enantioselectivity (entry 8) is clearly due to the association
of the basic amino group to the Lewis acid, which is likely
to inhibit any coordination to the coumarin. The coordina-
tion also explains the improved chemoselectivity of this pho-
tocycloaddition as compared to the reaction in the absence
of a Lewis acid (Table 1, entry 8). In the latter case, the free
electron pair of the amine causes oxidative side reactions,[35]
which are suppressed upon coordination to a Lewis acid.
Sulfur analogue 1d of 4-(pent-4-enyl)-coumarin (entry 4)
suffered in the presence of Lewis acid from a sulfur cleavage
reaction, indicated by a significant amount of 4-methylcou-
marin, which was isolated from the product mixture. The
low ee may be due to a partial coordination of the Lewis
acid to the sulfur atom.
For comparison, the [2+2] photocycloaddition of substrate
1c was also performed at alternative wavelengths. All other
conditions remained unchanged as compared to Table 2. At
l=300 nm (RPR-3000 ꢃ), the reaction was complete after
five hours and delivered product 11c in high yield (82%).
The enantioselectivity (34% ee) was significantly lower than
at l=366 nm (Table 2, entry 3), however. This observation
suggests a significant uncatalyzed background reaction at
l=300 nm. If the [2+2] photocycloaddition was attempted
at l >400 nm (RPR-4190 ꢃ) the reaction rate was very low.
No significant product formation was observed after five
hours. After 14 h, the conversion was 6% and product 11c
could be isolated in 5% yield (66% ee). Apparently, the
chosen wavelength is unsuited for excitation of the coumar-
in.
Figure 3. UV/Vis spectra of coumarin 1a dichloromethane solution (c=
0.8 mm) upon addition of 20 equiv BF3 (—), EtAlCl2 (- - -), or AlBr3 (· ·
·).
not UV active. The UV/Vis spectra of compound 1a with
BF3, EtAlCl2, and AlBr3 are depicted in Figure 3. In all
cases, 20 equivalents of the Lewis acid were used relative to
the coumarin (c=0.8 mm). Similar spectra were also ob-
tained upon treatment of coumarins 1b–e with Lewis acids
(see Supporting Information).
Although the maximum of the UV band at longest wave-
length is not in all cases red-shifted (cf. Figures 2 and 3), this
band is significantly broadended and shows absorption at
wavelengths up to 350 nm, for AlBr3 even up to 360 nm.
The observations are fully consistent with the data obtained
by Lewis et al. when treating coumarin with BF3 and
EtAlCl2.[9b] Since compounds 1 were irradiated with a light
source having its maximum emission at l=366 nm (see
Figure 2) the bathochromic shift is certainly one mode of
action for the observed catalysis.
Based on the data of Lewis et al.,[9b] a second contribution
to the catalytic Lewis acid activity was expected to stem
from an increased singlet lifetime of the coumarins. Fluores-
cence spectra were recorded in dichloromethane solution
(c=0.8 mm) at an excitation wavelength of lexc =300 nm.
Coumarin 1a turned out to be not fluorescent under these
conditions. Upon addition of Lewis acids a fluorescence
became visible with an emission maximum at l ffi 400 nm
(see Supporting Information). Best data were obtained for
BF3 and EtAlCl2 as Lewis acids and they are depicted in
Figure 4 (five equivalents of Lewis acid). For comparison
the emission spectrum of complex 1a and Lewis acid 2 is
also included in Figure 4. Quite clearly, the complex shows
different photochemical properties than the complexes with
Further photophysical data and mechanistic discussion:
Lewis acid 2 exhibits an unstructured UV/Vis absorption,
which reaches into the visible region (see Supporting Infor-
mation). This fact and the high lability of 2 towards mois-
ture and oxygen made it difficult to obtain meaningful UV/
Vis data for any potential complex with coumarins 1. The
bathochromic absorption shift, which putatively occurs upon
coordination, could be nicely visualized, however, upon
treatment of coumarins 1 with other Lewis acids, which are
Figure 4. Fluorescence spectra of coumarin 1a dichloromethane solution
(c=0.8 mm) in the presence of 5 equiv BF3 (—), EtAlCl2 (- -), or catalyst
2 (· · ·) (lexc =300 nm).
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T. Bach et al.
the transparent Lewis acids BF3 and EtAlCl2. The emission
maximum is redshifted (see also Supporting Information)
and the emission is weaker than the complexes with BF3
and EtAlCl2. The low signal-to-noise ratio is due to the in-
stability of the Lewis acid, which allowed only to record
a single fluorescence scan.
17 was obtained by performing the intramolecular [2+2]
photocycloaddition at l=300 nm (cf. Table 1). The Lewis
acid catalyzed reaction was performed at l=366 nm and
gave the enantiomerically enriched product 17 expectedly
with low selectivity (21% ee).
Although a quantitative analysis is not possible based on
the limited photophysical data, which we have recorded for
the Lewis acid complexes of compounds 1, it appears quali-
tatively safe to say that the effects of Lewis acid coordina-
tion to these compounds are similar to what was previously
observed for the parent coumarin.[9] Most notably, an in-
creased lifetime of the singlet state could be clearly proven
upon formation of a Lewis acid complex. The second mode
of action for catalysis, that is, increase of singlet state life-
time, has consequently been confirmed.
Based on previous experiments, in which the stereospecif-
ity of the intramolecular [2+2] photocycloaddition was
probed with (E)- and (Z)-12 it appears likely that a triplet
state is involved in the Lewis acid catalyzed reaction. In par-
ticular compared to the data obtained by uncomplexed cou-
marin (Z)-12 at l=300 nm (Scheme 6), the almost com-
pletely stereoconvergent reaction course observed in the re-
action catalyzed by Lewis acid 2 supports a pathway via trip-
let intermediates.[12]
The configuration of product 11a (Table 2) and of its
enantiomer ent-11a was proven earlier by crystallographic
evidence.[12] The enantioface differentiation is in line with
a previously suggested coordination mode of oxazaboroli-
dine-based Lewis acids to carbonyl compounds.[12,36] In this
model there is a second electrostatic interaction of the hy-
drogen atom at C3 in the coumarin with the oxygen atom of
the oxazaborolidine. If this was correct, one would expect
a decreased enantioselectivity if 3-substituted coumarins but
not 4-substituted coumarins were employed in the [2+2]
photocycloaddition.
The synthesis of an appropriate substrate to test this hy-
pothesis started from commercially available 3-hydroxycou-
marin (14), which was converted into the respective triflate
15 (Scheme 7). Negishi cross-coupling with pent-4-enyl zinc
bromide proceeded smoothly as for the synthesis of 1a and
yielded 3-(pent-4-enyl)coumarin (16). Racemic product rac-
Conclusion
In summary, a yet unexplored way to achieve enantioselec-
tive photochemical reactions was explored. The chiral oxa-
zaborolidine–AlBr3 complex 2 acts as a chiral Lewis acid in
the intramolecular [2+2] photocycloaddition reactions of
coumarins 1 and was shown to induce a significant enantio-
meric excess. Its mode of action is at least two-fold. UV/Vis
spectra indicate that Lewis acid coordination of coumarins
1 leads to a bathochromic absorption shift, which in turn fa-
cilitates their excitation at l=366 nm. In addition, the Lewis
acid stabilizes the excited singlet state as shown qualitatively
by fluorescence measurements. Due to the significant ab-
sorption of Lewis acid 2 in the same wavelength range (250–
350 nm) as coumarins 1, the photophysical parameters of
a potential complex 1·2 cannot be treated separately, howev-
er. It appears likely that the intersystem crossing rate of
coumarins in complex 1·2 is higher than for non-associated
coumarins. The involvement of triplet intermediates is sug-
gested by the previous observation[12] that the Lewis acid
mediated [2+2] photocycloaddition is stereoconvergent.
Experimental Section
General methods: All reactions sensitive to air or moisture were carried
out in flame-dried glassware under positive pressure of argon using stan-
dard Schlenk techniques. Photochemical experiments were performed in
flame-dried pyrex irradiation tubes (diameter: 1 cm, volume: 15 mL for
low temperature irradiation) under positive pressure of argon. Irradiation
experiments were performed in an RPR-100 photochemical reactor
(Southern New England Ultra Violet Company, Branford, CT, USA)
equipped with fluorescence lamps (lmax =419 nm, Philips black light blue
8 W, lmax =366 and 300 nm). For the photochemical reactions dry di-
chloromethane was used and degassed by purging with argon in an ultra-
sonicating bath for 15 min. Flash chromatography was performed on
silica gel 60 (Merck, 230–400 mesh) with the eluent mixtures given for
the corresponding procedures. Thin layer chromatography (TLC) was
performed on silica coated glass plates (silca gel 60 F 254). Compounds
were detected by UV (l=254 nm, 366 nm), CAM (cerium ammonium
molybdate solution) or KMnO4. All solvents for chromatography were
destilled prior to use. Analytical gaschromatography was performed at
a HP 6890 Series GC (Agilent, achiral stationary phase: HP-5 column,
poly-dimethyl/diphenyl-siloxane, 95/5; chiral stationary phase: 2,3-di-
methyl-6-TBDMS-b-cyclodextrin modified column) with a flame ionisa-
tion detector. The temperature method was given for the corresponding
compounds. Analytical HPLC was performed using a chiral stationary
phase (Daicel ChiralCell, Chemical Industries, flow rate: 1.0 mLminꢀ1
,
type and eluent was given for the corresponding compounds) and UV-de-
tection. IR: JASCO IR-4100. MS/HRMS: Finnigan MAT 8200. 1H and
13C NMR: Bruker AV-360 and AV-500 recorded at 300 K or 333 K.
Chemical shifts are reported relative to the solvent [CHCl3: d(1H)=
Scheme 7. Synthesis of 3-(pent-4-enyl)-coumarin (16) and its Lewis acid
catalyzed, intramolecular [2+2] photocycloaddition to product 17 (abso-
lute configuration not assigned, relative configuration as given).
(13C)=77.0 ppm, [D6]DMSO: d(1H)=2.50 ppm, (13C)=
7.26 ppm, dACHTUNGTRNENUNG dACHTUNGTRENNUNG
39.5 ppm] as reference. Appearant multiplets which occur as a result of
accidental equality of coupling constants to those of magnetically non-
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Photocycloaddition Reactions of 4-Substituted Coumarins
FULL PAPER
equivalent protons are marked as virtual (virt.). The relative configura-
tion of chiral products and the multiplicity of the 13C NMR signals were
determined by two-dimensional NMR spectra (COSY, NOESY, HSQC,
HMBC). Specific rotations were determined using a Perkin–Elmer 241
MC polarimeter (sodium vapor lamp). Melting points were measured on
a Bꢀchi 510 of the company Bꢀchi and are not corrected.
(d), 125.0 (d), 126.0 (s), 128.2 (d), 150.7 (s), 169.1 ppm (s). The obtained
data matched those reported in the literature.[12]
(3aS,4aS,10bS)-3,3a,4,4a-Tetrahydrofuro[3’,4’:2,3]cyclobutaACTHNUGTRNEUNG[1,2-c]chro-
men-5(1H)-one (11c): According to the representative procedure, the re-
action was performed with 1c (15.0 mg, 69.4 mmol, 1.0 equiv) and 2 in di-
chloromethane (1.0 mL, 34.7 mmol, 0.5 equiv) at l=366 nm for six hours
(c=20 mm). The title compound was obtained as a colorless, crystalline
solid (10.8 mg, 49.9 mmol, 72%, 88% ee). [a]2D0 = ꢀ9.4 (c=0.96, CH2Cl2)
(S)-3,3-Bis(3,5-dimethylphenyl)-1-(2-(trifluoromethyl)phenyl)hexahydro-
pyrrolo-[1,2-c]ACHTUNGTRENNUNG[1,3,2]oxazaborole (10): (S)-Bis(3,5-dimethylphenyl)(pyr-
[88% ee]; TLC: Rf =0.28 (P/EtOAc 4:1, [KMnO4]); chiral GC: t CHTUNGTRENNUNG(ent-
RA
(11c)=170 min [608C (1 min), 1358C (208Cminꢀ1),
1258C (220 min), 308Cminꢀ1 2208C (6 min)]; 1H NMR (360 MHz,
CDCl3, 300 K): d = 2.36 (ddd, 2J=12.7, 3J=11.2, 3J=3.9 Hz, 1H), 2.62
rolidin-2-yl)methanol (9) (736 mg, 2.38 mmol, 1.0 equiv) and 2,4,6-tris(2-
(trifluoromethyl)-phenyl)-1,3,5,2,4,6-trioxatriborinane (8)[27] (409 mg,
0.793 mmol, 0.33 equiv) were dissolved in dry toluene (30 mL) and was
heated at reflux in a Dean–Stark apparatus for 14 h. The solvent was re-
moved by distillation at ambient pressure and the procedure was repeat-
ed twice (refluxed for 4 h and 3 h). The solution was concentrated by dis-
tillation at ambient pressure and the remaining solvent was completely
removed in vacuo (p=10ꢀ1 mbar). The title compound was obtained as
slightly yellow oil or foam (1.10 g, 2.38 mmol, 100%) which was stored in
a glovebox or was diluted to a stock solution in 23.8 mL toluene (0.1m)
11c)=158 min, tRACTHNGUTERNNUG
,
2
3
3
(virt. dt, J=12.7, J ffi 8.7 Hz, 1H), 2.85–2.92 (m, 1H), 3.47 (dd, J=11.2,
3J=8.5 Hz, 1H), 3.78 (d, 2J=9.7 Hz, 1H), 3.95 (dd, 2J=9.6, 3J=5.8 Hz,
1H), 4.05 (d, 2J=9.6 Hz, 1H), 4.07 (d, J=9.7 Hz, 1H), 7.08 (dd, J=8.6,
2
3
4J=1.2 Hz, 1H), 7.16 (ddd, 3J=8.1 Hz, 3J=7.3 Hz, 4J=1.2 Hz, 1H), 7.24
4
3
3
4
(dd, 3J=8.1, J=1.5 Hz, 1H), 7.31 ppm (ddd, J=8.6, J=7.3, J=1.5 Hz,
1H); 13C NMR (91 MHz, CDCl3, 300 K): d = 28.3 (t), 37.3 (d), 48.2 (d),
49.6 (s), 74.9 (t), 78.4 (t), 117.9 (d), 120.9 (s), 125.2 (d), 125.9 (d), 129.2
(d), 151.3 (s), 168.1 ppm (s); IR (ATR): n˜ = 2937 (w, sp3-CH), 2854 (w,
sp3-CH), 1756 (s, CO), 1493 (m, sp2-CH), 1449 (s, sp2-CH), 1260 (s), 1196
(s), 1072 (s), 1012 (s), 910 (s), 756 (s, sp2-CH), 731 (m, sp2-CH), 699 cmꢀ1
(s); MS (EI, 70 eV): m/z (%): 216 (34) [M]+, 175 (8) [MꢀC3H5]+, 160
(100) [MꢀC3H4O]+, 132 (39) [MꢀC3H4OꢀCO]+, 119 (15), 103 (9)
[C8H7]+, 91 (24) [C7H7]+, 77 (12) [C6H5]+, 63 (8), 55 (16) [C4H7]+, 41
(10) [C3H5]+; HRMS (EI, 70 eV): m/z: calcd for C13H12O3: 216.0781;
found: 216.0777.
at ꢀ308C. GC: tR =20.18 min [608C, (3 min) 1258Cminꢀ1
, 3008C
(5 min)]; 1H NMR (360 MHz, CDCl3, 300 K): d = 1.50–1.67 (m, 3H),
1.67–1.80 (m, 2H), 2.20–2.40 (m, 12H), 2.87–3.07 (m, 1H), 3.07–3.27 (m,
1H), 6.75–6.85 (m, 2H), 7.07–7.22 (m, 4H), 7.30–7.70 ppm (m, 4H);
13C NMR (360 MHz, CDCl3, 300 K): d = 21.6 (q), 25.4 (t), 30.4 (t), 43.4
(t), 73.2 (d), 88.4 (s), 123.9 (d), 123.9 (d), 124.0 (d), 125.3 (d), 128.2 (d),
128.9 (d), 129.0 (d), 130.7 (s), 134.1 (s), 137.0 (s), 137.3 (d), 137.5 (s),
143.7 (s), 147.6 ppm (s); 11B NMR (116 MHz, CDCl3, 300 K):
d =
35.4 ppm; MS (EI, 70 eV): m/z (%): 463 (28) [M]+, 291 (55) [C21H26N]+,
276 (16), 239 (41), 223 (55), 207 (39), 196 (68), 156 (12) [C7H5BF3]+, 146
(24) [C7H4F3]+, 133 (100), 105 (31) [C8H9]+; HRMS (EI, 70 eV): m/z:
calcd for C28H29ON11BF3: 463.2289; found: 463.2281.
(3aS,4aS,10bS)-tert-Butyl-5-oxo-3a,4,4a,5-tetrahydro-1H-chromeno-
[4’,3’:1,4]cyclobuta
the representative procedure, the reaction was performed with 1e
(15.0 mg, 47.6 mmol, 1.0 equiv) and in dichloromethane (0.79 mL,
ACHTUNGTREN[NUGN 1,2-c]pyrrol-2(3H)-carboxylate (11e): According to
2
ACHTUNGTRENNUNG
23.8 mmol, 0.5 equiv) at l=366 nm for 7 h (c=20 mm). The title com-
pound was obtained as a colorless, very viscous oil (12.1 mg, 38.4 mmol,
81%, 90% ee). TLC: Rf =0.27 (P/EtOAc=4:1, [KMnO4]); [a]2D0 = +44.7
A
ACHTUNGTRENNUNG
(2): In situ preparation: 1.00 mL of a stock solution of 10 in toluene
(0.1m, 100 mmol, 1.0 equiv) was dried in vacuo in a Schlenk tube over
night. The residue was dissolved in dry, deaerated dichloromethane
(3.3 mL) and 100 mL of a solution of aluminum bromide (1.0m in dibro-
momethane, 100 mmol, 1.0 equiv) was added. The reaction mixture was
stirred for five minutes at room temperature and the resultant catalyst
solution was directly used for the [2+2] photocycloaddition reaction.
(c=0.65, CH2Cl2, 90% ee), chiral HPLC: tRACTHNUGTRNENUG(11e)=9.2 min, tRAHCTUNGRTENUNG(ent-11e)=
11.1 min (AD-H, n-hexane/isopropanol 90:10); 1H NMR (360 MHz,
[D6]DMSO, 333 K): d =1.46 (s, 9H), 2.21 (ddd, 2J=12.3, 3J=10.6, 3J=
3.7 Hz, 1H), 2.42–2.67 (m, 1H), 2.80–2.90 (m, 1H), 3.37 (ddd, 3J=10.6,
3J=8.3, 4J=1.3 Hz, 1H), 3.43 (d, 2J=11.9 Hz, 1H), 3.57–3.65 (m, 2H),
3.96 (d, 2J=11.9 Hz, 1H), 7.03 (dd, 3J=8.2, 4J=1.3 Hz, 1H), 7.19 (virt.
td, 3J=7.5 Hz, 4J=1.3 Hz, 1H), 7.32 (ddd, 3J=8.2, 3J=7.5, 4J=1.7 Hz,
1H), 7.43 ppm (dd, 3J=7.5 Hz, 4J=1.7 Hz, 1H); 13C NMR (91 MHz,
CDCl3, 300 K): d =28.5 (q), 28.8 (q), 38.1 (d), 46.1 (d), 48.9 (s), 52.5 (t),
58.3 (t), 80.2 (s), 117.8 (d), 122.0 (s), 125.3 (d), 126.5 (d), 129.3 (d), 151.0
(s), 154.7 (s), 167.5 ppm (s); IR (ATR): n˜ = 2974 (w, sp3-CH), 2931 (w,
sp3-CH), 2871 (w, sp3-CH), 1759 (m, CO-OAr), 1689 (s, CO-NR), 1608
(w, C=C), 1477 (w), 1449 (m, sp3-CH), 1391 (s), 1365 (s), 1198 (s), 1173
(s), 1152 (s), 1114 (s), 1105 (s), 872 (s), 757 cmꢀ1 (s, sp2-CH); MS (EI,
70 eV): m/z (%): 315 (4) [M]+, 259 (74) [MꢀC4H8]+, 242 (16)
(3aS,4aS,10bR)-3,3a,4,4a-Tetrahydro-1H-cyclopentaCAHUTNGTRENNUG[2,3]-cyclobutaACHTUNGTNER[NUGN 1,2-c]-
chromen-5(2H)-one (11a)
Representative procedure for the enantioselective catalyzed [2+2] photocy-
cloaddition reactions: 1a (43.0 mg, 200 mmol, 1.0 equiv) was dissolved in
dry, deaerated dichloromethane (2.1 mL) and transferred into an irradia-
tion tube (Duran glass). The catalyst 2, was transferred as a solution in
dry, deaerated dichloromethane (3.3 mL, 100 mmol, 0.5 equiv) from the
Schlenk tube (see above) into the irradiation tube via syringe. The
Schlenk tube was washed twice with dry, deaerated dichloromethane
(2.3 mL) and the solution was also transferred into the irradiation tube
via syringe. After pre-cooling to ꢀ758C for 30 min, the solution (c=
20 mm) was irradiated at l=366 nm for five hours at this temperature.
After the irradiation was complete, the reaction solution was allowed to
warm to room temperature and was washed with brine (8 mL). The
layers were separated and the aqueous layer was extracted with dichloro-
methane (3ꢄ6 mL). The combined organic layers were dried over
Na2SO4, filtrated and the solvent was removed under reduced pressure.
The residue was purified by flash column chromatography (pentane/ethyl
acetate 10:1) to afford the title compound as colorless oil (36.1 mg,
168 mmol, 84%, 82% ee). TLC: Rf =0.32 (P/EtOAc 10:1); chiral GC: tR-
[MꢀC4H9O]+,
215
(21)
[MꢀC4H8ꢀCO2]+,
174
(25)
[MꢀC4H8ꢀCO2ꢀC3H5]+, 160 (64) [MꢀC4H8ꢀCO2ꢀNC3H5]+, 131 (14)
[MꢀC4H8ꢀCO2ꢀNC3H5ꢀCO]+, 84 (100) [C5H10N]+, 70 (8) [C4H8N]+, 57
(93) [C3H7N]+, 49 (47); HRMS (EI, 70 eV): m/z: calcd for C18H21NO4:
315.1465; found: 315.1459.
Procedures and analytical data for the other products 11 (Table 2) can be
found in the Supporting Information.
(1aR,4aS,10bS)-1a,2,3,4-Tetrahydro-1H-cyclopenta
chromen-5(10bH)-one (17) and (1aS,4aR,10bR)-1a,2,3,4-tetrahydro-1H-
cyclopenta[1,4]cyclobuta[1,2-c]chromen-5(10bH)-one (ent-17): According
to the representative procedure, the reaction was performed with 16
(43.0 mg, 200 mmol, 1.0 equiv) and in dichloromethane (3.0 mL,
ACHTUGTNREN[UNG 1,4]cyclobutaACHTUNGTRENNUNG[1,2-c]-
AHCTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG(11a)=388 min, tRACHTUNGTRENNUNG
(ent-11a)=408 min [608C (1 min), 208Cminꢀ1, 1158C,
2
1158C (520 min), 308Cminꢀ1
,
2208C (4 min)]; 1H NMR (360 MHz,
100 mmol, 0.5 equiv) at l=366 nm for 9 h (c=20 mm). The title com-
pound was obtained as a colorless oil (40.0 mg, 186 mmol, 93%, 21% ee).
TLC: Rf =0.58 (P/EtOAc 9:1 [KMnO4]); chiral GC: tR =443 min, tR =
2
3
CDCl3, 300 K): d = 1.72 (dt, J=8.2, J=3.8 Hz, 1H), 1.86–1.98 (m, 3H),
2.05–2.17 (m, 3H), 2.55–2.61 (m, 1H), 2.61–2.67 (m, 2H), 3.14–3.20 (m,
1H), 7.02 (dd, 3J=8.1, 4J=1.1 Hz, 1H), 7.13 (ddd, 3J=8.1, 3J=6.9, 4J=
1.2 Hz, 1H), 7.17 (dd, 3J=7.8, 4J=2.0 Hz, 1H), 7.23 ppm (ddd, 3J=
8.2 Hz, 3J=6.9 Hz, 4J=2.0 Hz, 1H); 13C NMR (91 MHz, CDCl3, 300 K):
d = 25.9 (t), 28.6 (t), 33.2 (t), 37.8 (d), 40.8 (t), 47.2 (d), 48.6 (s), 117.4
458 min [608C (1 min), 208Cminꢀ1, 1008C, 1008C (500 min), 308Cminꢀ1
,
2208C (6 min)]; 1H NMR (360 MHz, CDCl3, 300 K): d =1.63–1.73 (m,
1H), 1.77–1.90 (m, 1H), 1.92–1.98 (m, 1H), 2.05–2.23 (m, 4H), 2.38 (virt.
td, 2J=12.3, 3J=7.7 Hz, 1H), 3.22 (virt. dt, 3J=6.4, 3J=9.2 Hz, 1H), 3.29
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T. Bach et al.
(dd, 3J=9.5, 3J=6.2 Hz, 1H), 6.90–7.04 (m, 2H), 7.08 (virt. td, 3J=7.4,
4J=1.2 Hz, 1H), 7.20 ppm (ddd, 3J=8.4, 3J=7.6, 4J=1.2 Hz, 1H);
13C NMR (91 MHz, CDCl3, 300 K): d = 26.0 (t), 32.9 (t), 33.3 (t), 36.2
(d), 37.7 (t), 46.3 (d), 49.3 (s), 117.3 (d), 124.8 (d), 124.9 (s), 127.8 (d),
128.1 (d), 150.2 (s), 172.0 ppm (s); IR (ATR): n˜ =2980 (w, sp3-CH), 1747
(s, CO), 1490 (m), 1455 (m, sp3-CH), 1343 (w), 1262 (m), 1214 (m), 1193
(m), 1168 (s), 1131 (s), 907 (s), 756 (s, sp2-CH), 727 cmꢀ1 (s); MS (EI,
70 eV): m/z (%): 214 (58) [M]+, 172 (28), 160 (100) [MꢀC6H11]+, 132
(13) [MꢀC6H11ꢀCO]+, 115 (15) [C9H7]+, 95 (18), 77 (10) [C6H5]+, 74
(59), 59 (89), 45 (69), 41 (29); HRMS (EI, 70 eV): m/z: calcd for
C14H14O2: 214.0994; found: 214.0995.
[6] a) A. Furutani, K. Katayama, Y. Uesima, M. Ogura, Y. Tobe, H.
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Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft
(DFG) (Graduiertenkolleg GRK 1626 Chemical Photocatalyis) and by
Fonds der Chemischen Industrie (scholarship to R.B.). H.G. wishes to ac-
knowledge support by the Alexander von Humboldt foundation. Olaf
Ackermann is thanked for his help in conducting the HPLC analyses.
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Photocycloaddition Reactions of 4-Substituted Coumarins
FULL PAPER
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strates, the reaction of which proceeds via triplet intermediates: A.
Received: December 23, 2011
Revised: March 2, 2012
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
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www.chemeurj.org
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T. Bach et al.
New frontiers: Lewis acid coordination
opens a new access to enantiomerically
enriched [2+2] photocycloaddition
products. Coumarins 1 (X=CH2,
CMe2, O, NBoc, NZ, NTs) react in the
presence of oxazaborolidine-based
Lewis acid 2 to the tetracyclic products
3, which are obtained as single diaster-
eosiomers in high yields and with sig-
nificant enantioselectivity (74–90%
ee).
Photochemistry
R. Brimioulle, H. Guo,
T. Bach* ....................... &&&& — &&&&
Enantioselective Intramolecular [2+2]
Photocycloaddition Reactions of 4-
Substituted Coumarins Catalyzed by
a Chiral Lewis Acid
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Chem. Eur. J. 0000, 00, 0 – 0
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These are not the final page numbers!