α-Photooxygenation of chiral aldehydes with singlet oxygen

Article abstract of DOI:10.3762/bjoc.15.205

Organocatalytic α-oxygenation of chiral aldehydes with photochemically generated singlet oxygen allows synthesizing chiral 3-substituted 1,2-diols. Stereochemical results indicate that the reaction in the presence of diarylprolinol silyl ethers is highly

Full text of DOI:10.3762/bjoc.15.205

α-Photooxygenation of chiral aldehydes with singlet oxygen
Dominika J. Walaszek1, Magdalena Jawiczuk1,2, Jakub Durka1,3, Olga Drapała1,3
and Dorota Gryko*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 2076–2084.
1
Institute of Organic Chemistry, Polish Academy of Sciences,
doi:10.3762/bjoc.15.205
Kasprzaka 44/52, 01-224 Warsaw, Poland, 2Centre of New
Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw,
Poland and 3Department of Chemistry, Warsaw University of
Technology, Noakowskiego 3, 00-664 Warsaw, Poland
Received: 06 June 2019
Accepted: 10 August 2019
Published: 30 August 2019
Email:
Associate Editor: P. Schreiner
Dorota Gryko* - dorota.gryko@icho.edu.pl
©
2019 Walaszek et al.; licensee Beilstein-Institut.
*
Corresponding author
License and terms: see end of document.
Keywords:
,2-diols; ECD; enamines; organocatalysis; porphyrins; silyl ethers of
1
diarylprolinols; singlet oxygen
Abstract
Organocatalytic α-oxygenation of chiral aldehydes with photochemically generated singlet oxygen allows synthesizing chiral
3
-substituted 1,2-diols. Stereochemical results indicate that the reaction in the presence of diarylprolinol silyl ethers is highly dia-
stereoselective and that the configuration of a newly created stereocenter at the α-position depends predominantly on the catalyst
structure. The absolute configuration of chiral 1,2-diols has been unambiguously established based on electronic circular dichroism
(
ECD) and TD-DFT methods.
Introduction
Carbonyl compounds are one of the most important building use not only in diastereoselective synthesis but also in enantio-
blocks in organic synthesis. As a consequence, there is a con- selective reactions [9,10].
stant need for new methodologies enabling their functionaliza-
tion, particularly in a stereoselective manner. Among them, Inspired by Cόrdova’s work [11-13], we explored the idea of
asymmetric α-oxygenation of aldehydes still represents a chal- merging enamine catalysis with photocatalytic oxygenation
lenging task. Most efficient methods require simultaneous use with singlet oxygen for α-hydroxylation of aldehydes [14,15].
of chiral amines or Brønsted acids, and harsh oxidants like Recently, we have reported that organocatalytic photooxygena-
nitrosobenzene [1-3], TEMPO [4], or benzoyl peroxide [5-8]. tion of aldehydes affords the desired diols (after in situ reduc-
Therefore, the use of environmentally friendly reagents instead tion) in decent yield with either (R)- or (S)-selectivity
is highly desirable. Along this line, singlet oxygen by being depending on a catalysts used [14]. In the presence of prolin-
easily photochemically generated from triplet oxygen in the amides the (R)-enantiomer predominates while the imidazolidi-
presence of organic dyes seems promising. Despite its high re- none-catalyzed reaction is (S)-enantioselective. Nevertheless,
activity and small molecule size, there are few examples of its the scope is limited to simple, achiral aldehydes. As the synthe-
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Beilstein J. Org. Chem. 2019, 15, 2076–2084.
sis of more complex targets often requires functionalization of detailed optimization of the catalyst structure [14]. Preliminary
molecules with stereocenters being already installed, we data for α-photooxygenation of chiral aldehydes suggested that
wondered whether and how preexisting stereochemical the stereocenter at the β-position has a strong impact on the
elements influence the stereoselectivity of this reaction. To this stereoselectivity level.
end we investigated α-photooxygenation of chiral aldehydes
with a stereocenter at the β-position (Scheme 1). In such a Model reaction
case, the outcome should depend on the relationships between Firstly, we tested three aldehydes 1–3 bearing substituents at
the absolute configuration of the starting material and the cata- the β-position. These substrates are easily accessible by photo-
lyst.
chemical means, according to the procedures reported by the
groups of Melchiorre or MacMillan [16-18]. Preliminary exper-
iments showed that photooxygenation of chiral aldehydes 1, 2
Results and Discussion
Our previous studies on α-photooxygenation of achiral alde- or 3 (used 1 as S/R 2:1 mixture of enantiomers, 2 as racemate,
hydes with 1O2 in the presence of chiral amines supported by and 3 as 1.4:1 mixture of diastereoisomers) in the presence of
DFT calculations indicate that the reaction is highly enantiose- N-isopropylbenzylamine (NiPBA, 4) as an organocatalyst and
lective only when both enamine structural fragments (substitu- meso-tetraphenylporphyrin (H2TPP, 5) as a photosensitizer fol-
ents originating from an aldehyde and an organocatalyst) lowed by in situ reduction with NaBH4, proceeded similarly to
interact with each other in such a way that one side of the en- the reported results for simple, achiral aldehydes giving the
amine is predominantly shielded from singlet oxygen. As a desired diols 6–8 in 31–41% yields with moderate conversion
result, small alterations to the aldehyde structure require and alcohols 9–11 as byproducts (Scheme 2) [14].
Scheme 1: Asymmetric α-photooxygenation of chiral aldehydes.
Scheme 2: α-Photooxygenation of β-substituted aldehydes.
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Beilstein J. Org. Chem. 2019, 15, 2076–2084.
Photooxygenation of 3,4-diphenylbutanal (1) affording the propanal (Table 1) [14]. The prolinamide-catalyzed reaction
desired diol 6 accompanied by alcohol 9 as the only byproduct furnished only small amounts of the desired product 6 (Table 1,
was chosen as a model reaction for optimization studies. From a entry 1), higher yields were obtained in the presence of imida-
practical point of view it was important that diastereoisomers zolidinone 16 and silyl ether (S)-17, 31% and 52%, respective-
syn-6 and anti-6 could be separated by column chromatography. ly (Table 1, entries 2 and 3). The yield further increased to 59%
upon the addition of phosphate buffer. The highest level of
Photooxygenation of 3,4-diphenylbutanal (1)
stereoselectivity was enforced by bulkier and electron-with-
drawing groups as diarylprolinol silyl ether 18 (Table 1, entries
with chiral organocatalysts
The highly enantioselective synthesis of 3,4-diphenylbutanal 4 and 5).
(
1), according to the procedure developed by Melchiorre,
requires the use of noncommercially available sterically bulky The absolute configuration of diastereoisomers formed was
silyl ethers [16]. For that reason, for our optimization studies assigned using chiroptical spectroscopic methods (see section
we used enantioenriched aldehyde 1 (S/R 2:1 mixture of enan- ‘Determination of the absolute configuration of the product by
tiomers) formed in the photochemical reaction of cinnamalde- electronic circular dichroism spectroscopy’). Functionalization
hyde (12) with benzyltrimethylsilane (BnTMS, 13) catalyzed by of 3,4-diphenylbutanal (1) at the α-position can lead to four
commercially available imidazolidinone cis-14 (Scheme 3) stereoisomers, but photooxygenation catalyzed by secondary
[
16]. Aldehyde 1 was subjected to photooxygenation in the amines 16, 17 and 18 furnished only two of them. The dia-
presence of various organocatalysts: amide 15, imidazolidinone stereoisomeric ratio was always close to 2:1, the same as er for
6, diarylprolinol silyl ethers (S)-17 and (S)-18 which proved enantioenriched substrate 1 thus indicating that the organocata-
1
the most effective in the photooxygenation of achiral 3-phenyl- lytic photooxygenation of aldehydes with singlet oxygen is
Scheme 3: Synthesis and α-photooxygenation of 3,4-diphenylbutanal (1).
Table 1: Stereoselectivity of α-photooxygenation reaction of 3,4-diphenylbutanal (1).
Entry
Cat.
Yield [%]
dr (syn:anti)
er (syn:syn')
er (anti:anti')
major (conf.)
minor (conf.)
1
2
3
4
5
15
16
(S)-17
(S)-18
(R)-18
<10
31
52 (59)a
35
n/a
1:2
1:2
1:2
2:1
n/a
n/a
–
–
20:80
19:81
13:87
96:4
90:10
91:9
87:13
4:96
anti (2S,3R)
anti (2S,3R)
anti (2S,3R)
syn (2R,3R)
syn’ (2S,3S)
syn’ (2S,3S)
syn’ (2S,3S)
anti’ (2R,3S)
40
aPhosphate buffer pH 7 was used as an additive.
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Beilstein J. Org. Chem. 2019, 15, 2076–2084.
highly diastereoselective. In the case, when two chiral com- Interestingly, to the best of our knowledge, there are no reports
pounds participate in a given reaction, they, according to on ‘one-pot’ reactions leading to difunctionalization at both α
Masamune, may be considered as matching or mismatching and β-positions. To this end, in subsequent experiments, we
pairs [19]. As a consequence, an increased or decreased level of attempted to merge two photochemical processes: β-benzyla-
stereoselectivity can be observed. In our case, enantiomeric tion (according to the Melchiorre method) [16] with
catalysts (S)-18 or (R)-18 impose the same level of stereoselec- α-photooxygenation in a one pot procedure. Cinnamaldehyde
tivity but with the opposite direction (Scheme 4).
(12) was reacted with benzyltrimethylsilane (13) in the pres-
ence of catalyst cis-14 yielding aldehyde 1. Once the reaction
No significant match/mismatch effect was observed as catalyst was completed, a solution of H2TPP and imidazolidinone 16
S)-18 provided two diasteroisomers with (S)-configuration of was added to the reaction mixture and oxygen was purged.
(
the newly created stereocenter in high predominance, while the After the reduction diol 6 was obtained in 12% yield, as a
reaction catalyzed by prolinol derivative (R)-18 almost exclu- nearly equimolar mixture of syn-(2R,3R)- and syn’-(2S,3S)-6
sively led to (2R)-diols. These results indicate that photooxy- enantiomers (Table 2, entry 1). So, in the one-pot procedure a
genation of chiral aldehydes with singlet oxygen provides the decrease in both yield and stereoselectivity was observed as
desired product and the configuration of the newly created compared to the two-step synthesis (Table 1, entry 2),
stereocenter depends mainly on the catalyst used. There is no suggesting that the reaction conditions are not compatible with
doubt that the presence of the phenyl substituent at the β-posi- one another.
tion of the aldehyde is necessary to ensure a high level of selec-
tivity (by effective shielding), but on the other hand the ability The use of silyl ether (S)-17 instead of imidazolidinone 16 and
to alter the configuration of a newly created stereocenter by phosphate buffer (pH 7) as an additive allowed to increase the
changing only the catalyst configuration is a quite unprece- yield of the ‘one-pot’ procedure to 30% (Table 2, entries 2 and
dented phenomenon in singlet oxygen reactions. Usually in 3). Additional experiments indicated that acetonitrile required
those reactions the introduction of a steric hindrance much in the first step has a negative effect on the subsequent
larger than the phenyl ring (i.e., adamantyl) or a chiral auxil- α-photooxygenation reaction (for details see Supporting Infor-
iary (i.e., oxazolidinone) into the substrate structure is required mation File 1).
for highly stereoselective reactions [20-22].
Determination of the absolute configuration of
‘
One-pot’ photochemical α,β-functionaliza-
the product by electronic circular dichroism
spectroscopy
tion of cinnamaldehyde
Over the last few years, photochemical methods for asym- Despite its rather simple structure diol 6 was not previously re-
metric functionalisation of carbonyl compounds at either α or ported in the literature. The ratio of stereoisomers 6 was deter-
β-position has been of particular interest [23]. Just to mention mined by HPLC analysis while the absolute configuration of the
Córdova’s α-oxygenation [11-13] or β-alkylation or β-arylation newly created stereocenter was established using a chiroptical
reported by Melchiorre [16] and MacMillan [17,18]) which spectroscopic method. Samples of stereoisomers syn-6 and
represents only a tip of an iceberg of photochemical methods anti’-6 obtained from the reaction with diarylprolinol silyl ether
for the introduction of substituents into an aldehydes’ structure. (R)-18 (Table 1, entry 5) were analyzed using electronic circu-
Scheme 4: Stereoselective α-photooxygenation of 3,4-diphenylbutanal (1) with 1O2.
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Beilstein J. Org. Chem. 2019, 15, 2076–2084.
Table 2: Photochemical difunctionalization of cinnamaldehyde (12) at the β and α-positions.
Entry
Orgcat. I/II
Buffer
pH]
Yield
[%]
dr
syn:anti
er
er
Main
stereoisomer
[
syn:syn’
anti:anti’
1
2
3
cis-14/16
cis-14/17
cis-14/17
–
6
7
12
28
30
>95:5
80:20
80:20
58:42
55:45
55:45
–
syn (2R,3R)
syn (2R,3R)
syn (2R,3R)
86:14
87:13
lar dichroism spectroscopy (ECD) and TD-DFT methods.
So-called in situ methodology with dimolybdenum tetraacetate
(
19) acting as auxiliary chromophores which proved a very use-
ful tool in solving stereochemical problems [24-26], allowed to
determine the absolute configuration at the C2 carbon atom of
obtained diols (Scheme 5) [27,28].
In this method the achiral Mo complex 19 forms optically
active complexes with chiral vic-diols allowing the application
of ECD to compounds transparent in the UV–vis region. In
solution, chirality of diols is transfered to the newly in situ-
formed complexes. The signs of Cotton effects (CEs) observed
in their spectra undergo the helicity rule linking the positive/
negative sign of CE at about 300–400 nm with positive/nega-
tive sign of O–C–C–O torsion angles of the diol unit [27-29].
The negative sign of CE at 310 nm in the recorded spectra for
both analyzed compounds syn-6 and anti’-6 correlates to the
negative O–C–C–O torsion angle. Based on the preferred
gauche conformation of the diol unit with large substituents
(
O–C–C–O fragments of molecule) in the antiperiplanar orien-
tation as a result of steric repulsion, the absolute configuration
at position 2 was assigned as (2R) in both compounds syn-6 and
anti’-6 (Figure 1a).
Figure 1: ECD spectra of diols syn-6 and anti’-6 recorded a) with 19 in
DMSO and b) in acetonitrile compared with simulated ECD spectra.
The absolute configuration of the second stereocenter at C3
with the phenyl substituent was determined based on the ECD
Scheme 5: Schematic representation of the in situ methodology and preferred conformation of diols with Mo2 core.
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Beilstein J. Org. Chem. 2019, 15, 2076–2084.
spectra recorded for pure syn-6 and anti’-6 diols (Figure 1b) etry (HRMS) data were obtained at the Synapt G2-S HDMS
[
29]. The comparison of the experimental ECD curves with the mass spectrometer equipped with an electrospray ion source
calculated ones for two possible stereoisomers (2R,3R) and and q-TOF type mass analyzer. Specific rotation was measured
2R,3S) allowed for unambiguous assignment of (2R,3R) on a JASCO P-2000 polarimeter. The enantiomeric purity of
(
absolute configuration to the syn-6 isomer and (2R,3S) to the diols was determined by chiral-phase HPLC analysis on Daicel
anti’-6 isomer. Based on the known relationship between syn-6 Chiralpak ID (250 mm × 4.6 mm inside diameter) using a
and anti’-6 diols and the other two diastereoisomers we hexane/iPrOH mixture as a mobile phase. Thin-layer chroma-
assigned their absolute configuration as (2S,3S) for syn’-6 and tography (TLC) was performed using Merck Silica Gel GF254,
(
2S,3R) for anti-6, respectively.
0.20 mm thickness. All solvents and chemicals used in the syn-
theses were of reagent grade and were used without further
purification. Aldehydes 1 [16,30], 2 [17], 3 [18] and organocat-
alysts 14 [31], 15 [32], 16 [33] were prepared by known proce-
Asymmetric synthesis of 3,4-diphenylbutane-
,2-diol
1
To confirm our conclusions concerning stereoselectivity in dures. Silyl ethers of diarylprolinols 17 and 18 were obtained
photooxygenation of chiral aldehydes, we synthesized enantio- from Sigma-Aldrich. Photochemical reactions were performed
merically pure aldehyde (S)-1 from cinnamyl bromide (20) ac- either using homemade photoreactors equipped with two LED
cording to a literature procedure [30]. The reaction of (S)-3,4- warm white light bulbs (α-photooxygenation, scale >0.5 mmol),
diphenylbutanal (1) with singlet oxygen catalyzed by diarylpro- green high power LED (scale ≤0.5 mmol) or LED tapes (photo-
linol silyl ether (R)-18 furnished, after in situ reduction, diol chemical aldehydes synthesis), see Supporting Information
(
(
2R,3R)-6 with high syn-diastereo- and enantioselectivity File 1 for details.
Scheme 6).
General procedure for α-photooxygenation
Conclusion
To a 10 mL vial a solution of meso-tetraphenylporphyrin
We have demonstrated that oxygenation of aldehydes with (H2TPP, 0.4 mg, 0.63 µmol, 0.25 mol %) in CCl4 (1 mL) and
singlet oxygen can be successfully achieved in the presence of NiPBA (17 μL, 0.1 mmol, 40 mol %) was added followed by
diphenylprolinol silyl ether affording diols in a highly aldehyde 1 (56 mg, 0.25 mmol), at 10 °C. The reaction mixture
diastereo- and enantioselective manner providing the presence was stirred with gentle oxygen bubbling under irradiation
of a substituent at the β-position. Using our procedure enan- (green high power LED) for 3 h. The light was turned off and a
tiopure (S)-3,4-diphenylbutanal ((S)-1) was transformed into solution was transferred to a round bottom flask with MeOH
(
2R,3R)-3,4-diphenylbutane-1,2-diol in a highly stereoselective (1 mL). The reaction mixture was then cooled to 0 °C before
manner. This high level of stereoselectivity is rarely observed NaBH4 (50 mg, 1.3 mmol) was added. After stirring for 15 min
for reactions of singlet oxygen with substrates that do not pos- at 0 °C the reaction was diluted with AcOEt, washed with a 1 N
sess chiral auxiliary or do not impose significant steric solution of HCl, and then saturated NaHCO3. The organic layer
hindrance.
was dried over Na2SO4, filtered and concentrated. The crude
mixture was purified by column chromatography (SiO2,
hexanes/AcOEt), affording alcohol 9 (25 mg, 45%), diastereo-
somer syn’-6 (14 mg, 23%), and diastereosomer anti-6 (11 mg,
Experimental
General information
1
H and 13C NMR spectra were recorded at rt on Bruker 400 and 18%). Diastereosomer syn’-6 was obtained as colorless oil,
Varian 600 MHz instruments with TMS as an internal standard. 14 mg, 23%. Rf: 0.40 (hexanes/AcOEt 1:2); IR (film, νmax,
The chemical shifts (δ) and coupling constants (J) are expressed cm−1): 3387, 3085, 3061, 3027, 2925, 1709, 1602, 1495, 1453,
in ppm and Hertz, respectively. High-resolution mass spectrom- 1409, 1181, 1094, 1068, 1031, 745, 700, 562, 534; 1H NMR
Scheme 6: Asymmetric synthesis of 3,4-diphenylbutane-1,2-diol.
2
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Beilstein J. Org. Chem. 2019, 15, 2076–2084.
(
400 MHz, CDCl3) δH 7.35–7.00 (m, 10H, ArH), 3.88 (dd, J = irradiation (green high power LED). The light was turned off
9
.1, 6.2 Hz, 1H, >CHOH), 3.65 (dd, J = 11.2, 3.2 Hz, 1H, and the mixture was left for phase separation. The organic layer
-
(
CHH-OH ), 3.42 (dd, J = 11.1, 7.4 Hz, 1H, -CHH-OH), 3.17 was transferred to a round bottom flask and mixed with MeOH
dd, J = 12.5, 6.4 Hz, 1H, >CH-Ph), 2.99 (dd, J 12.8, 6.7 Hz, (1 mL). The reaction mixture was then cooled to 0 °C before
1
H, -CHH-Ph), 2.93 (dd, J = 12.4, 8.2 Hz, 1H, CHH-Ph), 1.88 NaBH4 (50 mg, 1.3 mmol) was added. After stirring for 15 min
(
br s, 2H, 2 x OH); 13C NMR (100 MHz, CDCl3) δC 140.4, at 0 °C the reaction mixture was diluted with AcOEt, washed
1
3
2
39.9, 129.1, 128.9, 128.5, 128.2, 127.0, 126.0, 73.4, 65.3, 50.4, with 1 N solution of HCl, and then saturated NaHCO3. The
8.6; HRESIMS m/z: [M + Na]+ calcd. for C16H18O2Na, organic layer was dried over Na2SO4, filtered and concentrated.
65.1204; found, 265.1199. Diastereoisomer anti-6 obtained as The crude mixture was purified by column chromatography
colorless oil, 11 mg, 18%. Rf: 0,33 (hexanes/AcOEt 1:2); IR (SiO2, hexanes/AcOEt), affording (with pH 6.0 buffer) diastere-
film, νmax, cm−1): 3375, 3085, 3061, 3028, 2925, 1706, 1602, osomer syn’-6 (2S,3S-6, 14 mg, 23%), diastereosomer anti-6
495, 1452, 1097, 1070, 1048, 1030, 876, 761, 700, 626, 556; (2S,3R-6, 22 mg, 36%), respectively. The relative ratio of
H NMR (400 MHz, CDCl3) δH 7.25–7.08 (m, 6H, ArH), 7.04 stereoisomers was determined by HPLC analysis: Daicel
d, J = 6.7 Hz, 2H, ArH), 6.96 (d, J = 6.7 Hz, 2H, ArH), Chiralpak ID (250 mm × 4.6 mm), hexane/AcOEt, 80:20 (v/v)
.98–3.90 (m, 1H, >CHOH), 3.46–3.28 (m, 3H, -CH2OH, >CH- flow rate 1.5 mL/min. The retention times were 7.3; 7.9; 9.4
Ph), 2.92–2.90 (m, 2H, -CH2Ph), 2.38 (br s, 1H, OH) 1.56 (br s, and 13.4 min for (2S,3R), (2R,3S), (2R,3R) and (2S,3S), respec-
(
1
1
(
3
1
1
H, OH); 13C NMR (100 MHz, CDCl3) δC 140.8, 140.0, 129.1, tively.
28.4, 128.3, 128.0, 126.7, 125.8, 75.3, 65.0, 51.4, 38.7;
HRESIMS m/z: [M + Na]+ calcd for C16H18O2Na, 265.1204; One-pot two-step procedure
found, 265,1198. HPLC analysis on Daicel Chiralpak ID To a 10 mL vial filled with argon a solution of imidazolidinone
(
250 mm × 4.6 mm inside diameter) using a hexane/AcOEt, cis-14 (25 mg, 0.1 mmol, 20 mol %) in acetonitrile (1 mL),
8
1
0:20 (v/v) as a mobile phase, with the flow rate set at TFA (15 µL, 0.2 mmol, 40 mol %), benzyltrimethylsilane (13,
.5 mL/min. The retention times were 7.3; 7.9; 9.4 and 13.4 min 95 µL, 0.5 mmol) and cinnamaldehyde (12, 190 µL, 1.5 mmol)
for (2S,3R), (2R,3S), (2R,3R) and (2S,3S), respectively. Alcohol were added. The resulting solution was purged with argon for
was obtained as a colorless oil, 25 mg, 45%. 1H NMR 5 min before irradiation (violet high power LED), at rt, started.
400 MHz, CDCl3) δH 7.30–7.25 (m, 2H, ArH), 7.22–7.10 (m, After 24 h the light was turned off and the solution of meso-
9
(
6
3
2
1
H, ArH), 7.06–7.04 (m, 2H, ArH), 3.52–3.50 (m, 1H, >CH-), tetraphenylporphyrin (H2TPP, 0.8 mg, 1.25 µmol, 0.5 mol %),
.43–3.40 (m, 1H, -CHH-Ar), 2.99–2,90 (m, 1H, -CHH-Ar), catalyst (S)-17 (37 mg, 0.1 mmol, 20 mol %) in CCl4 (2 mL)
.91–2.88 (m, 2H, CH2OH) 1.98–1.93 (m, 1H, CHHCH2OH) and phosphate buffer solution (1 mL, 0.1 M, pH 6.0 or 7.0)
.86–1.80 (m, 1H, CHHCH2OH), 1.14 (br s, 1H, OH). Analyti- were added to the reaction mixture. The solution was then
cal data corresponds to the literature data [34].
stirred and irradiated (green single LED) for 3 h with gentle
oxygen bubbling. The light was turned off and the mixture was
left for phase separation. The organic layer was transferred to a
round bottom flask and mixed with MeOH (2 mL). The reac-
General procedure for α-photooxygenation
with chiral organocatalysts
Reactions with chiral organocatalysts 15–18 reported in Table 1 tion mixture was then cooled to 0 °C before NaBH4 (100 mg,
were performed according to the procedure described above but 2.6 mmol) was added. After stirring for 15 min at 0 °C the reac-
only 20 mol %, 0.05 mmol of catalyst were used. Reactions cat- tion mixture was diluted with AcOEt, washed with 1 N solu-
alyzed by diaryl prolinols (S)-18 and (R)-18 yielded anti-6 and tion of HCl and saturated NaHCO3. The organic layer was dried
syn-6, respectively. Enantiomer S,R (anti-6) 82% ee over Na2SO4, filtered and concentrated. The crude product was
[
[
α]D20 −147.0 (c 0.6, CHCl3). Enantiomer R,R (syn-6) 99% ee, purified by column chromatography (SiO2, hexanes/AcOEt,
α]D20 −104.0 (c 0.4, CHCl3).
80:20) affording 36 mg (30%, pH 7.0) or 34 mg (28%, pH 6.0)
of the desired product 6.
General procedure for α-photooxygenation
with phosphate buffer solution
Electronic circular dichroism
To a 10 mL vial a solution of meso-tetraphenylporphyrin The ECD spectra of free diols were collected at room tempera-
(
H2TPP, 0.4 mg, 0.63 µmol, 0.25 mol %) in CCl4 (1 mL) and ture in acetonitrile (for UV spectroscopy, Fluka) on a Jasco
organocatalyst (S)-17 (18 mg, 0.05 mmol, 20 mol %) were J-715 spectropolarimeter at 0.2 nm/step with an integration time
added followed by a phosphate buffer solution (0.5 mL, 0.1 M, of 0.5 s over the range 180–400 nm with 100 nm/min scan
pH 6.0 or 7.0). After cooling to 10 °C, aldehyde 1 (56 mg, speed, 5 scans. For the in situ ECD standard measurements the
0
.25 mmol) was added to the two-phase reaction mixture, which chiral vic-diol (1–8 mg, ca. 0.003 M/L) was dissolved in a stock
was then extensively stirred for 3 h with oxygen bubbling under solution of the [Mo2(O2CCH3)4] (4–6 mg, ca. 0.002 M/L) in
2
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Beilstein J. Org. Chem. 2019, 15, 2076–2084.
3
4
5
.
.
.
Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M. Tetrahedron Lett.
DMSO (5 mL) (for UV spectroscopy, Fluka) so that the molar
ratio of the stock complex to ligand was about 1.5:1, in general.
The measurements were performed on a Jasco J-715 spectropo-
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values are calculated in the usual way as Δε’ = ΔA/c × d, where
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2
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1
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Supporting Information
1
Supporting Information File 1
1
36, 6858–6861. doi:10.1021/ja502639e
Photochemical equipment, experiments for the optimization
of the one-pot procedure, analytical data for 7, 8, 10, 11,
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Acknowledgements
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This work was supported by the National Science Center,
research project Preludium 2014/13/N/ST5/03420 and in part
by PLGrid Infrastructure.
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ORCID® iDs
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