Combined Photoredox and Lewis Acid Catalyzed α-Hydroxyalkylation of Cyclic Ethers with Aromatic Ketones

Article abstract of DOI:10.1021/acs.joc.6b01085

The photochemically induced coupling of aromatic ketones with cyclic ethers such as tetrahydrofuran, tetrahydropyran, and 1,4-dioxane was studied. Direct photolysis of the substrates with UV-A light centered at 350 nm does not lead to photoinduced hydrogen transfer whereas the addition of a mixture of the Lewis acid catalysts Ti(OⁱPr)₄ and BF₃ enables the formation of the hydroxyalkylation products.

Full text of DOI:10.1021/acs.joc.6b01085

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Article
Combined Photoredox and Lewis Acid Catalyzed alpha-
Hydroxyalkylation of Cyclic Ethers with Aromatic Ketones
Melissa Reckenthaeler, Jörg-Martin Neudörfl, Elif Zorlu, and Axel G Griesbeck
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01085 • Publication Date (Web): 05 Jul 2016
Downloaded from http://pubs.acs.org on July 5, 2016
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The Journal of Organic Chemistry
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Combined Photoredox and Lewis Acid Catalyzed
α-Hydroxyalkylation of Cyclic Ethers
with Aromatic Ketones
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Melissa Reckenthäler, Jörg-M. Neudörfl, Elif Zorlu, and Axel G. Griesbeck*
Department of Chemistry, University of Cologne, Greinstr. 4, Cologne Dꢀ50939, Germany
AUTHOR EMAIL ADDRESS griesbeck@uniꢀkoeln.de
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RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
CORRESPONDING AUTHOR FOOTNOTE Axel Griesbeck, Department of Chemistry, Greinstr. 4, Dꢀ
50939 Köln – Cologne, Germany, Fax: + 49 221 470 3083; Tel: + 49 221 470 1166
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SYNOPSIS TOC.
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R´
O
hν (350 nm)
HO
Ti(OiPr)4, BF3 Et2O
.
O
R´
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X
O
R
R
X
ABSTRACT The photochemically induced coupling of aromatic ketones with cyclic ethers such as
tetrahydrofuran, tetrahydropyran and 1,4ꢀdioxane was studied. Direct photolysis of the substrates with
UVꢀA light centered at 350 nm does not lead to photoinduced hydrogen transfer whereas the addition
of a mixture of the Lewis acid catalysts Ti(OiPr)4 and BF3 enables the formation of the
hydroxyalkylation products.
KEYWORDS carbonꢀcarbon coupling, photoredox catalysis, ethers,
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Introduction:
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Carbonꢀcarbon bond forming processes using photoredox catalysis are currently complementing the
wellꢀestablished repertoire of transition metal catalysis and organocatalytic methods.1 Photoredox
catalysis adds one remarkable aspect, the large energy excess deposited in the electronically excited
catalyst applicable to trigger oxidative and/or reductive quenching processes that are energetically
highly improbable from the corresponding electronic ground states.2 This allows also processes that
are endergonic in total to be accomplished due to the high additional energy input by initial
photoexcitation.3 These processes can open the pathway to new reactivities, selectivities and also new
product types useful for organic synthesis.4
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When looking for new applications of photoredoxꢀinitiated reactions, one might consider three classes
of chemical reactions: i) thermal processes known from metalꢀ or organocatalysis that are adopted and
modified by photocatalysis (e.g. αꢀalkylation of enamines), ii) photochemical processes that are
modified and improved by photocatalysis (e.g. [2+2]ꢀphotocycloadditions), or iii) new processes that
were not yet realized by thermal or photochemical processes. Route iii is most demanding but
obviously highly desirable. Photoinduced reactions that deserve special attendance, beside the
impressive playground of cycloaddition chemistry, are hydrogen transfer processes from otherwise
hardꢀtoꢀactivate CH positions.5 Photoexcited substrates that are able to abstract hydrogen atoms are
triplet states of aromatic carbonyl compounds because of their long lifetimes and high excitation
energies.6 Two distinct modes for hydrogen transfer are possible: hydrogen atom transfer or protonꢀ
involved hydrogen transfer processes. The second route might involve a deprotonation/electron
transfer sequence or vice versa an oxidation step followed by proton transfer.7 For applications in
photoredox catalysis the last sequence is the most relevant because of the oxidative capability of many
photoexcited catalysts, such organic dyes,8 transition metal complexes9 or semiconductor particles.10
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Results and Discussion:
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We have recently reported on modifications of the Ti(IV)ꢀmediated photochemical hydroxymethylation
of ketones and keto esters.11 The Lewis acidꢀbase complex between the carbonyl acceptor and the
titanium metal center (from Ti(OR)2Cl2) enables photoinduced electron transfer from the methanol in
the ligand sphere to the carbonyl acceptor 1. Subsequent proton transfer and radicalꢀradical
combination delivers the hydroxymethylation product 2. In case of insufficient Lewis acidity of the
titanium complex Ti(OR)4, the addition of a second Lewis acid (e.g. BF3 or AlCl3) enables the return to
initial activity. The titanium catalyst with the lowest redox activity Ti(OiPr)4 still enables the formation of
reduction products (i.e. 1ꢀarylethanols) when applied without the second Lewis acid. A logical
extension of this process is the CꢀC coupling of carbonyl components with αꢀether radicals, a process
already known from direct photolyses of carbonyl compounds in ethereal solvents such as
tetrahydrofuran.12,13 These direct excitations needs shortꢀwavelength irradiation (usually the 254 nm
mercury line) and by nature turns on the unimolecular carbonyl photochemistry as well as the typical
reactions of electronically excited carbonyl compounds in the presence of hydrogen donors such as the
prevailing pinacol formation. The αꢀether alkyl radicals that are formed in these reactions can also
undergo a series of addition reactions to electronꢀpoor alkenes.14,15 The processes that involve free
ketyl radicals are often accompanied by the formation of the carbonyl pinacol coupling products and
thus do not allow conversions with high yields and selectivities. Furthermore, direct excitation of
carbonyl compounds does require shortꢀwavelength irradiation (λ = 254ꢀ300 nm). Therefore, we
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envisaged to transfer our experience from our hydroxymethylation studies to the αꢀhydroxyalkylation of
ethers (Scheme 1).
hν
Ti(IV)cat.
HO
Ar
OH
H2C OH
MeOH
R
hydroxymethyl
radical
2
O
Ar
R
O
hν
O
1
Ti(IV)cat.
HO
Ar
THF
αꢀether radical
R
3
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Scheme 1. Coupling routes of Cꢀradical formed by photoinduced electron transfer with aromatic carbonyl.
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4
In order to optimize the reaction conditions for long wavelength excitation of ketone/ether solutions, we
applied TiCl4, nanosized titanium dioxide, Ti(OiPr)4, and Ti(OiPr)4/BF3 as catalysts for the reaction of
acetophenone (1a) with tetrahydrofuran (Scheme 2, Table 1). The highly Lewis acidic titanium
tetrachloride is not able to induce bond formation even under 300 nm excitation. At the excitation
wavelengths applied for the other experiments (λ = 350 ± 30 nm), no reactivity was observed in the
absence of Lewis acids because of the very low absorptivity of acetophenone. A slurry of titanium
dioxide particles (applied as a 7:3 anatasꢀrutile mixture) and even better a mixture of Ti(OiPr)4 and BF3
led to high conversions and high yields of the coupling product 3a.
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Scheme 2. Model photoreaction of acetophenone with tetrahydrofuran.
hν
O
O
Ti(IV)cat.
HO
Ph
Ph
CH3
THF
CH3
3a
1a
Table 1. Photolysis of acetophenone in tetrahydrofuran in the presence of titanium reagents.
threo:
Entry a
Catalyst
Yield 3a
erythrof
b
1
2
3
0.5 equiv TiCl4
ꢀ
50%c
ꢀ
ꢀ
51:49
ꢀ
2.5 mg TiO2 P25
0.5 equiv Ti(OiPr)4
0.5 equiv Ti(OiPr)4/
1 equiv BF3
94%d
87%e
4
5
6
54:46
54:46
54:46
0.5 equiv Ti(OiPr)4/
0.5 equiv BF3
74%d
72%d
0.25 equiv Ti(OiPr)4/
0.5 equiv BF3
0.1 equiv Ti(OiPr)4/
0.2 equiv BF3
7
8
37%d
ꢀ
53:47
ꢀ
no catalyst / irradiation
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0.5 equiv Ti(OiPr)4/ 1 equiv
1
2
9
BF3/ no irradiation
ꢀ
ꢀ
3
4
5
6
a Reaction conditions: 0.75 mmol acetophenone (1a) in tetrahydrofuran (6 ml) was irradiated (λ = 350 nm) for 48 h
b
c
at room temp. under argon in the presence of the catalyst;
λ = 300 nm; yield determined via NMR,
f
acetophenone pinacol was formed as side product with 40%; d yield by GC; e isolated yield; by HꢀNMR, crude
reaction mixture.
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The latter reaction is catalytic in both Lewis acids (entries 5ꢀ7). Under titanium dioxide catalysis, the
pinacol from acetophenone was formed as an additional product in about 40%, a typical sideꢀreaction
for semiconductor photocatalysis that was also observed in the hydroxymethylation of acetophenone.11
In a second set of experiments, the application of the optimized conditions to the reaction of
benzophenone, benzaldehyde and four methylated substrates was investigated (Scheme 3, Table 2).
Benzophenone tends to the formation of the tetraphenylpinacol under reductive conditions whereas
benzaldehyde tends to the formation of benzylic alcohol. These products were also found under
standard conditions beside moderate yields of the CCꢀcoupling products to THF, 3b and 3c. The
radicalꢀinduced benzaldehyde addition to THF is a wellꢀstudied reaction in boraneꢀinduced THF radical
formation.16 The methylated substrates 1dꢀ1g gave results that depend strongly on the ring position of
the methyl substituents. From the metaꢀ and paraꢀmethylated substrates, identical yields of products 3
were determined whereas the ortho substrate 1f gave only traces (<5%) of 3f and the mesityl derivative
1g showed no product formation at all. From substrate 1f, the coupling product 417 was isolated in 25%
yield, possibly deriving from the hydroxyl orthoꢀquinodimethane formed by intramolecular hydrogen
transfer (in analogy to the photochemistry of 2ꢀmethylbenzophenone).18 This observation is interesting
because no direct excitation of the substrate 1f is possible unaromatic nucder these conditions and
thus, the formation of 4 has to be conducted via its radical anion.
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The Journal of Organic Chemistry
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Scheme 3. Aromatic ketones and benzaldehyde coupling with tetrahydrofuran.
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O
hν (350 nm)
HO R'
R' OH
.
Ti(OiPr)4, BF3 Et2O
O
O
R'
R
R
R
THF
threo-3
erythro-3
1
O
O
4
Table 2. Photolysis of aromatic ketones in tetrahydrofuran in the presence of Ti(OiPr)4 / BF3.
threo:
Entry a Product
Ar
R´
CH3
C6H5
H
Yield b
87%
36%c
19%
67%
66%
traces
ꢀ
erythrod
3a
1
Ph
54:46
3b
2
Ph
ꢀ
3c
3d
3e
3f
3
4
5
6
7
Ph
48:52
51:49
49:51
ꢀ
4ꢀMeC6H4
3ꢀ MeC6H4
2ꢀMeC6H4
2,4,6ꢀ(CH3)3C6H2
CH3
CH3
CH3
CH3
3g
ꢀ
a Reaction conditions: 1 equiv ketone, 0.5 equiv Ti(OiPr)4 and 1 equiv BF3—Et2O in tetrahydrofuran was irradiated
(λ = 350 nm) for 48 h at r.t. under argon; b isolated yields; c no diastereoisomers are formed here; d by HꢀNMR,
crude reaction mixture.
In a third set of experiments, the application of the optimized conditions to a series of acetophenone
derivatives was investigated (Scheme 4, Table 3). In the series of halogenated acetophenone
derivatives, the 4ꢀfluoro and 4ꢀchloro derivatives 1h and 1k, respectively, showed superior reactivity,
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the 2ꢀfluoro and 2ꢀmethoxy derivatives 1i and 1n gave the alkylation products in moderate yields. Only
low yields were obtained from 4ꢀbromoacetophenone due to increasing reactivity at the aromatic
nucleus (i.e. formation of substitution products at the phenyl group). Neither the perfluorinated
substrate 1j nor the nitro derivatives 1o,p showed the desired reactivity.
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Scheme 4. Photocatalytic acetophenone derivatives coupling with tetrahydrofuran.
O
hν (350 nm)
HO CH3
H3C OH
.
Ti(OiPr)4, BF3 Et2O
O
O
CH3
R
R
R
THF
threo-3
erythro-3
1
Table 3. Photolysis of acetophenone derivatives in tetrahydrofuran in the presence of Ti(OiPr)4 / BF3.
threo:
Entry a Product
Ar
Yield b
82%
42%
ꢀ
erythroe
3h
3i
1
2
3
4
5c
6
7
8
9
4ꢀFꢀC6H4
2ꢀFꢀC6H4
C6F5
52:48
59:41
3j
ꢀ
3k
3l
4ꢀClꢀC6H4
4ꢀBrꢀC6H4
4ꢀMeOꢀC6H4
2ꢀMeOꢀC6H4
4ꢀNO2ꢀC6H4
2ꢀNO2ꢀC6H4
64%
6%d
ꢀ
51:49
ꢀ
3m
3n
3o
3p
ꢀ
22%
ꢀ
57:43
ꢀ
ꢀ
ꢀ
a Reaction conditions: 1 equiv ketone, 0.5 equiv Ti(OiPr)4 and 1 equiv BF3—Et2O in tetrahydrofuran was irradiated
b
c
d
(λ = 350 nm) for 48 h at r.t. under argon; isolated yield; 1 equiv Ti(OiPr)4 and 2 equiv BF3—Et2O; yield of
erythroꢀ3l; e by HꢀNMR, crude reaction mixture.
Finally, the extension of this process to other cyclic ethers was investigated (Scheme 5, Table 4).
Under standard conditions, dihydropyran was reactive and coupling was a minor pathway beside
pinacolization. Only the erythro diastereoisomer 5a was isolated and characterized also by Xꢀray
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structure analysis. Better results were obtained with 1,4ꢀdioxane where both diastereoisomers of 6a
were formed and could be separated and characterized by Xꢀray structure analyses (Figure 1).
Unfortunately, 1,3ꢀdioxolane which is a formaldehyde equivalent could not be applied because of rapid
BF3ꢀinduced polymerization.
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Scheme 5. Acetophenone coupling with cyclic ethers.
HO CH3
O
hν (350 nm)
H3C OH
.
Ti(OiPr)4, BF3 Et2O
O
O
CH3
X
X
O
X
1a
3a (X = CH2)
5a (X = OCH2)
6a (X = CH2CH2)
Table 4. Photolysis of acetophenone and cyclic ethers in the presence of Ti(OiPr)4 / BF3.
threo:
entrya
ether
product
yieldb
87%
13%c
25%
erythrod
52:48
ꢀ c
3a
1
2
3
tetrahydrofuran
1,4ꢀdioxane
5a
6a
tetrahydropyran
55:45
4
1,3ꢀdioxolane
ꢀ
a Reaction conditions: 1 equiv ketone, 0.5 equiv Ti(OiPr)4 and 1 equiv BF3—Et2O in tetrahydrofuran was irradiated
(λ = 350 nm) for 48 h at r.t. under argon; b isolated yield; c only erythroꢀ5a was isolated and pinacol was formed as
major product (26% yield); d by HꢀNMR, crude reaction mixture.
Figure 1. Structures of the acetophenone photoaddition products with tetrahydropyran (diastereoisomers
erythroꢀ6a and threoꢀ6a) and with 1,4ꢀdioxane (5a) in the crystal.
Conclusion
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The reaction of aromatic ketones in methanol solution in the presence of a Ti(IV) photoredox catalyst
with low Lewis acidity (Ti(OiPr)4) leads to the formation of reduction products when performed by shortꢀ
wavelength irradiation (λ = 300 nm).11 The apparently low reactivity at excitation wavelengths > 300 in
the presence of this Ti(IV) photoredox catalysts can be attributed to the low absorbance of the redoxꢀ
active species. The addition of a second Lewis acid leads to a switch in chemoselectivity and the
formation of hydroxymethylation products but was also restricted to shortꢀwavelength irradiation. In
ethereal solutions, also longꢀwavelength irradiation leads to the formation of CCꢀcoupling products, e.g.
3a from acetophenone (Scheme 6). This combination of Lewisꢀacid catalysis and photoactivation
accounts for the mechanism as shown in Scheme 6. From the UVꢀvis spectra, of mixtures of
acetophenone with one or two of the Lewis acids no clearꢀcut decision about the absorbing species
could be made because only an unstructured shoulder in the longꢀwavelength region appeared. The
strong Lewis acid BF3 (as THF complex in solution) forms a complex with the respective ketone and, in
the presence of the Ti(IV) photoredox catalyst, is reduced to the radical species with concomitant
formation of the ether radical cation. Subsequent proton transfer leads to a radical pair that combines
to the coupling product 3a.
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Scheme 6. Acetophenone coupling behavior depending on Lewis acids and wavelengths.
OH
CH3
hν (300 nm)
O
hν (300 nm)
OH
.
Ti(OiPr)4
Ti(OiPr)4, BF3 Et2O
OH
CH3
CH3
CH3OH
CH3OH
2a
7a
1a
hν (350 nm)
Ti(OiPr)4
hν (350nm)
Ti(OiPr)4, BF3 Et2O
.
O
O
HO CH3
O
3a
BF3
BF3
CH3
O
O
hν
Ti(OiPr)4(THF)2
OH
CH3
.
BF3 THF
O
O
CH3
1a
3a
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Experimental part
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General aspects and methods. All chemicals were purchased from commercial suppliers and were
used as received, TiO2 Aeroxide® P25 was used. Tetrahydrofuran was dried by heating under reflux
over sodium and then distilled. 1H and 13C NMR spectra were recorded at 300, 400, or 500 MHz for 1H
and 75.4, 100.5 or 125.7 MHz for 13C. Chemical shifts are reported in parts per million relative to
tetramethylsilane with the solvent resonances of CDCl3 as the internal standards (center line of the
triplet at 77.0 ppm for 13C and singlet at 7.24 ppm for 1H). Gas chromatography equipped with a flame
ionization detector (FID) was carried out with a HPꢀ35 column as stationary phase and nitrogen as
carrier gas. Gas chromatography coupled to mass spectrometry (GCꢀMS) measurements was carried
out with a DBꢀ5HT column as stationary phase and helium 5.0 (99.999 % He) as carrier gas. For
chemical ionisation methane was used. The exact ion mass measurements of compounds 3e, 3h, 3i,
3k, 3l, 3n were conducted by EIꢀMS on a two sector instrument at a resolution of 3600 (10% valley
definition) with appropriate internal standard ions from perfluorokerosene PFK Uvasol (Merck,
Darmstadt). Samples of compounds 3e, 3h, 3i, 3k, 3l, 3n were introduced into the EIꢀMS ion source
(Ekineꢀ = 70eV; T = 473 K; P = 10ꢀ6 bar) with a cooled direct inlet probe (273 K). The exact ion mass
measurements were executed with an ICIS controlled peak matching algorithm. However, the very
volatile analytes 3e, 3h, 3i, 3k, 3l, 3n exhibit a disadvantageous vaporization behavior that lead to
significant signal fluctuation of the investigated low abundant molecular ion signals. The difficult
experimental conditions explain the observed relative experimental errors of about 15ꢀ20ppm (absolute
experimental errors in the range of 3ꢀ5 mmu). Infrared spectra were recorded with a fourier transform
(FTꢀIR) spectrometer. Irradiation experiments were carried out in a Luzchem CCPꢀ4V reactor using 14
coated lowꢀpressure mercury lamps (λ = 300 and 350 nm, respectively).
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General procedure (GP) for photoredox-catalyzed tetrahydrofuran addition to carbonyl
compounds. Argon gas was passed through a mixture of 0.75 mmol (1 eq) ketone in 6 ml of the ether
(tetrahydrofuran, tetrahydropyran or 1,4ꢀdioxane) containing 0.5 equiv titanium isopropoxide and 1
equiv BF3—Et2O for 15 min. The degassed solution was irradiated with UVꢀA light (350 ± 30 nm) for 48 h
at room temperature. After irradiation, the solution was poured into water and extracted three times
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with CH2Cl2. The organic phase was dried (Na2SO4) and the solvent was removed under reduced
pressure. The residual was purified via column chromatography.
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1-(Tetrahydrofuran-2-yl)-1-phenylethanol (3a).13 The crude product prepared by GP from 0.75 mmol
acetophenone and tetrahydrofuran, was purified by column chromatography [cꢀHex/EtOAc (20:1)].
(126 mg, 87 % yield); erythroꢀ3a: colorless oil; 1HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.35ꢀ1.45 (m, 1H),
1.62 (s, 3H), 1.56ꢀ1.68 (m, 1H), 1.73ꢀ1.82 (m, 2H), 2.58 (s, 1H), 3.80ꢀ3.94 (m, 2 H), 4.03ꢀ4.08 (m, 1H),
7.24 (d, J = 7.3 Hz, 1H), 7.32 (t, J = 7.5 Hz, 2H), 7.43 (d, J = 7.4 Hz, 2H); 13CꢀNMR (75 MHz, CDCl3)
δ (ppm) = 26.4, 26.5, 28.8, 69.5, 74.6, 85.9, 125.0,126.7, 128.1,145.0; IR (film): ν (cmꢀ1) = 3464, 2977,
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2874, 1772, 1773, 1684, 1602, 1496, 1447, 1371, 1177, 1064, 1027, 760, 700, 640; GCꢀMS τR = 10.88
min, m/z (%): 192 (1, [M]+), 174 (3, [MꢀH2O]+), 121 (100), 105 (20), 77 (22), 71 (28).CI m/z (%): 175 (37,
1
[MꢀOH]+), 121 (100), 105 (47), 91 (36), 77 (28), 51 (18); threoꢀ3a: colorless oil; HꢀNMR (300 MHz,
CDCl3) δ (ppm) = 1.46 (s, 3H), 1.84ꢀ1.93 (m, 4H), 2.63 (s, 1H), 3.73ꢀ3.87 (m, 2H), 4.18 (t, J = 7.1 Hz,
1H), 7.25 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.5 Hz, 2H), 7.49 (d, J = 8.7 Hz, 2H); 13CꢀNMR (75 MHz,
CDCl3) δ (ppm) = 25.8, 26.3, 26.5, 69.2, 75.1, 85.6, 125.2, 126.9, 128.6, 146.7; IR (film): ν (cmꢀ1) =
3462, 2975, 2873, 1770, 1770, 1684, 1602, 1496, 1447, 1371, 1177, 1064, 1027, 760, 700, 640;
GCꢀMS τ
R = 11.11 min, m/z (%): 192 (1, [M]+), 174 (8, [MꢀH2O]+), 121 (100), 105 (20), 91 (11), 77 (27),
71 (32); CI m/z (%): 175 (39, [MꢀOH]+), 121 (100), 105 (42), 91 (40), 77 (28), 51 (18).
(Tetrahydrofuran-2-yl)diphenylmethanol (3b).19 The crude product prepared by GP from 0.75 mmol
benzophenone and tetrahydrofuran, was purified by column chromatography [cꢀHex/EtOAc (10:1)].
1
(68 mg, 36% yield); colorless oil; HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.44ꢀ1.63 (m, 1H), 1.75ꢀ1.96
(m, 3H), 3.02 (s, 1H), 3.82ꢀ4.02 (m, 2H), 4.87 (t, J = 7.2 Hz, 1H), 7.12ꢀ7.35 (m, 6H), 7.36ꢀ7.44 (m, 2H),
7.53ꢀ7.62 (m, 2H); 13CꢀNMR (75 MHz, CDCl3) δ (ppm) = 26.3, 26.9, 69.9, 78.4, 83.0, 125.6, 126.7,
127.0, 127.1, 128.1, 128.2, 144.5, 146.7; IR (film): ν (cmꢀ1) = 3462, 3059, 3026, 2977, 2872, 1710,
1599, 1493, 1448, 1361, 1171, 1066, 748, 697, 636; GCꢀMS τR = 13.95 min, m/z (%): 236 (9, [Mꢀ
H2O]+), 180 (34), 165 (18), 130 (19), 105 (100); CI: m/z (%): 237 (100, [MꢀOH]+), 131 (33), 105 (89), 91
(36).
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The Journal of Organic Chemistry
Phenyl(tetrahydrofuran-2-yl)methanol (3c).16 The crude product prepared by GP from 0.75 mmol
benzaldehyde and tetrahydrofuran, was purified by column chromatography [cꢀHex/EtOAc (8:1)].
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(29 mg, 19% yield); erythroꢀ3c: colorless oil; HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.59ꢀ1.75 (m, 2H),
6
1.81ꢀ1.98 (m, 2H), 2.96 (s, 1H), 3.82ꢀ3.93 (m, 2H), 3.97ꢀ4.05 (m, 1H), 4.45 (d, J = 7.5 Hz, 1H), 7.29ꢀ
7.40 (m, 5H); 13CꢀNMR (75 MHz, CDCl3) δ (ppm) = 26.1, 27.9, 68.4, 76.6, 83.4, 127.0, 128.0, 128.4,
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140.7; IR (film): ν (cmꢀ1) = 3676, 3427, 2972, 2873, 1724, 1453, 1197, 1057, 760, 700; GCꢀMS τR
=
11.00 min, m/z (%): 160 (1, [MꢀH2O]+), 107 (12), 79 (37), 71 (100); threoꢀ3c: colorless oil; 1HꢀNMR (300
MHz, CDCl3) δ (ppm) = 1.62ꢀ1.69 (m, 2H), 1.78ꢀ1.91 (m, 2H), 2.52 (s, 1H), 3.77ꢀ3.87 (m, 2H), 4.12ꢀ4.06
(m, 1H), 4.94 (d, J = 3.7 Hz, 1H), 7.23ꢀ7.29 (m, 1H), 7.31ꢀ7.39 (m, 4H); 13CꢀNMR (75 MHz, CDCl3) δ
(ppm) = 24.9, 26.2, 69.2, 74.2, 83.2, 126.1, 127.6, 128.4, 140.6; IR (film): ν (cmꢀ1) = 3676, 3427, 2972,
2873, 1724, 1453, 1197, 1057, 760, 700; GCꢀMS
79 (43), 71 (100).
τ
R = 11.06 min, m/z (%): 160 (1, [MꢀH2O]+), 107 (11),
1-(Tetrahydrofuran-2-yl)-1-(p-tolyl)ethan-1-ol (3d).13 The crude product prepared by GP from
0.75 mmol 4‘ꢀmethylacetophenone and tetrahydrofuran, was purified by column chromatography [cꢀ
Hex/EtOAc (20:1)]. (103 mg, 67% yield); erythroꢀ3d: colorless oil; 1HꢀNMR (300 MHz, CDCl3) δ (ppm) =
1.36ꢀ1.47 (m, 1H), 1.60 (s, 3H), 1.54ꢀ1.69 (m, 1H), 1.70ꢀ1.87 (m, 2H), 2.33 (s, 3H), 2.51 (s, 1H), 3.78ꢀ
3.99 (m, 2H), 4.04 (dd, J = 8.1, 6.9 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H); 13Cꢀ
NMR (75 MHz, CDCl3) δ (ppm) = 21.1, 26.4, 26.5, 28.8, 69.5, 74.4, 85.9, 124.9, 128.9, 136.2, 142.1; IR
(film): ν (cmꢀ1) = 3469, 2976, 2872, 1775, 1682, 1607, 1515, 1451, 1370, 1180, 1068, 1046, 920, 815,
723; GCꢀMS τR = 11.53 min, m/z (%): 189 (17, [MꢀOH]+), 145 (22), 135 (100), 119 (19), 106 (11), 91
(23); CI: m/z (%): 189 (100, [MꢀOH]+), 119 (78); ); threoꢀ3d: colorless oil; 1HꢀNMR (300 MHz, CDCl3) δ
(ppm) = 1.48 (s, 3H), 1.79ꢀ2.02 (m, 4H), 2.36 (s, 3H), 2.68 (s, 1H), 3.71ꢀ4.01 (m, 2H), 4.20 (t,
13
J = 7.1 Hz), 7.19 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), CꢀNMR (75 MHz, CDCl3) δ (ppm) =
21.1, 25.8, 26.2, 26.4, 69.1, 74.9, 85.6, 125.1, 128.9, 136.3, 143.8; IR (film): ν (cmꢀ1) = 3443, 2977,
2870, 1512, 1447, 1372, 1184, 1071, 1051, 918, 815, 728; GCꢀMS τR = 11.74 min, m/z (%): 189 (25,
[MꢀOH]+), 145 (21), 135 (100), 118 (21), 91 (14); CI: m/z (%): 189 (100, [MꢀOH]+), 119 (78).
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1-(Tetrahydrofuran-2-yl)-1-(m-tolyl)ethan-1-ol (3e). The crude product prepared by GP from 1 mmol
3‘ꢀmethylacetophenone and tetrahydrofuran, was purified by column chromatography [cꢀHex/EtOAc
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(25:1→20:1)]. (136 mg, 66% yield); erythroꢀ3e: colorless oil; HꢀNMR (300 MHz, CDCl3) δ (ppm) =
6
1.37ꢀ1.47 (m, 1H), 1.61 (s, 3H), 1.56ꢀ1.69 (m, 1H), 1.74ꢀ1.84 (m, 2H), 2.36 (s, 3H), 2.47 (s, 1H), 3.77ꢀ
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4.00 (m, 2H), 4.06 (dd, J = 8.2, 6.9 Hz, 1H), 7.04ꢀ7.08 (m, 1H), 7.20ꢀ7.22 (m, 2H), 7.26 (s, 1H); Cꢀ
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NMR (75 MHz, CDCl3) δ (ppm) = 21.8, 26.4, 26.6, 29.0, 69.5, 74.6, 85.9, 122.1, 125.7, 127.5, 128.1,
137.7, 144.9; IR (film): ν (cmꢀ1) = 3676, 3476, 2976, 1607, 1451, 1375, 1233, 1167, 1067, 1056, 787,
707; GCꢀMS
τ
R = 11.49 min, m/z (%): 188 (73, [MꢀH2O]+), 135 (100), 117 (47), 91 (50); CI m/z (%): 189
1
(100, [MꢀOH]+), 119 (16); threo-3e: colorless oil; HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.44 (s, 3H),
1.84ꢀ1.94 (m, 4H), 2.36 (s, 3H), 2.63 (s, 1H), 3.74ꢀ3.87 (m, 2H), 4.18 (t, J = 7.2 Hz, 1H), 7.05 (d,
13
J = 6.9 Hz, 1H), 7.18ꢀ7.40 (m, 3H); CꢀNMR (75 MHz, CDCl3) δ (ppm) = 21.4, 25.4, 25.8, 26.1, 68.7,
74.5, 85.2, 121.8, 125.4, 127.2, 127.7, 137.3, 146.4; IR (film): ν (cmꢀ1) = 3443, 2978, 2868, 1608,
1458, 1372, 1172, 1073, 927, 788, 706; GCꢀMS τ
R = 11.68 min, m/z (%): 188 (99, [MꢀH2O]+), 173 (47),
145 (58), 135 (100), 117 (78), 91 (47); CI m/z (%): 189 (100, [MꢀOH]+), 119 (17).
1-(4-Fluorophenyl)-1-(tetrahydrofuran-2-yl)ethan-1-ol (3h). The crude product prepared by GP from
1 mmol 4‘ꢀfluoroacetophenone and tetrahydrofuran, was purified by column chromatography [cꢀ
Hex/EtOAc (20:1)]. (173 mg, 82% yield); erythroꢀ3h: colorless oil; 1HꢀNMR (500 MHz, CDCl3) δ (ppm) =
1.40ꢀ1.46 (m, 1H, Hꢀ7), 1.63 (s, 3H), 1.59ꢀ1.64 (m, 1H), 1.77ꢀ1.87 (m, 2H), 2.52 (s, 1H), 3.84ꢀ3.97 (m,
2H), 4.05 (dd, J = 8.4, 6.8 Hz), 7.00ꢀ7.07 (m, 2H), 7.39ꢀ7.46 (m, 2H); 13CꢀNMR (125 MHz, CDCl3)
δ (ppm) = 26.2, 26.4, 28.7, 69.4, 74.3, 85.7 (6JF,C = 0.9 Hz), 114.8 (2JF,C = 21.1 Hz),126.6
(3JF,C = 7.8 Hz),140.6 (4JF,C = 3.2 Hz), 161.7 (1JF,C = 244.7 Hz); IR (film): ν (cmꢀ1) = 3679, 3471, 2977,
2901, 1603, 1511, 1408, 1392, 1375, 1224, 1160, 1067, 1048, 837; GCꢀMS τR = 10.92 min, m/z (%):
192 (49, [MꢀH2O]+), 139 (100), 123 (40), 71 (24); CI m/z (%): 193 (100, [MꢀOH]+), 123 (26); threoꢀ3h:
colorless oil; 1HꢀNMR (400 MHz, CDCl3) δ (ppm) = 1.44 (s, 3H), 1.83ꢀ1.92 (m, 4H), 2.62 (s, 1H), 3.74ꢀ
13
3.87 (m, 2H), 4.11ꢀ4.16 (m, 1H), 6.93ꢀ7.15 (m, 2H), 7.36ꢀ7.54 (m, 2H); CꢀNMR (100 MHz, CDCl3) δ
(ppm) = 25.7, 25.8, 26.0, 69.2, 74.8, 85.5, 114.9 (2JF,C = 21.1 Hz),127.0 (3JF,C = 7.9 Hz),142.5
(4JF,C = 3.1 Hz), 161.9 (1JF,C = 244.8 Hz); IR (film): ν (cmꢀ1) = 3448, 2980, 2873, 1607, 1509, 1375,
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The Journal of Organic Chemistry
1225, 1162, 1074, 837; GCꢀMS τR = 11.16 min, m/z (%): 192 (38, [MꢀH2O]+), 139 (100), 123 (29), 71
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(31); CI m/z (%): 193 (100, [MꢀOH]+), 139 (30), 123 (35).
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1-(2-Fluorophenyl)-1-(tetrahydrofuran-2-yl)ethan-1-ol (3i). The crude product prepared by GP from
0.75 mmol 2‘ꢀfluoroacetophenone and tetrahydrofuran, was purified by column chromatography [cꢀ
1
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Hex/EtOAc (20:1)]. (66 mg, 42% yield); erythroꢀ3i: colorless oil; HꢀNMR (300 MHz, CDCl3) δ (ppm) =
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1.39ꢀ1.62 (m, 2H), 1.67 (d, J = 1.2 Hz, 3H), 1.75ꢀ1.94 (m, 2H), 2.77 (s, 1H), 3.91 (h, J = 8.1 Hz, 2H),
4.41 (ddd, J = 8.3, 7.1, 3.4 Hz, 1H), 6.98 (ddd, J = 12.0, 8.0, 1.2 Hz, 1H), 7.14 (td, J = 7.6, 1.3 Hz,
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1H), 7.22 (ddd, J = 9.8, 4.7, 2.1 Hz, 1H), 7.71 (td, J = 7.8, 1.9 Hz, 1H); CꢀNMR (75 MHz, CDCl3) δ
(ppm) = 26.5, 26.8, 27.8 (5JF,C = 3.3 Hz), 69.5, 73.8 (4JF,C = 4.9 Hz), 83.3 (5JF,C = 5.4 Hz), 115.7
(3JF,C = 23.6 Hz), 124.2 (4JF,C = 2.7 Hz), 127.7 (3JF,C = 5.1 Hz), 128.7 (3JF,C = 8.3 Hz), 132.1 (2JF,C = 39.8
Hz, Cꢀ2), 159.3 (1JF,C = 245.0 Hz); IR (film): ν (cmꢀ1) = 3461, 2978, 2873, 1685, 1615, 1581, 1486,
1450, 1371, 1212, 1068, 1032, 757; GCꢀMS τ
R = 10.58 min, m/z (%): 193 (21, [MꢀOH]+), 162 (13), 145
(32), 139 (100), 123 (44), 109 (18), 71 (18); CI m/z (%): 193 (100, [MꢀOH]+), 123 (56); threoꢀ3i:
colorless oil; 1HꢀNMR (400 MHz, CDCl3) δ (ppm) = 1.52 (d, J = 1.6 Hz, 3H), 1.86ꢀ2.04 (m, 4H), 2.94 (s),
3.70ꢀ3.80 (m, 1H), 3.83ꢀ3.88 (m, 1H), 4.38 (t, J = 7.8 Hz, 1H), 7.00 (ddd, J = 12.3, 8.1, 1.3 Hz, 1H),
7.13 (td, J = 7.6, 1.3 Hz, 1H), 7.20ꢀ7.25 (m, 1H), 7.60, (td, J = 8.1, 1.9 Hz, 1H); 13CꢀNMR (100 MHz,
CDCl3) δ (ppm) = 23.9 (5JF,C = 4.4 Hz), 26.0, 26.2, 69.1, 73.9 (4JF,C = 3.7 Hz), 84.0 (5JF,C = 5.0 Hz),
116.1 (3JF,C = 25.4 Hz), 124.2 (4JF,C = 3.3 Hz), 127.4 (3JF,C = 4.6 Hz), 128.9 (3JF,C = 8.6 Hz), 134.0
(2JF,C = 10.8 Hz), 159.5 (1JF,C = 239.2 Hz); IR (film): ν (cmꢀ1) = 3457, 2981, 2946, 2876, 1614, 1580,
1484, 1449, 1377, 1273, 1207, 1070, 920, 818, 758; GCꢀMS
OH]+), 123 (56).
τR = 11.50 min, CI m/z (%): 193 (100, [Mꢀ
1-(4-Chlorophenyl)-1-(tetrahydrofuran-2-yl)ethan-1-ol (3k). The crude product prepared by GP from
1 mmol 4‘ꢀchloroacetophenone and tetrahydrofuran, was purified by column chromatography [cꢀ
Hex/EtOAc (10:1)]. (144 mg, 64% yield); erythroꢀ3k: colorless oil; 1HꢀNMR (300 MHz, CDCl3) δ (ppm) =
1.35ꢀ1.46 (m, 1H), 1.59 (s, 3H), 1.54ꢀ1.64 (m, 1H), 1.72ꢀ1.88 (m, 2H), 2.53 (s, 1H), 3.78ꢀ3.97 (m, 2H),
13
4.02 (dd, J = 8.3, 6.8 Hz), 7.24ꢀ7.33 (m, 2H), 7.33ꢀ7.44 (m, 2H); CꢀNMR (75 MHz, CDCl3) δ (ppm) =
26.4, 26.5, 28.8, 69.5, 74.4, 85.7, 126.6, 128.3, 132.6, 143.5; IR (film): ν (cmꢀ1) = 3676, 3463, 2975,
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2904, 1494, 1403, 1067, 1048, 835 cmꢀ1; GCꢀMS τR = 12.22 min, m/z (%): 229 (8,[M+H]+]) , 227(9,
[M+H]+]), 182 (16), 180 (18), 118 (41), 102 (100), 90 (35), 75 (59), 50 (32); CI m/z (%): 211 (30, [Mꢀ
OH]+), 209 (100, [MꢀOH]+), 139 (14); threoꢀ3k: colorless oil; 1HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.44
(s, 3H), 1.81ꢀ1.97 (m, 4H), 2.57 (s, 1H), 3.69ꢀ3.93 (m, 2H), 4.11ꢀ4.16 (m, 1H), 7.27ꢀ7.35 (m, 2H), 7.38ꢀ
7.47 (m, 2H); 13CꢀNMR (75 MHz, CDCl3) δ (ppm) = 26.4, 26.7, 26.9, 69.7, 75.2, 85.9, 127.2, 128.8,
133.2, 145.8; IR (film): ν (cmꢀ1) = 3676, 3448, 2979, 2899, 1491, 1394, 1228, 1075, 1053, 833; GCꢀMS
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τR = 12.61 min, m/z (%): 200 (60), 198 (60), 183 (43), 185 (48), 157 (17), 120 (20), 102 (22), 91 (100),
77 (50), 65 (21), 50 (31); CI m/z (%): 211 (12, [MꢀOH]+), 209 (100, [MꢀOH]+), 139 (16)
1-(4-Bromophenyl)-1-(tetrahydrofuran-2-yl)ethan-1-ol (3l). The crude product prepared by GP from
1 mmol 4‘ꢀbromoacetophenone and tetrahydrofuran, was purified by column chromatography [cꢀ
Hex/EtOAc (20:1→8:1)]. (15 mg, 6% yield); erythroꢀ3l: colorless oil; 1HꢀNMR (500 MHz, CDCl3) δ (ppm)
= 1.40ꢀ1.47 (m, 1H), 1.61 (s, 3H), 1.58ꢀ1.64 (m, 1H), 1.78ꢀ1.87 (m, 2H), 2.52 (s, 1H), 3.85ꢀ3.96 (m,
13
2H), 4.04 (dd, J = 8.4, 6.8 Hz, 1H), 7.32ꢀ7.36 (m, 2H), 7.46ꢀ7.50 (m, 2H); CꢀNMR (125 MHz, CDCl3)
δ (ppm) = 26.4, 26.5, 28.8, 69.6, 74.5, 85.6, 120.8, 127.0, 131.3, 144.1; IR (film): ν (cmꢀ1) = 3676,
3473, 2975, 2091, 1679, 1592, 1489, 1395, 1251, 1198, 1067, 1009, 919, 894, 835; GCꢀMS τR = 12.71
min, m/z (%): 254 (32, [MꢀH2O]+), 252 (36, [MꢀH2O]+), 201 (89), 199 (87), 192 (100), 146 (35), 71 (47).
1-(2-Methoxyphenyl)-1-(tetrahydrofuran-2-yl)ethan-1-ol (3n). The crude product prepared by GP
from 0.75 mmol 2‘ꢀmethoxyacetophenone, was purified by column chromatography [cꢀHex/EtOAc
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(20:1)]. (37 mg, 22% yield); erythroꢀ3n: colorless oil; HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.45ꢀ1.59
(m, 2H), 1.63 (s, 3H), 1.71ꢀ1.88 (m, 2H), 3.24 (brs, 1H), 3.82 (s, 3H), 3.84ꢀ3.95 (m, 2H), 4.56 (t, J =
6.1 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 6.91ꢀ7.02 (m, 1H), 7.16ꢀ7.30 (m, 1H), 7.63 (d, J = 9.4 Hz, 1H);
13CꢀNMR (75 MHz, CDCl3) δ (ppm) = 26.2, 26.6, 26.7, 55.3, 69.4, 75.0, 83.3, 111.0, 120.9, 127.2,
128.2, 133.3, 156.1; IR (film): ν (cmꢀ1) = 3676, 3513, 2973, 2872, 1713, 1600, 1583, 1488, 1463, 1436,
1236, 1182, 1057, 1026, 754 cmꢀ1; GCꢀMS τR = 11.98 min, m/z (%): 205 (3, [MꢀOH]+), 189 (3), 151
(68), 133 (29), 105 (100), 79 (17), 55 (11); CI: m/z (%): 205 (100, [MꢀOH]+), 161 (26), 135 (22), 97 (21);
threoꢀ3n: colorless oil; 1HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.52 (s, 3H), 1.82ꢀ1.95 (m, 4H), 3.72ꢀ3.83
(m, 2H), 3.85 (s, 3H), 4.48ꢀ4.53 (m, 1H), 6.88ꢀ7.01 (m, 2H), 7.20ꢀ7.26 (m, 1H), 7.47ꢀ7.51 (m, 1H); 13Cꢀ
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NMR (75 MHz, CDCl3) δ (ppm) = 23.3, 26.4, 26.5, 55.5, 69.0, 75.6, 83.7, 111.6, 121.0, 126.9, 128.4,
134.5, 156.5; IR (film): ν (cmꢀ1) = 3673, 3512, 2971, 2870, 1713, 1600, 1581, 1485, 1460, 1437, 1229,
1180, 1057, 1026; GCꢀMS τR = 12.25 min, m/z (%): 204 (2, [MꢀH2O]+), 189 (11), 151 (37), 133 (23),
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121 (22), 105 (100), 91 (15), 79 (13); CI: m/z (%): 205 (100, [MꢀOH]+), 161 (26), 135 (22), 97 (21).
1-(4-Dioxan-2-yl)-1-phenylethan-1-ol (5a). The crude product prepared by GP from 0.75 mmol
acetophenone and 1,4ꢀdioxane, was purified by column chromatography [cꢀHex/EtOAc (20:1)]. (20 mg,
13% yield); the pinacol from acetophenone was formed as side product (24 mg, 26% yield) erythroꢀ5a:
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colorless crystals; m.p. 71ꢀ72°C; HꢀNMR (300 MHz, CDCl3) δ (ppm) = 1.60 (s, 3H), 2.70 (s, 1H), 3.24
(dd, J = 11.7, 2.6 Hz, 1H), 3.41 (dd, J = 11.6, 10.3 Hz, 1H), 3.47ꢀ3.58 (m, 1H), 3.60ꢀ3.72 (m, 2H),
3.77ꢀ3.92 (m, 2H), 7.22ꢀ7.30 (m, 1H), 7.30ꢀ7.38 (m, 2H), 7.40ꢀ7.43 (m, 2H); 13CꢀNMR (75 MHz, CDCl3)
δ (ppm) = 28.0, 66.2, 67.0, 67.4, 74.3, 80.6, 124.9, 127.2, 128.4, 143.4; GCꢀMS τR = 11.56 min, m/z
(%): 146 (100), 121 (81), 105 (41), 91 (19), 79 (21), 77 (44); CI: m/z (%): 191 (2, [MꢀOH]+), 147 (11),
129 (61), 105 (100), 91 (19), 79 (14).
1-Phenyl-1-(tetrahydro-2H-pyran-2-yl)ethan-1-ol (6a). The crude product prepared by GP from
1 mmol acetophenone and tetrahydropyran, was purified by column chromatography [cꢀHex/EtOAc
(15:1)]. (52 mg, 25% yield); erythroꢀ6a: colorless crystals; m.p. 55ꢀ57 °C; 1HꢀNMR (500 MHz, CDCl3) δ
(ppm) = 1.03ꢀ1.13 (m, 1H), 1.20ꢀ1.53 (m, 5H), 1.58 (s, 3H), 1.71ꢀ1.79 (m, 1H), 2.81 (s, 1H), 3.37ꢀ3.40
(m, 1H), 3.46ꢀ3.60 (m, 1H), 4.02ꢀ4.15 (m, 1H), 7.20ꢀ7.25 (m, 1H), 7.32 (t, J = 7.5 Hz, 2H), 7.37ꢀ7.45 (m,
2H); 13CꢀNMR (125 MHz, CDCl3) δ (ppm) = 23.4, 25.4, 26.1, 27.8, 69.2, 75.6, 83.8, 125.4, 126.6, 128.1,
144.8; IR (film): ν (cmꢀ1) = 3559, 3484, 3092, 3059, 3030, 2936, 2855, 1494, 1448, 1371, 1209, 1178,
1088, 1063, 1029, 897, 701; GCꢀMS τR = 11.43 min, m/z (%): 188 (58, [MꢀH2O]+), 173 (24), 144 (51),
129 (47), 105 (55), 85 (100), 77 (56), 67 (52); CI m/z (%): 189 (28, [MꢀOH]+), 121 (43), 105 (74), 77
(92), 67 (100), 51 (33); threoꢀ6a: colorless crystals; m.p. 90ꢀ91 °C; 1HꢀNMR (500 MHz, CDCl3) δ (ppm)
= 1.47 (s, 3H), 1.32ꢀ1.62 (m, 5H), 1.73ꢀ1.92 (m, 1H), 3.12 (s, 1H), 3.32ꢀ3.54 (m, 2H), 3.92ꢀ4.09 (m,
1H), 7.18ꢀ7.28 (m, 1H), 7.33ꢀ7.36 (m, 2H), 7.44ꢀ7.53 (m, 2H); 13CꢀNMR (125 MHz, CDCl3) δ (ppm) =
23.5, 23.5, 25.8, 26.1, 69.1, 75.9, 84.3, 125.9, 126.9, 128.1, 145.9; IR (film): ν (cmꢀ1) = 3671, 3476,
3087, 3056, 2938, 2855, 1726, 1496, 1447, 1376, 1207, 1089, 1045, 893, 765; GCꢀMS τR = 11.63 min,
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m/z (%): 188 (76, [MꢀH2O]+), 173 (30), 144 (100), 129 (86), 105 (67), 85 (75), 77 (61), 67 (57); CI m/z
(%): 121 (37), 105 (66), 77 (100), 67 (95), 51 (32); Anal. calcd. for C12H16O2: C, 75.69; H, 8.80. found:
C, 75.16; H, 8.43.
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Acknowledgments We thank the Deutsche Forschungsgemeinschaft (DFG) for constant financial
support.
Supporting Information: NMR spectra (1H and 13C) of all (separated) erythro / threo diastereoꢀ
isomeric products. Thermal ellipsoid plots for the Xꢀray diffraction structures, information on the crystal
structure determination, crystal parameters and refinement metrics. The crystal data for the three
structures threoꢀ6a, erythroꢀ6a, and erythroꢀ5a were deposited at the CCDC with the following
numbers: threoꢀ6a: CCDC 1477826, erythroꢀ6a: CCDC 1477824, erythroꢀ5a: CCDC 1477825.
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