Highly stereoselective metal-mediated domino aldol reactions of propiophenone enolates with heteroaromatic, aliphatic, and unsaturated aldehydes

Article abstract of DOI:10.1007/s00706-016-1841-4

The one-pot reaction of propiophenone with heteroaromatic, aliphatic, and unsaturated aldehydes in the presence of metal halides furnishes racemic tetrahydro-2H-pyran-2,4-diols in a highly diastereo-selective manner. The mechanism for the stereoselective

Full text of DOI:10.1007/s00706-016-1841-4

Monatsh Chem
DOI 10.1007/s00706-016-1841-4
ORIGINAL PAPER
Highly stereoselective metal-mediated domino aldol reactions
of propiophenone enolates with heteroaromatic, aliphatic,
and unsaturated aldehydes
M. Emin Cinar1 Michael Schmittel1
•
Received: 5 July 2016 / Accepted: 30 August 2016
Ó Springer-Verlag Wien 2016
Abstract The one-pot reaction of propiophenone with
heteroaromatic, aliphatic, and unsaturated aldehydes in the
presence of metal halides furnishes racemic tetrahydro-2H-
pyran-2,4-diols in a highly diastereo-selective manner. The
mechanism for the stereoselective product formation as
well as the surprising formation of a side product was
explained on the basis of DFT computations.
procedures generally only encompass one aldol step, tan-
dem reactions with two consecutive aldol steps often end
up with the trimerization of enolates [16, 17].
Metal (Ti, Zr, Si, and Sn) and boron enolates have
achieved a considerable impact, because of their proven
ability to control the stereochemical outcome of the C–C
bond formation [18]. In contrast, other group 13 metal
enolates have widely been neglected over the years
[19–22]. Using a wide selection of metal centers, we have
Graphical abstract
reported
a
domino aldol–aldol–hemiacetal process
(Scheme 1) that furnishes racemic tetrahydro-2H-pyran-
2,4-diols in a highly stereoselective manner via metal oli-
goenolates (2, 3, or 4 enolate residues) [18, 23–29].
In this paper, we evaluate the potential of this domino
aldol–aldol–hemiacetal scheme to tolerate a range of
aldehydes (heteroaromatic, aliphatic, and unsaturated
aldehydes) while varying the metal centers (Al, In, Zr, and
Sn). In addition, the process is assessed computationally.
Keywords Tetrahydropyran Á Enolates Á
Diastereo-selective reaction Á Aldol reactions Á
Natural products Á Density functional theory
Introduction
Results and discussion
Heteroaromatic aldehydes
The aldol reaction has extensively been used in the syn-
thesis of natural products [1–3], in a multitude of
stereoselective synthetic strategies [4–6], and in tandem
protocols [7–11] due to its high synthetic utility for the
carbon–carbon bond formation [12–15]. While standard
To probe aldehydes with additional donor sites, a small
series of heteroaromatic aldehydes (3b–3f) were investi-
gated (Scheme 2; Table 1).
Despite several attempts with 2-pyridinaldehyde (3d),
no domino-aldol product was afforded as the reaction
stopped at the mono aldolate. Pleasingly, with 3- and
4-pyridinecarboxaldehydes (3e and 3f), the domino prod-
ucts 5e and 5f were obtained smoothly as single
diastereomers with the same relative configuration as in 5a,
respectively. In contrast, the reaction with 2- and 3-furfural
(3b and 3c) led to the formation of the diastereomerically
& M. Emin Cinar
emin.cinar@uni-siegen.de
& Michael Schmittel
schmittel@chemie.uni-siegen.de
1
¨
Department Chemie-Biologie, Universitat Siegen,
Adolf-Reichwein-Str. 2, 57068 Siegen, Germany
123

M. Emin Cinar, M. Schmittel
Scheme 1
Scheme 2
and axial position (5b0) (Scheme 3). To understand the
formation of diastereomer 5b0 more closely, the reaction of
the aluminum tris(propiophenone enolate) with 2-furfural
(3b) was investigated varying the conversion (Table 2) and
the temperature (Table 3). In the time dependence study at
room temperature (Table 2), the ratio of 5b:5b0 (4:1)
remained constant. In contrast, in the temperature depen-
dence study, the ratio 5b:5b0 increased from 2:1 at -20 °C
to 5:1 at 50 °C (Scheme 4; Table 3).
Table 1 Reactions of various heteroaromatic aldehydes 3a–3f with
propiophenone (1) enolate
Yield /%
Prod. RCHO
AlCl3
64a
InCl3
85a
SnCl4
ZrCl4
76c
5a
36 (+29)b,c
5b
5c
5d
5e
5f
40 (+10)b
51 (+25)b
46 (+21)b
27
-
53 (+25)b
47 (+23)b
The formation of 5b0 possessing a methyl group in the
axial position may be attributed to the ability of the furan
oxygen in 3b to act as a donor in the aldol reactions. The
results of DFT calculations at M06/6-31G(d)/-LANL2DZ//
B3LYP/6-31G(d)/LANL2DZ level are shown in Scheme 5.
Throughout the computations, hexa-coordination at the
aluminum center was used, which required filling the
remaining coordination sites with THF molecules.
-
-
-
-
d
d
-
-
-
52
50
-
45
47
-
According to the computations, the 2-furfural (3b) first
coordinates to the aluminum trisenolate E in an endergonic
step affording complex C. One enolate subunit in C reacts
with the aluminum-activated subunit 3b furnishing the
a
Ref. [25]
b
c
d
rac-5a in the product
Ref. [28]
anti-aldolate A1 in
a downhill process liberating
82.0 kJ mol-1. The second aldol reaction affords u,l-A2 or
u,u-A2, both having a chair conformation in processes that
are downhill by 30 and 2.9 kJ mol-1. Finally, the ther-
modynamically less stable hemiacetals A3 and A30 are
formed in a chair conformation, while the metalladioxane
ring adopts a half-chair conformation. The DFT calcula-
tions indicate the absence of coordination between the ring
oxygen of furfural (3b) and Al throughout all the steps. The
computational results suggest that the metal-bound hemi-
acetals A3 and A30 are not direct precursors to the domino-
aldol products 5b and 5b0. Because the second aldol
Only mono aldol product
pure products 5b and 5c as well as unexpectedly to the
formation of 5a. The ESI–MS spectrum showed signals at
m/z = 397 and 387 Da that could be assigned to domino-
aldol products 5a and 5b as (M ? Na?), thus both asso-
ciated with sodium cations.
A special situation emerged with 2-furfural (3b) as an
electrophile as, in this case, a mixture of C3 epimers
formed with the methyl group being in the equatorial (5b)
123

Highly stereoselective metal-mediated domino aldol reactions of propiophenone enolates with…
Scheme 3
Table 2 Time dependence of the domino reaction with AlCl3 using
benzaldehyde (3a) or furfural (3b) at room temperature
Table 3 Temperature dependence of the reaction with AlCl3 using
2-furfural (3b) (time = 2 h)
a
5b0
6bb
6bcc
Time/
min
Yield/% with
2-furfural
Yield/% with
benzaldehyde
Temperature/°C
5b
-40
-20
0
3
11
29
40
23
22
–
66
44
33
30
11
12
–
a
5b
21
23
27
36
40
5b0
5
5a
34
37
40
56
65
6a
14
12
10
9
6
–
10
20
40
80
120
a
13
10
6
–
6
25
40
50
a
–
7
11
19
9
4
10
8
5b0 is a C3 epimer of 5b
Ref. [30]
5b0 is a C3 epimer of the 5b
b
c
Ref. [31]
reaction in this cascade affords the, thermodynamically,
most stable products, i.e., u,l-A2 and u,u-A2, we expect
that their hydrolysis will provide the end products 5b and
5b0. This suggestion is equally in alignment with the
increase of the products ratios from 2:1 to 4:1 at higher
temperature.
Meerwein–Ponndorf–Verley (MPV) [32] reaction, whose
transition state (TS) has a relative energy of 130 kJ mol-1
with respect to Me-Aldol in the reaction of propiophenone
enolate and butyraldehyde (for the calculation, acetalde-
hyde was considered). The newly generated aldolate Ph-
Aldol, more stable than Me-Aldol by 4.64 kJ mol-1, is
considered to undergo a retro-Aldol process giving rise to
the benzaldehyde coordinated PhCHO Complex
(Scheme 6).
Aliphatic and unsaturated aldehydes
To further probe the synthetic versatility, aliphatic alde-
hydes 3 g–3 k were utilized (Scheme 2; Table 4). Despite
the fact that these enolizable electrophiles are much more
critical, tetrahydropyran-2,4-diols were furnished in yields
up to 47 %. Again, in the all cases, the yields are higher
with the larger indium than with aluminum. Notably, with
aliphatic aldehydes, always two minor diastereomers were
additionally observed beside the main product. For exam-
ple, in the reaction with InCl3 and isobutyraldehyde (3 h),
the main product 5 h was afforded in 33 % yield accom-
panied by two diastereomers (11 and 3 % yields) (Table 4).
In the reactions of aldehydes with a-hydrogens, such as
butyraldehyde (3 g) and (-)-myrtenal (3 k), the standard
product 5a is also formed additionally, sometimes even
exclusively. A plausible explanation for this transformation
invokes an intramolecular hydrogen shift, analogous to the
Conclusion
The present results demonstrate a domino-aldol reaction of
heteroaromatic, aliphatic, and unsaturated aldehydes with
several metals that is far superior to the method with TiCp2
[17]. While the reaction with 2-furfural (3b) results not
only in the anticipated product 5b, but also in its C3-epimer
5b0, aldehydes with a-hydrogen provide a mixture of three
diastereomers along with the standard benzaldehyde pro-
duct rac-5a. The phenomena observed with furfural and
butyraldehyde were rationalized using DFT-level compu-
tations, which suggest
a
Meerwein–Ponndorf–Verley
123

M. Emin Cinar, M. Schmittel
Scheme 4
Scheme 5
123

Highly stereoselective metal-mediated domino aldol reactions of propiophenone enolates with…
atmosphere and Schlenk techniques were employed for all
Table 4 Reactions of various aliphatic and unsaturated aldehydes
3 g–3 k with propiophenone (1) enolate
reactions. THF was distilled under nitrogen directly over
1
potassium. H NMR and 13C NMR were measured on a
Yield /%
Bruker AC 200 (200 MHz) or AC 400 (400 MHz). All the
NMR measurements were carried out at room temperature
in CDCl3; chemical shifts refer to tetramethylsilane. IR
spectra were recorded on a Perkin-Elmer FT-IR 1605.
Elemental analyses were performed on a Carlo Erba Ele-
mental Analyzer 1106. Uncorrected melting points were
determined by using a Mettler FP5.0. Purification of
compounds was performed using HPLC quipped with RP-
18 Lichrosorb column.
Product
RCHO
AlCl3 InCl3 SnCl4
ZrCl4
12
5g
17a,c
21a
-
37a
47a
21b
18
33
-
5h
5i
-
Computation
15
DFT calculations were performed using the Gaussian 09
[33]. B3LYP [34–36] was employed with Pople’s split-
valence 6-31G(d) basis set on C, H, and O atoms and
double-f quality basis set (LANL2DZ) [37–39] containing
Hay and Wadt’s effective core potential (ECP) on hexa-
coordinate aluminum (aluminum trichloride forms AlCl3-
(THF)3 complex in THF [40]). The remaining coordination
sites of metals were occupied by THF molecules. The
minima of the calculated structures were verified by ana-
lyzing the harmonic vibrational frequencies using the
analytical second derivatives, which have NImag = 0.
Single-point calculations with M06 functional [41] were
performed using the same basis sets.
5j
4
-
11
31
-
-
5k
13c
5
a
Three diastereomers
b
c
d
1:1.4 mixture of rac-5i and rac-5a
1:5 mixture of rac-5k and rac-5a
(-)-Myrtenal
General procedure
(MPV) analogous intramolecular hydride shift followed by
a retro-aldol reaction. The variations in the metal fragment
are promising with regard to the development of an enan-
tioselective version of the above reaction and further
variations in the substrates.
Synthesis of racemic tetrahydro-2H-pyrans was realized
according to a literature procedure given in Ref. [29]. To a
solution of lithium diisopropylamide, which was prepared
from 1.26 cm3 diisopropylamine (9.00 mmol) in 30 cm3
THF with 3.00 cm3 of n-butyllithium (2.5 M in n-hexane,
7.50 mmol) at 0 °C, was added 1.01 cm3 propiophenone
(1, 7.50 mmol) at -40 °C and the mixture was stirred for
1 h at the same temperature. Then, 2.5 mmol of the metal
halide were introduced and the resulting yellow reaction
mixture was stirred for 30 min at -40 °C and for 1 h at
Experimental
Starting materials were purchased from Acros Organics,
Aldrich, Merck, or Lancaster, and used as received.
Aldehydes were distilled if necessary. Standard inert
Scheme 6
123

M. Emin Cinar, M. Schmittel
2.50 mmol) in 30 cm3 THF was added. The crude product
was purified by HPLC using methanol/water (4:1) as eluent
providing with InCl3 419 mg (1.15 mmol, 46 %) and with
ZrCl4 428 mg (1.18 mmol, 47 %) of 5c as a colorless solid.
room temperature. After the treatment of the metal enolate
with a solution of 250 mg benzaldehyde (3a, 2.50 mmol)
in 30 cm3 of THF, the mixture was stirred at the given
reaction temperature for 2 h (see Tables in manuscript). It
was quenched with 50 cm3 saturated NH4Cl(aq) solution
and the aqueous layer was extracted three times with
30 cm3 diethyl ether. The combined organic phases were
washed with brine and dried over Na2SO4.
1
M.p.: 164 °C; H NMR (400 MHz, CDCl3): d = 0.49 (d,
J = 6.8 Hz, 3H), 0.56 (d, J = 7.1 Hz, 3H), 2.32 (qd,
J = 7.1, 1.2 Hz, 1H), 2.70 (qd, J = 6.8, 10.8 Hz, 1H), 3.83
(s, 1H), 4.05 (d, J = 1.2 Hz, 1H), 5.14 (d, J = 10.8 Hz,
1H), 6.34 (dd, J = 3.3, 2.0 Hz, 1H), 6.38 (dd, J = 3.3,
0.8 Hz, 1H), 7.32–7.38 (m, 4H), 7.43 (dd, J = 2.0, 0.8 Hz,
1H), 7.49 (m, 2H), 7.61–7.65 (m, 2H), 7.70 (m, 2H) ppm;
13C NMR (50 MHz, CDCl3): d = 9.5, 10.8, 46.6, 47.9,
75.6, 78.1, 101.8, 106.4, 111.2, 125.8, 126.4, 126.7, 127.7,
128.0, 128.2, 128.4, 143.3, 143.4, 145.2 ppm; and IR
In the case of ZrCl4: The aldehyde was added in neat.
The overall amount of THF was 30 cm3. In the case of
SnCl4: 5.00 mmol of lithium diisopropylamide were reac-
ted with 660 mm3 of propiophenone (5.00 mmol).
(l,l,l,u)-6-(Furan-2-yl)-3,5-dimethyl-2,4-diphenyltetrahy-
dro-2H-pyran-2,4-diol (5b) [26]
ꢀ
(KBr): m = 3394, 3090, 3061, 3029, 2976, 2941, 1602,
1533, 1455, 1446, 1388, 1378, 1314, 1226, 1152, 1135,
AlCl3 (333 mg, 2.50 mmol), 555 mg InCl3 (2.50 mmol)
and 583 mg ZrCl4 (2.50 mmol) were used as coordination
metals in separate experiments in combination with a
solution of 210 mm3 furfural (3b, 2.50 mmol) in 30 cm3
THF. The crude product was purified by HPLC methanol/
water (4:1) affording with AlCl3 364 mg (1.00 mmol,
40 %), with InCl3 465 mg (1.28 mmol, 51 %), and with
ZrCl4 485 mg (1.33 mmol, 53 %) of 5b as a colorless
solid. M.p.: 160 °C. The results of the spectroscopic
measurements are well in agreement with the reported
ones.
1074, 1058, 1034, 1028, 1016, 1005, 997, 967, 699 cm-1
.
(l,l,l,u)-3,5-Dimethyl-2,4-diphenyl-6-(pyridin-3-yl)tetrahy-
dro-2H-pyran-2,4-diol (5e, C24H25NO3)
As coordination metals 555 mg InCl3 (2.50 mmol) and
583 mg ZrCl4 (2.50 mmol) were used. 3-Pyridinecarbox-
aldehyde (3e, 236 mm3, 2.50 mmol) was added. The crude
product was recrystallized from n-hexane furnishing
488 mg (1.30 mmol, 52 %) and 422 mg (1.13 mmol,
45 %) of 5e as a colorless solid using InCl3 and ZrCl4,
1
respectively. M.p.: 174 °C; H NMR (200 MHz, CDCl3):
(u,u,l,u)-6-(Furan-2-yl)-3,5-dimethyl-2,4-diphenyltetrahy-
dro-2H-pyran-2,4-diol (5b0, C23H24O4) [26]
d = 0.41 (d, J = 6.6 Hz, 3H), 0.59 (d, J = 6.9 Hz, 3H),
2.25–2.40 (m, 2H), 4.83 (s, 1H), 5.09 (d, J = 10.6 Hz, 1H),
7.20–7.45 (m, 4H), 7.66 (d, J = 7.1 Hz, 2H), 7.66 (d,
J = 7.1 Hz, 2H), 7.77 (d, J = 7.6 Hz, 1H), 7.89 (d,
J = 8.1 Hz, 1H), 8.20 (d, J = 4.7 Hz, 1H), 7.53–7.60 (m,
3H), 8.51 (s, 1H) ppm; 13C NMR (50 MHz, CDCl3):
d = 9.5, 10.6, 46.5, 47.9, 74.4, 77.9, 101.6, 122.9, 123.6,
125.9, 126.6, 127.7, 128.0, 128.2, 128.3, 132.2, 143.3,
In a second fraction, we obtained for aluminum(III)
chloride 91.0 mg (250 lmol, 10 %) and with indium(III)-
chloride 228 mg (625 lmol, 25 %) and with zirconium(IV)
chloride 228 mg (625 lmol, 25 %) of 5b0 as a colorless
solid. M.p.: 185 °C; 1H NMR (200 MHz, CDCl3):
d = 0.44 (d, J = 6.8 Hz, 3H), 0.59 (d, J = 7.0 Hz, 3H),
2.36 (m, 2H), 3.81 (d, J = 1.7 Hz, 1H), 3.91 (s, 1H), 5.05
(d, J = 10.8 Hz, 1H), 6.34 (d, J = 2.0 Hz, 1H), 7.18–7.40
(m, 7H), 7.49 (m, 2H), 7.70 (m, 3H) ppm; 13C NMR
(50 MHz, CDCl3): d = 9.4, 10.6, 43.6, 47.7, 68.7, 78.1,
101.7, 123.8, 126.0, 126.3, 126.6, 127.7, 128.0, 128.2,
128.3, 142.3, 143.0, 144.0, 153.4 ppm; and IR (KBr):
ꢀ
143.9, 149.1, 150.2 ppm; and IR (KBr): m = 3376, 3025,
2978, 2931, 1602, 1585, 1446, 1229, 1160, 1054, 1021,
1001, 965, 814, 750, 701, 621 cm-1
.
(l,l,l,u)-3,5-Dimethyl-2,4-diphenyl-6-(pyridin-4-yl)tetrahy-
dro-2H-pyran-2,4-diol (5f, C24H25NO3)
ꢀ
As coordination metals 555 mg InCl3 (2.50 mmol) and
583 mg ZrCl4 (2.50 mmol) were used. 4-Pyridinecarbox-
aldehyde (3f, 236 mm3, 2.50 mmol) was added. The crude
product was purified by crystallization from n-hexane
furnishing 469 mg (1.25 mmol, 50 %) of 5f using InCl3
and 443 mg (1.18 mmol, 47 %) of 5f in the presence of
ZrCl4 as a colorless solid. M.p.: 204 °C (decomp.); 1H
NMR (200 MHz, CDCl3): d = 0.43 (d, J = 6.9 Hz, 3H),
0.58 (d, J = 7.1 Hz, 3H), 2.15–2.40 (m, 2H), 4.53 (s, 1H),
5.00 (d, J = 10.3 Hz, 1H), 7.15–7.46 (m, 10H), 7.63–7.78
(m, 4H), 8.38 (s, 1H) ppm; 13C NMR (50 MHz, CDCl3):
d = 9.6, 10.6, 46.3, 47.9, 73.1 (2C), 101.6, 123.6, 124.0,
126.0, 126.4, 127.9, 128.0, 135.6, 143.7, 144.3, 148.5,
m = 3394, 3090, 3061, 3029, 29726, 2941, 1602, 1533,
1455, 1446, 1388, 1378, 1314, 1226, 1152, 1135, 1074,
1058, 1034, 1028, 1016, 1005, 997, 967, 699 cm-1
.
(E)-3-(Furan-2-yl)-2-methyl-1-phenylprop-2-en-1-one
(6bc)
The results of the spectroscopic measurements are in
agreement with the literature values [31].
(l,l,l,u)-6-(Furan-3-yl)-3,5-dimethyl-2,4-diphenyltetrahy-
dro-2H-pyran-2,4-diol (5c, C23H24O4)
InCl3 (555 mg, 2.50 mmol) and 583 mg ZrCl4
(2.50 mmol) were added as coordination metals in separate
experiments. A solution of 210 mm3 3-furanal (3c,
123

Highly stereoselective metal-mediated domino aldol reactions of propiophenone enolates with…
148.7 ppm; and IR (KBr): mꢀ = 3388, 3060, 3035, 2977,
2941, 1602, 1447, 1387, 1225, 1135, 1059, 1034, 1015,
J = 15.3, 7.6 Hz, 1H), 5.82 (dd, J = 15.3, 6.4 Hz, 1H),
7.10–7.32 (m, 4H), 7.46-7.54 (m, 2H), 7.57–7.71 (m, 4H)
ppm; 13C NMR (50 MHz, CDCl3): d = 9.5, 10.7, 23.8,
44.9, 47.6, 75.6, 78.1, 101.0, 123.7, 125.0, 126.4, 127.7,
128.0, 128.3, 129.8, 130.4, 140.7, 144.2 ppm; and IR
999, 968, 820, 777, 701, 630, 552 cm-1
.
(l,l,l,l)-3,5-Dimethyl-2,4-diphenyl-6-propyltetrahydro-2H-
pyran-2,4-diol (5g, C22H28O3) [25]
ꢀ
(KBr): m = 3396, 3058, 3032, 2977, 2941, 1677, 1600,
1497, 1447, 1387, 1313, 1229, 1156, 1135, 1075, 1030,
The following amounts of metal chloride have been used:
333 mg AlCl3 (2.50 mmol), 555 mg InCl3 (2.50 mmol),
583 mg ZrCl4 (2.50 mmol), and 326 mg SnCl4
(1.25 mmol). n-Butyraldehyde (3g, 136 mg, 2.50 mmol)
was reacted. The crude product was recrystallized from
ethanol providing with AlCl3 76.6 mg (225 lmol, 9 %),
with InCl3 136 mg (400 lmol, 16 %), with ZrCl4
(300 lmol, 12 %), and with SnCl4 153 mg (450 lmol,
965, 921, 768, 746, 699, 614 cm-1
.
(l,l,l,l)-(E)-3,5-Dimethyl-2,4-diphenyl-6-styryltetrahydro-
2H-pyran-2,4-diol (5j) [26]
AlCl3 (333 mg, 2.50 mmol), 555 mg InCl3 (2.50 mmol),
and 652 mg SnCl4 (2.50 mmol) were added as coordina-
tion metals. A solution of 310 mm3 cinnamaldehyde (3j,
2.50 mmol) in 30 cm3 THF was introduced. The crude
product was purified by crystallization from ethanol
furnishing with AlCl3 40.1 mg (100 lmol, 4 %), with
InCl3 110 mg (280 lmol, 11 %), and with SnCl4 311 mg
(776 lmol, 31 %) of 5j as a colorless solid. M.p.: 163 °C.
The spectra are matching well with the literature ones.
1
18 %) of 5g as a colorless solid. M.p.: 161 °C; H NMR
(200 MHz, CDCl3): d = 0.52 (d, J = 7.1 Hz, 3H), 0.64 (d,
J = 6.7 Hz, 3H), 0.94 (t, J = 7.3 Hz, 3H), 1.45–1.77 (m,
4H), 2.10 (qd, J = 10.3, 6.7 Hz, 1H), 2.36 (dq, J = 7.1,
1.2 Hz, 1H), 3.68 (s, 1H), 3.72 (d, J = 1.2 Hz, 1H), 4.11
(ddd, J = 10.3, 7.1, 3.0 Hz, 1H), 7.11–7.17 (br m, 1H),
7.21 (tt, J = 7.3, 1.2 Hz, 1H), 7.27–7.38 (m, 5H), 7.60–
7.62 (m, 2H), 7.64–7.68 (m, 1H) ppm; 13C NMR (50 MHz,
CDCl3): d = 9.6, 10.6, 14.3, 17.9, 35.1, 44.0, 47.8, 70.9,
78.3, 100.6, 123.8, 126.1, 126.3, 126.4, 127.8, 127.8,
(l,l,l,l)-6-(6,6-Dimethylbicyclo[3.1.1]hept-2-en-3-yl)-3,5-
dimethyl-2,4-diphenyltetrahydro-2H-pyran-2,4-diol
(5k, C28H34O3)
As coordination metals 555 mg InCl3 (2.50 mmol) and
583 mg ZrCl4 (2.50 mmol) were added. (-)-Myrtenal (3 k,
376 mg, 2.50 mmol) was added. The crude product was
purified by recrystallization from ethanol providing
136 mg (325 lmol, 13 %) using InCl3 and 52 mg
(125 lmol, 5 %) in the presence of ZrCl4. M.p.: 167 °C;
1H NMR (200 MHz, CDCl3): d = 0.52 (d, J = 7.1 Hz,
3H), 0.60 (d, J = 6.9 Hz, 3H), 0.85 (s, 3H), 1.35 (s, 3H),
2.02–2.18 (m, 2H), 2.31 (d, J = 1.5 Hz, 2H), 2.42–2.62
(m, 2H), 3.74 (d, J = 1.2 Hz, 1H), 3.98 (s, 1H), 4.45 (d,
J = 10.6 Hz, 1H), 5.59 (s, 1H), 7.10–7.42 (m, 7H), 7.51–
7.60 (m, 2H), 7.65–7.75 (m, 3H) ppm; 13C NMR (50 MHz,
CDCl3): d = 9.5, 10.7, 23.8, 26.5, 31.3, 32.0, 37.7, 40.4,
41.9, 42.6, 47.5, 75.6, 78.0, 100.9, 121.2, 123.7, 125.9,
126.3, 126.5, 127.7, 127.8, 128.1, 143.8, 144.7 ppm; and
ꢀ
128.2, 144.8 ppm; and IR (KBr): m = 3439, 3405, 3090,
3058, 3031, 2983, 2953, 2929, 2907, 2865, 1496, 1458,
1446, 1392, 1377, 1229, 1143, 1114, 1074, 1050, 1034,
997, 965, 744, 699, 616 cm-1
.
(l,l,l,l)-6-Isopropyl-3,5-dimethyl-2,4-diphenyltetrahydro-
2H-pyran-2,4-diol (5h) [25, 26]
The following amounts of metal chloride were used:
333 mg AlCl3 (2.50 mmol), 555 mg InCl3 (2.50 mmol),
583 mg ZrCl4 (2.50 mmol), and 326 mg SnCl4
(1.25 mmol). Isobutyraldehyde (3h, 136 mg, 2.50 mmol)
was reacted. The crude product was purified by recrystal-
lization from ethanol resulting in with AlCl3 93.6 mg
(275 lmol, 11 %), with InCl3 281 mg (825 mmol, 33 %),
and with SnCl4 281 mg (825 mmol, 33 %) of 5h as a
colorless solid. M.p.: 56 °C. The spectroscopic measure-
ments are well in agreement with the literature spectra.
ꢀ
IR (KBr): m = 3406, 3060, 2985, 2937, 1719, 1493, 1449,
1384, 1255, 1033, 997, 968, 770, 750, 701 cm-1
.
(l,l,l,l)-(E)-3,5-Dimethyl-2,4-diphenyl-6-(prop-1-enyl)te-
trahydro-2H-pyran-2,4-diol (5i, C22H26O3)
Acknowledgments Financial
support
from
the
DFG
(Graduiertenkolleg, SFB) and the Fonds der Chemischen Industrie is
gratefully acknowledged. We are grateful to Dr. Thomas Koy and
Wolfgang Henn for their valuable preparative work and helpful dis-
cussions in the early stage of this manuscript. We are indebted to the
High-Performance-Computing (HPC) Linux Cluster HorUS of the
University of Siegen for computational support.
As coordination metals 555 mg InCl3 (2.50 mmol) and
583 mg ZrCl4 (2.50 mmol) were chosen. Crotonic alde-
hyde (3i, 175 mg, 2.50 mmol) was reacted. The crude
product was purified by crystallization from ethanol giving
178 mg (525 lmol, 21 %) and 127 mg (375 lmol, 15 %)
of 5i using InCl3 and using ZrCl4, respectively. M.p.:
140 °C; 1H NMR (200 MHz, CDCl3): d = 0.51 (d,
J = 7.1 Hz, 3H), 0.61 (d, J = 6.6 Hz, 3H), 1.73 (dd,
J = 6.2, 1.2 Hz, 3H), 2.00–2.26 (m, 2H), 3.77 (s, 1H), 3.99
(s, 1H), 4.47 (dd, J = 10.3, 7.6 Hz, 1H), 5.60 (dd,
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