Chiral chromium(III) porphyrins as highly enantioselective catalysts for Hetero-Diels-Alder reactions between aldehydes and dienes

Article abstract of DOI:10.1002/adsc.200505249

Starting from enantiomerically pure 5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2, 3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracene-9-yl]porphyrin, treatment with CrCl₂ and subsequent air oxidation afforded the corresponding Cr(III) complex, with chlo

Full text of DOI:10.1002/adsc.200505249

FULL PAPERS
DOI: 10.1002/adsc.200505249
Chiral Chromium(III) Porphyrins as Highly Enantioselective
Catalysts for Hetero-Diels--Alder Reactions Between Aldehydes
and Dienes
´
Albrecht Berkessel,* Erkan Ertürk, Cecile Laporte
Institut für Organische Chemie der Universität zu Kçln, Greinstrasse 4, 50939 Kçln, Germany
Fax: (þ49)-221-470-5102, e-mail: berkessel@uni-koeln.de
Received; June 17, 2005; Accepted: October 10, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Starting from enantiomerically pure methylsilyloxy)butadiene (“Danishefskyꢀs diene”),
5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octa-
enantiomeric excesses >90% were achieved in a
hydro-1,4:5,8-dimethanoanthracene-9-yl]porphyrin,
number of cases, with furfural affording the highest
treatment with CrCl2 and subsequent air oxidation af- ee (97%). Metal-coordinating aldehydes such as pyri-
forded the corresponding Cr(III) complex, with chlor- dine-2-carbaldehyde do not inactivate the Cr(III) por-
ide as counterion, in 96% yield. Anion exchange with phyrin catalyst. The cycloaddition of less electron-rich
AgBF4 gave the corresponding tetrafluoroborate. dienes (such as 1-methoxybutadiene) is effected as
These hitherto unknown chiral chromium porphyrins well, affording diastereoselectivities up to >99:1,
are efficient and highly enantioselective catalysts for and enantiomeric excesses >80%.
the hetero-Diels–Alder reaction of aliphatic, aromat-
ic, and heteroaromatic aldehydes with dienes of vary- Keywords: asymmetric catalysis; chromium; hetero-
ing electron density. In the case of 1-methoxy-3-(tri- Diels–Alder reactions; Lewis acids; porphyrins
Introduction
The hetero-Diels–Alder reaction (HDA) between an
electron-rich diene and an aldehyde provides pyran de-
rivatives in one single step.[1] In 1982, Danishefsky et al.
reported the seminal observation that the hetero-
Scheme 1. The HDA between Danishefskyꢀs diene 1 and al-
Diels–Alder reaction between an aldehyde 2 and 1-me-
dehydes 2.
thoxy-3-(trimethylsilyloxy)butadiene (1; “Danishef-
skyꢀs diene”) is catalyzed by Lewis acids.[2] When chiral
Lewis acids are employed, the dihydropyranones 3 can
Organocatalysis is gaining more and more importance
be obtained in enantiomerically enriched form in asymmetric synthesis.[5a] Very recently, organocatalyt-
(Scheme 1). Chiral pyran derivatives are synthetically ic and highly enantioselective HDA reactions of alde-
most useful intermediates, and the HDA approach hydes with Rawalꢀs diene (1-dimethylamino-3-tert-bu-
for their synthesis has been extended to numerous di- tyldimethylsilyloxy-1,3-butadiene) through hydrogen
ene components other than 1.[3] Various chiral Lewis bonding by TADDOL[5b] and by BAMOL[5c] (1,1’-biar-
acids have been developed for the highly enantioselec- yl-2,2’-dimethanol) for the synthesis of dihydropyra-
tive HDA of aldehydes with electron-rich dienes.[4] Re- none derivatives were reported. Another extension of
cent developments in this field comprise the use of tita- this approach for the synthesis of d-lactones from alde-
nium in combination with BINOL derivatives by Ding hydes and Brassardꢀs diene [1,3-dimethoxy-1-(trime-
et al.[4l,m] and of chromium-Schiff base complexes by Ja- thylsilyloxy)butadiene] was also reported using TAD-
cobsen et al.[4f,g,k,s] By the latter two approaches, enan- DOL.[5d] Certain metal complexes of porphyrins are
tioselectivies up to 99% were reported for the cycload- well known to act as Lewis acid catalysts.[6] However,
dition of benzaldehyde (2, R¼Ph) to Danishefskyꢀs di- there appears to be no report on the use of chiral por-
ene 1 (Scheme 1).
phyrin complexes as catalysts for the asymmetric
Adv. Synth. Catal. 2006, 348, 223 – 228
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223

Albrecht Berkessel et al.
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HDA reaction. In this paper, we report that (i) Cr(III) benzaldehyde (2, R¼Ph) and Danishefskyꢀs diene (1),
porphyrins such as 4a,b (Figure 1) are highly reactive because the catalytic activities of 4a and 5a as Lewis
catalysts that effect the HDA shown in Scheme 1 at acids are similar to each other. Of the various solvents
low loading, that (ii) the chiral Cr(III) porphyrins 5a,b tried, methyl tert.-butyl ether (MTBE) afforded the
effect the HDA between Danishefskyꢀs diene 2 and a highest catalytic activity. Effects of substrate concentra-
series of aldehydes with up to 97% ee, and that (iii) tion, catalyst loading and temperature are summarized
even less electron-rich dienes can be reacted with alde- in Table 1.
hydes in the presence of the chiral porphyrin catalyst 5b.
Optimal conditions were found at 2 M aldehyde con-
centration, where an almost quantitative yield of the
product rac-3 resulted when 3 mol % of the catalyst 4a
was applied at ꢀ188C for 18 h (Table 1, entry 3). Signif-
icantly longer reaction times were needed at lower sub-
Results and Discussion
The Cr(III) porphyrin 4a was prepared according to a strate concentrations (entries 1, 2). Lower catalyst load-
procedure by Groves et al.[7] The chiral porphyrin pres- ing (2 mol %, entry 4) or further lowering of the temper-
ent in the complexes 5a,b was first introduced by Halter- ature (entry 5) retard the cycloaddition, but still result in
man et al. and is routinely produced in our laboratory on acceptable yields at reasonable reaction times.
a multi-gram scale.[8] We achieved the insertion of chro-
The optimized reaction conditions of Table 1, entry 3
mium into the latter porphyrin by first reacting it with were applied to the asymmetric HDA using the catalyst
excess chromium(II) chloride (CrCl2) in refluxing di- 5a. As shown in Table 2, entry 1, the HDA product 3a
glyme under argon, removal of excess chromium salt, was obtained in high yield (85%) and excellent enantio-
and subsequent air oxidation to form the Cr(III) com- meric purity (95% ee). This initial success prompted us
plex. By this route, the air-stable paramagnetic Cr(III) toexamine a number ofother aldehydes in the asymmet-
porphyrin 5a was isolated in 96% yield (see Experimen- ric HDA with Danishefskyꢀs diene 1, catalyzed by the
tal Section). The complexation of Cr(III) results in a chiral Cr(III) porphyrins 5a,b. The results are summar-
shift of the Soret band of the free ligand (lmax
¼
ized in Table 2: Both aromatic (entries 1, 2, 5) and ali-
421 nm) to lmax ¼453 nm. The tetrafluoroborates 4b phatic (entries 3, 4) aldehydes could be reacted with
and 5b were obtained from the corresponding chlorides the diene 1 to afford the expected dihydropyranones
4a and 5a upon treatment with AgBF4 in THF.
3a–d in good yields and enantiomeric purities. In partic-
We first employed the achiral Cr(III) porphyrin 4a to ular, n-heptanal (2c) and furfural (2d) gave 92% and
optimize the reaction conditions for the HDA between 97% ee, respectively (entries 4, 5).
trans-Cinnamic aldehyde (2e), an example for a,b-un-
saturated aldehydes, underwent cycloaddition relatively
sluggishly, and the reaction temperature had to be raised
to 08C (entry 6). Most interestingly, pyridine-2-carbal-
dehyde (2f) could be reacted without any problem (en-
try 7). The latter result underpins the synthetic utility
of our chiral porphyrin catalysts 5a,b because transition
metal catalysts tend to be inactivated by coordinating
substrates (such as the pyridine derivative 2f). In fact,
this appears to be the first example of a successful Cr-
catalyzed asymmetric HDA of a pyridinecarbalde-
hyde.[9] We attribute the pleasing catalytic activity of
the Cr(III) porphyrin 5a in the HDA of pyridine-2-car-
baldehyde (2f) with Danishefskyꢀs diene (1) to the fact
that, in the porphyrin 5a, access to the Lewis acidic
Figure 1. Chromium(III) porphyrins 4a,b and 5a,b.
Table 1. Optimization of the HDA of diene 1 with benzaldehyde (2, R¼Ph) using the Cr(III) porphyrin 4a as catalyst.[a]
Entry
Catalyst loading [mol %]
T [8C]
Substrate concentration [M]
Time [h]
Yield of 3 [%]
1
2
3
4
5
4
3
3
2
3
ꢀ18
ꢀ18
ꢀ18
ꢀ18
ꢀ25
1.0
1.0
2.0
2.0
2.0
42
32
18
18
19
91
94
97
84
82
[a]
All reactions were performed in MTBE in the presence of dry 4 Š molecular sieves. Yields were determined by capillary
GC.
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Hetero-Diels–Alder Reactions Between Aldehydes and Dienes
Table 2. Asymmetric HDA of the aldehydes 2a – f with the diene 1 using the Cr(III) porphyrins 5a, b as catalysts.[a]
FULL PAPERS
Entry
Aldehyde
Catalyst
T [8C]
Yield of 3a–f [%][b]
ee of 3a–f [%][c]
1
2
3
4
5
6
7
2a
2a
2b
2c
2d
2e
2f
5a
5b
5a
5a
5a
5a
5a
ꢀ18
ꢀ18
ꢀ18
ꢀ18
ꢀ18
0
85
92
76
75
70
55
70
95
88
88
92
97
74
78
ꢀ18
[a]
The reactions were performed at 2.0 M substrate concentration in MTBE in the presence of 3 mol % of the catalysts 5a,b
and dry 4 Š molecular sieves for 24–40 h.
Yield determined after isolation by column chromatography.
[b]
[c]
Enantiomeric excess determined by capillary GC.
Cr(III) centre is sterically quite limited. Inspection of
models suggests that the carbaldehyde function in the
2-position of the pyridine derivate 2f prohibits binding
via N. Instead, coordination via the aldehyde oxygen
atom occurs, as with the other aldehydes examined.
Comparison of entries 1 and 2 of Table 2 reveals that
the change from a (coordinating) chloride anion in cat-
alyst 5a to a (presumably non-coordinating) tetrafluoro-
borate anion in 5b led to higher reactivity but somewhat
decreased enantioselectivity. Unfortunately, tertiary al-
dehydes such as pivaldehyde showed very low reactivity
towards the diene 1 even in the presence of the tetra-
fluoroborate catalyst 5b.
Next, the suitability of the catalysts 5a,b for the HDA
between benzaldehyde (2a) and dienes of lower electron
density [compared to Danishefskyꢀs diene (1)] was ad-
dressed (Scheme 2). In fact, a slow reaction between
(Z,E)-3-trimethylsilyloxy-2,4-hexadiene (6) and ben-
zaldehyde (2a) was effected by the more active catalyst
Scheme 2. Asymmetric HDA of benzaldehyde (2a) with the
less electron-rich dienes 6 and 8, catalyzed by the Cr(III)-por-
phyrin 5b.
5b, whereas no substrate conversion occurred in the Scheme 2 refer to 40 h reaction time at room tempera-
presence of 5a. The all-cis diastereomer 7 shown in ture. At prolonged reaction times, or at increased cata-
Scheme 2 (top) was formed exclusively, with an enantio- lyst loading, the cycloadditions shown proceed to com-
meric excess of 60%. Somewhat lower diastereoselectiv- pletion (as do the ones with Danishefskyꢀs diene 1).
ity (>95% de) was reported by Jacobsen et al. for this
transformation, at an enantiomeric excess of the all-cis
product of up to 90%.[4g]
Even the less activated diene 1-methoxybutadiene (8)
Conclusion
could be reacted with benzaldehyde (2a) (Scheme 2, In summary, we could show that the readily available
bottom). In the presence of the catalyst 5b, the HDA chiral Cr(III) porphyrins 5a,b perform excellently in a
product was obtained as a trans/cis (9a/9b) mixture, number of HDA reactions, affording enantiomeric ex-
the predominant trans-product 9a showing an enantio- cesses >90% in a number of cases. It is particularly
meric excess of 82%. The latter example appears to be noteworthy that coordinating aldehydes such as pyri-
the only reported asymmetric addition of an aromatic al- dine-2-carbaldehyde (2f) can be reacted without any
dehyde to 1-methoxybutadiene (8). The yields stated in sign of catalyst inactivation. To the best of our knowl-
Adv. Synth. Catal. 2006, 348, 223 – 228
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225

Albrecht Berkessel et al.
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solution was then allowed to cool to room temperature, brine
(150 mL) was added, and the mixture was stirred under air dur-
ing 12 h. The mixture was then extracted with dichloromethane
(2ꢁ150 mL). The organic phase was washed with H2O (2ꢁ
150 mL), dried over Na2SO4, filtered and evaporated under re-
duced pressure. The residue was purified by column chroma-
tography on neutral alumina (Fluka, Brockmann activity I) us-
ing gradient elution, from dichloromethane to 3% methanol-
dichloromethane. The fractions containing the product were
combined and stirred with saturated aqueous NH4Cl
(150 mL) overnight. The organic phase was separated, washed
successively with aqueous NaHCO3 (150 mL), brine (3ꢁ
150 mL) and dried over Na2SO4. After filtration and evapora-
tion under reduced pressure, a deep-green solid was obtained
which was dried overnight under vacuum (5ꢁ10ꢀ2 mbar);
edge, this is the first report of a chiral metal porphyrin
being used as catalyst in the HDA reaction. Our labora-
tory has shown previously that electronic tuning of por-
phyrin ligands can significantly enhance the perform-
ance of, e.g., their Ru complexes in epoxidation and cy-
clopropanation.[10] We expect similar advantageous ef-
fects for porphyrin-based Lewis acid catalysts.
Experimental Section
General Remarks
Catalysis experiments were performed under an argon atmos-
phere using standard Schlenk techniques. CrCl2 (99.99%) was
purchased from Aldrich. The solvents and aldehydes were first
dried and freshly distilled prior to use, using standard tech-
yield: 207 mg (96%); mp
>2508C; HR-ESI-MS
(CH2Cl2 MeOH): calcd. for C87H7652CrN4 ¼1192.5475
(Mþ ꢀCl); found¼1192.547 (Mþ ꢀCl); ESI-MS (CH2Cl2
ꢀMeOH): m/z [%]¼1192.53 [Por*52Cr, 20.3], 1224.54
[Por*52Cr(MeOH), 16.4], 1256.61 [Por*52Cr(MeOH)2, 100],
ꢀ
niques.[11]
1-Methoxy-3-[(trimethylsilyl)oxy]-1,3-butadiene
(Danishefskyꢀs diene, 1) and 1-methoxybutadiene (8) were
purchased from Fluka or Aldrich. According to the NMR spec-
trum, the 1-methoxybutadiene purchased consisted exclusive-
ly of the trans-isomer. (Z,E)-3-Trimethylsilyloxy-2,4-hexa-
diene (6) was synthesized according to a literature proce-
dure.[12] NMR spectra were taken on a Bruker AC 300 instru-
ment. Chemical shifts d (ppm) were referenced against the sol-
vent signal; multiplicities are indicated as follows: br (broad
signal), s (singlet), d (doublet), t (triplet), m (multiplet). The
IR measurements were performed on a Perkin Elmer Paragon
1000 spectrometer. The band intensities are indicated as s
(strong), m (medium) and w (weak). ESI mass spectra were re-
corded on a Finnigan MAT 900. EI mass spectra were meas-
ured on a Hewlett-Packard HP 6890 gas chromatograph equip-
ped with an HP 5973 mass selective detector using a GC-MS
standard method (Column HP-5; helium 1.0 mL minꢀ1 (con-
stant flow modus); inj.: 2508C (split modus); det.: FID 2508C;
oven: 1008C (5 min), 208C minꢀ1, 2008C (15 min). The signs
of the optical rotation for 3a–e were determined on a Perkin
Elmer polarimeter 343plus, and the CD spectra of 3a and 3f
were measured on a Jasco J-810 spectropolarimeter. The abso-
lute configuration of the pyranone products 3a–e and 7 was de-
termined by comparison of their sense of optical rotation with
literature data.[4f,g] The absolute configuration of 3f was as-
signed by comparison of its CD spectrum with that of 3a. The
cis/trans-assignment of the diastereomers 9a/9b was done by
NMR spectroscopy (NOE). Capillary GC data were obtained
using a Hewlett-Packard HP 6890 GC system with flame ioni-
zation detector and HP-ChemStation software revised version
A.05.01. AWCOT-FS, CP Chirasil-Dex CB column (25 m) was
used for analytical chiral GLC separation with N2 as carrier gas.
1257.6 [Por*53Cr(MeOH)2, 98.6], 1258.6 [Por*54Cr(MeOH)2,
54
˜
54.3], 1259.6 [Por* Cr(MeOH)2, 19.9]; IR (film): n¼2956
ꢀ
ꢀ
ꢀ
[s, n(C H) alkyl], 2917 [m, n(C H) alkyl], 2865 [m, n(C H)
alkyl], 1575, 1525, and 1497 [w, n(C C) aryl], 1470 and 1445
[w, d(C H) alkyl],1325 [w], 1290 [m], 1261 [w], 1203 and 1194
[w], 1105 [s], 1071 and 1063 [m], 1008 [s], 960 and 947 [m],
¼
ꢀ
ꢀ
ꢀ
861 [m, d(C H) aryl], 797 [s, d(C H) aryl], 753, 733, and 710
[m] cmꢀ1; UV-VIS: lmax ¼453 nm (CH2Cl2).
{5,10,15,20-Tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-
octahydro-1,4:5,8-dimethanoanthracene-9-
yl]porphyrinato}chromium(III) Tetrafluoroborate (5b)
To a solution of the chloride 5a (100 mg, 0.081 mmol) in THF
(3 mL) was added AgBF4 (17.4 mg, 0.089 mmol) at room tem-
perature. The reaction mixture was refluxed for 2 h under ar-
gon. It was then allowed to cool to room temperature and fil-
tered through a plug of celite. Evaporation of the solvent under
reduced pressure afforded a deep green solid; yield: 96 mg
(92%); 19F NMR (CDCl3, 470.51 MHz): d¼ ꢀ146.4 (brs) [ref-
erence: d (CF3CO2H)¼ ꢀ77.5].
The same protocol was applied for anion exchange of the
chloride 4a, affording 94% of tetrafluoroborate 4b.
General Procedure for the Hetero-Diels–Alder
Reaction of Aldehydes with Danisheskyꢀs Diene (1)
The chromium porphyrin 4a or 5a and the aldehyde (2a–f,
0.50 mmol) were dissolved in MTBE (0.25 mL), and 4 Š mo-
lecular sieves (200 mg) were added under argon. The reaction
was started by the addition of Danishefskyꢀs diene (1,
0.53 mmol, 1.06 equivs.) at the temperature stated in the Ta-
ble 2. After stirring for 24–40 h under argon, the reaction mix-
ture was diluted with 3 mL of dichloromethane, and two drops
of TFA were added. The solution was then evaporated under
reduced pressure to afford a deep green oil. The crude residue
was purified by column chromatography as described individ-
ually below.
Chloro-{5,10,15,20-tetrakis[(1S,4R,5R,8S)-
1,2,3,4,5,6,7,8-octahydro-1,4:5,8-
dimethanoanthracene-9-
yl]porphyrinato}chromium(III) (5a)
The porphyrin ligand[8] (200 mg, 0.175 mmol) was suspended in
diglyme (200 mL) and heated to reflux under argon. CrCl2
(215 mg, 1.75 mmol) was added in two portions over a 10 min
period. After ca. 15 min, the mixture turned into a homogene-
ous deep-green solution and was refluxed for another 6 h. The
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Hetero-Diels–Alder Reactions Between Aldehydes and Dienes
FULL PAPERS
modus); det.: FID 1808C; oven: 1608C (25 min), 158C minꢀ1
,
(R)-2-Phenyl-2,3-dihydropyran-4-one [(R)-3a]
1808C (2 min)], tR(minor)¼18.91 min (S), tR(major)¼
After purification by flash chromatography on silica gel (cyclo-
hexane/ethyl acetate, 7:3), the product (R)-3a was obtained as
a clear oil; yield: 73 mg (0.42 mmol, 84%); 95% ee determined
by chiral GC analysis [CP Chirasil-Dex CB; N2 0.9 mL minꢀ1
(constant flow modus); inj.: 1808C (split modus); det.: FID
1808C; oven: 1708C (16 min)], tR(minor)¼11.46 min (S),
tR(major)¼11.89 min (R).
20.59 min (R).
(2R,3R,6R)-2-Phenyl-3,6-dimethyltetrahydropyran-4-
one [(2R,3R,6R)-7]
The chromium porphyrin 5b (32 mg, 25 mmol, 5 mol %) and
benzaldehyde (2a, 52.2 mg, 0.50 mmol) were dissolved in
MTBE (0.25 mL), and 4 Š molecular sieves (200 mg) were
added at room temperature under argon. The reaction was
started by the addition of (Z,E)-3-(trimethylsilyloxy)-hexa-
2,4-diene (6, 90 mg, 0.53 mmol, 1.06 equivs.). After stirring
for 40 h at room temperature, the reaction mixture was diluted
with 2 mL of THF. The temperature was lowered to 08C, and
acetic acid (57 mL, 1 mmol) and a solution of 1 M tetrabutylam-
moniumfluoride in THF (735 mL, 0.75 mmol) were added. Stir-
ring was continued for another 0.5 h. The resulting mixture was
extracted with hexane:diethyl ether (2:1, 30 mL). The organic
phase was washed successively with H2O (2ꢁ15 mL), saturat-
ed aqueous NaHCO3 (15 mL), brine (15 mL), and dried over
MgSO4. After filtration, the solution was evaporated under re-
duced pressure. Purification of the residue by flash chromatog-
raphy (silica gel, cyclohexane/EtOAc, 7:3) afforded the prod-
uct (2R,3R,6R)-7 as a pale yellow oil; yield: 56 mg (0.275 mmol,
55%); 60% ee determined by chiral GC analysis [CP Chirasil-
Dex CB; N2 0.9 mL minꢀ1 (constant flow modus); inj.: 1808C
(split modus); det.: FID 1808C; oven: 1708C (16 min)],
(R)-2-Cyclohexyl-2,3-dihydropyran-4-one [(R)-3b]
After purification by flash chromatography on silica gel (cyclo-
hexane/ethyl acetate, 7:3), the product (R)-3b was obtained as
a clear oil; yield: 68 mg (0.38 mmol, 76%); 88% ee determined
by chiral GC analysis [CP Chirasil-Dex CB; N2 0.9 mL minꢀ1
(constant flow modus); inj.: 1808C (split modus); det.: FID
1808C; oven: 1608C (20 min), 158C minꢀ1, 1708C (2 min)],
tR(minor)¼15.19 min (S), tR(major)¼15.84 min (R).
(S)-2-(n-Hexyl)-2,3-dihydropyran-4-one [(S)-3c]
After purification by flash chromatography on silica gel (cyclo-
hexane/ethyl acetate, 8:2), the product (S)-3cwas obtainedas a
clear oil; yield: 68 mg (0.375 mmol, 75%); 92% ee determined
by chiral GC analysis [CP Chirasil-Dex CB; N2 0.9 mL minꢀ1
(constant flow modus); inj.: 1808C (split modus); det.: FID
1808C; oven: 1508C (17.5 min), 158C minꢀ1, 1808C (2 min)],
tR(minor)¼14.61 min (R), tR(major)¼15.13 min (S).
tR(minor)¼7.80 min
(2S,3S,6S),
tR(major)¼8.80 min
(2R,3R,6R); GC-MS (EI): tR ¼10.50 min, m/z (%)¼204 (Mþ,
1
66), 117 (73), 98 (49), 77 (29), 56 (100); H NMR (300 MHz,
CDCl3): d¼7.32–7.20 (m, 6H), 4.70 (d, J¼2.8 Hz, 1H), 3.81
3
(R)-2-(2-Furyl)-2,3-dihydropyran-4-one [(R)-3d]
3
3
3
3
(m, J¼6.0 Hz, J¼2.8 Hz, 1H), 2.55 (ddd, J¼7.2 Hz, J¼
2.8 Hz, J¼1.2 Hz, 1H), 2.47 (dd, 2J¼14.6 Hz, 3J¼11.5 Hz,
1H), 2.25 (ddd, 2J¼14.6 Hz, 3J¼2.8 Hz, 4J¼1.3 Hz, 1H), 1.36
(dt, 2Jt ¼19.9 Hz, 3Jd ¼6.1 Hz, 3H), 0.82 (dt, 2Jt ¼19.9 Hz,
3Jd ¼7.2 Hz, 3H); 13C NMR (75.5 MHz, CDCl3): d¼211.6,
138.7, 128.3, 127.3, 125.5, 80.0, 73.7, 50.7, 45.6, 22.2, 11.4.
After purification by flash chromatography on silica gel (cyclo-
hexane/ethyl acetate, 7:3), the product (R)-3d was obtained as
a clear oil; yield: 58 mg (0.35 mmol, 70%); 97% ee determined
by chiral GC analysis [CP Chirasil-Dex CB; N2 0.9 mL minꢀ1
(constant flow modus); inj.: 1808C (split modus); det.: FID
1808C; oven: 1508C (17.5 min), 158C minꢀ1, 1808C (2 min)],
tR(minor)¼12.49 min (S), tR(major)¼12.79 min (R).
6-Methoxy-2-Phenyl-3,6-dihydro-2H-pyran [9a, b]
The chromium porphyrin 5b (32 mg, 25 mmol, 5 mol %) and
benzaldehyde (2a, 52.2 mg, 0.50 mmol) were dissolved in
MTBE (0.25 mL), and 4 Š molecular sieves (200 mg) were
added at room temperature under argon. The reaction was
started by the addition of 1-methoxybutadiene (8, 44.1 mg,
0.52 mmol, 1.06 equivs.). After stirring for 40 h at room tem-
perature, the reaction mixture was evaporated under reduced
pressure. The residue was purified by column chromatography
(silica gel, cyclohexane:EtOAc, 7:3) to afford a pale yellow oil;
yield: 37 mg [0.2 mmol, 40% which contained both the trans-
and cis-diastereomers 9a and 9b (9a/9b¼60:40)], 83% ee for
trans-diastereomer (9a) and 75% ee for cis-diastereomer (9b)
determined by chiral GC analysis [CP Chirasil-Dex CB; N2
0.9 mL minꢀ1 (constant flow modus); inj.: 1808C (split modus);
det.: FID 1808C; oven: 1708C (16 min)], tR(9a-minor)¼
6.87 min, tR(9a-major)¼7.06 min, tR(9b-minor)¼7.99 min,
tR(9b-major)¼8.21 min); GC-MS (EI): tR(9a)¼9.64 min, tR
(9b)¼9.89 min, m/z (%)¼159 (Mþ-31, 14), 129 (13), 115
(13), 91 (25), 84 (100); 9a (trans): 1H NMR (300 MHz,
(R)-2-(trans-b-Styryl)-2,3-dihydropyran-4-one [(R)-
3e]
After purification by flash chromatography on silica gel (cyclo-
hexane/ethyl acetate, 7:3), the product (R)-3e was obtained as
a clear oil; yield: 55 mg (0.275 mmol, 55%); 74% ee determined
by chiral GC analysis [CP Chirasil-Dex CB; N2 0.9 mL minꢀ1
(constant flow modus); inj.: 1808C (split modus); det.: FID
1808C; oven: 1608C (80 min), 158C minꢀ1, 1808C (2 min)],
tR(minor)¼59.71 min (S), tR(major)¼61.87 min (R).
(R)-2-(2-Pyridyl)-2,3-dihydropyran-4-one [(R)-3f]
After purification by column chromatography on neutral alu-
mina (cyclohexane/ethyl acetate, 1:1), the product (R)-3f
was obtained as a clear oil; yield: 61.3 mg (0.35 mmol, 70%);
78% ee determined by chiral GC analysis [CP Chirasil-Dex
CB; N2 0.9 mL minꢀ1 (constant flow modus); inj.: 1808C (split
Adv. Synth. Catal. 2006, 348, 223 – 228
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
227

Albrecht Berkessel et al.
FULL PAPERS
CDCl3): d¼7.40ꢀ7.17 (m, 5H), 6.08ꢀ5.98 (m, 1H), 5.77 (dtd,
Jd ¼10.5 Hz, Jt ¼2.8 Hz, Jd ¼1.5 Hz, 1H), 4.96ꢀ4.94 (m, 1H),
4.84 (dd, 3J¼11.0 Hz, 4J¼4.2 Hz, 1H) 3.38 (s, 3H), 2.36ꢀ2.12
(m, 2H), 13C NMR (75.5 MHz, CDCl3): d¼142.3, 129.1,
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1
128.5, 127.6, 126.2, 125.5, 96.4, 68.4, 55.3, 32.2; 9b (cis): H
NMR (300 MHz, CDCl3): d¼7.40ꢀ7.17 (m, 5H), 6.08ꢀ5.98
(m, 1H), 5.67 (dqt, Jd ¼10.2 Hz, Jqt ¼1.3 Hz, 1H), 5.24ꢀ5.19
3
4
(m, 1H), 4.72 (dd, J¼9.9 Hz, J¼4.0 Hz, 1H), 3.47 (s, 3H),
2.36ꢀ2.12 (m, 2H), 13C NMR (75.5 MHz, CDCl3): d¼137.5,
129.6, 128.4, 128.3, 127.5, 125.7, 99.2, 74.0, 55.2, 32.9.
SupportingInformation
Further characterization data for compounds 3a–f, 7 and 9a, b
are given in the Supporting Information.
Acknowledgements
This work was financially supported by the Fonds der Chemi-
schen Industry and by the BASF AG, Ludwigshafen.
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Adv. Synth. Catal. 2006, 348, 223 – 228