Synthesis of annulated 1,4-dioxanes and perhydro-1,4-oxazines by domino-wacker-carbonylation and domino-wacker-mizoroki-heck reactions

Article abstract of DOI:10.3987/COM-08-S(F)91

Palladium(II) -catalyzed domino reactions for the formation of 1,4-dioxanes and perhydro-1,4-oxazines starting from hydroxy alkenes are described. The domino-Wacker-carbonylation comprises a Wacker oxidation, subsequent CO-insertion and a nucleophilic substitution of the intermediately formed Pd-species. The domino-Wacker-Mizoroki-Heck reaction proceeds via a Wacker oxidation, subsequent insertion into the olefinic π-bond of α,β-unsatura-ted carbonyl compounds and β-hydride elimination.

Full text of DOI:10.3987/COM-08-S(F)91

HETEROCYCLES, Vol. 77, No. 2, 2009
1123
HETEROCYCLES, Vol. 77, No. 2, 2009, pp. 1123 - 1146. © The Japan Institute of Heterocyclic Chemistry
Received, 2nd August, 2008, Accepted, 7th October, 2008, Published online, 9th October, 2008
DOI: 10.3987/COM-08-S(F)91
SYNTHESIS OF ANNULATED 1,4-DIOXANES AND PERHYDRO-1,4-
OXAZINES
BY
DOMINO-WACKER-CARBONYLATION
AND
DOMINO-WACKER-MIZOROKI-HECK REACTIONS
Lutz F. Tietze,*a Arne Heins,a Mohammad Soleiman-Beigi,a and Christian
Raitha
a)Prof. Dr. Dr. h.c. L. F. Tietze, Dipl.-Chem. A. Heins, Dipl.-Chem. M.
Soleiman-Beigi, Dipl.-Chem. C. Raith, Institute of Organic and Biomolecular
Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077
Göttingen (Germany), E-mail: ltietze@gwdg.de, FAX: +49 (0)551 399476
Dedicated to Professor Emeritus Keiichiro Fukumoto on the occasion of his 75th
birthday
Abstract – Palladium(II)-catalyzed domino reactions for the formation of
1,4-dioxanes and perhydro-1,4-oxazines starting from hydroxy alkenes are
described. The domino-Wacker-carbonylation comprises a Wacker oxidation,
subsequent CO-insertion and a nucleophilic substitution of the intermediately
formed Pd-species. The domino-Wacker-Mizoroki-Heck reaction proceeds via a
Wacker oxidation, subsequent insertion into the olefinic π-bond of α,β-unsatura-
ted carbonyl compounds and β-hydride elimination.
INTRODUCTION
The domino-Wacker-carbonylation and the domino-Wacker-Mizoroki-Heck reaction are versatile
methods for the synthesis of chromanes.1 The procedure has been used by us not only for the preparation
of natural products and analogues as vitamin E (1)2 and 4-dehydroxydiversonol (3),3 but also for the
production of different heterocycles.4
OH O
OH
OH
HO
O
O
4-dehydroxydiversonol (2)
vitamin E (1)
Scheme 1. Structures of compounds synthesized using a Pd-catalyzed domino-reaction

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HETEROCYCLES, Vol. 77, No. 2, 2009
In these transformations a phenol as 3 containing an unsaturated side chain is treated with Pd(OTFA)2 and
an α,β-unsaturated carbonyl compound or an alcohol under a CO-atmosphere. Thus, reaction of 3 with
methyl vinyl ketone (4) in the presence of a catalytic amount of the (S,S)-Bn-BOXAX ligand (5)5 led to
chroman 6 in up to 86% yield with 97% ee, which was transformed in a few steps into 1.
Pd(OTFA)2,
p-benzoquinone,
(S,S)-Bn-BOXAX (5),
BnO
BnO
O
O
CH2Cl2, rt, 88%,
97% ee
OH
O
3
4
6
O
N
Bn
Bn
N
O
5
Scheme 2. Enantioselective formation of the precursor 6 for the synthesis of vitamin E (1)
However, as described in this article, these domino reactions can not only be performed using phenols but
also alicyclic alcohols as substrates to give 1,4-dioxanes. Moreover, it also allows the synthesis of
perhydro-1,4-oxazines.
RESULTS AND DISCUSSION
The
synthesis
of
1,4-dioxanes
and
perhydro-1,4-oxazines
using
a
Pd-catalyzed
domino-Wacker-carbonylation and a domino-Wacker-Mizoroki-Heck reaction, respectively, requires the
use of mono-O-allylated aliphatic 1,2-diols or N-allylated 2-aminoalcohols as substrates. The synthesis of
these compounds can efficiently be accomplished by a selective allylation of one of the two hydroxy
groups of the 1,2-diols or the nitrogen of N-Boc protected 2-aminoalcohols by a nucleophilic substitution
with allyl halides 7 or 8. The further transformation of these compounds to give the desired products is
accomplished using a catalytic amount of Pd(OTFA)2 or PdCl2, equimolar amounts of p-benzoquinone
for reoxidizing the in situ formed Pd0 species and either CO and an alcohol usually MeOH or a
α,β-unsaturated carbonyl compound 9 or 10 (Scheme 3).

HETEROCYCLES, Vol. 77, No. 2, 2009
1125
X
Pd(II),
Y
YH
OH
R'
Z
Y
R'
Z
R'
Z
CO, ROH
O
7: X = Br
8: X = Cl
OH
O
Y
OR
n
n
n
n
O
1,2-cis and trans
Z = CH2, O
R'
Z
Pd(II)
R
O
9: R = OMe 10a: R = H
10b: R = Me
Y = NBoc, O
O
R
10c: R = Et
Scheme 3. General scheme for the synthesis of 1,4-dioxanes and perhydro-1,4-oxazines using
Pd-catalyzed domino-reactions
SYNTHESIS OF THE SUBSTRATES FOR DOMINO-REACTIONS
The
substrates
22–29
for
the
domino-Wacker-carbonylation
reactions
and
the
domino-Wacker-Mizoroki-Heck reactions were prepared by allylation of either mono- or unprotected
1,2-diols 11–18 with β-methallyl bromide (7) or chloride (8) and sodium hydride as base (Scheme 4).
Using β-methally chloride (8) as reagent TBAI had to be added to allow a reasonable transformation.
The enantiomerically pure dihydroxy-compounds 11 and 12 were obtained via an epoxidation of
cyclohexene and 1,4-dihydronaphthalene, respectively followed by an enantioselective opening of the
meso-compounds using an enantiopure Co-salene complex and benzoate.6 Enantiopure compound 13 was
synthesized using a Sharpless-dihydroxylation of indene and selective TBS protection.7 Allylation of
these compounds with 7 or 8 followed by removal of the protecting groups led to 22, 23 and 24 in
40–50% yield over two steps.
The substrates rac-25–rac-29 were prepared directly from the corresponding 1,2-diols rac-14–rac-15 and
the meso compounds 16–18 by monoallylation in 35–60% yield together with the bisallylated compounds
and starting material.
As the domino-transformations did not tolerate basic amino functionalities, N-Boc protected substrates
rac-30, 31 and 32 were prepared from rac-19, enantiopure 20 and 21. To assure a selective N-allylation,
the employed corresponding 2-aminoalcohols were transformed into the N-Boc amides, then the hydroxy
group was protected as silyl ether. The allylation with 7 or 8 and the following silyl ether cleavage led to
rac-30 as well as enantiopure 318 and 32 in 49–68% yield over two steps.

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HETEROCYCLES, Vol. 77, No. 2, 2009
1. 8, NaH, TBAI, DMF, 60°C, 4 h
OH
O
2. NaOMe, MeOH, rt, 3.5 d
40% (2 steps)
OBz
OH
11
12
22
1. 7, NaH, DMF, rt, 20 h
OH
OBz
O
2. NaOMe, MeOH, rt, 4.5 d
42% (2 steps)
OH
23
1. 8, NaH, TBAI, DMF, rt, 24 h
OH
OTBS
O
2. TBAF, THF, rt, 2 h
51% (2 steps)
OH
24
13
OH
OH
O
8, NaH, TBAI, DMF, 60°C, 4 h
OH
n
n
rac-14: n = 1
rac-15: n = 2
rac-25: n = 1, 44%
rac-26: n = 2, 50%
OH
O
8, NaH, TBAI, DMF, 60°C, 4 h
OH
OH
n
n
16: n = 1
17: n = 2
rac-27: n = 1, 60%
rac-28: n = 2, 35%
OH
O
7, NaH, DMF, 60°C, 4 h
O
O
48%
OH
OH
18
rac-29
1. 7, NaH, DMF, rt, 18 h
Boc
N
NHBoc
2. TBAF, THF, rt, 30 min
49% (2 steps)
OTIPS
OH
rac-19
rac-30
1. 8, NaH, TBAI, DMF, rt, 24 h
Boc
N
NHBoc
OTIPS
2. TBAF, THF, rt, 2 h
68% (2 steps)
OH
20
31
1. 7, NaH, DMF, rt, 18 h
Boc
N
NHBoc
2. TBAF, THF, rt, 30 min
58% (2 steps)
OTIPS
OH
21
32
Scheme 4. Synthesis of the substrates for the Pd-catalyzed domino reactions
DOMINO-WACKER-CARBONYLATION REACTION
The domino-Wacker-carbonylation reaction of enantiopure 22 and 23 as well as of rac-22, rac-27 and

HETEROCYCLES, Vol. 77, No. 2, 2009
1127
rac-30 using palladium(II)chloride in methanol under an atmosphere of CO for 1.5–4 h at 60 °C led to the
desired compounds 31–38 in 72–90% yield. As expected two diastereomers were obtained in a 19:81 to
34:66 ratio (Table 1).
Y
R'
O
PdCl2,
p-benzoquinone,
CO-atm., MeOH, 60 °C
O
OMe
OMe
n
Y
R'
Y
R'
OH
n
O
O
n
Scheme 5. Domino-Wacker-carbonylation reactions
Interestingly, the cis-1,2-disubstituted cyclohexane derivative rac-28 and the trans-1,2-disubstituted
cyclopentane derivative rac-25 did not react under these conditions. The reaction of the N-Boc protected
compound rac-30 gave a mixture of rac-37 and rac-38 in 79% yield in a ratio of 22:78 after a reaction
time of 4 h, which is probably due to a strong steric hindrance caused by the BOC-group.
Table 1. Domino-Wacker-carbonylation reactions
yield
[%]
substrate
condictions
2 h[a]
product
ratio
H
H
O
O
O
O
O
O
O
+
22
90
19:81
OMe
O
32
O
OMe
H
H
H
H
31
O
+
rac-22
2 h[a]
88
19:81
O
OMe
O
OMe
O
H
H
rac-31
rac-32
H
H
O
O
O
23
1.5 h[a]
72
86
34:66
29:71
O
OMe
O
H
OMe
H
33
34
H
H
H
O
O
O
O
O
O
2 h[a]
+
rac-27
OMe
OMe
H
rac-35
rac-36

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HETEROCYCLES, Vol. 77, No. 2, 2009
Boc
N
Boc
N
H
H
H
H
O
O
+
rac-30
4 h[a]
79
70
22:78
O
OMe
O
OMe
rac-38
rac-37
Boc
N
O
6 h[b]
87 % ee
*
32
O
OMe
30
[a] 0.10 eq. PdCl2, 4.00 eq. p-benzoquinone, CO-atmosphere, MeOH, 60 °C.
[b] 0.05 eq. Pd(TFA)2, 0.15 eq. (S,S)-Bn-BOXAX, 4.00 eq. p-benzoquinone, CO-atm., MeOH, 60 °C.
For comparison we also used achiral 32 which could be transformed in an asymmetric reaction in the
presence of the BOXAX ligand 5 to give 39 in 70% yield and 87% ee. We have also tried to perform a
kinetic resolution using rac-22 and rac-27 in the presence of BOXAX ligand 5. However, under these
conditions the reaction slowed down considerably, that even after 10 days less than 10% of the desired
product was formed.
DOMINO-WACKER-MIZOROKI-HECK REACTION
For the domino-Wacker-Mizoroki-Heck reactions of the alkenyl phenols we used Pd(OTFA)2 and
equimolar amounts of p-benzoquinone in the presence of methyl acrylate (9), acrolein (10a), methyl vinly
ketone (10b) and ethyl vinyl ketone (10c) in CH2Cl2 as solvent at rt. These conditions had also been used
in the already described transformations using phenols.2,4a Thus, reaction of the trans- and
cis-cyclopentanediol and cis-tetrahydrofuran-3,4-diol derivatives rac-25, rac-27 and rac-29 led to the
1,4-dioxanes rac-40–rac-54 in yields of 33 to 77%. The lowest yield was obtained using acrolein (10a),
whereas the highest yield was observed using methyl acrylate (9). However, methyl and ethyl vinyl
ketone (10b and 10c) gave comparable yields. Interestingly, using the domino-Wacker-Mizoroki-Heck
reaction also the trans-disubstituted cyclopentane derivative rac-25 reacted though in only 39% yield,
whereas in the domino-Wacker-carbonylation reaction a transformation could not be achieved with this
substrate. On the other hand, the usage of methyl crotylate as a more hindered α,β-unsaturated carbonyl
compound failed since only traces of the desired product were formed within five days. Also, a kinetic
resolution starting with racemic substrates in the presence of the (S,S)-Bn-BOXAX (5) ligand was not
possible due to a strong reduction of the reaction rate. However, enantiopure 1-(methallyloxy)indane-2-ol
(24) and N-Boc-protected 1-(methallylamino)indane-2-ol 31 provided the annulated tricyclic 1,4-dioxans
54 and 55 and the perhydro-1,4-oxazines 56 and 57 in 56 and 91% yield, respectively. In all
transformations, diastereomers were formed as expected ranging from 50:50 to 70:30.

HETEROCYCLES, Vol. 77, No. 2, 2009
1129
It should be noted that there is a main difference between the domino-Wacker-carbonylation reaction and
the domino-Wacker-Heck-Mizoroki reaction, which concerns the reaction rate. Whereas using the first
procedure a full transformation is accomplished within a few hours, the second procedure usually needs a
few days.
H
Y
R'
O
O
Z
Pd(OTFA)2,
O
R
R
H
H
Y
p-benzoquinone,
R'
Z
O
CH2Cl2, rt
R
Y
R'
Z
OH
9: R = OMe
10a: R = H
10b: R = Me
10c: R = Et
O
H
Scheme 6. Domino-Wacker-Mizoroki-Heck reaction of hydroxy alkenes
Table 2. Domino-Wacker-Mizoroki-Heck reaction according to scheme 6
condi-
tions[a]
yield ratio
[%]
substrate
product
H
H
H
H
O
O
O
O
O
O
rac-25
3 d
3 d
3 d
2 d
39 50:50
70 50:50
61 50:50
33 65:55
OMe
OMe
rac-40
rac-42
rac-44
rac-46
rac-41
rac-43
rac-45
rac-47
H
H
O
O
O
O
O
O
rac-27
rac-27
rac-29
H
H
H
H
H
H
O
O
O
O
O
OMe
O
OMe
H
H
O
O
O
O
O
O
O
O
H
H
H
H

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HETEROCYCLES, Vol. 77, No. 2, 2009
H
H
H
O
O
O
O
O
O
O
rac-29
rac-29
rac-29
24
2 d
3 d
3 d
4 d
2 d
68 55:45
62 70:30
77 60:40
56 60:40
91 60:40
O
H
rac-48
rac-50
rac-52
54
rac-49
rac-51
rac-53
55
H
H
H
H
O
O
O
O
O
O
O
O
H
H
O
O
O
O
O
O
O
OMe
O
OMe
H
H
H
H
O
O
O
O
O
O
O
O
OMe
OMe
H
H
H
H
H
H
Boc
N
Boc
N
31
O
OMe
O
OMe
56
57
[a] Pd(OTFA)2 (0.10 eq.), p-benzoquinone (4.0 eq), α,β-unsaturated carbonyl compound (3.0 eq.), rt
STRUCTURE DETERMINATION
The relative configuration of the obtained diastereomers could be determined for 31, 32, 37 and 38 using
NOESY experiments. In all other cases a differentiation employing NMR spectroscopy was not possible.
CONCLUSION
We have reported on a new and operationally simple methods for the preparation of 1,4-dioxanes and
perhydro-1,4-oxazines starting from rapidly available precursors. The methodology is based on an
efficient palladium-catalyzed domino-reaction, initiated by a Wacker oxidation and subsequent insertion
of the Pd-species formed into the π-bonds of CO or α,β-unsaturated carbonyl compounds.
EXPERIMENTAL
General Procedure A: Allylation using NaH: The substrate, dissolved in dry DMF (3 mL/mmol), was

HETEROCYCLES, Vol. 77, No. 2, 2009
1131
carefully treated with NaH (1.00 eq.) at 0 °C. After warming up to rt and the end of gas release, the allyl
hallide 7 or 8 as well as TBAI (cat.) in the case of using 8 were added and the reaction mixture stirred for
2–24 h at 60 °C (TLC-Control). Then H2O (5 mL/mmol) was added, the solution neutralized with 1 N
HCl and the aqueous phase extracted with Et2O (3 × 5 mL/mmol). The combined organic layers were
washed with H2O (15 mL/mmol) and brine, dried over MgSO4 and the solvent removed in vacuo. The
crude product was purified by column chromatography on silica gel.
General Procedure B: Domino-Wacker-carbonylation reaction: A mixture of palladium(II)chloride
(0.10 eq.), p-benzoquinone (4.00 eq.) and the substrate in MeOH (2 mL) was stirred at 60 °C for 1–4 h
under a CO-atmosphere using a balloon filled with carbon monoxide. Then the reaction mixture was
treated with 1 N HCl (50 mL) and the aqueous phase extracted with Et2O (3 × 50 mL). The combined
organic phases were washed with 1 N NaOH (3 × 10 mL), brine and dried over MgSO4. The solvent was
removed in vacuo and the crude product purified by column chromatography on silica gel.
General Procedure C: Domino-Wacker-Mizoroki-Heck reaction: A mixture of palladium
trifluoroacetate (0.032 mmol) and p-benzoquinone (1.29 mmol) in CH2Cl2 (0.5 mL) was stirred at rt for
30 min. Afterwards the substrate (0.320 mmol) and the α,β-unsaturated carbonyl compound 9 or 10 (0.96
mmol) were added as solution in CH2Cl2 (0.5 mL) and the mixture was stirred at rt. After complete
conversion (TLC-control, typically several days) the mixture was treated with 1N HCl (5 mL) and the
aqueous phase extracted with Et2O (3 × 5 mL). The combined organic phases were washed with 1N
NaOH solution (3 × 5 mL) and brine and dried over MgSO4. The solvent was removed in vacuo and the
crude product purified by column chromatography on silica gel.
(1R,2R)-2-Hydroxycyclohexyl
benzoate
(11):
A
solution
of
(S,S)-(+)-N,N-bis-
(3,5-di-tert-butylsalicyliden)-1,2-cyclohexanediaminocobalt (31.0 mg, 51.0 μmol) and benzoic acid
(680 mg, 5.60 mmol) in TBME (2 mL) was stirred under O2 for 30 min. Volatile materials were removed
in vacuo. The flask was recharged with nitrogen, i-Pr2NEt (724 mg, 976 μL, 5.60 mmol) was added, and
the stirred mixture was cooled to 4 °C. Cyclohexene oxide (500 mg, 5.09 mmol) was added and the
resulting dark brown solution was stirred at 4 °C for 5 d. The product mixture was diluted with Et2O
(10 mL), washed with 1 N aq. HCl (5 × 2 mL) and saturated aq. NaHCO3 (2 × 2 mL), dried over MgSO4,
and filtered. The solution was concentrated in vacuo and the resulting solid was recrystallized four times
from CH2Cl2/heptane to afford the product 11 (567 mg, 2.62 mmol, 51%) as colorless crystals. 1H-NMR
(300 MHz, CDCl3): δ = 1.21–2.20 (m, 8 H, 3-H2, 4-H2, 5-H2, 6-H2), 2.39 (d, J = 3.7 Hz, 1 H, OH),
3.65–3.75 (m, 1 H, 2-H), 4.79 (mc, 1 H, 1-H), 7.38–7.45 (m, 2 H, Ph-Hm), 7.54 (tt, J = 7.4, 2.2 Hz, 1 H,
13
Ph-Hp), 8.00–8.07 (m, 2 H, Ph-Ho). C-NMR (50.3 MHz, C6D6): δ = 23.67 (C-4), 23.83 (C-5), 29.94

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HETEROCYCLES, Vol. 77, No. 2, 2009
(C-6), 32.94 (C-3), 72.70 (C-2), 77.21 (C-1), 128.31 (Ph-CHm), 129.61 (Ph-CHo), 130.28 (Ph-Ci), 132.98
(Ph-CHp), 166.38 (Ph-CO2). IR (KBr): ν (cm-1) = 3533, 2936, 2860, 1692, 1454, 1323, 1279, 1133, 1071,
995, 917, 850, 711. UV (CH3CN): λmax (lg ε) = 192.5 nm (4.5717), 197.5 (4.5997), 227.5 (4.1039), 272
(2.9441), 279.5 (2.8488). MS (DCI, 200 eV): m/z (%) = 458 (15) [2M+NH4]+, 255 (10) [M+NH3+NH4]+,
238 (100) [M+NH4]+.
(2R,3R)-(3-Hydroxy-1,2,3,4-tetrahydronaphthalene-2-yl)(phenyl)methanone 12: A solution of 1,4-di-
hydronaphthalene (779 mg, 5.98 mmol) in CH2Cl2 (11 mL) was cooled to 0 °C and mCPBA (2.21 g,
8.97 mmol) was added. The mixture was stirred at rt for 16 h, then aq. NaHCO3 (10 mL) was added and
stirring was continued for another 30 min. The organic layer was washed with aq. NaHCO3 (2 ×10 mL),
dried over MgSO4 and the solvent removed in vacuo to provide meso-1a,2,7,7a-tetrahydro-
naphtho[2,3-b]oxirene (873 mg, 5.97 mmol, quant.) after column chromatography on silica gel
1
(P/Et2O = 8:1) as a colourless solid. H-NMR (300 MHz, CDCl3): δ = 3.18 (d, J = 17.6 Hz, 2 H, 2-Ha,
7-Ha), 3.31 (d, J = 17.6 Hz, 2 H, 2-Hb, 7-Hb), 3.47 (dd, J = 2.4, 1.3 Hz, 2 H, 1a-H, 7a-H), 7.04 (dd, J = 5.6,
3.5 Hz, 2 H, 4-H, 5-H), 7.14 (dd, J = 5.6, 3.5 Hz, 2 H, 3-H, 6-H). 13C-NMR (75.5 MHz, CDCl3): δ =
29.66 (C-2, C-7), 51.69 (C-1a, C-7a), 126.48 (C-4, C-5), 129.20 (C-5, C-8), 131,42 (C-2a, C-6a). IR
(film): ν (cm-1) = 3343, 3004, 2909, 2247, 1498, 1456, 1422, 1062, 1043, 818, 746. UV (CH3CN): λmax
(lg ε) = 194.5 nm (4.5457), 264 (2.4285), 271 (2.4009). MS (DCI, 200 eV): m/z (%) = 181 (12)
[M+NH3+NH4]+,
164
(100)
[M+NH4]+.
A
solution
of
(S,S)-(+)-N,N-bis-
(3,5-di-tert-butylsalicyliden)-1,2-cyclohexanediaminocobalt (62.0 mg, 103 μmol,) and benzoic acid
(276 mg, 2.26 mmol) in TBME (2 mL) was stirred under O2 for 30 min. Volatile materials were removed
in vacuo. The flask was recharged with nitrogen, i-Pr2NEt (292 mg, 393 μL, 2.26 mmol) and
meso-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene (300 mg, 2.05 mmol) was added (300 mg, 2.05 mmol)
and the resulting dark brown solution stirred at rt for 3 d. The product mixture was diluted with Et2O
(10 mL), washed with 1 N aq. HCl (5 ×2 mL) and saturated aq. NaHCO3 (2 × 2 mL), dried over MgSO4,
and filtered. The solution was concentrated in vacuo and the resulting solid was recrystallized 4 times
from CH2Cl2/heptane to afford the product 12 (386 mg, 1.43 mmol, 70%) as a colourless solid. 1H-NMR
(300 MHz, CDCl3): δ = 2.93 (dd, J = 16.1, 8.8 Hz, 1 H, 4-Ha), 2.99 (dd, J = 16.1, 8.6 Hz, 1 H, 1-Ha), 3.28
(dd, J = 16.5, 5.7 Hz, 1 H, 4-Hb), 3.41 (dd, J = 16.5, 5.8 Hz, 1-H, 4-Hb), 4.24 (ddd, J = 8.8, 8.4, 5.7 Hz,
1 H, 3-H), 5.29 (ddd, J = 8.6, 8.4, 5.8 Hz, 1 H, 2-H), 7.13 (mc, 4 H, 5-H, 6-H, 7-H, 8-H), 7.44 (mc, 2 H,
13
Ph-Hm), 7.57 (mc, 1 H, Ph-Hp), 8.05 (mc, 2 H, Ph-Ho). C-NMR (125 MHz, CDCl3): δ = 33.31, 36.08
(C-1, C-4), 69.59 (C-3), 75.25 (C-2), 126.48, 126.53 (C-6, C-7), 128.44 (Ph-CHm), 128.67, 128.87 (C-5,
C-8), 129.69 (Ph-CHo), 129.95 (Ph-Ci), 132.99, 133.34 (C-4a, C-8a), 133.24 (Ph-CHp), 166.65 (CO2Ph).
IR (pellet): ν (cm-1) = 3517, 2933, 2901, 2851, 1692, 1452, 1278, 1124, 1028, 991, 713, 438. UV

HETEROCYCLES, Vol. 77, No. 2, 2009
1133
(CH3CN): λmax (lg ε) = 192.5 nm (4.9177), 194.5 (4.9452), 216.5 (4.1612), 228 (4.1613), 265 (3.1388),
272 (3.1773), 279.5 (2.9243). MS (DCI, 200 eV): m/z (%) = 554 (15) [2M+NH4]+, 286 (100) [M+NH4]+,
269 (10) [M+H]+.
tert-Butyl rac-trans-2-(triisopropylsilyloxy)cyclohexylcarbamate rac-19: A suspension of 2-amino-
cyclohexanol hydrochloride (1.00 g, 6.60 mmol) in THF (30 mL) was treated with NaH (60% in mineral
oil, 264 mg, 6.60 mmol) and stirred at rt for 1.5 h. Afterwards di-tert-butyl dicarbonate (1.51 g,
6.93 mmol) was added, and the mixture was stirred at rt for 4 h. The solvent was removed in vacuo, H2O
(10 mL) was added and the aqueous phase was extracted with Et2O (3 × 30 mL). The solvent was
removed under reduced to provide rac-tans-tert-butyl 2-hydroxycyclohexylcarbamate (940 mg,
4.37 mmol, 66%) as a colourless solid. 1H-NMR (300 MHz, CDCl3): δ = 1.45 (s, 9 H, C(CH3)3), 1.67 (s,
1 H, OH), 1.06–1.37 (m, 4 H, 4-H2, 5-H2), 1.64–1.76 (m, 2 H, 3-Ha, 6-Ha), 1.91–2.09 (m, 2 H, 3-Hb, 6-Hb),
3.21–3.39 (m, 2 H, 1-H, 2-H), 4.54 (sbr, 1 H, NH). 13C-NMR (125 MHz, CDCl3): δ = 24.00, 24.68 (C-4,
C-5), 28.32 (C(CH3)3), 31.74, 34.13 (C-3, C-6), 56.35 (C-1), 75.35 (C-2), 79.93 (C(CH3)3), 157.20
(CO2C(CH3)3). IR (pellet): ν (cm-1) = 3329, 2932, 1681, 1535, 1449, 1363, 1240, 1176, 1125, 1068, 1016,
854, 645. MS (ESI): m/z (%) = 238 (100) [M+Na]+, 453 (8) [2M+Na]+. To a solution of
rac-tans-tert-butyl 2-hydroxycyclohexylcarbamate (940 mg, 4.37 mmol) and imidazole (446 mg,
6.55 mmol) in CH2Cl2 (20 mL) was added Chlorotriisopropylsilane (1.26 g, 1.40 mL, 6.55 mmol). The
mixture was stirred at rt for 3 d, H2O (10 mL) was added. The aqueous phase was extracted with CH2Cl2
(3 × 20 mL), dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified
by column chromatography on silica gel (P/Et2O = 20:1) to provide rac-19 (1.16 g, 3.14 mmol, 72 %) as
a colourless solid. 1H-NMR (300 MHz, CDCl3): δ = 1.07 (s, 18 H, 3 × CH(CH3)2), 1.43 (s, 9 H, C(CH3)3),
0.84–1.57 (m, 7 H, 3 × CH(CH3)2, 4-H2, 5-H2), 1.63–1.90 (m, 3 H, 3-H2, 6-Ha), 2.02–2.14 (m, 1 H, 6-Hb),
3.34–3.64 (m, 2 H, 1-H, 2-H), 4.55 (mc, 1 H, NH). 13C-NMR (150 MHz, CDCl3): δ = 12.55 (CH(CH3)2),
18.16 (CH(CH3)2), 23.13, 23.45 (C-4, C-5), 28.40 (C(CH3)3), 30.45, 33.69 (C-3, C-6), 55.23 (C-1), 72.80
(C-2), 82.18 (C(CH3)3), 155.51 (CO2(C(CH3)3). IR (pellet): ν (cm-1) = 3368, 2943, 2866, 1686, 1532,
1462, 1366, 1321, 1179, 1107, 1045, 1023, 883, 779, 678. MS (ESI): m/z (%) = 372 (100) [M+H]+.
HRMS (ESI): calcd for [C20H41NO3Si + Na]+: 371.286; confirmed.
tert-Butyl 2-(triisopropylsilyloxy)phenylcarbamate 21: 2-Aminophenol (2.00 g, 18.3 mmol) in THF
(20 mL) was treated with di-tert-butyl dicarbonate (4.20 g, 19.2 mmol) and stirred at rt for 13 h.
Afterwards the solvent was removed unter reduced pressure, H2O (50 mL) was added and the aqueous
phase was extracted with EtOAc (3 × 50 mL). The combined organic layers were dried over MgSO4, the
solvent was removed in vacuo and the resulting solid washed with CCl4 (4 × 50 mL) to give tert-butyl
1
2-hydroxyphenylcarbamate (2.98 g, 14.2 mmol, 78%) as a colourless solid. H-NMR (300 MHz,

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HETEROCYCLES, Vol. 77, No. 2, 2009
CD3OD): δ =1.53 (s, 9 H, C(CH3)3), 6.52–6.90 (m, 4 H, 3-H, 4-H, 5-H, 6-H), 7.62 (d, J = 7.9 Hz,
1 H, NH). 13C-NMR (125 MHz, CD3OD): δ =28.64 (C(CH3)3), 81.27 (C(CH3)3), 116.12, 120.67, 121.03,
124.69, 127.69 (C-1, C-3, C-4, C-5, C-6), 148.19 (C-2), 155.48 (CO2C(CH3)3). IR (pellet): ν (cm-1) =
3427, 3292, 2986, 1691, 1614, 1522, 1456, 1326, 1227, 1151, 1054, 927, 842, 777, 750, 735, 611. UV
(CH3CN): λmax (lg ε) = 204.5 nm (4.6047), 235.0 (4.0397), 281.5 (3.5691). MS (ESI): m/z (%) = 232
(100) [M+Na]+. To a solution of tert-butyl 2-hydroxyphenylcarbamate (2.00 g, 9.56 mmol) and imidazole
(977 mg, 14.3 mmol) in CH2Cl2 (30 mL) was added Chlorotriisopropylsilane (2.76 g, 14.3 mmol). The
mixture was stirred at rt for 20 h, H2O (15 mL) was added. The aqueous phase was extracted with CH2Cl2
(3 × 40 mL), dried over Na2SO4 and the solvent was removed in vacuo. The crude product was purified
by column chromatography on silica gel (P/Et2O = 100:1) to provide 21 (2.86 g, 7.82 mmol, 82%) as a
1
colorless oil. H-NMR (300 MHz, CDCl3): δ = 1.12 (d, J = 7.3 Hz, 18 H, 3 × CH(CH3)2), 1.24–1.41 (m,
3 H, 3 × CH(CH3)2), 1.51 (s, 9 H, C(CH3)3), 6.78–6.89 (m, 2 H, 3-H, 5-H), 6.93 (dt, J = 6.9, 2.2 Hz, 1 H,
4-H), 7.11 (sbr, 1 H, NH), 7.99 (d, J = 8.0 Hz, 1 H, 6-H). 13C-NMR (125 MHz, CDCl3): δ = 12.71
(3 × CH(CH3)2), 17.89 (3 × CH(CH3)2), 28.30 (C(CH3)3), 80.00 (C(CH3)3), 117.31, 118.54, 121.53,
122.18 (C-3, C-4, C-5, C-6), 129.83 (C-1), 143.92 (C-2), 152.75 (CO2C(CH3)3). IR (film):
ν (cm-1) = 3438, 2946, 2869, 1735, 1598, 1520, 1450, 1392, 1367, 1328, 1265, 1234, 1158, 1113, 1049,
998, 916, 883, 828, 749, 707, 683. UV (CH3CN): λmax (lg ε) = 206.5 nm (4.6141), 237 (4.155), 280
(3.493). MS (DCI, 200 eV): m/z (%) = 749 (53) [2M+NH4]+, 383 (100) [M+NH4]+, 367 (35) [M+H]+.
SYNTHESIS OF MONOALLYL ETHERS
(1R,2R)-trans-2-(2-Methallyloxy)cyclohexanol (22): According to general procedure A, 11 (551 mg,
2.50 mmol) was reacted with β-methallyl chloride (8) (451 mg, 488 μL, 5.00 mmol) within 24 h at 60 °C
to provide (1R,2R)-2-(2-methallyloxy)cyclohexyl benzoate (612 mg, 2.23 mmol, 89%) as a colorless
liquid after column chromatography on silica gel (P/Et2O = 20:1). 1H-NMR (300 MHz, CDCl3): δ = 1.65
(s, 3 H, 2'-CH3), 1.16–2.12 (m, 8 H, 3-H2, 4-H2, 5-H2, 6-H2), 3.44–3.53 (m, 1 H, 1-H), 3.94 (d,
J = 12.4 Hz, 1 H, 1'-Ha), 4.02 (d, J = 12.4 Hz, 1 H, 1'-Hb), 4.78 (mc, 1 H, 3'-Ha), 4.96 (mc, 1 H, 3'-Hb),
5.01– 5.11 (m, 1 H, 2-H), 7.33–7.49 (m, 2 H, Ph-Hm), 7.51–7.60 (m, 1 H, Ph-Hp), 8.02–8.10 (m, 2 H,
13
Ph-Ho). C-NMR (125 MHz, CDCl3): δ = 13.41 (2'-CH3), 23.03, 23.11 (C-4, C-5), 29.58, 29.62 (C-3,
C-6), 68.10 (C-1'), 73.47 (C-1), 78.02 (C-2), 111.92 (C-3'), 128.25 (Ph-Cm), 129.54 (Ph-Co), 129.60
(Ph-Ci), 132.70 (Ph-Cp), 142.63 (C-2'), 166.22 (CO2Ph). UV (CH3CN): λmax (lg ε) = 192.5 nm (4.6262),
194.5 (4.6446), 228.0 (4.1016), 272 (2.9359), 279.5 (2.8395). MS (ESI): m/z (%) = 297 (100) [M+Na]+,
275 (5) [M+H]+. A solution of (1R,2R)-2-(2-methallyloxy)cyclohexyl benzoate (612 mg, 2.23 mmol) in
MeOH (36 mL) was cooled to 0 °C, and a 0.5 M NaOMe-solution was added dropwise. The mixture was
stirred at rt for 3.5 d, aq. saturated NH4Cl (10 mL) was added and the aqueous phase was extracted with

HETEROCYCLES, Vol. 77, No. 2, 2009
1135
Et2O (3 × 30 mL). The combined organic phases were dried over MgSO4 and the solvent was removed in
vacuo. The crude product was purified by column chromatography on silica gel (P/Et2O = 5:1) to provide
22 (169 mg, 995 μmol, 45%) as a colorless liquid. 1H-NMR (300 MHz, C6D6): δ = 1.73 (s, 3 H, 2'-CH3),
1.04–2.09 (m, 8 H, 3-H2, 4-H2, 5-H2, 6-H2), 2.69 (s, 1 H, OH), 3.05 (ddd, J = 10.5, 8.7, 4.4 Hz, 1 H, 2-H),
3.44 (mc, 1 H, 1-H), 3.85 (d, J = 12.3 Hz, 1 H, 1'-Ha), 4.02 (d, J = 12.3 Hz, 1 H, 1'-Hb), 4.86 (mc, 1 H,
3'-Ha), 4.95 (mc, 1 H, 3'-Hb). 13C-NMR (125 MHz, CDCl3): δ = 19.61 (2'-CH3), 23.93, 24.19 (C-4, C-5),
29.04 (C-6), 31.98 (C-3), 72.64 (C-1'), 73.84 (C-2), 83.21 (C-1), 112.07 (C-3'), 142.55 (C-2'). IR (film):
ν (cm-1) = 3442, 3075, 2934, 2861, 1656, 1373, 1233, 1082, 997, 898, 848. MS (DCI, 200 eV):
m/z (%) = 188 (100) [M+NH4]+. GC: temperature: 90 °C, pressure: 65 kPa, column:
heptakis(6-O-TBDMS-2,3-di-O-methyl)-β-cyclodextrin (50% in OV 1701), tR = 19.865 min (E1), 20.687
(E2); ee = 86%.
rac-trans-2-(2-Methallyloxy)cyclohexanol (rac-22): According to general procedure A,
rac-trans-cyclohexane-1,2-diol (15, 2.00 g, 17.2 mmol) was reacted with β-methallyl chloride (8) (1.87 g,
2.02 mL, 20.7 mmol) within 12 h at 60 °C to provide rac-22 (1.45 g, 8.55 mmol, 50%) as a colorless
liquid after column chromatography on silica gel (P/Et2O = 4:1). 1H-NMR (300 MHz, CDCl3): δ = 1.75
(s, 3 H, 2'-CH3), 1.04-2.14 (m, 8 H, 3-H2, 4-H2, 5-H2, 6-H2), 2.73 (s, 1 H, OH), 3.08 (mc, 1 H, 2-H), 3.45
(mc, 1 H, 1-H), 3.87 (d, J = 12.3 Hz, 1 H, 1'-Ha), 4.05 (d, J = 12.3 Hz, 1 H, 1'-Hb), 4.88 (mc, 1 H, 3'-Ha),
13
4.94 (mc, 1 H, 3'-Hb). C-NMR (125 MHz, CDCl3): δ = 19.61 (2'-CH3), 23.93, 24.19 (C-4, C-5), 29.04
(C-6), 31.98 (C-3), 72.64 (C-1'), 73.84 (C-2), 83.21 (C-1), 112.07 (C-3'), 142.55 (C-2'). IR (film):
ν (cm-1) = 3418, 3076, 2934, 2861, 1725, 1656, 1451, 1373, 1234, 1082, 997, 899, 849. MS (DCI,
200 eV): m/z (%) = 188 (100) [M+NH4]+. HRMS (ESI): calcd for [C10H18O2 + Na]+: 193.1204;
confirmed.
(2R,3R)-3-(2-Methallyloxy)-1,2,3,4-tetrahydronaphthalen-2-ol 23: According to general procedure A,
12 (234 mg, 870 μmol) was reacted with β-methallyl bromide (7) (235 mg, 175 μL, 1.74 mmol) within
20 h at rt to provide (2R,3R)-3-(2-methallyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl benzoate (127 mg,
395 μmol, 45%) as a colourless solid after column chromatography on silica gel (P/Et2O = 10:1).
1H-NMR (300 MHz, CDCl3): δ = 1.69 (s, 3 H, 2'-CH3), 2.94 (t, J = 6.1 Hz, 1 H, 4-Ha), 2.99 (t, J = 6.2 Hz,
1 H, 1-Ha), 3.22 (dd, J = 16.8, 5.0 Hz, 1 H, 1-Hb), 3.39 (dd, J = 17.0, 5.0 Hz, 1 H, 4-Hb), 3.96 (ddd,
J = 6.6, 6.5, 5.1 Hz, 1 H, 3-H), 4.06 (s, 1 H, 1'-H2), 4.85 (mc, 1 H, 3'-Ha), 4.95 (mc, 1 H, 3'-Hb), 5.51 (dd,
J = 12.0, 6.0 Hz, 1 H, 2-H). 7.13 (mc, 4 H, 5-H, 6-H, 7-H, 8-H), 7.40 (mc, 2 H, Ph-Hm), 7.53 (mc, 1 H,
Ph-Hp), 7.98 (mc, 2 H, Ph-Ho). 13C-NMR (125 MHz, CDCl3): δ = 19.52 (2'-CH3), 32.45, 32.71 (C-1, C-4),
71.67 (C-2), 73.64 (C-1'), 74.31 (C-3), 112.50 (C-3'), 126.27, 126.30 (C-6, C-7), 128.39 (Ph-CHm),

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HETEROCYCLES, Vol. 77, No. 2, 2009
128.84, 128.97 (C-5, C-8), 129.68 (Ph-CHo), 130.39 (Ph-Ci), 133.03 (Ph-CHp), 133.14, 133.41 (C-4a,
C-8a), 142.31 (C-2'), 166.04 (CO2Ph). IR (film): ν (cm-1) = 3414, 3065, 3023, 2929, 1719, 1602, 1584,
1494, 1451, 1350, 1272, 1176, 1110, 1026, 904, 743, 711. UV (CH3CN): λmax (lg ε) = 192.5 nm (4.7873),
195.5 (4.8457), 216.5 (4.1586), 228 (4.1696), 265 (3.1466), 272 (3.1821), 280 (2.9322). MS (DCI,
200 eV): m/z (%) = 357 (54) [M+NH3+NH4]+, 340 (100) [M+NH4]+, 323 (10) [M+H]+. A solution of
(2R,3R)-3-(2-methallyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl benzoate (120 mg, 372 μmo) in MeOH
(6 mL) was cooled to 0 °C, and a 5.4 M NaOMe-solution (7.50 μL, 37.2 μmol) was added dropwise. The
mixture was stirred at rt for 3.5 d, saturated aq. NH4Cl (5 mL) was added and the aqueous phase was
extracted with Et2O (3 × 15 mL). The combined organic phases were dried over MgSO4, and the solvent
was removed in vacuo. The crude product was purified by column chromatography on silica gel
1
(P/Et2O = 5:1) to provide 23 (169 mg, 995 μmol, 45%) as a colorless liquid. H-NMR (300 MHz,
CDCl3): δ = 1.79 (s, 3 H, 2'-CH3), 2.73 (dd, J = 16.2, 10.0 Hz, 1 H, 4-Ha), 2.82 (dd, J = 16.4, 10.1 Hz, 1 H,
1-Ha), 2.87 (s, 1 H, OH), 3.20 (dd, J = 10.8, 5.6 Hz, 1 H, 1-Hb), 3.25 (dd, J = 10.5, 5.6 Hz, 1 H, 4-Hb),
3.57 (ddd, J = 9.8, 9.1, 5.5 Hz, 1 H, 3-H), 3.96 (mc, 1 H, 2-H), 3.99 (d, J = 12.3 Hz, 1 H, 1'-Ha), 4.14 (d,
J = 12.3 Hz, 1-H, 1'-Hb), 4.92 (mc, 1 H, 3'-Ha), 5.01 (mc, 1 H, 3'-Hb), 7.11 (mc, 4 H, 5-H, 6-H, 7-H, 8-H).
13C-NMR (125 MHz, CDCl3): δ = 19.63 (2'-CH3), 33.74 (C-4), 36.03 (C-1), 70.54 (C-2), 73.27 (C-1'),
79.19 (C-3), 112.62 (C-3'), 126.16, 126.27 (C-6, C-7), 128.89, 128.92 (C-5, C-8), 133.63, 133.85 (C-4a,
C-8a), 142.21 (C-2'). IR (film): ν (cm-1) = 3440, 3065, 3021, 2907, 1655, 1494, 1454, 1373, 1216, 1112,
902, 744. UV (CH3CN): λmax (lg ε) = 265 nm (2.7335), 272 (2.7432). MS (DCI, 200 eV): m/z (%) = 253
(12) [M+NH3+NH4]+, 236 (100) [M+NH4]+. HPLC (Chiralcel OD): Wavelength: 211 nm, Eluent:
n-hexane / iso-propanol = 98:1, Flow: 0.8 mL/min, tR = 9.64 min , ee > 99.99 %.
rac-trans-2-(2-Methallyloxy)cyclopentanol (rac-25): According to general procedure A,
rac-trans-cyclopentane-1,2-diol (14, 1.00 g, 9.79 mmol) was reacted with β-methallyl chloride (8)
(974 mg, 1.05 mL, 10.8 mmol) within 3 h at 60 °C to provide rac-25 (666 mg, 4.27 mmol, 44%) as a pale
1
yellow oil after column chromatography on silica gel (P/Et2O = 3:1). H-NMR (300 MHz, CDCl3): δ =
1.75 (s, 3 H, 2'-CH3), 1.80 (d, J = 2.9 Hz, 1 H, OH), 1.50–2.16 (m, 6 H, 3-CH2, 4-H2, 5-H2), 3.66–3.72
(m, 1 H, 2-H), 3.89 (d, J = 12.6 Hz, 1 H, 1'-Ha), 3.94 (d, J = 12.6 Hz, 1 H, 1'-Hb), 4.14 (mc, 1 H,
1-H), 4.88 (mc, 1 H, 3'-Ha), 4.97 (mc, 1 H, 3'-Hb). 13C-NMR (150 MHz, CDCl3): δ = 19.54 (2'-CH3),
20.43, 29.22, 32.05 (C-3, C-4, C-5), 73.23 (C-1'), 76.79 (C-1), 86.23 (C-2), 111.93 (C-3'), 142.54 (C-2').
IR (film): ν (cm-1) = 3383, 3076, 2966, 1657, 1453, 1348, 1099, 898. MS (DCI, 200 eV): m/z (%) = 191
(60) [M+NH3+NH4]+, 174 (100) [M+NH4]+. HRMS (ESI): calcd for [C9H16O2 + Na]+: 179.1043;
confirmed.

HETEROCYCLES, Vol. 77, No. 2, 2009
1137
rac-cis-2-(2-Methallyloxy)cyclopentanol (rac-27): According
to
general
procedure
A,
meso-cyclopentane-1,2-diol (16, 1.10 g, 10.8 mmol) was reacted with β-methallyl chloride (8) (1.07 g,
1.16 mL, 11.9 mmol) within 2 h at 60 °C to provide rac-27 (1.01 g, 6.49 mmol, 60%) as a colorless liquid
1
after column chromatography on silica gel (P/Et2O = 3:1). H-NMR (300 MHz, CDCl3): δ = 1.42–1.91
(m, 6 H, 3-H2, 4-H2, 5-H2), 1.76 (s, 3 H, 2'-CH3), 2.50 (d, J = 4.0 Hz, 1 H, OH), 3.69–3.77 (m, 1 H, 2-H),
13
3.94 (mc, 2 H, 1'-H2), 4.06–4.12 (m, 1 H, 1-H), 4.89 (mc, 1 H, 3'-Ha), 4.98 (mc, 1 H, 3'-Hb). C-NMR
(150 MHz, CDCl3): δ = 19.50 (2'-CH3), 19.65, 27.81, 31.14 (C-3, C-4, C-5), 72.16 (C-1), 73.29 (C-1'),
80.95 (C-2), 112.11 (C-3'), 142.12 (C-2'). IR (film): ν (cm-1) = 3461, 3076, 2968, 1656, 1450, 1335, 1098,
899. MS (DCI, 200 eV): m/z (%) = 174 (100) [M+NH4]+. HRMS (ESI): calcd for [C9H16O2 + Na]+:
179.1043; confirmed.
rac-cis-2-(2-Methallyloxy)cyclohexanol
(rac-28):
According
to
general
procedure
A,
meso-cyclohexane-1,2-diol (17, 1.00 g, 8.61 mmol) was reacted with β-methallyl chloride (8) (857 mg,
926 μL, 9.47 mmol) within 4 h at 60 °C to provide rac-28 (519 mg, 3.03 mmol, 35%) as a colorless liquid
after column chromatography on silica gel (P/Et2O = 5:1). 1H−NMR (300 MHz, CDCl3): δ = 1.75 (s, 3 H,
2'-CH3), 1.20–1.88 (m, 8 H, 3-H2, 4-H2, 5-H2, 6-H2), 2.28 (s, 1 H, OH), 3.42 (mc, 1 H, 1-H), 3.83 (mc, 1 H,
2-H), 3.88 (d, J = 12.5 Hz, 1 H, 1'-Ha), 3.97 (d, J = 12.5 Hz, 1 H, 1'-Hb), 4.88 (mc, 1 H, 3'-Ha), 4.96 (mc,
1 H, 3'-Hb); 13C−NMR (125 MHz, CDCl3): δ = 19.52 (2'-CH3), 21.18, 22.12 (C-4, C-5), 26.49 (C-6),
30.42 (C-3), 68.69 (C-1'), 72.04 (C-1), 77.81 (C-2), 111.84 (C-3'), 142.50 (C-2'); IR (film): ν
(cm-1) = 3410, 3076, 2936, 2861, 1726, 1449, 1368, 1249, 1080, 985, 910, 848; MS (DCI, 200 eV):
m/z (%) = 188 (100) [M+NH4]+. HRMS (ESI): calcd for [C10H18O2 + Na]+: 193.1204; confirmed.
(rac)-cis-4-(2-Methallyloxy)tetrahydrofuran-3-ol (rac-29): According to general procedure A
cis-tetrahydrofuran-3,4-diol (18, 2.08 g, 20.0 mmol)) was reacted in dry DMF (60 mL) with β-methallyl
chloride (7,1.99 g, 22.0 mmol) for 6.5 h at rt. After work-up and column chromatography (silica gel,
1
n-pentane/Et2O = 1 / 1) rac-29 (1.54 g, 9.6 mmol, 48%) was provided as colorless oil. H NMR
(300 MHz, CDCl3) δ = 1.76 (sbr, 3 H, 3’-CH3), 2.86 (d, J = 5.7 Hz, 1 H, OH), 3.73–3.80 (m, 2 H, 5-Ha,
5-Hb), 3.88–3.93 (m, 2 H, 2-Ha, 2-Hb), 3.99–4.03 (m, 3 H, 4 –H, 1’-Ha, 1’-Hb), 4.28 (ddd, J = 10.5, 5.30,
5.30 Hz, 1 H, 3-H), 4.95 (sbr, 1 H, 3’-Ha), 5.00 (sbr, 1 H, 3’-Hb) ppm; 13C NMR (75 MHz, CDCl3):
δ = 19.37 (2’-CH3), 69.93 (C-5), 70.23 (C-3), 73.33, 74.21 (C-2, C-1’), 77.79 (C-4), 113.01 (C-3’),
-1
~
141.23 (C-2’) ppm; IR (Film): ν = 2941 cm , 2870, 1656, 1455, 1409, 1375, 1334, 1261, 1215, 1193,
1132, 1071, 1008, 905.6, 824.1, 731.4; MS (70 eV, EI): m/z (%) = 158.2 (12) [M]+, 103.1 (8) [M – C4H7]+,
87.1 (16) [M – OC4H7]+, 72.1 (48) [C4H7O]+, 55.1 (100) [C4H7]+; HRMS (ESI): calcd for
[C8H14O3 + Na]+: 181.0841; confirmed.

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HETEROCYCLES, Vol. 77, No. 2, 2009
tert-Butyl rac-trans-2-hydroxycyclohexyl(2-methallyl)carbamate rac-30: According to general
procedure A, rac-19 (1.15 g, 3.11 mmol) was reacted with β-methallyl bromide (7) (1.26 g, 940 μL,
9.33 mmol) within 24 h at 60 °C to provide rac-trans-tert-butyl 2-methallyl-(2-(tri-
isopropylsilyloxy)cyclohexyl)carbamate (1.02 g, 2.41 mmol, 77%) as a colorless liquid after column
1
chromatography on silica gel (P/Et2O = 100:1). H-NMR (300 MHz, CDCl3): δ = 1.03 (s, 18 H,
3 × CH(CH3)2), 1.39 (s, 9 H, 3 × C(CH3)2), 1.68 (s, 3 H, 2'-CH3), 1.10–2.06 (m, 11 H, CH(CH3)3, 3-H2,
4-H2, 5-H2, 6-H2), 3.47–4.23 (m, 4 H, 1-H, 2-H, 1'-H2), 4.78 (mc, 2 H, 3'-H2). 13C-NMR (150 MHz,
CDCl3): δ = 12.89 (3 × CH(CH3)2), 18.29 (3 × CH(CH3)2), 20.19 (2'-CH3), 24.48, 24.64 (C-4, C-5), 28.38
(C(CH3)3), 25.60, 36.47 (C-3, C-6), 64.64 (C-1'), 71.43 (C-1), 78.81 (C-2), 79.24 (C(CH3)3), 110.86
(C-3'), 143.15 (C-2'), 155.57 (CO2C(CH3)3). IR (film): ν (cm-1) = 2941, 2866, 1693, 1365, 1325, 1172,
1110, 989, 883, 775, 678. MS (ESI): m/z (%) = 448 (100) [M+Na]+. To a solution of rac-trans-tert-butyl
2-methallyl(2-(triisopropylsilyloxy)cyclohexyl)carbamate (1.02 g, 2.41 mmol) in THF (25 mL) was
added TBAF · 3 H2O (1.14 g, 3.61 mmol). The mixture was stirred at rt for 1 h, the solvent removed in
vacuo to provide rac-30 (405 mg, 1.50 mmol, 63 %) as a colorless liquid after column chromatography
1
on silica gel (P/Et2O = 1:1). H-NMR (300 MHz, CDCl3): δ = 1.42 (s, 9 H, C(CH3)3), 1.71 (s, 3 H,
2'-CH3), 1.10–1.33 (m, 4 H, 4-H2, 5-H2), 1.61–2.08 (m, 4 H, 3-H2, 6-H2), 2.40 (sbr, 1 H, OH), 3.70 (sbr,
2 H, 1'-H2), 3.43–3.78 (m, 2 H, 1-H, 2-H), 4.82 (mc, 2 H, 3'-H2). 13C-NMR (150 MHz, CDCl3): δ = 20.26
(2'-CH3), 24.35, 25.35 (C-4, C-5), 29.30, 35.07 (C-3, C-6), 28.31 (C(CH3)3), 49.13 (C-1'), 61.82, 71.43
(C-1, C-2), 79.96 (C(CH3)3), 110.57 (C-3'), 143.34 (C-2'), 157.03 (CO2C(CH3)3). IR (film):
ν (cm-1) = 3438, 2934, 2860, 1692, 1454, 1365, 1246, 1170, 977, 882, 768. MS (ESI): m/z (%) = 561 (11)
[2M+Na]+, 292 (100) [M+Na]+. HRMS (ESI): calcd for [C15H27NO3 + Na]+: 292.1883; confirmed.
tert-Butyl 2-hydroxyphenyl(2-methallyl)carbamate 32: According to general procedure A, 21 (2.84 g,
7.77 mmol) was reacted with β-methallyl bromide (7) (3.15 g, 2.35 mL, 23.3 mmol) within 18 h at rt to
provide tert-butyl 2-methallyl (2-(triisopropylsilyloxy)phenyl)carbamate (2.53 g, 6.02 mmol, 77 %) as a
1
colorless solid after column chromatography on silica gel (P/Et2O = 50:1). H-NMR (300 MHz,
DMSO-d6): δ = 1.15 (d, J = 7.1 Hz, 18 H, 3 × CH(CH3)2), 1.27–1.42 (m, 3 H, 3 × CH(CH3)2), 1.33 (s, 9 H,
C(CH3)3), 1.71 (s, 3 H, 2'-CH3), 2.99 (s, 2 H, 1'-H2), 4.68 (mc, 1 H, 3'-Ha), 4.75 (mc, 1 H, 3'-Hb),
6.82–6.92 (m, 2 H, 3-H, 5-H), 7.08 (dd, J = 8.2, 1.8 Hz, 1 H, 6-H), 7.14 (ddd, J = 8.3, 7.3, 1.8 Hz, 1 H,
4-H). 13C-NMR (75.5 MHz, DMSO-d6): δ = 11.88 (3 × CH(CH3)2), 17.21 (3 × CH(CH3)2), 19.38
(2'-CH3), 27.39 (C(CH3)3), 78.29 (C(CH3)3), 111.52 (C-3'), 118.27, 119.85, 127.28, 130.21 (C-3, C-4, C-5,
C-6), 130.21 (C-1), 141.17 (C-2'). IR (pellet): ν (cm-1) = 2967, 2946, 2867, 1693, 1599, 1581, 1499, 1381,
1365, 1346, 1300, 1284, 1254, 1206, 1173, 1142, 1116, 1057, 1040, 999, 939, 908, 881, 868, 801, 756,
719, 683, 669, 620, 582, 517, 441. UV (CH3CN): λmax (lg ε) = 272.5 nm (3.2899), 278 (3.2546). MS (EI,

HETEROCYCLES, Vol. 77, No. 2, 2009
1139
70 eV): m/z (%) = 419 (47) [M]+, 346 (100) [M-C4H9O]+. To
a
solution of tert-butyl
2-methallyl-(2-(tri-isopropylsilyloxy)phenyl)carbamate (2.53 g, 6.02 mmol) in THF (50 mL) was added
TBAF · 3 H2O (2.85 g, 9.02 mmol). The mixture was stirred at rt for 1 h, the solvent was removed in
vacuo to provide 32 (1.19 g, 4.52 mmol, 75%) as a colourless solid after column chromatography on
silica gel (P/Et2O = 10:1). 1H-NMR (300 MHz, CDCl3): δ = 1.49 (s, 9 H, C(CH3)3), 1.72 (s, 3 H, 2'-CH3),
4.16 (s, 2 H, 1'-H2), 4.87 (mc, 2 H, 3'-H2), 6.90 (dt, J = 7.4, 1.5 Hz, 1 H, 5-H), 7.01 (dd, J = 8.2, 1.2 Hz,
1 H, 3-H), 7.10–7.19 (m, 2 H, 4-H, 6-H). 13C-NMR (125 MHz, CDCl3): δ = 20.12 (2'-CH3), 28.17
(C(CH3)3), 56.79 (C-1'), 82.06 (C(CH3)3), 111.54 (C-3'), 119.5 (C-3), 121.06 (C-5), 127.69 (C-4, C-6),
130.90 (C-1), 141.25 (C-2'), 150.99 (C-2), 155.53 (CO2C(CH3)3). IR (pellet): ν (cm-1) = 3247, 2972, 1650,
1596, 1513, 1403, 1366, 1321, 1293, 1241, 1158, 1109, 1056, 902, 861, 759. UV (CH3CN): λmax (lg
ε) = 194 nm (4.6041), 274.5 (3.4139). MS (EI, 70 eV): m/z (%) = 263 (6) [M]+, 207 (66) [M-C4H7]+, 57
(100) [tBu]+.
DOMINO-WACKER-CARBONYLATION REACTION
Methyl rac-2-(2-methyloctahydrobenzo[b][1,4]dioxin-2-yl)acetate (rac-31) and (rac-32): According
to general procedure B, rac-22 (50.7 mg, 298 μmol) was reacted with p-benzoquinone (129 mg,
1.19 mmol) and PdCl2 (5.28 mg, 29.8 μmol) within 2 h to provide a mixture of rac-31 and rac-32
(59.7 mg, 262 μmol, 88%, 19:81) as a pale yellow liquid after column chromatography on silica gel
(P/Et2O = 5:1). 1H-NMR (300 MHz, C6D6): δ = 1.21 (s, 2.4 H, 2'-CH3), 1.49 (s, 0.6 H, 2'-CH3), 0.92–1.86
(m, 8 H, 5'-H2, 6'-H2, 7'-H2, 8'-H2), 2.32 (d, J = 14.4 Hz, 0.2 H, 2-Ha), 2.40 (d, J = 14.4 Hz, 0.2 H, 2-Hb),
2.51 (d, J = 13.5 Hz, 0.8 H, 2-Ha), 2.89 (ddd, J = 11.2, 9.2, 4.3 Hz, 1 H, 4a'-H), 3.04 (d, J = 13.5 Hz,
0.8 H, 2-Hb), 3.26 (s, 0.6 H, OCH3), 3.27 (dd, J = 11.5, 0.7 Hz, 0.8 H, 3'-Ha), 3.32 (s, 2.4 H, OCH3), 3.87
(ddd, J = 11.1, 9.0, 4.2 Hz, 0.2 H, 8a'-H), 3.54 (ddd, J = 11.0, 9.1, 4.6 Hz, 0.8 H, 8a'-H), 3.64 (dd,
J = 11.3, 0.9 Hz, 0.2 H, 3'-Ha), 3.69 (dd, J = 11.5 Hz, 0.8 H, 3'-Hb), 3.83 (d, J = 11.3 Hz, 0.2 H, 3'-Hb).
13C-NMR (150 MHz, C6D6): δ = 19.80, 23.66 (2'-CH3), 24.42, 24.43, 24.52, 24.53 (C-6', C-7'), 30.36,
30.38, 30.97 (C-5', C-8'), 38.86, 44.76 (C-2), 50.96, 51.00 (OCH3), 71.90, 72.03 (C-2'), 73.62, 73.75
(C-8a'), 74.24, 74.37 (C-3'), 80.61, 80.77 (C-4a'), 170.17, 170.91 (CO2CH3). IR (film): ν (cm-1) = 2939,
2864, 1738, 1513, 1322, 1227, 1095, 1020, 853. UV (CH3CN): λmax (lg ε) = 286 nm (2.2717). MS (DCI,
200 eV): m/z (%) = 246 (100) [M+NH4]+, 229 (45) [M+H]+. HRMS (ESI): calcd for [C12H20O4 + Na]+:
251.2746; confirmed.
Methyl
2-((4aR,10aR)-2-methyl-2,3,4a,5,10,10a-hexahydronaphtho[2,3-b][1,4]dioxin-2-yl)acetate
(33) and (34): According to general procedure B, 23 (45.0 mg, 206 μmol) was reacted with
p-benzoquinone (89.1 mg, 825 μmol) and PdCl2 (3.62 mg, 22.9 μmol) within 90 min to provide a mixture

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HETEROCYCLES, Vol. 77, No. 2, 2009
of 37 and 38 (41.0 mg, 148 μmol, 72%, 34:64) as a colorless liquid after column chromatography on
1
silica gel (P/Et2O = 5:1). H-NMR (300 MHz, CDCl3): δ = 1.28 (s, 2 H, 2'-CH3), 1.50 (s, 1 H, 2'-CH3),
2.51 (s, 0.7 H, 2-H2), 2.68 (d, J = 13.7 Hz, 0.7 H, 2-Ha), 2.81 (mc, 2 H, 10'-Ha, 5'-Ha), 2.96 (dd, J = 16.0,
5.9 Hz, 1 H, 5'-Hb), 3.07 (d, J = 13.7 Hz, 0.7 H, 2-Hb), 3.06, 3.12 (2 x dd, J = 6.0, 2.5 Hz, 1 H, 10'-Hb),
3.49 (d, J = 11.8 Hz, 1 H, 3'-Ha), 3.50 (mc, 1 H, 4a' H), 3.68 (s, 3 H, OCH3), 3.82 (d, J = 11.8 Hz, 1 H,
3'-Hb), 3.92 (ddd, J = 10.8, 9.8, 5.8 Hz, 0.66 H, 10a'-H), 4.00 (ddd, J = 10.8, 9.9, 5.9 Hz, 0.34 H, 10a'-H),
13
7.10 (mc, 4 H, 6'-H, 7'-H, 8'-H, 9'-H). C-NMR (125 MHz, CDCl3): δ = 19.54, 23.33 (2'-CH3), 34.33,
34.34 (C-5'), 35.01, 35.03 (C-10'), 38.54, 44.54 (C-2), 51.60 (OCH3), 69.95, 70.12 (C-10a'), 73.48, 73.72
(C-3'), 76.43, 76.60 (C-4a'), 126.22, 126.24, 126.26, 128.96, 128.99 (C-6', C-7', C-8', C-9'), 133.48,
133.56 (C-5a'), 133.76, 133.80 (C-9a'), 170.47, 171.16 (CO2CH3). MS (DCI, 200 eV): m/z (%) = 574 (10)
[2M+Na]+, 299 (100) [M+Na]+. HRMS: calcd for [C16H20O4 + Na]+: 299.1259; confirmed.
Methyl rac-2-(2-methyl-hexahydro-2H-cyclopenta[b][1,4]dioxin-2-yl)acetate (rac-35) and (rac-36):
According to general procedure B, rac-27 (49.7 mg, 318 μmol) was reacted with p-benzoquinone
(127 mg, 1.27 mmol) and PdCl2 (5.65 mg, 31.8 μmol) within 75 min to provide a mixture of rac-35 and
rac-36 (58.7 mg, 274 μmol, 86%, 29:71) as a pale yellow liquid after column chromatography on silica
1
gel (P/Et2O = 8:1). H-NMR (600 MHz, CDCl3): δ = 1.21 (s, 2.1 H, 2'-CH3), 1.35 (s, 0.9 H, 2'-CH3),
1.41–2.03 (m, 6 H, 5'-H2, 6'-H2, 7'-H2), 2.46 (d, J = 14.1 Hz, 0.3 H, 2-Ha), 2.52 (d, J = 14.1 Hz, 0.3 H,
2-Hb), 2.66 (d, J = 13.8 Hz, 0.7 H, 2-Ha), 2.85 (d, J = 13.8 Hz, 0.7 H, 2-Hb), 3.29 (d, J = 11.7 Hz, 0.3 H,
3'-Ha), 3.41 (d, J = 11.8 Hz, 0.7 H, 3'-Ha), 3.53 (d, J = 11.8 Hz, 0.7 H, 3'-Hb), 3.65 (s, 0.9 H, OCH3), 3.66
(s, 2.1 H, OCH3), 3.81 (d, J = 11.7 Hz, 0.3 H, 3'-Hb), 3.96 (dt, J = 7.8, 4.5 Hz, 0.3 H, 4a'-H), 4.01 (dt,
J = 8.4, 4.5 Hz, 0.7 H, 4a'-H), 4.04 (dd, J = 4.7, 2.3 Hz, 0.3 H, 7a'-H), 4.12 (dt, J = 4.8, 1.7 Hz, 0.7 H,
7a'-H). 13C-NMR (125 MHz, CDCl3): δ = 20.12, 23.70 (2'-CH3), 20.39, 20.51, 24.49, 25.75, 30.76, 30.93
(C-5', C-6', C-7'), 38.93, 44.18 (C-2), 51.46, 51.52 (OCH3), 66.19, 66.59 (C-3'), 69.94, 70.21 (C-7a'),
70.59, 70.69 (C-2'), 76.29, 76.91 (C-4a'), 170.77, 171.28 (CO2CH3). IR (film): ν (cm-1) = 2953, 1737,
1437, 1316, 1223, 1131, 1024, 969, 914. UV (CH3CN): λmax (lg ε) = 288 nm (1.6481). MS (DCI,
200 eV): m/z (%) = 249 (5) [M+NH3+NH4]+, 232 (100) [M+NH4]+, 215 (75) [M+H]+. HRMS (ESI): calcd
for [C11H18O4 + Na]+: 237.1103; confirmed.
tert-Butyl
rac-2-(2-methoxy-2-oxoethyl)-2-methyloctahydrobenzo[b][1,4]oxazine-4-carboxylate
(rac-37) and (rac-38): According to general procedure B, rac-30 (49.0 mg, 181 μmol) was reacted with
p-benzoquinone (78.6 mg, 728 μmol) and PdCl2 (3.23 mg, 18.1 μmol) within 4 h to provide a mixture of
rac-37 and rac-38 (47.3 mg, 144 μmol, 79%, 22:78) as a colorless liquid after column chromatography
1
on silica gel (P/Et2O = 5:1). H-NMR (600 MHz, CDCl3): δ = 1.12 (ddd, J = 23.5, 12.0, 3.4 Hz, 1 H,

HETEROCYCLES, Vol. 77, No. 2, 2009
1141
5a-Ha), 1.21 (s, 2.3 H, 2-CH3), 1.27 (s, 0.7 H, 2-CH3), 1.24–1.32 (m, 3 H, 6-Ha, 7-Ha, 8-Ha), 1.42 (s, 2 H,
C(CH3)3), 1.43 (s, 7 H, C(CH3)3), 1.64 (mc, 1 H, 7-Hb), 1.72 (mc, 1 H, 6-Hb), 1.86 (mc, 1 H, 8-Hb), 2.18
(dd, J = 10.3, 2.3 Hz, 1 H, 5-Hb), 2.42 (d, J = 15.9 Hz, 0.2 H, 1'-Ha), 2.46 (d, J = 14.1 Hz, 0.8 H, 1'-Ha),
2.53 (d, J = 14.1 Hz, 0.8 H, 1'-Hb), 3.09 (d, J = 14.6 Hz, 0.2 H, 3-Ha), 3.26 (ddd, J = 10.8, 10.7, 3.4 Hz,
1 H, 4a-H), 3.43 (d, J = 14.3 Hz, 0.8 H, 3-Ha), 3.48 (ddd, J = 10.7, 8.4, 4.0 Hz, 1 H, 8a-H), 3.63 (s, 0.7 H,
OCH3), 3.65 (s, 2.3 H, OCH3), 3.78 (d, J = 14.3 Hz, 0.8 H, 3-Hb), 4.06 (d, J = 14.6 Hz, 0.2 H, 3-Hb).
13C-NMR (125 MHz, CDCl3): δ = 23.37, 25.67 (2-CH3), 24.40, 24.57, 24.62 (C-6, C-7), 28.30, 28.38
(C(CH3)3), 29.31, 29.56 (C-5), 31.98, 32.03 (C-8), 43.09, 44.00 (C-1), 45.77, 45.89 (C-3), 51.34, 51.58
(OCH3), 60.21, 60.28 (C-4a), 71.78, 72.68 (C-8a), 75.47, 75.73 (C-2), 79.69 (C(CH3)3), 155.36, 155.72
(CO2C(CH3)3), 170.65, 170.78 (CO2OCH3). IR (Film): ν (cm-1) = 2935, 1740, 1695, 1407, 1366, 1157,
1016, 862. HRMS (ESI): calcd for [C17H29NO5 + Na]+: 350.1943; confirmed.
tert-Butyl 2-(2-methoxy-2-oxoethyl)-2-methyl-2,3-dihydrobenzo[b][1,4]oxazine-4-carboxylate 39: A
mixture of Pd(OTFA)2 (3.21 mg, 9.65 μmol) and (S,S)-Bn-BOXAX (16.6 mg, 28.9 μmol) in MeOH
(2 mL) was stirred at rt for 10 min. Afterwards p-benzochinone (83.3 mg, 772 μmol) and 32 (50.8 mg,
193 μmol) were added and the mixture stirred under CO-atmosphere at 60 °C for 6 h. After workup
according to general procedure B and column chromatography on silica gel (P/Et2O = 5:1) 30 was
1
obtained as a yellow liquid (43.1 mg, 134 μmol, 70%). H-NMR (300 MHz, C6D6): δ = 1.30 (s, 3 H,
2-CH3), 1.41 (s, 9 H, C(CH3)3), 2.38 (d, J = 15.4 Hz, 1 H, 1'-Ha), 2.44 (d, J = 15.4 Hz, 1 H, 1'-Hb), 3.23 (s,
3 H, OCH3), 3.52 (d, J = 13.5 Hz, 1 H, 3-Ha), 3.94 (d, J = 13.5 Hz, 1 H, 3-Hb), 6.84 (mc, 2 H, 6-H, 7-H),
13
6.95 (mc, 8 H), 8.07 (mc, 1 H, 5-H). C-NMR (125 MHz, C6D6): δ = 22.40 (2-CH3), 28.11 (C(CH3)3),
41.26 (C-1'), 48.93 (C-3), 51.10 (OCH3), 74.67 (C-2), 80.94 (C(CH3)3), 117.68 (C-8), 124.87, 127.92
(C-6, C-7), 128.29 (C-5), 145.49 (CO2C(CH3)3), 169.77 (CO2OCH3). IR (film): ν (cm-1) = 2978, 1784,
1704, 1586, 1495, 1372, 1151, 1020, 927, 861. UV (CH3CN): λmax (lg ε) = 211 nm (4.5992), 239.5
(3.9811), 281.5 (3.5323). MS (EI, 70 eV): m/z (%) = 344 (100) [M+Na]+, 665 (11) [2M+Na]+. HRMS
(ESI): calcd for [C17H23NO5 + Na]+: 344.3580; confirmed.
DOMINO-WACKER-MIZOROKI-HECK REACTION
rac-trans-(E)-Methyl 4-(2-methylhexahydro-2H-cyclopenta[b][1,4]dioxin-2-yl)but-2-enoate (rac-40)
and (rac-41): According to general procedure C rac-25 (50.0 mg, 0.330 mmol) was reacted with methyl
acrylate (9, 78.0 mg, 0.96 mmol) for 3 d at rt. After work-up and column chromatography (silica gel,
n-pentane/EtOAc = 4 / 1) rac-40 and rac-41 (30.0 mg, 0.125 mmol, 39%, 50:50 mixture) were provided
1
as yellow oil. H-NMR (300 MHz, CDCl3, * indicates the minor epimer ): δ = 1.12*, 1.39 (s, 1.8 H,
2'-CH3), 1.39–1.92 (m, 6 H, 5'-H2, 6-H2, 7'-H2), 2.35 (m, 2 H, 4-H2), 3.05–3.30 (m, 1 H, 4'a-H), 3.22–3.72

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HETEROCYCLES, Vol. 77, No. 2, 2009
(m, 3 H, 3-H2, 7'a-H), 3.74 (s, 3 H, OCH3), 5.90 (m, 1 H, 2-H), 7.00 (m, 1 H, 3-H). 13C-NMR (125 MHz,
CDCl3): δ = 16.25, 20.43 (2-CH3), 23.14, 23.85, 23.88, 24.46, 24.48(C-5', C-6', C-7'), 36.22, 42.35 (C-4),
51.42, 51.44 (OCH3), 73.00, 73.17 (C-3'), 74.21, 74.42 (C-7a'), 74.54, 74.72 (C-2'), 81.39, 81.68(C-4a'),
123.93, 123.97 (C-2), 143.61, 144.15 (C-3), 166.55 (CO2CH3). IR (film): ν (cm-1) = 2973, 2881, 1724,
1657, 1436, 1384, 1274, 1127, 1022, 984, 895. UV (CH3CN): λmax (lg ε) = 206 nm (4.0901). MS (DCI,
200 eV): m/z (%) = 258 (100) [M+NH4]+.
rac-cis-(E)-5-(2-Methylhexahydro-2H-cyclopenta[b][1,4]dioxin-2-yl)pent-3-en-2-one (rac-42) and
(rac-43): According to general procedure C rac-27 (50.0 mg, 0.330 mmol) was reacted with methyl vinyl
ketone (10b, 67.3 mg, 0.96 mmol) for 2 d at rt. After work-up and column chromatography (silica gel,
n-pentane/EtOAc = 4 / 1) rac-42 and rac-43 (51.0 mg, 0.228 mmol, 70%, 50:50 mixture) were provided
as yellow oil. 1H-NMR (300 MHz, CDCl3, * indicates the minor epimer ): δ = 1.09, 1.24 (s, 3 H, 2'-CH3),
1.44–2.12 (m, 6 H, 5'-H2, 6'-H2, 7'-H2), 2.25–2.50 (m, 2 H, 4-H2), 2.25 (s, 3 H, 1-CH3), 3.19, 3.26 (d, J =
11.7 Hz, 1 H, 3'-Ha), 3.57 (d, J = 11.7 Hz, 1 H, 3'-Hb), 4.03 (m, 2 H, 4'a-H, 7'a-H), 6.13 (m, 1 H, 2-H),
6.85 (m, 1 H, 3-H). 13C-NMR (150 MHz, CDCl3): δ = 20.24, 23.57 (2'-CH3), 20.27, 20.57, 24.34, 25.84,
30.65, 30.98 (C-5', C-6', C-7'), 26.70, 26.88 (1-CH3), 36.61, 42.80 (C-4), 66.55, 67.29 (C-3'), 69.79, 70.17
(C-7a'), 71.34, 71.40 (C-2'), 76.21, 76.96 (C-4a'), 133.71, 133.90 (C-2) 143.25, 143.38 (C-3), 198.39
(COCH3). IR (film): ν (cm-1) = 2968, 1697, 1673, 1628, 1435, 1361, 1254, 1130, 1057, 981. UV
(CH3CN): λmax (lg ε) = 221 nm (1.1073). HRMS (ESI): calcd for [C13H20O3 + Na]+: 247.13047;
confirmed.
Methyl rac-cis-(E)-4-(2-methyl-hexahydro-2H-cyclopenta[b][1,4]dioxin-2-yl)but-2-enoate rac-44
and rac-45: According to general procedure C rac-27 (50.0 mg, 0.330 mmol) was reacted with methyl
acrylate (57, 78.0 mg, 0.96 mmol) for 3 d at rt. After work-up and column chromatography (silica gel,
n-pentane/EtOAc = 4 / 1) rac-44 and rac-45 (47.0 mg, 0.196 mmol, 61%, 50:50 mixture) were provided
as yellow oil. 1H-NMR (300 MHz, CDCl3): δ = 1.09 (s, 1.5 H, 2'-CH3), 1.24 (s, 1.5 H, 2'-CH3), 1.41–2.12
(m, 6 H, 5'-H2, 6'-H2, 7'-H2), 2.25–2.45 (m, 2 H, 4-H2), 3.18 (d, J = 11.6 Hz, 0.5 H, 3'-Ha), 3.25 (d,
J = 11.7 Hz, 0.5 H, 3'-Ha), 3.55 (d, J = 11.7 Hz, 0.5 H, 3'-Hb), 3.57 (d, J = 11.6 Hz, 0.5 H, 3'-Hb), 3.74 (s,
13
3 H, OCH3), 4.03 (m, 2 H, 4'a-H, 7'a-H), 5.90 (m, 1 H, 2-H), 7.00 (m, 1 H, 3-H). C-NMR (125 MHz,
CDCl3): δ = 20.09, 23.64 (2'-CH3), 20.37, 20.59, 24.53, 25.73, 30.78, 30.99 (C-5', C-6', C-7'), 36.51,
42.55 (C-4), 51.45 (OCH3), 66.58, 67.27 (C-3'), 69.85, 70.24 (C-7a'), 71.39, 71.42 (C-2'), 76.87(C-4a'),
123.71, 123.90 (C-2) 144.36, 144.59 (C-3), 166.66 (CO2CH3). IR (film): ν (cm-1) = 2953, 1724, 1657,
1436, 1274, 1198, 1131, 1091, 1057. UV (CH3CN): λmax (lg ε) = 206 nm (4.0711). MS (EI):
m/z (%) = 141 (100) [M–C4H7O2]+. HRMS (ESI): calcd for [C13H20O4 + Na]+: 263.12538; confirmed.

HETEROCYCLES, Vol. 77, No. 2, 2009
1143
(rac)-4-(2-Methylhexahydro-(cis-furo[3,4-b][1,4]dioxin)-2-yl)but-2-enal (rac-46) and (rac-47): Ac-
cording to general procedure C rac-29 (51.0 mg, 0.320 mmol) was reacted with acrolein (10a, 54.0 mg,
0.960 mmol) for 2 d at rt. After work-up and column chromatography (silica gel, n-pentane/EtOAc =
1
2 / 1) rac-46 and rac-47 (22.6 mg, 0.106 mmol, 33%, 65:35 mixture) were provided as yellow oil. H
NMR (300 MHz, CDCl3, * indicates the minor epimer): δ = 1.23*, 1.26 (s, 3 H, 2’-CH3), 2.38–2.63,
2.98–3.06* (m, 2 H, 4-Ha, 4-Hb), 3.23, 3.30* (d, J = 11.9 Hz, 1 H, 3’-Ha), 3.59, 3.60* (d, J = 11.9 Hz, 1 H,
3’-Hb), 3.79–4.04 (m, 4 H, 5’-Ha, 5’-Hb, 7’-Ha, 7’-Hb), 4.14–4.35 (m, 2 H, 4a’-H, 7a’-H), 6.14, 6.21*
(dddd, J = 15.7, 7.8, 1.3, 1.3 Hz, 1 H, 2-H), 6.85*, 6.94 (ddd, J = 15.7, 7.7, 6.9 Hz, 1 H, 4-H), 9.53, 954*
(d, J 7.8 Hz, 1 H, 1-H) ppm; 13C NMR (75 MHz, CDCl3, * indicates the minor epimer): δ = 20.25, 23.55*
(2’-CH3), 37.18*, 42.84 (C-4), 66.25*, 67.55*, 67.71, 68.26, 68.57*, 68.93, 73.02*, 73.13, 73.47*, 74.62
(C-3’, C-4a’, C-5’, C-7’, C-7a’), 71.36*, 71.53 (C-2’), 135.6, 135.8* (C-2), 152.5*, 152.9 (C-3), 193.5*,
193.7 (C-1) ppm; MS (ESI): m/z (%) = 251.1 (50) [M + K]+, 235.1 (100) [M + Na]+; HRMS (ESI): calcd
for [C11H16O4 + Na]+: 235.0946; confirmed.
(rac)-5-(2-Methylhexahydro(cis-furo[3,4-b][1,4]dioxin)-2-yl)pent-3-en-2-one (rac-48) and (rac-49):
According to general procedure C rac-29 (51.0 mg, 0.320 mmol) was reacted with methyl vinyl ketone
(10b, 78.0 mg, 0.960 mmol) for 2 d at rt. After work-up and column chromatography (silica gel,
n-pentane/EtOAc = 2 / 1) rac-48 and rac-49 (49.0 mg, 0.220 mmol, 68%, 55:45 mixture) were provided
as yellow oil. 1H NMR (300 MHz, CDCl3, * indicates the minor epimer): δ = 1.17*, 1.27 (s, 3 H, 2’-CH3),
2.27*, 2.28 (s, 3 H, 1-H3), 2.31–2.54, 2.85–2.96* (m, 1 H, 5-Ha), 3.21–3.33, 3.58–3.62* (m, 1 H, 3’-Hb),
3.81–4.06 (m, 4 H, 5’-Ha, 5’-Hb, 7’-Ha, 7’-Hb), 4.18–4.35 (m, 2 H, 4a’-H, 7a’-H), 6.12*, 6.20 (ddd, J =
15.9, 1.2, 1.2 Hz, 1 H, 3-H), 6.79, 6.87* (ddd, J = 15.9, 8.0, 6.9 Hz, 1 H, 4-H) ppm; 13C NMR (75 MHz,
CDCl3, * indicates the minor epimer): δ = 20.12, 23.56* (2’-CH3), 26.86, 27.10* (C-1), 37.01, 42.68
(C-5), 66.27*, 68.19 (C-3’), 67.49*, 67.59, 73.04*, 73.13 (C-5’, C-7’), 68.49*, 68.81 (C-4a’), 71.40,
71.56 (C-2’), 73.48*, 74.56 (C-7a’), 134.1, 134.2* (C-3), 142.3, 142.7* (C-4), 198.1*, 198.4 (C-2) ppm;
-1
~
IR (Film): ν = 2955 cm , 2926, 2872, 1697, 1673, 1628, 1461, 1428, 1363, 1256, 1186, 1132, 1079,
984.5, 951.0, 897.3, 870.1, 831.3, 789.6, 716.6; UV (CH3CN): λmax (lg ε) = 222.0 (4.058) nm; MS (ESI):
m/z (%) = 265.1 (15) [M + K]+, 249.1 (100) [M + Na]+, 244.2 (60) [M + NH4]+, 227.1 (50) [M + H]+;
HRMS (ESI): calcd for [C12H18O4 + Na]+: 249.1103; confirmed.
(rac)-6-(2-Methylhexahydro(cis-furo[3,4-b][1,4]dioxin)-2-yl)hex-4-en-3-one (rac-50) and (rac-51):
According to general procedure C rac-29 (51.0 mg, 0.320 mmol) was reacted with ethyl vinyl ketone (10c,
80.1 mg, 0.960 mmol) for 3 d at rt. After work-up and column chromatography (silica gel,
n-pentane/EtOAc = 2 / 1) rac-50 and rac-51 (52.0 mg, 0.220 mmol, 62%, 70:30 mixture) were provided
as yellow oil. 1H NMR (300 MHz, CDCl3, * indicates the minor epimer) δ = 1.02*, 1.02 (t, J = 7.3 Hz, 3

1144
HETEROCYCLES, Vol. 77, No. 2, 2009
H, 1-H3), 1.08, 1.17* (s, 3 H, 2’-CH3), 2.22–2.43, 2.74–2.80* (m, 2 H, 6-Ha, 6-Hb), 2.25 (q, J = 7.30 Hz,
2-H2), 3.13–3.25 (m, 1 H, 3’-Ha), 3.48–3.54 (m, 1 H, 3’-Hb), 3.71–3.96 (m, 4 H, 5’-Ha, 5’-Hb, 7’-Ha,
7’-Hb), 4.10–4.25 (m, 2 H, 4a’-H, 7a’-H), 6.05*, 6.13 (ddd, J = 15.9, 1.4, 1.4 Hz, 1 H, 4-H), 6.74, 6.80*
(ddd, J = 15.9, 8.1, 6.9 Hz, 1 H, 5-H) ppm; 13C NMR (75 MHz, CDCl3, * indicates the minor epimer): δ
= 7.86, 7.92* (C-1), 19.94*, 23.43 (2’-CH3), 32.96*, 33.28 (C-2), 36.87, 42.51* (C-6), 66.12, 67.31,
67.34*, 67.98*, 68.35, 68.67* 69.98*, 71.45, 72.91, 72.98*, 73.35, 74.36* (C-2’, C-3’, C-4a’, C-5’, C-7’,
C-7a’), 132.9*, 132.9 (C-4), 140.9*, 141.1 (C-5), 200.4, 200.7* (C-3) ppm; MS (ESI): m/z (%) = 481.28
[2M + H]+, 265.1 (100) [M + Na]+, 241.1 (6) [M + H]+; HRMS (ESI): calcd for [C13H20O4 + Na]+:
263.1259; confirmed.
(rac)-4-(2-Methylhexahydro(cis-furo[3,4-b][1,4]dioxin)-2-yl)but-2-enoic acid methyl ester (rac-52)
and (rac-53): Accor-ding to general procedure C rac-29 (51.0 mg, 0.320 mmol) was reacted with methyl
acrylate (9, 78.0 mg, 0.960 mmol) for 2 d at rt. After work-up and column chromatography (silica gel,
n-pentane/EtOAc = 7 / 1 → 4 / 1) rac-52 and rac-53 (60.0 mg, 0.230 mmol, 77%, 60:40 mixture) were
provided as yellow oil. 1H NMR (300 MHz, CDCl3, * indicates the minor epimer) δ = 1.12, 1.22* (s, 3 H,
2’-CH3), 2.25–2.47, 2.74–2.84* (m, 2 H, 4-Ha, 4-Hb), 3.17–3.28 (m, 1 H, 3’-Ha), 3.51–3.57 (m, 1 H,
3’-Hb), 3.70*, 3.70 (s, 3 H, OCH3), 3.75–4.01 (m, 4 H, 5’-Ha, 5’-Hb, 7’-Ha, 7’-Hb), 4.13–4.29 (m, 2 H,
4a’-H, 7a’-H), 5.85*, 5.91 (ddd, J = 15.7, 1.4, 1.4 Hz, 1 H, 2-H), 6.87–6.96 (m, 1 H, 3-H) ppm; 13C NMR
(75 MHz, CDCl3, * indicates the minor epimer): δ = 19.80*, 23.47 (2’-CH3), 36.68, 42.18* (C-4), 51.46*,
51.50 (OCH3), 66.10, 67.14*, 67.29, 67.98*, 68.39, 68.72*, 69.98*,71.33*, 71.47, 73.02, 73.39, 74.25*
(C-2’, C-3’, C-4a’, C-5’, C-7’, C-7a’), 125.1*, 124.2 (C-2), 143.6*, 143.7 (C-3), 166.5, 166.5* (C-1)
-1
~
ppm; IR (Film): ν = 2952 cm , 2874, 1723, 1657, 1460, 1437, 1276, 1201, 1133, 1079, 987.2, 950.6,
906.7, 853.0, 791.1, 731.8; UV (CH3CN): λmax (lg ε) = 207.0 (4.058) nm; MS (ESI): m/z (%) = 506.9 (12)
[2M + Na]+, 265.1 (100) [M + Na]+, 243.1 (6) [M + H]+; HRMS (ESI): calcd for [C11H18O5 + Na]+:
265.1052; confirmed.
4-(2-Methyl-2,3,9,9a-tetrahydro-4aH-1,4-dioxafluoren-2-yl)but-2-enoic acid methyl ester (54) and
(55): According to general procedure C 24 (68.4 mg, 0.320 mmol) was reacted with methyl acrylate (9,
78.0 mg, 0.960 mmol) for 2 d at rt. After work-up and column chromatography (silica gel,
n-pentane/EtOAc = 7 / 1) 54 and 55 (51.8 mg, 0.180 mmol, 56%, 60:40 mixture) were provided as pale
1
yellow oil. H NMR (300 MHz, CDCl3, * indicates the minor epimer): δ = 1.38, 1.81* (s, 3 H, 2’-CH3),
2.05 (ddd, J = 14.1, 8.4, 1.3 Hz, 1 H, 4-Ha), 2.17 (ddd, J = 14.1, 7.0, 1.4 Hz, 1 H, 4-Hb), 2.48* (ddd, J =
14.1, 8.4, 1.3 Hz, 1 H, 4-Ha), 2.72* ddd, J = 14.1, 7.0, 1.4 Hz, 1 H, 4-Hb), 2.95–3.11 (m, 2 H, 9-Ha, 9-Hb),
3.24–3.47 (m, 2 H, 3’-Ha, 3’-Hb), 3.69*, 3.75 (s, 3 H, OCH3), 4.56 (mc, 1 H, 9a’-H), 5.04–5.08 (m, 1 H,
4a’-H), 5.76*, 5.98 (ddd, J = 15.6, 1.4, 1.4 Hz, 1 H, 2-H), 6.84*, 7.01 (ddd, J = 15.6, 8.4, 7.0 Hz, 1 H,

HETEROCYCLES, Vol. 77, No. 2, 2009
1145
13
3-H), 7.23–7.39 (m, 4 H, 5-H, 6-H, 7-H, 8-H) ppm; C NMR (75 MHz, CDCl3, * indicates the minor
epimer): δ = 18.73, 19.57* (2’-CH3), 35.76, 37.67*, 37-73, 41.84* (C-4, C9’), 51.37*, 51, 45
(OCH3),66.74, 67.35* (C-3’), 70.53, 70.75* (C9a’), 71.17*, 71.30 (C-2’), 77.95, 78.31* (C-4a’), 123.8*,
124.1 (C-2), 125.5*, 125.5, 125.5*, 125.6, 126.6, 128.1*, 128.1, 128.9* (C-5’, C-6’, C-7’, C-8’), 138.9,
139.0* (C-4b’), 140.8, 140.9* (C-8a’), 143.5*, 144.5 (C-3), 166.5*, 166.6 (C-1) ppm; MS (ESI): m/z (%)
= 311.1 (100) [M + Na]+, 289.1 (25) [M + H]+; HRMS (ESI): calcd for [C17H20O4 + Na]+: 311.1259;
confirmed.
2-(3-Methoxycarbonylallyl)-2-methyl-2,3,9,9a-tetrahydro-4aH-1-oxa-4-azafluorene-4-carboxylic
acid tert-butyl ester (56) and (57): According to general procedure C 21 (106.0 mg, 0.320 mmol) was
reacted with methyl acrylate (9, 78.0 mg, 0.960 mmol) for 4 d at rt. After work-up and column
chromatography (silica gel, n-pentane/EtOAc = 7 / 1) 56 and 57 (117 mg, 0.300 mmol, 91%, 60:40
1
mixture) were provided as pale yellow oil. H NMR (300 MHz, DMSO, 100°C, * indicates the minor
epimer): δ = 0.92, 1.21* (s, 3 H, 2’-CH3), 1.51, 1.52* (s, 9 H, OC(CH3)3), 2.24–2.16 (m, 1 H, 1’-Ha), 2.49
(mc, 1 H, 1-’Hb), 2.46–2.71 (m, 2 H, 3-Ha, 3-Hb), 2.76 (d, J = 15.6 Hz, 1 H, 9-Ha), 3.09 (dd, J = 15.6, 4.3
Hz, 9-Hb), 3.63, 3.69* (s, 3 H, OCH3), 4.53–4.58 (m, 1 H, 9a-H), 5.32 (sbr, 1 H, 4a-H), 5.83, 6.00* (ddd, J
= 15.6, 1.3, 1.3 Hz, 1 H, 3’-H), 6.74, 6.88* (ddd, J = 15.6, 7.6, 7.6 Hz, 1 H, 2’-H), 7.04–7.07 (m, 1 H),
7.19–7.28 (m, 4 H, 5-H, 6-H, 7-H, 8-H) ppm; 13C NMR (75 MHz, CDCl3, * indicates the minor epimer):
δ = 17.88, 23.49* (2-CH3), 27.51*, 27.55 (C(CH3)3), 34.62, 37.35, 37.42*, 41.57 (C-3, C-9, C-1’), 50.31,
50.40* (OCH3), 70.91*, 71.04 (C-9a), 71.34*, 71.56 (C-2), 79.06, 79.19* (OC(CH3)3), 122.4, 124.6,
124.6*, 125.9, 125.9*, 126.9, 126.9* (C-5, C-6, C-7, C-8), 123.1, 123.3* (C-3’), 138.7*, 138.7, 140.5,
140.5* (C-4b, C-8a), 142.8, 143.4* (C-2’), 154.1, 154.3 (C=O), 165.1, 165.2* (C-1’) ppm; IR (Film):
-1
~
ν = 2977 cm , 2931, 1724, 1694, 1417, 1393, 1366, 1320, 1276, 1219, 1198, 1169, 1131, 1100, 1084,
1065, 1019, 991.1, 957.4, 927.2, 910.0, 880.6, 862.8, 851.0, 823.7, 746.2; UV (CH3CN): λmax
(lg ε) = 264.5 (3.014), 271.0 (3.017), 257.5 (2.92,) nm; MS (ESI): m/z (%) = 426.2 (25) [M + K]+, 410.2
(100) [M + Na]+, 405.2 (90) [M + NH4]+, 388.2 (20) [M + H]+; HRMS (ESI): calcd for
[C22H29NO5 + Na]+: 410.1943; confirmed.
ACKNOWLEDGEMENTS
This work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the Fonds der Chemischen
Industrie (VCI). C.R. thanks the Fonds der Chemischen Industrie for a Ph.D. scholarship. Generous gifts
of chemicals by BASF, Bayer-Schering, and Wacker Chemie are greatly appreciated.

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HETEROCYCLES, Vol. 77, No. 2, 2009
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