Mechanistic Insights into Enantioselective C-H Photooxygenation of Aldehydes via Enamine Catalysis

Article abstract of DOI:10.1002/adsc.201500056

Organocatalytic photooxygenation of aldehydes at the α-position proceeds via enamine catalysis, though enamines should be easily oxidized by singlet oxygen respectively to amides and carbonyl compounds. Moreover, the formation of a zwitterionic enamine peroxide intermediate was postulated based on experimental and theoretical data. The reaction affords desired diols (after in situ reduction) in a decent yield and (S)- or (R)-enantioselectivity depending on a catalyst used. The (S)-enantiomer predominated in imidazolidinone-catalyzed reactions, while prolineamides assured the formation of the (R)-stereoisomer. DFT calculation suggests that the enamine-oxygen complex with the lowest energy has the E,s-cis conformation for the prolineamide derivative and E,s-trans for the imidazolidinone catalyst, explaining the opposite stereoselectivity in the photooxygenation reaction.

Full text of DOI:10.1002/adsc.201500056

FULL PAPERS
DOI: 10.1002/adsc.201500056
Very Important Publication
À
Mechanistic Insights into Enantioselective C H Photooxygena-
tion of Aldehydes via Enamine Catalysis
a
a
a
´
´
Dominika J. Walaszek, Katarzyna Rybicka-Jasinska, Sabina Smolen,
Maksymilian Karczewski,a and Dorota Grykoa,*
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
a
Fax: (+48) 22 632 66 81; e-mail: dorota.gryko@icho.edu.pl
Received: January 21, 2015; Revised: February 18, 2015; Published online: May 7, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500056.
Abstract: Organocatalytic photooxygenation of alde- tions, while prolineamides assured the formation of
hydes at the a-position proceeds via enamine cataly- the (R)-stereoisomer. DFT calculation suggests that
sis, though enamines should be easily oxidized by the enamine–oxygen complex with the lowest energy
singlet oxygen respectively to amides and carbonyl has the E, s-cis conformation for the prolineamide
compounds. Moreover, the formation of a zwitterion- derivative and E, s-trans for the imidazolidinone cat-
ic enamine peroxide intermediate was postulated alyst, explaining the opposite stereoselectivity in the
based on experimental and theoretical data. The re- photooxygenation reaction.
action affords desired diols (after in situ reduction)
in a decent yield and (S)- or (R)-enantioselectivity Keywords: enamines; hydroxyaldehydes; organoca-
depending on a catalyst used. The (S)-enantiomer talysis; photocatalysis; photooxidation; singlet
predominated in imidazolidinone-catalyzed reac- oxygen
Introduction
Reactions with singlet oxygen, generated via photo-
sensitization of organic dyes (e.g. tetraphenylporphyr-
The term ꢀphotochemical reactionꢁ describes a chemi- in, TPP), are considered an effective and environmen-
cal process stimulated by absorption of ultraviolet, tal friendly tool for the oxidation of organic com-
visible, or infrared radiation.[1] For many years photo- pounds.[11] Although, there are many successful exam-
chemical processes were limited to substrates that ples of singlet oxygen in diastereoselective synthesis,
absorb light, however the introduction of photocataly- only few describe enantioselective reactions.[12]
sis allowed further synthetic advancement in the Among those reported, Bachꢁs[13] photooxygenation
field.[2] Recently, photocatalysis has been merged with of 2-pyridones (with ee 69–90%) and Córdovaꢁs[14] a-
ꢀground stateꢁ modes of activation (hydrogen-bond- oxidation of carbonyl compounds are of particular im-
ing,[3] enamine,[4] NHC[5] or transition-metal cataly- portance. Traditional organocatalytic a-oxidations of
sis[6]) giving access to synthetically difficult com- aldehydes or ketones were achieved mainly via enam-
pounds, especially in terms of asymmetric synthesis.[7] ine catalysis with hazardous oxidants: nitrosoben-
In case of enantioselective a- and b-substitutions of zene,[15] TEMPO,[16] benzoyl peroxide,[17] oxaziri-
carbonyl compounds, its arsenal was considerably ex- dines[18] or iodosobenzene.[19] Córdova found that the
panded through the photoredox–enamine dual-cataly- reaction of singlet oxygen with ketones was catalyzed
sis mode of action. In the case of a-functionalization, by various amino acids, with l-alanine being the most
a carbonyl compound is activated via the formation effective, giving a-hydroxyketones in good yield,
of an enamine that reacts with a radical generated, in which after reduction furnished the respective diols
situ, via single-electron transfer from the photocata- (ee ꢀ 72%).[14a] The methodology was subsequently
lyst to a halide, giving the respective product and con- extended to aldehydes, for which l-proline and TMS-
sequentially regenerating the photocatalyst.[4,8,9] In b- protected diarylprolinols ensured a highly enantiose-
substitution, the enamine is first oxidized (SET, lective reaction.[14b,c] It was suggested that the photo-
single-electron transfer) to enaminyl radical cation, oxygenation proceeded via an enamine intermediate,
subsequent loss of proton gives a b-enaminyl radical but no products of enamine oxidation or decomposi-
that reacts with the second reacting partner.[10]
tion were observed.
Adv. Synth. Catal. 2015, 357, 2061 – 2070
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2061

FULL PAPERS
Dominika J. Walaszek et al.
Table 1. Screening of various catalysts.
Scheme 1. Reactions of singlet oxygen with a) secondary
amines[20] and b) enamines.[21]
Interestingly, it is well known that secondary
amines and enamines are easily oxidized by singlet
oxygen respectively to a) imines and b) amides with
the release of carbonyl compounds (Scheme 1).[20,21]
These contradictory reports seemed very intriguing
and we wondered why photooxygenation of aldehydes
was possible via enamine catalysis affording a-hy-
droxy-derivatives in high yields even though enamines
should be easily oxidized to carbonyls. Herein, we
give a detailed study on this issue, describing the in-
fluence of the organocatalystsꢁ structure and reaction
conditions on the course of organocatalytic photooxy-
genation of aldehydes.
Entry Catalyst Yield of 2[a] [%] ee [%]
Solvent
1[b]
2
3
4
23 (91[14b]
)
)
14(S) (48(R)[14b]) DMF
16 (77[14b]
50(S) (66(R)[14b]) DMF
3
4
5
6
5
6
7
8
<5
0
0
0
0
46
52
20
37
<5
–
–
–
–
DMF
DMF
DMF
DMF
DMF
DMF
CCl4
CCl4
CCl4
CCl4
Results and Discussion
While working on a different project we came across
a problem in synthesizing optically active a-hydroxy-
aldehydes and organocatalytic enantioselective photo-
oxygenation attracted our attention.[14]
7
9
–
8[c]
9[c]
10[c]
11[c]
12
10
10
11
12
13
9(R)
74(R)
62(R)
0
In a preliminary experiment 3-phenylpropanal (1)
was reacted with oxygen photosensitized by TPP in
the presence of l-proline, giving (after reduction) de-
sired diol 2 in low yield and enantioselectivity. Addi-
tionally, according to Córdova, (R)-enantiomer predo-
minated in this reaction,[14b] however based on the
specific rotation and HPLC analysis, the newly
formed stereogenic center should be assigned as
having (S)-configuration.[22] Since we found that the
reactivity and stereoselectivity remained a problem,
other amino acids and various organocatalysts were
examined (Table 1).
–
13[b] 14
11 (70)[14c]
62
62(S) (87(S))[14c] CCl4
14
15
80(S)
CCl4
[a]
Reaction conditions: aldehyde (1.5 mmol), organocata-
lyst (20 mol%), TPP (0.25 mol%) in 6 mL of solvent,
3 h.
[b]
[c]
The results reported by Córdova with 5 mol% of TPP[14b]
could not be reproduced.
TPP (0.04 mol%)
Among all amino acids studied, only those with
a secondary amino group 3–5 generated the desired tested. In reactions catalyzed by amide 10 or thioa-
product, though with low yield and enantioselectivity mide 11 the (R)-enantiomer predominated, while
(entry 1–3). As l-proline amides proved superior cata- MacMillan catalyst 15 led to the formation of the op-
lysts in the aldol reaction we utilized them in our posite enantiomer in 62% yield and 80% ee (com-
model photooxygenation.[23] In the presence of amide pare entries 9, 10 and 14).
10, 3-phenylpropane-1,2-diol (2) was obtained in mod-
In order to explain the opposite enantioselectivity
erate yield (46%) and low ee (entry 8). Gratifyingly, in reactions catalyzed by catalysts 10 and 15, calcula-
the selectivity was significantly improved when DMF tions were performed using Gaussian 03 with M062X
was replaced with CCl4 (entries 8 and 9), the pre- method with 6-31G(d,p) basis set and PCM set for
ferred solvent for singlet oxygen reactions (1O2 life- CCl4.[25] We established that the three most important
time in CCl4: t=460 ms[24]). As a consequence, other factors affecting the stereochemistry of the newly
organocatalysts soluble in chlorinated solvents were formed stereogenic center are as follow: (a) configu-
2062
asc.wiley-vch.de
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2061 – 2070

À
FULL PAPERS
Mechanistic Insights into Enantioselective C H Photooxygenation
the Si face. As a result, the (R)-enantiomer predomi-
nantly forms.
On the other hand, the most stable enamine-1O2
complex 17 has the E, s-trans conformation (Fig-
ure 1d). This is consistent with Mayrꢁs results showing
that E, s-trans conformation of enamines derived
from imidazolidinones predominates in the crystal
structure as well as in a solution.[26] Moreover, we
have also observed a very characteristic CH–p inter-
action between the benzyl group at position 5 and
one of the methyl groups at position 2 of the imidazo-
lidinone ring, that was described previously by Houk
(exploring iminium ions derived from imidazolidi-
nones).[27] In this complex, the same benzyl group
(catalyst part) interacts also with the phenyl group
from the substrate, thus preventing the re attack, fa-
voring attack from the Si face and formation of (S)-
enantiomer.
Unfortunately, in both cases the calculated differen-
ces in relative free energies between E, s-cis and E, s-
trans conformers are very small (1.0 and 1.8 kcalmolÀ1
for amide and MacMillan derived enamines respec-
tively). Since conformers E, s-cis and E, s-trans led to
the opposite enantiomers, the model photooxygena-
tion is not fully enantioselective (more details in SI).
For many years, it was believed that photooxidation
of enamines yields unstable dioxetanes that decom-
pose giving two carbonyl derivatives (Scheme 1).[21]
However, in 1979 Saito and Matsuura reported that
enamines in the first step, form zwitterionic peroxide
19 which depending on the solvent used either trans-
form into dioxetane 20 or undergo ene reaction if
bearing allylic hydrogens, (leading to 21), (Scheme 2).
The key intermediate – zwitterionic peroxide 19 – was
trapped by performing the reaction with alcohols at
low temperature.[28]
Figure 1. a) A schematic representation of the most stable
conformers of enamine 16; b) a schematic representation of
the most stable conformers of enamine 17; c) the lowest
energy conformation of enamine-1O2 complex 16; d) the
lowest energy conformation of enamine-1O2 complex 17.
Based on their results we envisaged that the photo-
oxygenation of aldehydes starts with enamine forma-
tion (16 or 17 depending on a catalyst used) followed
by the reaction with singlet oxygen giving zwitterionic
imine–peroxide 24 or 25, similar to that postulated by
ration of the enamine double bond (E/Z), (b) confor-
À
mation of the C N single bond between the pyrroli-
dine ring and the double bond (s-cis or s-trans), and
(c) the steric hindrance imposed by the phenyl sub-
stituent (from aldehyde) and either the amide group
or the benzyl ring present in enamine 16 and 17 re-
spectively, controlling the si/re attack of singlet
oxygen on the enamine moiety (Figure 1a,b). Initial
data indicated E-configuration being superior to Z,
thus subsequent calculations were performed only for
E-isomers.
Enamine-1O2 16 dioxygen complex with the lowest
energy has E, s-cis-conformation (Figure 1c). The
proton attached to the phenyl ring (from substrate)
interacts with the amide oxygen atom, thus shielding Scheme 2. The reaction of indoles with singlet oxygen.
Adv. Synth. Catal. 2015, 357, 2061 – 2070
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2063

FULL PAPERS
Dominika J. Walaszek et al.
Scheme 3. The proposed mechanism.
Saito et al.[28] The peroxide then either hydrolyses to ed peroxide 24 or protonated dioxetane 27 suggesting
hydroperoxyaldehyde 26, which after reduction gives the course of side-reactions. As a consequence of di-
desired product 2 (R or S depends on a catalyst used), oxetane 27 decomposition, products amide 29 and al-
or forms dioxetane 27 or 28 leading to phenylacetal- dehyde 31 should be observed. Indeed, the signal at
dehyde (31) and formylamide 29 or 30 respectively. m/z 185.1296 Da corresponded to N-formylated cata-
Hydroperoxyaldehyde 26 theoretically can exist in lyst 29, similar to that reported in the literature.[21]
equilibrium with hydroxydioxetane 35, as compounds The presence of phenylacetaldehyde (31) was con-
of similar structure (alkoxydioxetanes and dioxeta- firmed by GC-MS analysis. Neither GC-MS nor
nones) have been postulated as intermediates during UPLC-MS analysis supported the hypothesis that
chemiluminescence of luciferins (firefly biolumines- photooxidation of catalyst 10 to imines 32 or 33 takes
cence).[29] However, based on low temperature NMR place. Moreover, such compounds have never been
experiments and GC MS we can neither confirm nor isolated proving that proline amides remain stable to-
exclude formation of compound 35 (see SI). We wards singlet oxygen oxidation contrary to imidazoli-
assume that such dioxetane is too unstable to be iso- dinones.
lated or to be detected by MS or NMR analysis as it
Analysis of the reaction catalyzed by imidazolidi-
can easily decompose to phenylacetaldehyde (31). none 15 by UPLC-MS revealed the presence of enam-
Moreover, as previously mentioned, secondary ine 17 and dioxygen adduct m/z 367.2017 Da [17+
amines can be oxidized by singlet oxygen to imines O2 +H]+. Its structure could be assigned as protonat-
(Scheme 1).[20] Thus hypothetical products of catalysts ed peroxide 25 or protonated dioxetane 28 similarly
10 and 15 photooxidation are imines 32, 33, and 34 to the former case. Moreover, the presence of formy-
(Scheme 3).
lamide 30, was confirmed by the observed signal at
To confirm the enamine mode of catalysis, photo- m/z 247.1451 Da. The main difference, between these
oxygenation reactions of 3-phenylpropanal (1) cata- two reactions was the presence of signal m/z
lysed by amide 10 or MacMillan catalyst 15 were 217.1341 Da, corresponding to imine 34, suggesting
studied. To this end, the composition of the reaction that the photooxidation of imidazolidinone ring might
mixture, after 3 h of light exposure, was analyzed occur. Additionally, we managed to isolate compound
using NMR, GC-MS and UPLC-MS techniques.
34 and its structure was confirmed by NMR spectra.
UPLC-MS analysis of the proline amide (10)-cata-
It is worth noting that phenylacetaldehyde (31) and
lyzed reaction mixture showed a signal at m/z formylamides 29 or 30 were observed only by MS
273.1967 Da corresponding to protonated enamine analysis. According to GS-MS analysis amount of
[16+H]+ directly supporting the enamine mechanism. phenylacetaldehyde (31) is about four times lower
Furthermore, the mass 305.1869 Da [m/z] is in accord than unreacted substrate 1 (see SI). Although, the un-
with the protonated enamine-1O2 adduct 16 with [16+ wanted dioxetane (27, 28) formation plays a minor
O2 +H]+ whose structure can be assigned as protonat- role in the reaction pathway, its presence and decom-
2064
asc.wiley-vch.de
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2061 – 2070

À
FULL PAPERS
Mechanistic Insights into Enantioselective C H Photooxygenation
Scheme 5. Catalytic properties of imidazolidinones.
tendency was observed for l-proline (3) and 4-hy-
droxy-l-proline (5) (Table 1, entries 1 and 3).
In order to eliminate undesired photooxidation of
the amine moiety, other imidazolidinones with various
patterns of substituents were synthesized and tested
in the model reaction.[31] Changing substituents at po-
sition 2 in the imidazolidinone ring from methyl
groups to bulkier Ph or tBu led to a decrease in yield
Scheme 4. Catalytic properties of various prolinamides.
position products (29–31) additionally prove the en- (Scheme 5, compare 15 with 46–49). Surprisingly cata-
amine mechanism for the tested reaction. lysts 46 and 48, with bulky substituents in trans-con-
Further optimization studies with respect to the figuration were more selective then their cis-counter-
amide structure were conducted, examining if the parts, 47 and 49 respectively, contrary to the common-
enantioselectivity of the reaction could be further in- ly accepted model.[31b,32] Using catalyst 50, with only
creased (Scheme 4). Photooxygenation of 3-phenyl- one bulky tBu group at position 2, allowed to main-
propanal (1) in CCl4 catalyzed by amide 10 gave (R)- tain a high level of selectivity, but caused a decrease
diol 2 with 74% ee. Surprisingly, the use of simple l- in yield.
proline amide 36 (inactive in the aldol reaction)[30] as-
Subsequently, the conditions for reaction catalyzed
sured decent enantioselectivity, while tertiary isopro- by imidazolidinone 15 were optimized. The influence
pylamide 37 caused a significant decrease in both the of solvent polarity in competitive reactions of electron
1
yield and enantioselectivity, suggesting the presence rich olefins with O2 (e.g. ene reaction versus [2+2]
of the amide proton may be crucial. This is supported cycloaddition) is well documented.[28,33] Thus, various
by the lack of the selectivity in the reaction catalyzed solvents and additives were screened in the model re-
by ester 12 (Table 1, entry 11).
action (Table 2, entry 1–8). As previously discovered
Its known that as the acidity of the amide proton (Table 1, entries 10 and 11), the use of CCl4 increased
increases the enantioselectivity of the aldol reaction both the yield and enantioselectivity. However, when
increases.[23] Therefore, we tested this effect in a pho- the imidazolidinone-catalyzed reaction was performed
tooxygenation reaction. Secondary amides 38–41 pos- in CCl4 for 3 h at 108C, full conversion of the sub-
sessing an N-aryl group showed decent enantioselec- strate was not observed, and further prolonging of the
tivities 66–79% but in low yields. The differences in reaction time led to a decrease in the yield (Table 2,
enantioselectivities were minimal and showed rather compare entries 1 and 9). Lowering the reaction tem-
opposite tendency than those reported by Tang.[23]
perature to 58C, limited the catalyst decomposition
Reactions catalysed by secondary proline amides thus allowing for an increase in reaction time to 5 h;
42–45, derived from l-proline and chiral amines, were diol 2 was isolated in 67% yield (entries 10, 11). The
not more selective than the reaction in the presence addition of acids or bases had a detrimental effect on
of isopropyl proline amide 10. Amide 42 provided the the yield, but not on enantioselectivity (more details
product in decent yield, while amide 45 showed very in the SI). Addition of water (3 mmol, 2 equiv.,
poor activity, suggesting that the presence of the hy- entry 12) significantly decreased both the yield and
1
droxy group might have a negative effect. A similar enantioselectivity, because the lifetime of O2 in water
Adv. Synth. Catal. 2015, 357, 2061 – 2070
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2065

FULL PAPERS
Dominika J. Walaszek et al.
Table 2. Optimisation studies.
80% yield. Following Boc deprotection using TFA/
anisole in CH2Cl2, compound 56 was reacted with
MeNH2 in MeOH in the presence of NaCN affording
amide 57 in 96% yield. Noteworthy, the deprotection
step should be perform before amidation otherwise
amide 57 yield would be significantly decreased. Sub-
sequent reaction of amide 57 with either benzalde-
hyde or acetone furnished catalysts 58 and 59, or 60,
possessing a tetrasubstituted carbon at position 5
(Scheme 7).
Imidazolidinones 58–60 were tested in the photo-
oxygenation of 3-phenylpropanal (1). Catalysts 58 and
59 remained stable upon irradiation and could be re-
covered in 80% yield, confirming our hypothesis
about their photostability. In the model reaction these
catalysts gave desired diol 2 in 50–60% yield, but pro-
longing of the reaction time to exceed 3 h did not im-
prove the yield. Hence photostability of the catalyst is
important, but not a crucial factor. The reaction cata-
lyzed by 58 (trans-isomer) gave the desired product,
Entry
Yield of 2[a] [%]
ee [%]
Solvent
1
2
3
62
32
6
80 (S)
65 (S)
70 (S)
–
CCl4
DCE
CHCl3
CH2Cl2
4
0
5
6
<5
7
–
DMF
57 (S)
68 (S)
79 (S)
80 (S)
78 (S)
78 (S)
32 (S)
81 (S)
77 (S)
80 (S)
81 (S)
MeOH[b]
7
8
9
10
11
12
13
14
15
16
39
31
37
58
67
16
15
18
67
35
toluene
C6F6
CCl4[c(]5 h)
CCl4
CCl4 (5 h)[c]
CCl4/H2O (3 mmol)
CCl4/buffer pH 3[d]
CCl4/buffer pH 6[e]
CCl4/buffer pH 7[e]
CCl4/buffer pH 8[e]
[a]
Reaction conditions: aldehyde (1.5 mmol), organocata-
lyst 15 (20 mol%), TPP (0.25 mol%) in 6 mL of solvent,
3 h, temperature of reaction mixture was maintained at slightly enriched with (S)-enantiomer; compound 59
108C.
possessing two bulky substituents in cis-configuration
[b]
Tetra(p-hydroxyphenyl)porphyrin was used instead of
TPP.
Temperature of reaction mixture was 58C.
2 mL of acetate buffer (0.1m) was added.
2 mL of phosphate buffer (0.1m) was added.
[c]
[d]
[e]
is very short.[24] Interestingly, in two-phase experi-
ments, CCl4/pH 7 buffer, the product was isolated in
a surprising high yield 67% and 80% ee (entry 15).
In order to find a more stable catalyst, the effect of
imidazolidinonesꢁ photooxidation was studied in
detail. NMR and MS experiments revealed that,
while catalyst 15 decomposed to imine 34, imidazoli-
dinone 46 possessing hydrogen in both positions 2
and 5, formed only imine 51 (Scheme 6). Hence, we
assumed that imidazolidinone catalysts possessing tet-
rasubstituted stereogenic carbon at the 5 position
should exhibit higher stability towards photooxida-
tion.
Commercially available a-methyl-l-DOPA (53, a-
methyl-b-3,4-dihydroxyphenyl-l-alanine) was convert-
ed to its N-Boc methyl ester 54[34] and treated with
CH3I in acetone affording dimethoxy-derivative 55 in
Scheme 6. Photodecomposition of imidazolidinones.
Scheme 7. Synthesis of catalysts 58–60.
2066
asc.wiley-vch.de
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2061 – 2070

À
FULL PAPERS
Mechanistic Insights into Enantioselective C H Photooxygenation
Table 3. Photooxygenation of phenylacetaldehyde (1) in the
presence of imidazolidinones 58–60.
Conclusions
1
Combining the enamine catalysis with O2 oxidation
requires fine tuning of the reaction conditions and or-
ganocatalysts structure with respect to their stability
as secondary amines and the respective enamines can
be oxidized thus halting the catalytic cycle. In our ex-
periments l-proline amides remained stable, but imi-
dazolidinones with hydrogen at position 5 were slowly
oxidized to imines. Among all organocatalysts tested
Entry
Catalyst
Yield of 2[a] [%]
ee [%]
Time
1
2
3
4
58
59
59
60
60
56
49
30
12 (S)
69 (R)
74 (R)
rac
3 h
3 h
5 h
3 h
[a]
Reaction conditions: aldehyde (1.5 mmol), organocata-
lyst (20 mol%), TPP (0.25 mol%) in 6 mL of CCl4.
À
in the C H photooxygenation of aldehydes, imidazoli-
dinone 15, and l-proline amides 10 and 42 were
found to be the most effective.
Table 4. Photooxygenation of different aldehydes.
Interestingly, imidazolidinone 15 provides (S)-enan-
tiomer while l-proline amides assured the formation
of the opposite isomer. DFT calculation suggested
that the enamine–1O2 complex with the lowest energy
has the E, s-cis-conformation for the proline amide
derivative and E, s-trans- for the imidazolidinone cat-
alyst explaining the opposite stereoselectivity in the
photooxygenation reaction. Thus, the difference in
Entry R1, R2
Catalyst Yield of
diol[a] [%]
ee [%]
À
the conformation of the C N single bond between
1
31: H, Ph
31: H, Ph
61: H, (CH2)7CH3 15
61: H, (CH2)7CH3 42
62: CH3, Ph
62: CH3, Ph
15
42
20
32
74
36
0
58 (S)
65 (R)
79 (S)
75 (R)
–
the pyrrolidine ring and the double bond (s-cis or s-
trans) accounts for the opposite enantioselectivity.
Additionally, the enamine mechanism of the reaction
was confirmed by MS techniques. Signals correspond-
ing to the enamine, its complex with dioxygen, and
typical enamine oxidation products (aldehydes and
amides) were identified.
2[b]
3
4[b]
5
15
42
6[b]
30
16 (S)
[a]
Reaction conditions: an aldehyde (1.5 mmol), an organo-
catalyst (20 mol%), TPP (0.25 mol%) in 6 mL of CCl4,
3 h.
[b]
TPP (0.04 mol%).
Experimental Section
General Information
afforded product with higher (R)-enantioselectivity.
Amino acids (3–9) and Jørgensen catalysts (13, 14) were ob-
Surprisingly, compound 60, possessing two tetrasubsti- tained commercially. Proline derivatives: 10 and 11,[35] 12,[36]
36[37] and imidazolidinones: 15,[31a] 46 and 47,[31b] 48–50,[31c]
tuted carbons at positions 2 and 5 decomposed to
many uncharacterizable products (presumably with
decomposition of 5-membered ring) (Table 3).
Selected catalysts 15 and 42 were tested in photo-
oxygenation of different aldehydes (Table 4).
Unbranched aldehydes 31 and 61 gave products
with decent enantioselectivies, but only 1,2-decanediol
matography was performed using silica gel (230–400 mesh).
(64) was obtained in high yield. The direction of the
were prepared by known procedures. Amides 37–45 were
prepared in a manner analogous to the amide 10.[35]
Unless otherwise noted, all commercially available start-
ing materials were used directly without further purification.
Reactions under anhydrous conditions were performed in
dried and distilled solvents under argon. Flash column chro-
1H and 13C NMR were recorded at room temperature at 500
and 400 MHz for protons, and at 125 and 100 MHz for
asymmetric induction was consistent with previous ex-
periments: S in imidazolidinone-, R in the amide-cata- carbon-13, respectively. Chemical shifts are reported relative
1
to the TMS as an internal standard for H (d=0 ppm) and
to the central line of the deuterated solvent for 13C (CDCl3:
d=77.0 ppm, CD3OD: d=49.0 ppm). High resolution mass
spectrometry (HRMS) data were obtained at the Synapt
G2-S HDMS mass spectrometer equipped with an electro-
spray ion source and q-TOF type mass analyzer. Specific ro-
tation was measured on Polarimeter JASCO P-2000. The
enantiomeric purity of diols was determined by chiral-phase
HPLC analysis on Daicel Chiralpak AS-H or OD-H
(250 mm ” 4.6 mm inside diameter) using a hexane/iPrOH
mixture as a mobile phase.
lyzed reaction. Photooxygenation of 2-phenylproprio-
naldehyde (62) afforded the tertiary alcohol product
65 with a new tetrasubstituted carbon stereogenic
center in only 30% yield and poor ee. However, itꢁs
known that the formation of tetrasubstituted carbon
stereogenic centers may be problematic, thus further
optimization studies will be performed for this class
of aldehydes.
Adv. Synth. Catal. 2015, 357, 2061 – 2070
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2067

FULL PAPERS
Dominika J. Walaszek et al.
a-Methyl-b-3,4-dimethoxyphenyl-l-alanine methyl ester
(56): Compound 55 (2.2 g, 6.2 mmol) was dissolved in dry
CH2Cl2 (20 mL), TFA (5 mL) was added followed by a drop
of anizole at 08C. The reaction mixture was allowed to
warm up to r.t. and stirred for 3 h. It was then diluted with
CH2Cl2, washed by saturated aq. NaHCO3 and brine. The
organic layer was dried over Na2SO4, filtered and concen-
trated. Product 56 was obtained as yellowish oil; yield 86%
(1.35 g, 5.33 mmol). A sample was added to a mixture of
Et2O and 4m HCl solution in dioxane in order to obtain
crystalline 56·HCl salt and compare NMR spectra of 56·HCl
General procedure for photooxidation of aldehydes:
Catalyst (0.3 mmol, 20 mol%) and TPP (2.3 mg, 3.8 mmol,
0.25 mol%) were placed in a reaction vessel and dissolved
in CCl4 (6 mL) or in DMF (6 mL). The reaction mixture was
cooled to 108C before an aldehyde (1.5 mmol) was added,
and the light (2”300 Lm LED warm white lamp) was
turned on. The reaction mixture was stirred at 108C for 3 h
with a continuous flow of oxygen. After that, the light was
turned off, MeOH (6 mL) was added, the reaction mixture
was cooled below 08C, followed by in situ reduction with
excess of NaBH4 (300 mg, 8 mmol). After 10 min at 08C the
reaction mixture was diluted with AcOEt, transferred into
a separating funnel and 1m HCl was added. The aqueous
phase was separated and then extracted with another por-
tion of AcOEt. The combined organic layers were washed
with saturated aq. NaHCO3, dried over MgSO4, filtered and
concentrated. The crude product was purified by flash chro-
matography using silica gel (hexanes/AcOEt) to afford the
corresponding diol.
Imines 34 and 51 were obtained as by-products in the
photooxidation of aldehydes 2, 61–62 catalyzed by com-
pounds 15 and 46, respectively, performed according to the
procedure described above, as well as in the background
test reactions performed without an aldehyde.
Imine 34 was obtained as yellowish oil; Rf =0.4 (hexane -
AcOEt, 1:2 (v/v)); 1H NMR (400 MHz, CCl4 with
[D6]DMSO as external standard): d=7.05 (d, J=7.5 Hz,
2H, ArH), 6.97 (t, J=7.5 Hz, 2H, ArH), 6.89 (t, J=7.2 Hz,
1H, ArH), 3.54 (s, 2H, CH2Ph), 2.63 (s, 3H, NHCH3), 1.09
(s, 6H, 2 x CH3) ppm; 13C NMR (100 MHz, CCl4 with
[D6]DMSO as external standard): d=166.1, 160.9, 134.6,
128.6, 127.6, 125.8, 82.7, 33.8, 24.4, 23.7 ppm; HRMS (EI):
m/z 216.1273 (calcd. for C13H16N2O [M]+ 216.1263).
Imine 51 was obtained as colorless oil, solidified upon
cooling; Rf =0.5 (hexane - AcOEt, 1:1 (v/v)); 1H NMR
(400 MHz, CDCl3): d=13.01 (s, 1H,>CHPh), 7.51–7.44 (m,
1H, ArH), 7.38–7.32 (m, 2H, ArH), 7.19 (s, 5H, ArH), 7.09
À7.03 (m, 2H, ArH), 3.34 (d, J=12.5 Hz, 1H, CHH), 3.27
(d, J=12.5 Hz, 1H, CHH), 2.71 (s, 3H, NHCH3) ppm;
13C NMR (100 MHz, CDCl3): d=178.6, 166.1, 132.5, 131.6,
130.5, 128.8, 128.0, 127.9, 127.7, 127.3, 101.2, 39.5, 28.2 ppm.
N-Boc-a-methyl-b-3,4-dimethoxyphenyl-l-alanine methyl
ester (55): Compound 54 (2.5 g, 7.7 mmol) was dissolved in
acetone (80 mL), then K2CO3 (5.3 g, 39 mmol) and CH3I
(2.0 mL, 32 mmol) was added. The reaction mixture was
stirred for 1 day at r.t. It was then diluted with AcOEt,
washed with saturated aq. Na2S2O3 and then saturated aq.
NaHCO3. The organic layer was dried over Na2SO4, filtered
and concentrated. The crude product was purified by flash
chromatography using silica gel (hexanes/AcOEt, 7:3 (v/v)).
Product 55 was obtained as colorless oil, yield 80% (2.2 g,
6.2 mmol); Rf =0.5 (hexane/AcOEt, 1:1 (v/v)); 1H NMR
(400 MHz, CDCl3): d=6.76 (d, J=8.0 Hz, 1H, ArH), 6.62
(m, 2H, ArH), 5.16 (br s, 1H, NH), 3.85 (s, 3H, Ar-OCH3),
3.83 (s, 3H, Ar-OCH3), 3.75 (s, 3H, OCH3), 3.28 (br d, J=
13.7 Hz 1H, CHH), 3.13 (d, J=13.7 Hz, 1H, CHH), 1.56 (s,
3H, CH3), 1.46 (s, 9H, Boc) ppm; 13C NMR (100 MHz,
CDCl3): d=174.5, 154.3, 148.6, 148.1, 122.2, 113.4, 111.0,
60.5, 55.83, 55.79, 52.4, 28.4, 23.7 ppm; HRMS (ESI): m/z
376.1729 (calcd. for C18H27NO6Na [M + Na]+ 376.1736). The
data is consistent with the literature.[38]
1
with literature data. H NMR (400 MHz, CD3OD): d=6.95
(d, J=8.1 Hz, 1H, ArH), 6.78 (d, J=2.0 Hz, 1H, ArH), 6.75
(dd, J=8.1 and 2.0 Hz, 1H, ArH), 3.86 (s, 3H, OCH3), 3.83
(s, 3H, Ar-OCH3), 3.82 (s, 3H, Ar-OCH3), 3.66 (s, 2H,
NH2), 3.26 (d, J=14.3 Hz, 1H, CHH), 3.06 (d, J=14.3 Hz,
1H, CHH), 1.63 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CD3OD): d=172.3, 150.8, 150.6, 126.7, 123.8, 114.9, 113.4,
68.1, 62.1, 56.54, 56.49, 53.9, 43.7, 22.6 ppm; HRMS (ESI):
m/z 254.1392 (calcd. for C13H20NO4 [M + H]+ 254.1392).
The data is consistent with the literature.[39]
a-Methyl-b-3,4-dimethoxyphenyl-l-alanine methyl amide
(57): Compound 56 (1.3 g, 5.1 mmol) was dissolved in a 8m
MeNH2/MeOH solution (10 mL) and NaCN (20 mg,
0.4 mmol) was added. After 6 days of stirring and another
portion of the 8m MeNH2/MeOH solution (10 mL) was
added and stirred for 3 days. The solvent was then removed
and the crude product was dissolved in CHCl3 and washed
with brine. The organic layer was dried over Na2SO4, fil-
tered and concentrated. Product 57 was obtained as yellow-
ish oil; yield 96% (1.25 g, 4.9 mmol); Rf =0.1 (ethyl ace-
tate); 1H NMR (500 MHz, CDCl3): d=7.45 (br s, 1H,
NHMe), 6.78 (d, J=8.1 Hz, 1H, ArH), 6.72 (d, J=1.7 Hz,
1H, ArH), 6.68 (dd, J=8.1 and 1.7 Hz, 1H, ArH), 3.85 (s,
3H, Ar-OCH3), 3.84 (s, 3H, Ar-OCH3), 3.40 (d, J=13.4 Hz,
1H, CHH), 2.74 (d, J=5.0 Hz, 3H, NHCH3), 2.50 (d, J=
13.4 Hz, 1H, CHH), 1.67 (br s, 2H, NH2), 1.38 (s, 3H, CH3)
ppm; 13C NMR (125 MHz, CDCl3): d=176.9, 148.8, 147.9,
129.6, 122.2, 113.2, 110.9, 58.4, 55.8, 46.4, 27.9, 26.0 ppm;
HRMS (ESI): m/z 275.1368 (calcd. for C13H20N2O3Na [M +
Na]+ 275.1372). Data consistent with the literature.[40]
(2R,5S)-5-(3’,4’-Dimethoxyphenyl)-3,5-dimethyl-2-phenyl-
imidazolidin-4-one (58) and (2S,5S)-5-(3’,4’-dimethoxyphen-
yl)-3,5-dimethyl-2-phenylimidazolidin-4-one (59): Com-
pound 57 (400 mg, 1.6 mmol) was dissolved in MeOH
(6 mL). Benzaldehyde (330 mL, 3.2 mmol, 2 equiv) and
TsOH·H2O (32 mg, 0.16 mmol, 0.1 equiv) were then added.
The resulting mixture was refluxed for 3 days, and then con-
centrated. The crude products were purified by flash chro-
matography using silica gel with hexane/AcOEt, 1:1 (v/v) to
elute benzaldehyde, hexane/AcOEt, 1:2 (v/v) to eluent com-
pound 58, and then AcOEt to collected compound 59. The
relative stereochemistry of catalyst 58 and 59 was confirmed
by NOE NMR studies.
Compound 58 was obtained as a white solid; yield 68%
(370 mg, 1.09 mmol); Rf =0.4 (hexane/AcOEt, 1:1 (v/v));
1
m.p.: 105–1078C; H NMR (500 MHz, CDCl3): d=7.35 (m,
3H, ArH), 7.16 (m, 2H, ArH), 6.91 (s, 1H, ArH), 6.87 (dd,
J=8.2 and 1.7 Hz, 1H, ArH), 6.82 (d, J=8.1 Hz, 1H, ArH),
2
4.17 (s, 1H, CH), 3.90 (s, 3H, Ar-OCH3), 3.89 (s, 3H, Ar-
OCH3), 3.08 (d, J=13.3 Hz, 1H, CHH), 2.62 (d, J=13.3 Hz,
5
1H, CHH), 2.40 (s, 3H, NHCH3), 1.48 (s, 3H, CH3) ppm;
2068
asc.wiley-vch.de
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2061 – 2070

À
FULL PAPERS
Mechanistic Insights into Enantioselective C H Photooxygenation
13C NMR (125 MHz, CDCl3): d=177.1, 148.5, 148.0, 138.9,
129.4, 129.0, 126.9, 122.3, 113.2, 110.7, 64.1, 55.92, 55.86,
44.9, 27.3, 25.9 ppm; HRMS (ESI): m/z 363.1688 (calcd. for
A. Albini, Chem. Soc. Rev. 2013, 42, 97–113; h) X.
Lang, X. Chen, J. Zhao, Chem. Soc. Rev. 2014, 43, 473–
486.
C20H24N2O3Na [M
+
Na]+ 363.1685); anal. calcd. for
[3] a) A. Bauer, F. Westkämper, S. Grimme, T. Bach,
Nature 2005, 436, 1139–1140; b) C. Müller, A. Bauer, T.
Bach, Angew. Chem. 2009, 121, 6767–6769; Angew.
Chem. Int. Ed. 2009, 48, 6640–6642; c) C. Müller, A.
Bauer, M. M. Maturi, M. C. Cuquerella, M. A. Miran-
da, T. Bach, J. Am. Chem. Soc. 2011, 133, 16689–16697;
d) M. M. Maturi, M. Wenninger, R. Alonso, A. Bauer,
A. Pçthig, E. Riedle, T. Bach, Chem. Eur. J. 2013, 19,
7461–7472; e) R. Alonso, T. Bach, Angew. Chem. 2014,
126, 4457–4460; Angew. Chem. Int. Ed. 2014, 53, 4368–
4371; f) M. M. Maturi, T. Bach, Angew. Chem. 2014,
126, 7793–7796; Angew. Chem. Int. Ed. 2014, 53, 7661–
7664.
[4] a) D. A. Nicewicz, D. W. C. MacMillan, Science 2008,
322, 77–80; b) D. A. Nagib, M. E. Scott, D. W. C. Mac-
Millan, J. Am. Chem. Soc. 2009, 131, 10875–10877;
c) H.-W. Shih, M. N. Vander Wal, R. L. Grange,
D. W. C. MacMillan, J. Am. Chem. Soc. 2010, 132,
13600–13603.
C20H24N2O3: C, 70.56; H, 7.11; N, 8.23%; found: C, 70.50; H,
7.29; N, 8.28%; [a]D25 = ++ 18.38 (c=1.0, CHCl3).
Compound 59 was obtained as colorless oil, solidified
upon cooling; yield 13% (70 mg, 0.21 mmol); Rf =0.2
1
(hexane/AcOEt, 1:1 (v/v)); H NMR (600 MHz, CDCl3): d=
7.28 (m, 1H, ArH), 7.18 (t, J=7.7 Hz, 2H, ArH), 6.81 (d,
J=1.9 Hz, 1H, ArH), 6.79 (d, J=8.1 Hz, 1H, ArH), 6.69
(dd, J=8.1 Hz, 1.9, 1H, ArH), 6.57 (d, J=8.1 Hz, 2H,
ArH), 5.08 (s, 1H, 2CH), 3.90 (s, 3H, Ar-OCH3), 3.78 (s,
3H, Ar-OCH3), 3.40 (d, J=13.9 Hz, 1H, CHH), 2.58 (d, J=
13.9 Hz, 1H CHH), 2.50 (s, 3H, NHCH3), 1.77 (s, 1H,
NHCH3), 1.41 (s, 3H, 5CH3) ppm; 13C NMR (125 MHz,
CDCl3): d=177.2, 149.3, 148.4, 138.0, 129.4, 129.0, 128.9,
126.8, 122.4, 113.3, 111.3, 76.0, 64.0, 56.0, 55.9, 42.5, 27.4,
24.7; HRMS (ESI): m/z 363.1686 (calcd. for C20H24N2O3Na
[M + Na]+ 363.1685); anal. calcd. for C20H24N2O3: C, 70.56;
H, 7.11; N, 8.23%; found: C, 70.63; H, 7.26; N, 8.12%;
[a]25 =– 38.78 (c=0.9, CHCl3).
(DS)-5-(3’,4’-Dimethoxyphenyl)-2,2,3,5-tetramethylimidazo-
lidin-4-one (60): Compound 57 (200 mg, 0.8 mmol) was dis-
solved in MeOH (8 mL), then acetone (2 mL) and
TsOH·H2O (p-toluenesulfonic acid monohydrate, 10 mg,
0.05 mmol) was added. The mixture was refluxed for 3 days,
then concentrated. The crude product was purified by flash
chromatography using silica gel with pure AcOEt. Product
60 was obtained as colorless oil; yield 40% (94 mg,
[5] D. A. DiRocco, T. Rovis, J. Am. Chem. Soc. 2012, 134,
8094–8097.
[6] D. Kalyani, K. B. McMurtrey, S. R. Neufeldt, M. S. San-
ford, J. Am. Chem. Soc. 2011, 133, 18566–18569.
[7] a) M. N. Hopkinson, B. Sahoo, J.-L. Li, F. Glorius,
Chem. Eur. J. 2014, 20, 3874–3886; b) A. Nijland, S. R.
Harutyunyan, Catal. Sci. Technol. 2013, 3, 1180–1189;
c) C. Müller, T. Bach, Aust. J. Chem. 2008, 61, 557–564.
[8] M. Neumann, S. Füldner, B. Kçnig, K. Zeitler, Angew.
Chem. 2011, 123, 981–985; Angew. Chem. Int. Ed. 2011,
50, 951–954.
1
0.32 mmol); Rf =0.3 (AcOEt); H NMR (400 MHz, CDCl3):
d=6.78 (d, J=8.1 Hz, 1H, ArH), 6.76 (d, J=1.9 Hz, 1H,
ArH), 6.69 (dd, J=8.1 and 1.9 Hz, 1H, ArH), 3.85 (s, 3H,
Ar-OCH3), 3.83 (s, 3H, Ar-OCH3), 3.24 (d, J=13.8 Hz, 1H,
CHH), 2.69 (s, 3H, NHCH3), 2.51 (d, J=13.8 Hz, 1H,
[9] Y. Zhu, L. Zhang, S. Luo, J. Am. Chem. Soc. 2014, 136,
14642–14645.
[10] a) M. T. Pirnot, D. A. Rankic, D. B. C. Martin, D. W. C.
2
CHH), 1.95 (br s, 1H, NH), 1.39 (s, 3H, CH3), 1.29 (s, 3H,
2CH3), 0.78 (s, 3H, 5CH3) ppm; 13C NMR (100 MHz,
CDCl3): d=175.3, 148.9, 148.0, 129.4, 122.2, 113.0, 110.9,
74.3, 63.3, 55.8, 43.9, 28.3, 27.6, 27.1, 25.2 ppm; HRMS
(ESI): m/z 293.1864 (calcd. for C16H25N2O3 [M + H]+
293.1865); [a]D25 =– 59.98 (c=0.7, CHCl3).
MacMillan, Science 2013, 339, 1593–1596; b) F. R. Pet-
´
ronijevic, M. Nappi, D. W. C. MacMillan, J. Am. Chem.
Soc. 2013, 135, 18323–18326; c) J. A. Terrett, M. D.
Clift, D. W. C. MacMillan, J. Am. Chem. Soc. 2014, 136,
6858–6861.
[11] a) E. L. Clennan, Tetrahedron 2000, 56, 9151–9179;
b) E. L. Clennan, A. Pace, Tetrahedron 2005, 61, 6665–
6691; c) M. N. Alberti, M. Orfanopoulos, Synlett 2010,
999–1026.
Acknowledgements
[12] a) Y. Kuroda, T. Sera, H. Ogoshi, J. Am. Chem. Soc.
1991, 113, 2793–2794; b) A. G. Griesbeck, M. A. Miran-
da, J. Uhlig, Photochem. Photobiol. Sci. 2011, 10, 1431–
1435; c) A. Joy, R. J. Robbins, K. Pitchumani, V. Rama-
murthy, Tetrahedron Lett. 1997, 38, 8825–8828.
[13] C. Wiegand, E. Herdtweck, T. Bach, Chem. Commun.
2012, 48, 10195–10197.
This work was supported by the Ministry of Science and
Higher Education, grant number N NT204 187139.
References
[14] a) H. SundØn, M. Engqvist, J. Casas, I. Ibrahem, A.
Córdova, Angew. Chem. 2004, 116, 6694–6697; Angew.
Chem. Int. Ed. 2004, 43, 6532–6535; b) A. Córdova, H.
SundØn, M. Engqvist, I. Ibrahem, J. Casas, J. Am.
Chem. Soc. 2004, 126, 8914–8915; c) I. Ibrahem, G.
Zhao, H. SundØn, A. Córdova, Tetrahedron Lett. 2006,
47, 4659–4663.
[15] a) G. Zhong, Angew. Chem. 2003, 115, 4379–4382;
Angew. Chem. Int. Ed. 2003, 42, 4247–4250; b) S. P.
Brown, M. P. Brochu, C. J. Sinz, D. W. C. MacMillan, J.
[1] S. E. Braslavsky, Pure Appl. Chem. 2007, 79, 293–465.
[2] a) B. Kçnig (Ed.), Chemical Photocatalysis, De Gruyt-
er, 2013; b) C. K. Prier, D. A. Rankic, D. W. C. MacMil-
lan, Chem. Rev. 2013, 113, 5322–5363; c) J. M. R. Nar-
ayanam, C. R. J. Stephenson, Chem. Soc. Rev. 2011, 40,
102–113; d) Y. Xi, H. Yi, A. Lei, Org. Biomol. Chem.
2013, 11, 2387–2403; e) J. Xuan, W.-J. Xiao, Angew.
Chem. 2012, 124, 6934–6944; Angew. Chem. Int. Ed.
2012, 51, 6828–6838; f) S. Fukuzumi, K. Ohkubo,
Chem. Sci. 2013, 4, 561–574; g) D. Ravelli, M. Fagnoni,
Adv. Synth. Catal. 2015, 357, 2061 – 2070
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2069

FULL PAPERS
Dominika J. Walaszek et al.
Am. Chem. Soc. 2003, 125, 10808–10809; c) Y. Hayashi,
J. Yamaguchi, K. Hibino, M. Shoji, Tetrahedron Lett.
2003, 44, 8293–8296.
[27] R. Gordillo, K. N. Houk, J. Am. Chem. Soc. 2006, 128,
3543–3553.
[28] I. Saito, S. Matsugo, T. Matsuura, J. Am. Chem. Soc.
1979, 101, 7332–7338.
[29] G. Zomer, in: Chemiluminescence and Bioluminescence
Past, Present and Future (Ed.: A. Roda), RSC Publish-
ing, 2011, pp. 51–63.
[16] M. P. Sibi, M. Hasegawa, J. Am. Chem. Soc. 2007, 129,
4124–4125.
[17] a) T. Kano, H. Mii, K. Maruoka, J. Am. Chem. Soc.
2009, 131, 3450–3451; b) H. Gotoh, Y. Hayashi, Chem.
Commun. 2009, 3083–3085; c) M. J. P. Vaismaa, S. C.
Yau, N. C. O. Tomkinson, Tetrahedron Lett. 2009, 50,
3625–3627.
[18] M. Engqvist, J. Casas, H. SundØn, I. Ibrahem, A. Cór-
dova, Tetrahedron Lett. 2005, 46, 2053–2057.
[19] N. Momiyama, in: Comprehensive Chirality (Eds.: E.
M. Carreira, H. Yamamoto), Elsevier, 2012, vol. 6,
pp. 414–433.
[20] a) G. Jiang, J. Chen, J.-S. Huang C.-M. Che, Org. Lett.
2009, 11, 4568–4571; b) M. Matsumoto, Y. Kitano, H.
Kobayashi, H. Ikawa, Tetrahedron Lett. 1996, 37, 8191–
8194.
[21] a) C. S. Foote, J. W.-P. Lin, Tetrahedron Lett. 1968, 9,
3267–3270; b) J. E. Huber, Tetrahedron Lett. 1968, 9,
3271–3272; c) C. S. Foote, A. A. Dzakpasu, J. W.-P. Lin,
Tetrahedron Lett. 1975, 16, 1247–1250; d) J. Li, S. Cai, J.
Chen, Y. Zhao, D. Z. Wang, Synlett 2014, 25, 1626–
1628.
[22] a) Š. J. Carlsson, P. Bauer, H. Ma, M. Widersten, Bio-
chemistry 2012, 51, 7627–7637; b) H. Sone, T. Shibata,
T. Fujita, M. Ojika, K. Yamada, J. Am. Chem. Soc.
1996, 118, 1874–1880.
[23] Z. Tang, F. Jiang, X. Cui, L.-Z. Gong, A.-Q. Mi, Y.-Z.
Jiang, Y.-D. Wu, Proc. Natl. Acad. Sci. USA 2004, 101,
5755–5760.
[24] R. H. Young, D. R. Brewer, in: Singlet Oxygen – reac-
tions with organic compounds and polymers (Eds.: B.
Ranby, J. F. Rabek), Wiley, 1978, pp. 40.
[30] B. List, R. A. Lerner, C. F. Barbas III, J. Am. Chem.
Soc. 2000, 122, 2395–2396.
[31] a) K. A. Ahrendt, Ch. J. Borths, D. W. C. MacMillan, J.
Am. Chem. Soc. 2000, 122, 4243–4244; b) A. B. Northr-
up, D. W. C. MacMillan, J. Am. Chem. Soc. 2002, 124,
2458–2460; c) L. Samulis, N. C. O. Tomkinson, Tetrahe-
dron 2011, 67, 4263–4267.
[32] a) N. A. Paras, D. W. C. MacMillan, J. Am. Chem. Soc.
2002, 124, 7894–7895; b) S. Bräse, N. Volz, F. Gläser,
M. Nieger, Beilstein J. Org. Chem. 2012, 8, 1385–1392.
[33] a) K. Gollnick, K. Knutzen-Mies, J. Org. Chem. 1991,
56, 4017–4027; b) W. Ando, K. Watanabe, J. Suzuki, T.
Migita, J. Am. Chem. Soc. 1974, 96, 6766–6768.
[34] K. Wright, F. Melandri, C. Cannizzo, M. Wakselman,
J.-P. Mazaleyrat, Tetrahedron 2002, 58, 5811–5820.
´
[35] D. Gryko, R. Lipinski, Eur. J. Org. Chem. 2006, 3864–
3876.
[36] T. J. Trivedi, K. S. Rao, T. Singh, S. K. Mandal, N. Su-
tradhar, A. B. Panda, A. Kumar, ChemSusChem 2011,
4, 604–608.
[37] a) Synthesis according to: M. Satyanarayana Reddy, S.
Eswaraiah, G. Venkat Reddy, B. Kondal Reddy (MNS
Laboratories Limited), WO 2011/101861 A1, 2011,
Page 18; b) NMR data compare with: C. Andreu, G.
Asensio, Tetrahedron 2011, 67, 7050–7056.
[38] N. Shao, X. Huang, A. Palani, R. Aslanian, A. Buevich,
J. Piwinski, R. Huryk, C. Seidel-Dugan, Synthesis 2009,
2855–2872.
[25] M. J. Frisch et al., Gaussian 09, Revision A.02, Gaussi-
[39] L. Meyer, J.-M. Poirier, P. Duhamel, L. Duhamel, J.
Org. Chem. 1998, 63, 8094–8095.
an, Inc., Wallingford CT, 2009.
[26] S. Lakhdar, B. Maji, H. Mayr, Angew. Chem. 2012, 124,
5837–5840; Angew. Chem. Int. Ed. 2012, 51, 5739–5742.
[40] I. Ojima, H.-J. C. Chen, X. Qiu, Tetrahedron 1988, 44,
5307–5318.
2070
asc.wiley-vch.de
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2061 – 2070