7-Siloxy-Substituted Hexahydronaphthalene Derivatives: Samarium Diiodide Promoted Synthesis and Typical Reactions

Article abstract of DOI:10.1055/s-0040-1707889

The samarium diiodide promoted reductive cyclization of a series of γ-aryl ketones with acetoxy, alkoxy, and siloxy groups in ortho -, meta -, and para -positions was investigated. Only precursors with p -acetoxy, p - tert -butoxy, or p -siloxy substituen

Full text of DOI:10.1055/s-0040-1707889

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–J
paper
A
en
A. Niermann, H.-U. Reissig
Paper
Synthesis
7-Siloxy-Substituted Hexahydronaphthalene Derivatives:
Samarium Diiodide Promoted Synthesis and Typical Reactions
André Niermann
Hans-Ulrich Reissig*
0
0
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0-0
0
0
2-
1
9
1
2-9
6
3
5
additions
SmI2
Institut für Chemie und Biochemie, Freie Universität Berlin,
Takustr. 3, 14195 Berlin, Germany
hans.reissig@chemie.fu-berlin.de
O
TBSO
TBSO
H
OH
hydrolysis
Dedicated to Professor Helmut Vorbrüggen on the occasion of
his 90th birthday
aldol reaction
cycloadditions
Received: 21.04.2020
Accepted after revision: 25.05.2020
Published online: 24.06.2020
SmI2, THF
ROH
O
R
DOI: 10.1055/s-0040-1707889; Art ID: ss-2020-t0216-op
R
H
OH
A
H
B
Abstract The samarium diiodide promoted reductive cyclization of a
series of -aryl ketones with acetoxy, alkoxy, and siloxy groups in ortho-,
meta-, and para-positions was investigated. Only precursors with
p-acetoxy, p-tert-butoxy, or p-siloxy substituents furnished decent yields
of the desired 7-oxy-1,2,3,4,6,8a-hexahydronaphthalene derivatives.
The products were formed without contamination with the regio-
isomeric bicyclic products containing conjugated double bonds. Typical
reactions exploiting the silyl enol ether moiety of the 7-(tert-butyl-
dimethylsiloxy)-1,2,3,4,6,8a-hexahydronaphthalene derivative were
performed, allowing stereoselective access to highly substituted
hexahydro-, octahydro-, or decahydronaphthalene derivatives.
SmI2
O
R
TS
R
R
SmI2, THF
ROH
H
H
O
OH
C
D
Key words dearomatization, ketyl, hexahydronaphthalene, radical,
samarium diiodide, silyl enol ether
Scheme 1 Samarium diiodide promoted cyclizations of -aryl and
-naphthyl ketones A and C to bicyclic and tricyclic products B and C
The dearomatization of arenes or heteroarenes is a fas-
cinating strategy to generate complexity from simple start-
ing materials.1 Among the reductive methods,2 samarium
diiodide promoted3 cyclizations of -aryl ketones allow ef-
ficient and stereoselective access to a variety of polycyclic
carbo- and heterocyclic compounds.4–7 Scheme 1 reveals
the overall transformation of simple benzene and naphtha-
lene derivatives A and C, which provide bicyclic and tricy-
clic compounds of type B and D. These reactions require (at
least) two equivalents of samarium diiodide and in many
cases the addition of strong Lewis bases such as HMPA8 that
strongly increase the reductive power of divalent samari-
um.9 The mechanistic details of this transformation have
been discussed earlier.4–7 The stereochemical outcome of
the samarium ketyl cyclization is plausibly rationalized by a
transition state TS (Scheme 1), assuming a chair-like folding
of the linker moiety between the carbonyl group and the
aryl rings, analogously to the Beckwith–Houk model devel-
oped for radical processes.10
For simple monosubstituted -aryl ketones, we system-
atically investigated the influence of different substituents
on the ortho-, meta-, or para-position on efficacy, stereo-
selectivity, and position of the two remaining double bonds
in the products.11,12 For most substituents, we obtained
clear results, but alkoxy-substituted compounds E behaved
fairly capriciously (Scheme 2). Standard products of type F
were obtained in low yield for the o-methoxy-substituted
precursor, whereas the m-methoxy-substituted starting
material did not undergo the cyclization at all. The p-substi-
tuted precursor provided reasonable yields of the cycliza-
tion products, but the ratio of the two regioisomers F and G
scattered strongly from experiment to experiment.13 In ad-
dition, in most cases, simple reduction products H and re-
aromatized cyclization products I were isolated in varying
quantities.
The 1,2,3,4,6,8a-hexahydronaphthalene derivatives F
are synthetically valuable intermediates, since they
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
A. Niermann, H.-U. Reissig
Paper
Synthesis
OSiEt3
OSiEt3
SmI2, HMPA
ROH, THF
SmI2, HMPA
tBuOH, THF
+
O
O
O
OH
r.t., 17 h
MeO
MeO
H
H
MeO
OH
OH
OH
37%
OAc
4
5
E
F
G
OAc
OAc
SmI2, HMPA
tBuOH, THF
+
OH
+
OH
MeO
MeO
r.t., 17 h
I
H
H
OH
Scheme 2 Samarium diiodide promoted cyclizations of methoxy-
26%
ca. 10%
8
6
7
substituted -aryl ketones E and bicyclic products F, G, and I, as well as
simple reduction product H
SmI2, HMPA
TBSO
HO
tBuOH, THF
O
OH
r.t., 24 h
(SiO2)
incorporate two olefinic moieties that should allow a vari-
ety of subsequent reactions leading to highly substituted
compounds in a stereoselective fashion. It was therefore
highly desirable to investigate precursors related to E that
would reliably lead to compounds of type F. In this report
we discuss cyclization reactions of a series of oxygen-sub-
stituted precursor compounds and also describe derivatiza-
tion of the efficiently obtained 7-(tert-butyldimethylsi-
loxy)-substituted 1,2,3,4,6,8a-hexahydronaphthalene, lead-
ing to a quite diverse small library of bicyclic compounds.
The starting materials required for this study were pre-
pared by standard synthetic methods often employing pal-
ladium-catalyzed coupling reactions (see Supporting Infor-
mation). As a typical example, Scheme 3 illustrates the
preparation of tert-butyldimethylsiloxy-substituted -aryl
ketone 3. Following the protocol of Tamaru et al.,14 the pro-
tected p-iodophenol (1)15 was coupled under palladium ca-
talysis with the zinc/copper species obtained from -iodo
ketone 2,16 giving the desired compound 3 in good yield.
9
82%
10
Scheme 4 Attempted reductive cyclizations of ortho- and meta-substi-
tuted precursors 4, 6, and 9 (cyclization products such as 7 are formed
as racemic mixtures, the drawn formulas in this report describe the rela-
tive configuration of products)
Whereas the o-triethylsiloxy-substituted compound 4
did not give the expected cyclization product, but only low
yields of the simple reduction product 5, the o-acetoxy-
substituted precursor 6 afforded the desired bicyclic product 7
in 26% yield and the secondary alcohol 8 (together with low
quantities of unknown impurities) in 10% yield (Scheme 4).
These results confirm that ortho-donor-substituted -aryl
ketones are poor substrates for samarium diiodide promot-
ed cyclizations,11 but 5-acetoxy-substituted 1,2,3,4,6,8a-
hexahydronaphthalenes such as 7 are available at least in
low yields. No attempts to optimize this reaction were
undertaken. The m-(tert-butyldimethylsiloxy)-substituted
-aryl ketone 9 underwent reduction to the secondary alco-
hol 10 (under complete desilylation of the phenol moiety
during chromatographic purification) and no cyclization
was observed (Scheme 4), which may be explained by the
unfavorable electronic effect of donor substituents in this
position.11
I
O
2
I
1. Zn/Cu (1.7 equiv)
TBSO
O
2. Pd(PPh3)4 (0.04 equiv)
toluene, HMPA
40 °C, 20 h
TBSO
1
3
Our preliminary experiments11 indicated that para-sub-
stituted precursor compounds should afford higher cycliza-
tion yields. The p-tert-butoxy-substituted -aryl ketone 11
provided a 73:27 mixture of 7-tert-butoxy-1,2,3,4,6,8a-
hexahydronaphthalene 12 and its oxidation product 13 in
59% yield (Scheme 5). The secondary alcohol 14 was also
isolated in 19% yield. Compound 13 was very likely formed
from 12 by oxidation during workup and/or chromatogra-
phy. By improving these stages of the experiment, it should
be possible to achieve higher amounts of 12, but no
attempts were made to avoid this undesired oxidation. The
p-acetoxy precursor 15 furnished the expected bicyclic
product 16, isolated in a mixture with deacetylated starting
material 17 (88:12, 50% yield) (Scheme 5). In other fractions
we found small amounts of compounds 18–20 (2–7%).
While these two experiments look promising, we did not
69%
Scheme 3 Synthesis of -aryl ketone 3 by Tamaru coupling of p-iodo-
phenol 1 with -iodo ketone 2
For the cyclization reactions we employed the well-
established standard reaction conditions4,11 for this process,
which involve the use of an excess of samarium diiodide (2–
4 equiv, 0.1 M solution in THF), hexamethylphosphoramide
(HMPA) (14–24 equiv) as Lewis base and tert-butyl alcohol
(2 equiv) as proton source. In most experiments, the reac-
tions were performed at room temperature with aqueous
workup after 17 hours. The attempted reductive cycliza-
tions of two ortho-substituted precursor compounds 4 and
6 are shown in Scheme 4.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

C
A. Niermann, H.-U. Reissig
Paper
Synthesis
pursue an optimization by modifying the reaction condi-
tions since the precursors with p-siloxy substituents turned
out to be clearly superior (see below).
TBSO
TBSO
H
OH
SmI2, HMPA
57%
21
+
tBuOH, THF
O
O
r.t., 17 h
TBSO
RO
R = tBu
3
11
OH
SmI2, HMPA
r.t., 17 h
tBuOH, THF
12%
22
+
+
OH
RO
RO
RO
TBDPSO
H
H
OH
59% (73:27)
OH
O
OH
19%
12
13
15
14
SmI2, HMPA
61%
24
tBuOH, THF
+
O
0 °C, 17 h
TBDPSO
AcO
23
OH
TBDPSO
SmI2, HMPA
0 °C, 17 h
17%
25
tBuOH, THF
SmI2, HMPA
H
OH
tBuOH, THF
+
O
HO
O
AcO
r.t., 18 h
H
TBSO
TBSO
OH
26
16
17
50% (88 : 12)
53%
27
Scheme 6 Reductive cyclizations of p-siloxy-substituted precursors 3,
23, and 26 leading to bicyclic products 21 and 24 and reduction prod-
ucts 22, 25, and 27
OH
HO
RO
OH
2% 18
R = Ac
R = H
7% 19
3% 20
(Scheme 6). Due to the better atom economy, (tert-butyldi-
methylsiloxy) compound 3 is the precursor of choice. We
therefore studied a few typical subsequent reactions of its
cyclization product 21. This diastereomerically pure com-
pound is interestingly functionalized, since it contains a
silyl enol ether unit, a second (less activated) trisubstituted
double bond and a tertiary alcohol group.
Scheme 5 Reductive cyclizations of para-substituted precursors 11
and 15 leading to bicyclic products 12 and 16 as major products
The reactions of three p-siloxy-substituted precursor
compounds 3, 23, and 26 are depicted in Scheme 6. The
p-(tert-butyldimethylsiloxy)-substituted -aryl ketone 3
was smoothly converted into the desired 1,2,3,4,6,8a-hexa-
hydronaphthalene 21, cleanly obtained in 57% yield. The
only side product we identified was the secondary alcohol
22 (12%). A very similarly efficient cyclization was observed
with precursor 23 bearing the even more bulky p-(tert-
butyldiphenylsiloxy) substituent. Now the cyclization
product 24 was obtained in 61% yield and the reduction
product 25 in 17% yield. Inspired by these good results, we
also subjected -aryl aldehyde 26 to the cyclization condi-
tions, but only the primary alcohol 27 was isolated as a
result of the simple reduction of the aldehyde function by
samarium diiodide. This confirms our earlier findings that
-aryl aldehydes are generally unsuitable starting materials
for the dearomatizing cyclization process.4,11
We first cleaved the silyl enol ether moiety by employ-
ing catalytic amounts of hydrogen chloride generated in
situ from TiCl4 in methanol providing the expected ketone
28 in almost quantitative yield (Scheme 7). This compound
is also available in 83% yield by saponification of the ace-
toxy-substituted compound 16. The unconjugated double
bond was shifted under basic conditions to give the ,-un-
saturated ketone 29 with a newly formed stereogenic cen-
ter at the bridgehead, resulting in a 57:43 mixture of the
two diastereomers. A Mukaiyama aldol condensation17 re-
action using benzaldehyde and the Lewis acid titanium tet-
rachloride shows the potential of the electron-rich double
bond of 21 to react with strong electrophiles. The enone 30
was isolated in 31% yield (Scheme 7). The most intriguing
transformation of 21 concerns its exhaustive hydrobora-
tion. Reaction with an excess of borane–THF complex, fol-
lowed by standard oxidative workup provided the silylated
precursor of tetrol 31 (47% yield). Desilylation with tetra-n-
butylammonium fluoride gave compound 31 in 39% overall
In summary, we observed that the two siloxy-substituted
precursor ketones 3 and 23 delivered the highest conver-
sions in favor of cyclization and the best yields of the de-
sired 7-oxy-1,2,3,4,6,8a-hexahydronaphthalene derivatives
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

D
A. Niermann, H.-U. Reissig
Paper
Synthesis
yield (Scheme 7). Both double bonds apparently undergo
the hydroboration in an entirely stereoselective fashion, al-
though the moderate mass balance does not exclude forma-
tion of other isomers. Compound 31 is a solid, but suitable
crystals for an X-ray analysis could not be obtained. The
tentative configurational assignment is compatible with the
we could demonstrate that donor–acceptor cyclopropanes21
of this type are also available from 7-siloxy-1,2,3,4,6,8a-
hexahydronaphthalene derivatives. Of the four diastereo-
mers possible, only those two are formed that derive from
an attack of the copper carbenoid to the sterically more ac-
cessible convex face cis to the bridgehead hydrogen.22 As a
consequence, by acid-promoted ring-opening23 of the sil-
oxycyclopropanes 34, only the resulting bicyclic -keto
ester 35 was isolated as a single diastereomer (58% yield).
1
coupling constants observed in the H NMR spectrum and
the conformation of the cis-decalin system as depicted in
Scheme 7. Bridgehead proton 8a-H shows coupling con-
stants of 4.2 Hz to 4a-H and 11.1 Hz to 1-H, which in turn
couples with 2-H (8.8 Hz); the signal for 2-H appears as a
ddd with coupling constants of 5.1, 8.8, and 13.7 Hz, indi-
cating the 2-OH and 1-OH are in equatorial positions. The
assumed configuration is the result of two subsequent bo-
rane additions to the more sterically available convex face
of 21. Compounds such as 31 can be regarded as cis-fused
polycyclitols and bicyclic sugar analogs. They may also be of
interest as building blocks for supramolecular chemistry.18
Na2CO3
TBSO
CH2Cl2
O
OH
Br
H
r.t., 10 d
35%
N
N
OH
CF3
F3C
33
32
O
TBSO
H
H
OH
OH
H
MeO2C
basic Al2O3
35
21
TiCl4, MeOH
EtOAc
–78 °C to r.t.
17 h
O
O
TiCl4, MeOH
r.t., 17 h
76%
O
H
H
OH
OH
58%
–78 °C to r.t.
54 h
N2
99%
28
29
OMe
dr 57:43
Cu(acac)2
EtOAc
PhCHO, TiCl4
CH2Cl2
TBSO
H
reflux, 10 d
31%
OH
H
MeO2C
dr 5:1
–78 °C to r.t., 15 h
31%
TBSO
O
H
H
34
OH
OH
Ph
21
30
Scheme 8 Cycloadditions of compound 21 leading to 1,2-oxazine de-
rivative 33 and donor–acceptor cyclopropane 34
1. BH3•THF
THF, –30 °C, 3 h
2. H2O2, NaOH
0 °C to r.t., 18 h
H
OH
H
The transformations depicted in Schemes 7 and 8 were
not optimized, since the focus of this study was the effi-
cient generation of bicyclic precursor compounds such as
21. Nevertheless, the results demonstrate that 7-siloxy-sub-
stituted 1,2,3,4,6,8a-hexahydronaphthalenes are excellent
starting materials for many subsequent reactions leading to
interestingly functionalized products of synthetic value.
Compounds such as 28–30 or 33–35 offer various possibili-
ties for further functionalization.
HO
HO
2
H
H
HO
HO
8a
H
1
4a
OH
Me
H
3. TBAF, THF
0 °C to r.t., 1 h
HO
OH
overall 39%
31
Scheme 7 Typical reactions of compound 21 leading to ketone 28,
enone 29, aldol condensation product 30, and tetrol 31
Silyl enol ethers are often suitable substrates in cycload-
dition reactions with electron-deficient species and we
therefore employed 21 in a hetero-Diels–Alder reaction
with an in situ generated fluorinated -nitrosoalkene
(Scheme 8). Treatment of -bromo oxime 32 with base gen-
erated 3,3,3-trifluoro-2-nitrosopropene,19 which slowly
added to the electron-rich double bond of 21. This transfor-
mation required a large excess of the nitrosoalkene precur-
sor (10 equiv), since additions to silyl enol ethers with sub-
stituents in the -position to the siloxy group are known to
be less efficient;20 the moderate yield of 35% for compound
33 was therefore not unexpected. The copper-catalyzed cy-
clopropanation of 21 was also not high yielding, but, with
this reaction leading to siloxycyclopropane 34 in 31% yield,
In this study we reinvestigated the samarium diiodide
promoted cyclizations of -aryl ketones with oxygen sub-
stituents in different positions of the aryl group. The results
confirm earlier findings that only para-substituted precur-
sor compounds provide the expected dearomatized cycliza-
tion products in good yields and reasonable chemoselectiv-
ity. Although p-tert-butoxy- and p-acetoxy-substituted
precursors 11 and 15 gave the expected 1,2,3,4,6,8a-hexa-
hydronaphthalene derivatives 12 and 16 in moderate
yields, these transformations are not practical, since the
side products could not be removed easily. Good results
were obtained with p-(tert-butyldimethylsiloxy)- and
p-(tert-butyldiphenylsiloxy)-substituted aryl ketones 3 and
23 that afforded the desired dearomatized compounds 21
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

E
A. Niermann, H.-U. Reissig
Paper
Synthesis
and 24 in ca. 60% yield after chromatographic purification.
Probably due to the low polarity, size, and stability of the
siloxy groups, small amounts of side products could be eas-
ily separated from the major components 21 and 24. No
isomeric products were identified with differing position of
the double bonds. The silyl enol ether moiety of 21 was em-
ployed in a screening of typical subsequent reactions. These
transformations demonstrate that 7-siloxy-substituted
1,2,3,4,6,8a-hexahydronaphthalenes are good precursor
compounds for the synthesis of functionalized bicyclic
compounds in a stereoselective fashion.
N aq HCl (50 mL) and sat. aq NaHCO3 (50 mL). The organic phase was
dried (MgSO4) and concentrated in vacuo. After column chromatogra-
phy (silica gel, hexanes/EtOAc 18:1), ketone 3 was isolated.
Yield: 2.84 g (69%); colorless oil.
IR (film, ATR): 3025–2860 (=C-H, C-H), 1715 (C=O), 1510 (C=C), 1250
(Si-Me) cm–1
.
1H NMR (500 MHz, CDCl3):  = 0.18 (s, 6 H, SiMe2), 0.97 (s, 9 H, CMe3),
1.86 (quin, J = 7.4 Hz, 2 H, 4-H), 2.11 (s, 3 H, 1-H), 2.41 (t, J = 7.4 Hz, 2
H, 3-H), 2.54 (t, J = 7.4 Hz, 2 H, 5-H), 6.75, 7.01 (2 d, J = 8.4 Hz, 2 H
each, Ar).
13C NMR (126 MHz, CDCl3):  = –4.5 (q, SiMe2), 18.2 (s, CMe3), 25.4 (t,
C-4), 25.7 (q, CMe3), 29.9 (q, C-1), 34.2 (t, C-5), 42.8 (t, C-3), 119.9,
129.3, 134.2, 153.7 (2 d, 2 s, Ar), 208.0 (s, C-2).
Anal. Calcd for C17H28O2Si (292.5): C, 69.81; H, 9.65. Found: C, 69.38;
H, 9.66.
NMR spectra were recorded on either Bruker (AC 250, AC 500,
AVANCE III) or JOEL (ECX 400, Eclipse 500) instruments at 300 K. 13
C
NMR spectra are proton-decoupled. For detailed peak assignments,
2D spectra were obtained (COSY, HMQC, HMBC, and NOESY). For H
1
Preparation of a 0.1 M SmI2 Stock Solution
THF (320 mL) was placed in a flame-dried and argon-filled flask at-
tached with a three-way valve. Argon was bubbled through the sol-
vent for 40 min. Samarium (5.54 g, 36.8 mmol) and iodine (8.13 g,
32.0 mmol) were subsequently added. The suspension was stirred at
r.t. until the color turned to dark blue (2–18 h). The flask was then
wrapped in aluminum foil to exclude light and stored at r.t. The con-
centration was determined by titration of the SmI2 solution against a
0.1 M iodine solution in THF.
NMR spectroscopy, the singlets of chloroform ( = 7.26) or benzene (
= 7.28) were used as internal standards; for 13C NMR spectroscopy, ei-
ther the triplet of CDCl3 ( = 77.0) or the doublet of C6D6 ( = 128.5)
was used. IR spectra were recorded on a JASCO FT/IR-4100 type A in-
strument with a TGS detector. Mass spectra were recorded on an Agi-
lent 6210 ESI-TOF or a Finnigan MAT 711 (EI, 80 eV, 8 kV) instrument.
Elemental analyses were performed on a Perkin-Elmer CHN-Analyzer
2400, Vario EL, or Vario ELIII instrument. Melting points were mea-
sured on a Reichert apparatus Thermovar and are uncorrected.
SmI2-Promoted Cyclizations; General Procedure (GP)
Preparative column chromatography was performed on silica gel
(230–400 mesh, Merck or Fluka) or on neutral alumina (100–250
mesh, Fluka, activity grade I; deactivation to obtain activity grade III
by addition of 6% H2O). HPLC separations were performed on a Nucle-
osil 50-5 column with a Rheodyne injection system. The compounds
were detected with a Knauer variable UV detector and Knauer refrac-
tometer.
HMPA (14–24 equiv) was added to a previously prepared 0.1 M stock
solution of SmI2 in THF (2–4 equiv) under argon and the solution was
stirred for 20 min. The solution turned from dark blue to dark violet.
In a second flask, the substrate (1 equiv) and tBuOH (2 equiv) were
dissolved in THF (10 mL/mmol cyclization precursor) under argon.
Argon was bubbled through the solution for 20 min. The substrate
solution was then transferred by syringe to the SmI2 solution at r.t. if
not mentioned otherwise. The mixture was stirred until the color
changed from violet to grey. Sat. aq NaHCO3 solution or sat. aq Na-K-
tartrate solution (20 mL) was added and the mixture was extracted
with Et2O (3 × 30 mL). The combined organic layers were washed with
H2O and brine (2 × 30 mL each) and dried (MgSO4) and the solvents
were removed under reduced pressure to give the crude product still
containing small amounts of HMPA. Flash chromatography on silica
gel or on alumina (activity grade III) yielded the products.
Solvents: anhydrous THF, CH2Cl2, Et2O, and MeCN were prepared by
using a Braun Solvent Purification System 800. HMPA and Et3N were
distilled before use (CaH2) and stored over activated 4 Å molecular
sieves or KOH. MeOH, tBuOH, dimethylacetamide (DMA), and DMF
were purchased in p.A. quality and stored under argon with activated
4 Å molecular sieves. Hexane (mixture of isomers) was distilled from
CaH2. EtOAc was distilled from K2CO3 and CaCl2.
Reactions were generally performed under argon in flame-dried
flasks. Solvents and reagents were added by syringes (polypropylene
or Hamilton microliter syringes) through a septum or a three-way
valve under positive argon pressure. Solids were added as a solution
or as powder or chunks under positive argon pressure.
Cyclization of Aryl Ketone 6
According to the GP, 6 (100 mg, 0.45 mmol), SmI2 (11.4 mL, 1.14
mmol), HMPA (1.19 mL, 1.22 g, 6.81 mmol), and tBuOH (0.09 mL, 67
mg, 0.91 mmol) furnished after 17 h and workup with Na-K-tartrate
solution the crude product. After column chromatography (silica gel,
hexanes/EtOAc 7:3) cyclization product 7 was isolated (26 mg, 26%).
In a second fraction, a mixture of 7 and 8 containing small amounts of
an unidentified olefin was isolated (14 mg).
For syntheses of starting materials, descriptions of unsuccessful cy-
clization reactions, and copies of NMR spectra of selected compounds,
see the Supporting Information.
5-[4-(tert-Butyldimethylsiloxy)phenyl]pentan-2-one (3)
Analogous to the literature procedure,15 the Zn/Cu couple (1.57 g, 24.2
mmol) and 216 (3.15 g, 14.9 mmol) were suspended in toluene (25
mL) and HMPA (6.89 mL, 7.35 g, 41.0 mmol) was added. The mixture
was stirred for 1 h at 40 °C. To this suspension was added a solution of
(1R*,8aR*)-5-Acetoxy-1-methyl-1,2,3,4,6,8a-hexahydro-1-naph-
thol (7)
Yield: 26 mg (26%); colorless oil.
1
14 (4.73 g, 14.2 mmol) and Pd(PPh3)4 (0.65 g, 0.57 mmol) in toluene
IR (film, ATR): 3400 (O-H), 3010–2860 (=C-H, C-H), 1750 (C=O), 1600
(10 mL). The mixture was stirred for 20 h at 40 °C and then cooled to
r.t.; then Et2O (25 mL) was added and the mixture was washed with 1
(C=C) cm–1
.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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A. Niermann, H.-U. Reissig
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Synthesis
1H NMR (500 MHz, CDCl3):  = 1.10 (s, 3 H, 1-Me), 1.34 (tq, J = 4.0, 13.4
Hz, 1 H, 3-H), 1.52–1.60 (m, 2 H, 2-H1, 4-H1), 1.62–1.72 (m, 2 H, 3-H2,
OH), 1.79 (dddd, J = 1.6, 2.8, 4.0, 12.4 Hz, 1 H, 2-H2), 2.14 (s, 3 H,
COMe), 2.47 (mc, 1 H, 4-H2), 2.71–2.76 (m, 2 H, 6-H), 2.83 (mc, 1 H, 8a-H),
5.76 (dtd, J = 1.4, 3.3, 10.2 Hz, 1 H, 7-H), 5.83 (tdd, J = 2.0, 3.1, 10.2 Hz,
1 H, 8-H).
13C NMR (176 MHz, CDCl3):  = 23.5 (q, C-1), 27.6 (t, C-3), 28.8 (q,
CMe3), 35.2 (t, C-5), 38.8 (t, C-3), 68.0 (d, C-2), 78.1 (s, CMe3), 124.1,
128.6 (2 d, Ar), 137.2, 153.2 (2 s, Ar).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H24O2Na: 259.1663;
found: 259.1645.
13C NMR (126 MHz, CDCl3):  = 20.7 (q, COMe), 21.7 (q, 1-Me), 22.9 (t,
C-3), 25.7 (t, C-4), 28.3 (t, C-6), 41.5 (t, C-2), 50.4 (d, C-8a), 74.7 (s, C-1),
122.8 (s, C-4a), 124.1, 124.2 (2 d, C-7, C-8), 138.9 (s, C-5), 169.1 (s,
CO).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H18O3Na: 245.1154;
found: 245.1122.
Cyclization of Aryl Ketone 15
According to the GP, 15 (229 mg, 1.04 mmol), SmI2 (31.2 mL, 3.12
mmol), HMPA (3.28 mL, 3.35 g, 18.7 mmol), and tBuOH (154 mg, 2.08
mmol) furnished after 17 h at 0 °C and workup with NaHCO3 solution
the crude product. After column chromatography (alumina, hexanes/
EtOAc 3:1) three fractions were obtained. Fraction 1: 19: yield: 15 mg
(7%); fraction 2: mixture of 16 and 17 (88:12): yield: 115 mg (50%;
calculated yields 44% and 6%); fraction 3: mixture of 20 and 18
(60:40): yield: 10 mg (3% and 2%).
2-(4-Hydroxypentyl)phenyl Acetate (8)
1H NMR (500 MHz, CDCl3):  = 1.21 (d, J = 6.2 Hz, 3 H, 5-H), 2.17 (s, 3
H, COMe), 3.93 (sext, J = 6.2 Hz, 1 H, 4-H), 6.75–6.89, 7.03–7.13 (2 m, 2
H each, Ar).
(1R*,8aR*)-7-Acetoxy-1-methyl-1,2,3,4,6,8a-hexahydro-1-naph-
thol (16)
13C NMR (176 MHz, CDCl3):  = 20.5 (q, COMe), 23.9 (q, C-5), 68.7 (d,
1H NMR (400 MHz, CDCl3):  = 1.07 (s, 3 H, Me), 1.33 (tq, J = 4.1, 13.3
Hz, 1 H, 3-H1), 1.54 (br s, 1 H, OH), 1.58 (dt, J = 4.1, 13.3 Hz, 1 H, 2-H1),
1.65–1.74 (m, 1 H, 3-H2), 1.77–1.84 (m, 1 H, 2-H2), 1.85–1.98 (m, 1 H,
4-H1), 2.11 (s, 3 H, COMe), 2.19 (tdt, J ≈ 1.7, 4.1, 13.3 Hz, 1 H, 4-H2),
2.70–2.77 (m, 2 H, 6-H), 2.85 (dt, J = 3.5, 7.7 Hz, 1 H, 8a-H), 5.37 (tt, J =
C-4), 115.6, 120.5, 127.2, 130.2 (4 d, Ar), 153.9 (s, CO).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H18O3Na: 245.1154;
found: 245.1142.
Cyclization of Aryl Ketone 11
1
1.7, 3.4 Hz, 1 H, 5-H), 5.54 (td, J = 1.5, 3.5 Hz, 1 H, 8-H); the H NMR
data agree with those of the literature.11b
According to the GP, 11 (200 mg, 0.85 mmol), SmI2 (25.6 mL, 2.56
mmol), HMPA (2.69 mL, 2.75 g, 15.4 mmol), and tBuOH (0.16 mL, 127
mg, 1.71 mmol) furnished after 17 h and workup with NaHCO3 solu-
tion the crude product. After column chromatography (alumina,
hexanes/EtOAc 4:1), 12 and 13 were isolated as a mixture (73:27);
yield: 120 mg (59%). In a second fraction, 14 was isolated as colorless
oil; yield: 38 mg (19%).
Phenol 17
1H NMR (400 MHz, CDCl3):  = 1.86 (quin, J = 7.4 Hz, 2 H, 4-H), 2.12 (s,
3 H, 1-H), 2.43 (t, J = 7.4 Hz, 2 H, 3-H), 2.54 (t, J = 7.4 Hz, 2 H, 5-H), 5.75
(br s, 1 H, OH), 6.77, 7.01 (2 d, J = 8.6 Hz, 2 H each, Ar).
Diol 18
(1R*,8aR*)-7-tert-Butoxy-1-methyl-1,2,3,4,6,8a-hexahydro-1-
1H NMR (400 MHz, CDCl3):  = 1.53 (s, 3 H, Me), 5.17 (br s, 1 H, OH),
6.68 (dd, J = 2.70, 8.3 Hz, 1 H, Ar), 6.94 (d, J = 8.3 Hz, 1 H, Ar), 7.07 (d,
J = 2.7 Hz, 1 H, Ar).
naphthol (12)
1H NMR (700 MHz, CDCl3):  = 1.07 (s, 3 H, Me), 1.42 (s, 9 H, CMe3),
1.63 (dt, J = 4.1, 12.9 Hz, 1 H, 2-H1), 2.26 (mc, 1 H, 4-H1), 5.31 (td, J =
1.8, 3.6 Hz, 1 H, 8-H), 5.42 (tt, J = 1.5, 3.5 Hz, 1 H, 5-H).
13C NMR (176 MHz, CDCl3):  = 22.4 (q, 1-Me), 30.1 (q, CMe3), 106.0
(d, C-8), 119.3 (d, C-5).
Pentan-2-ol 19
1H NMR (400 MHz, CDCl3):  = 1.20 (d, J = 6.3 Hz, 3 H, 5-H), 1.47–1.66
(m, 4 H, 2-H, 3-H), 2.03 (s, 3 H, COMe), 2.54 (t, J = 7.4 Hz, 2 H, 1-H),
4.91 (sext, J = 6.3 Hz, 1 H, 4-H), 4.98 (br s, 1 H, OH), 6.75, 7.03 (2 d, J =
8.6 Hz, 2 H each, Ar).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H24O2Na: 259.1663;
found: 259.1655.
7-tert-Butoxy-1-methyl-1,2,3,4-tetrahydro-1-naphthol (13)
1H NMR (700 MHz, CDCl3):  = 6.80 (dd, J = 2.5, 8.2 Hz, 1 H, Ar), 6.99
(d, J = 8.2 Hz, 1 H, Ar), 7.27 (d, J = 2.5 Hz, 1 H, Ar).
13C NMR (176 MHz, CDCl3):  = 30.3 (q, CMe3), 33.1 (q, 1-Me), 123.8,
Pentan-2-ol 20
1H NMR (400 MHz, CDCl3):  = 1.18 (d, J = 6.2 Hz, 3 H, 5-H), 2.55 (t, J =
7.5 Hz, 2 H, 1-H), 3.82 (sext, J = 6.2 Hz, 1 H, 4-H), 5.51 (br s, 1 H, OH),
6.74, 7.03 (2 d, J = 8.6 Hz, 2 H each, Ar).
124.4, 130.4 (3 d, Ar).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H22O2Na: 257.1512;
Cyclization of Aryl Ketone 3
found: 257.1510.
According to the GP, 3 (400 mg, 1.37 mmol), SmI2 (54.7 mL, 5.47
mmol), HMPA (5.71 mL, 5.88 g, 32.8 mmol), and tBuOH (0.26 mL, 203
mg, 2.74 mmol) furnished after 17 h and workup with NaHCO3 solu-
tion the crude product. After column chromatography (alumina, hex-
anes/EtOAc 9:1), 21 was isolated as a colorless solid (231 mg, 57%). In
other fractions, precursor 3 (19 mg, 5%) and 22 (50 mg, 12%) were
isolated.
5-(4-tert-Butoxyphenyl)pentan-2-ol (14)
IR (film, ATR): 3370 (O-H), 3025–2855 (=C-H, C-H), 1610 (C=C), 1160
(C-O) cm–1
.
1H NMR (700 MHz, CDCl3):  = 1.18 (d, J = 6.2 Hz, 3 H, 1-H), 1.32 (s, 9
H, CMe3), 1.43–1.53 (m, 3 H, 3-H, OH), 1.59–1.76 (m, 2 H, 4-H), 2.58
(mc, 2 H, 5-H), 3.80 (sext, J = 6.2 Hz, 1 H, 2-H), 6.88, 7.05 (2 d, J = 8.5
Hz, 2 H each, Ar).
(1R*,8aR*)-7-(tert-Butyldimethylsiloxy)-1-methyl-1,2,3,4,6,8a-
hexahydro-1-naphthol (21)
Mp 46–48 °C.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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A. Niermann, H.-U. Reissig
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Synthesis
IR (ATR): 3325 (O-H), 3030–2820 (=C-H, C-H), 1700 (C=C), 1660 (C=C),
1200 (C-O) cm–1
1H NMR (400 MHz, CDCl3):  = 1.10 (s, 9 H, CMe3), 1.16 (d, J = 6.2 Hz, 3
H, 1-H), 1.33 (br s, 1 H, OH), 1.36–1.51, 1.59–1.70 (2 m, 2 H each, 3-H,
4-H), 2.50 (t, J = 7.6 Hz, 2 H, 5-H), 3.78 (sext, J = 6.2 Hz, 1 H, 2-H), 6.69,
(2 d, J = 8.5 Hz, 2 H each, Ar), 7.34–7.40, 7.40–7.46, 7.71–7.75 (3 m, 4
H, 2 H, 4 H, Ph).
.
1H NMR (500 MHz, CDCl3):  = 0.16 (s, 6 H, SiMe2), 0.93 (s, 9 H, CMe3),
1.04 (s, 3 H, 1-Me), 1.34 (tq, J = 4.1, 13.4 Hz, 1 H, 3-H1), 1.38 (br s, 1 H,
OH), 1.58 (dt, J = 4.1, 13.1 Hz, 1 H, 2-H1), 1.67–1.75 (m, 1 H, 3-H2),
1.78–1.84 (m, 1 H, 2-H2), 1.90–1.99 (m, 1 H, 4-H1), 2.19 (tdd, J = 2.2,
4.1, 13.4 Hz, 1 H, 4-H2), 2.59–2.64 (m, 2 H, 6-H), 2.78 (mc, 1 H, 8a-H),
5.02 (td, J = 1.8, 3.6 Hz, 1 H, 8-H), 5.37 (tt, J = 1.6, 3.4 Hz, 1 H, 5-H).
(8R*,8aR*)-8-Hydroxy-8-methyl-3,5,6,7,8,8a-hexahydronaphtha-
len-2(1H)-one (28)
13C NMR (176 MHz, CDCl3):  = –4.3 (q, SiMe2), 18.0 (s, CMe3), 21.9 (q,
1-Me), 24.2 (t, C-3), 25.7 (q, CMe3), 30.8 (t, C-6), 34.3 (t, C-4), 41.7 (t,
C-2), 50.7 (d, C-8a), 74.9 (s, C-1), 101.3 (d, C-8), 117.7 (d, C-5), 136.0
(s, C-4a), 149.7 (s, C-7).
TiCl4 (1 drop) was added to a solution of silyl enol ether 21 (71 mg,
0.24 mmol) in MeOH (16 mL) at –78 °C. The solution was stirred at
this temperature for 2 h. Due to incomplete conversion, additional
TiCl4 (1 drop) was added and the solution was stirred overnight and
the mixture was allowed to reach r.t. H2O (10 mL) and brine (10 mL)
were added and the mixture was extracted with Et2O (3 × 30 mL). The
combined organic extracts were dried (MgSO4) and concentrated in
vacuo. After column chromatography (silica gel, hexanes/EtOAc 4:1),
ketone 28 was isolated.
Anal. Calcd for C17H30O2Si (294.5): C, 69.33; H, 10.27. Found: C, 68.72;
H, 10.34.
5-[4-(tert-Butyldimethylsiloxy)phenyl]pentan-2-ol (22)
IR (film, ATR): 3355 (O-H), 3060–2855 (=C-H, C-H), 1620 (C=C) cm–1
.
Yield: 43 mg (99%); colorless oil.
1H NMR (500 MHz, CDCl3):  = 0.19 (s, 6 H, SiMe2), 0.99 (s, 9 H, CMe3),
1.18 (d, J = 6.2 Hz, 3 H, 1-H), 1.40–1.52 (m, 2 H, 3-H), 1.58–1.74 (m, 3
H, 4-H, OH), 2.56 (t, J = 7.6 Hz, 2 H, 5-H), 3.80 (sext, J = 6.2 Hz, 1 H, 2-H),
6.55, 7.03 (2 d, J = 8.4 Hz, 2 H each, Ar).
13C NMR (176 MHz, CDCl3):  = –4.5 (q, SiMe2), 18.1 (s, CMe3), 23.4 (q,
C-1), 25.7 (q, CMe3), 27.7 (t, C-4), 35.0 (t, C-5), 38.8 (t, C-3), 67.9 (d, C-2),
119.7, 129.1 (2 d, Ar), 135.0, 153.5 (2 s, Ar).
IR (film, ATR): 3400 (O-H), 3040 (=C-H), 2965–2865 (C-H), 1700 (C=O)
cm–1
.
1H NMR (500 MHz, CDCl3,):  = 0.97 (s, 3 H, Me), 1.38 (tq, J = 4.4, 13.2
Hz, 1 H, 6-H1), 1.54 (dt, J = 4.4, 13.2, Hz, 1 H, 7-H1), 1.67–1.78 (m, 2-H,
6-H2, 7-H2), 1.91–2.02 (m, 1 H, 5-H1), 2.22 (tdd, J = 2.1, 4.4, 13.1 Hz, 1
H, 5-H2), 2.48 (ddd, J = 1.1, 8.9, 15.1 Hz, 2 H, 1-H1, OH)*, 2.60 (d, J ≈ 8.9
Hz, 1 H, 8a-H), 2.67–2.77 (m, 2 H, 3-H1, 1-H2), 2.86–2.94 (m, 1 H, 3-H2),
5.41 (m, 1 H, 4-H); * broad signal for OH.
13C NMR (126 MHz, CDCl3):  = 20.8 (q, Me), 24.5 (t, C-6), 34.6 (t, C-5),
38.1 (t, C-1) 39.3 (t, C-3), 42.2 (t, C-7), 51.2 (d, C-8a), 74.5 (s, C-8),
117.2 (d, C-4), 138.4 (s, C-4a), 210.5 (s, C-2).
Anal. Calcd for C17H30O2Si (294.5): C, 69.33; H, 10.27. Found: C, 69.96;
H, 9.73.
Cyclization of Aryl Ketone 23
According to the GP, 23 (540 mg, 1.30 mmol), SmI2 (38.9 mL, 3.90
mmol), HMPA (4.08 mL, 4.18 g, 23.3 mmol), and tBuOH (192 mg, 2.59
mmol) furnished after 17 h and workup with NaHCO3 solution the
crude product. After column chromatography (alumina, hexanes/EtOAc
9:1), 24 was isolated. In a second fraction, 25 was isolated.
HRMS (EI, 80 eV, 40 °C): m/z [M]+ calcd for C12H16O2: 180.1150; found:
180.1151.
(8R*,8aR*)-8-Hydroxy-8-methyl-4a,5,6,7,8,8a-hexahydro-
naphthalen-2(1H)-one (29)
Ketone 28 (9 mg, 0.05 mmol) was dissolved in EtOAc (0.5 mL), and
then basic alumina (100 mg) was added. The suspension was stirred
at r.t. overnight and then filtered through Celite. The filtrate was con-
centrated under reduced pressure and enone 29 was isolated as a
mixture of cis and trans isomers.
(1R*,8aR*)-7-(tert-Butyldiphenylsiloxy)-1-methyl-1,2,3,4,6,8a-
hexahydro-1-naphthol (24)
Yield: 330 mg (61%); colorless oil.
IR (film, ATR): 3380 (O-H), 3070–2855 (=C-H, C-H), 1660 (C=C), 1610
(C=C), 1110 (C-O) cm–1
.
Yield: 7 mg (76%); cis/trans 57:43.
1H NMR (500 MHz, CDCl3):  = 0.63 (s, 3 H, Me), 1.06 (s, 9 H, CMe3),
1.24 (tq, J = 4.3, 13.0 Hz, 1 H, 3-H1), 1.45 (dt, J ≈ 4.1, 13.0 Hz, 1 H, 2-H1),
1.57 (br s, 1H, OH), 1.60–1.67 (m, 2 H, 2-H2, 3-H2), 1.81–1.90, 2.10–
2.15 (2 m, 1 H each, 4-H), 2.55–2.63 (m, 1 H, 8a-H), 2.69–2.75 (m, 2 H,
6-H), 4.66 (d, J = 3.6 Hz, 1 H, 8-H), 5.28–5.35 (tt, J ≈ 1.6, 3.3 Hz, 1H, 5-H),
7.35–7.46, 7.71–7.77 (2 m, 6 H, 4 H, Ph).
13C NMR (101 MHz, CDCl3):  = 19.1 (s, CMe3), 21.3 (q, Me), 24.0 (t, C-3),
26.5 (q, CMe3), 30.9 (t, C-6), 34.1 (t, C-4), 40.4 (t, C-2), 50.5 (d, C-8a),
74.6 (s, C-1), 101.2 (d, C-8), 117.2 (d, C-5), 127.6, 129.8 (2 d, Ph), 133.4
(s, Ph), 135.5 (d, Ph), 136.0 (s, C-4a), 149.5 (s, C-7).
IR (film, ATR): 3355 (O-H), 3055–2845 (=C-H, C-H), 1675 (C=O) cm–1
.
1H NMR (700 MHz, CDCl3):  (major isomer) = 1.20 (s, 3 H, 8-Me),
1.44–1.82 (m, 7 H, OH, 5-H, 6-H, 7-H), 2.11 (mc, 1 H, 8a-H), 2.32 (dd,
J = 14.3 Hz, 16.7 Hz, 1 H, 1-H1), 2.37 (dd, J = 5.0, 16.7 Hz, 1 H, 1-H2),
2.73–2.82 (m, 1 H, 4a-H), 5.96 (d, J = 10.7 Hz, 1 H, 3-H), 7.02 (dd, J =
5.9, 10.7 Hz, 1 H, 4-H).
13C NMR (176 MHz, CDCl3):  (major isomer) = 28.9 (q, Me), 33.5 (d,
C-4a), 36.5 (t, C-1), 44.2 (d, C-8a), 128.3 (d, C-3), 155.4 (d, C-4), 199.4
(s, C-2).
1H NMR (700 MHz, CDCl3):  (minor isomer) = 1.23 (s, 3 H, 8-Me),
1.44–1.82 (m, 7 H, OH, 5-H, 6-H, 7-H), 2.17 (dd, J = 14.5, 16.5 Hz, 1 H,
1-H1), 2.25 (mc, 1 H, 8a-H), 2.49 (dd, J = 1.0, 16.5 Hz, 1 H, 1-H2), 2.59
(mc, 1 H, 4a-H), 5.90 (dd, J = 1.0, 10.1 Hz, 1 H, 3-H), 6.78 (d, J = 10.1 Hz,
1 H, 4-H).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C27H34O2NaSi: 441.2258;
found: 441.2218.
5-[4-(tert-Butyldiphenylsiloxy)phenyl]pentan-2-ol (25)
Yield: 90 mg (17%).
13C NMR (176 MHz, CDCl3):  (minor isomer) = 28.8 (q, Me), 38.2 (t,
C-1), 49.9 (d, C-8a), 126.4 (d, C-3), 157.1 (d, C-4), 198.2 (s, C-2).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C11H16O2Na: 203.1048;
found: 203.1030.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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A. Niermann, H.-U. Reissig
Paper
Synthesis
(8R*,8aS*,Z)-1-Benzylidene-8-hydroxy-8-methyl-3,5,6,7,8,8a-
hexahydronaphthalen-2(1H)-one (30)
Yield: 29 mg (82%); colorless solid; mp 79–81 °C.
IR (ATR): 3450–3250 (O-H), 2965–2830 (=C-H, C-H) cm–1
.
A 1 M solution of TiCl4 in CH2Cl2 (0.37 mL, 0.37 mmol) was diluted
with CH2Cl2 (2.7 mL). At –78 °C a solution of 21 (100 mg, 0.34 mmol)
in CH2Cl2 (1.2 mL) was added. After addition of benzaldehyde (37 L,
39 mg, 0.37 mmol) at this temperature, the solution was stirred over-
night and the temperature was allowed to reach r.t. H2O (10 mL) was
added and the mixture was extracted with Et2O (3 × 30 mL). The com-
bined organic extracts were dried (MgSO4) and concentrated under
reduced pressure. After column chromatography (silica gel, hexanes/
EtOAc 3:1), a mixture of enone 30 and substrate 21 (9:1, 33 mg) was
isolated as colorless oil.
1H NMR (500 MHz, CDCl3):  = 1.17–1.33 (m, 2 H, 5-H), 1.34 (s, 3 H,
8-Me), 1.47–1.58 (m, 2 H, 6-H1, 7-H1), 1.59–1.69 (m, 2 H, 3-H1, 7-H2),
1.77 (tq, J = 4.3, 12.9 Hz, 1 H, 6-H2), 1.88 (dd, J = 4.2, 11.1 Hz, 1 H,
8a-H), 1.93 (mc, 1 H, 3-H2), 2.36 (mc, 1 H, 4a-H), 3.50 (dd, J = 8.8, 11.1
Hz, 1 H, 1-H), 3.70 (ddd, J = 5.1, 8.8, 13.7 Hz, 1 H, 2-H), 3.75 (mc, 1 H,
4-H).
13C NMR (126 MHz, CDCl3):  = 22.6 (t, C-5), 26.9 (t, C-6), 32.5 (q,
8-Me), 35.9 (t, C-7), 36.3 (t, C-3), 41.4 (d, C-4a), 47.7 (d, C-8a), 72.2 (d,
C-4), 73.1 (s, C-8), 73.5 (d, C-2), 74.4 (d, C-1).
Anal. Calcd for C11H20O4 (216.3): C, 61.09; H, 9.32. Found: C, 61.08; H,
9.31.
Calculated yields: enone 30: 30 mg (31%); 21: 3 mg (3%).
IR (film, ATR): 3375 (O-H), 3020–2855 (=C-H, C-H), 1690 (C=O), 1635,
1590 (C=C) cm–1
.
(4aR*,10R*,10aR*,10bR*)-4a-(tert-Butyldimethylsiloxy)-10-
methyl-2-(trifluoromethyl)-4a,5,7,8,9,10,10a,10b-octahydro-1H-
naphtho[1,2-e][1,2]oxazin-10-ol (33)
1H NMR (700 MHz, CDCl3):  = 1.04 (s, 3 H, Me), 1.41 (tq, J = 4.3, 13.4
Hz, 1 H, 6-H1), 1.65 (dt, J = 4.0, 13.4 Hz, 1 H, 7-H1), 1.73 (br s, 1 H, OH),
1.81–1.83 (m, 1 H, 7-H2), 1.84–1.89 (m, 1 H, 6-H2), 2.18 (dt, J = 5.1,
13.0 Hz, 1 H, 5-H1), 2.36 (mc, 1 H, 5-H2), 2.69–2.71 (m, 2 H, 3-H1, 8a-H),
3.02 (mc, 1 H, 3-H2), 6.75 (mc, 1 H, 4-H), 7.27 (s, 1 H, PhCH), 7.30–7.32
(m, 1 H, Ar), 7.37–7.39, 7.42–7.43 (2 m, 2 H each, Ar).
13C NMR (176 MHz, CDCl3):  = 21.0 (q, Me), 25.0 (t, C-6), 35.6 (t, C-5),
37.7(t, C-3), 42.1 (t, C-7), 50.2 (d, C-8a), 75.3 (s, C-8), 119.1 (d, C-4),
128.2, 128.4, 129.8 (3 d, Ph), 129.9 (d, PhC), 130.9 (s, C-1), 135.6 (s,
Ar), 143.8 (s, C-4a), 199.9 (s, C-2).
Compound 21 (50 mg, 0.17 mmol), -bromo oxime 32 (35 mg, 0.17
mmol), and Na2CO3 (360 mg, 3.4 mmol) were suspended in CH2Cl2 (30
mL) and the mixture was stirred at r.t. for 4 d. Additional 32 (in total:
350 mg, 1.70 mmol) was added in six portions over a period of 6 d.
The mixture was filtered through a pad of Celite and concentrated in
vacuo. After column chromatography (silica gel, hexanes/EtOAc 9:1),
33 was isolated.
Yield: 25 mg (35%); colorless solid; mp 54–56 °C.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H20O2Na: 291.1361;
found: 291.1359.
IR (ATR): 3450 (O-H), 3080–2860 (=C-H, C-H), 1635 (C=N), 1500
(C=C), 1190, 1140 (CF3) cm–1
.
1H NMR (700 MHz, CDCl3):  = 0.08, 0.19 (2 s, 3 H each, SiMe2), 0.85 (s,
9 H, CMe3), 1.16 (s, 3 H, 10-Me), 1.23 (br s, 1 H, OH), 1.34 (tq, J = 4.1,
13.4 Hz, 1 H, 8-H1), 1.57 (dt, J = 4.1, 13.0 Hz, 1 H, 9-H1), 1.63–1.68 (m,
1 H, 8-H2), 1.72–1.76 (m, 1 H, 9-H2), 1.83–1.87 (m, 1H, 10a-H), 1.89–
1.96 (m, 1 H, 7-H1), 2.18 (tdd, J = 2.2, 4.1, 14.0 Hz, 1 H, 7-H2), 2.27–
2.33 (m, 2 H, 5-H1, 10b-H), 2.52 (dd, J = 17.2, 6.3 Hz, 1 H, 5-H2), 2.71
(ddd, J = 1.0, 6.8, 18.6 Hz, 1 H, 1-H1), 3.07 (d, J = 18.6 Hz, 1 H, 1-H2),
5.28–5.32 (m, 1 H, 6-H).
13C NMR (176 MHz, CDCl3):  = –4.1, –2.7 (2 q, SiMe2), 17.8 (s, CMe3),
21.7 (q, 10-Me), 22.4 (t, C-1), 23.3 (t, C-8), 25.6 (q, CMe3), 28.1 (d,
C-10), 32.6 (d, C-10b), 34.4 (t, C-7), 36.4 (t, C-5), 43.9 (t, C-9), 51.4 (d,
C-10a), 116.8 (d, C-6), 120.7 (q, JCF = 274.4 Hz, CF3), 122.1 (s, C-4a),
136.8 (s, C-6a), 147.5 (q, JCF = 33.7 Hz, C-2).
(1R*,3R*,4R*,4aS*,5R*,8aR*)-3-(tert-Butyldimethylsiloxy)-5-methyl-
decahydronaphthalene-1,4,5-triol
Compound 21 (102 mg, 0.31 mmol) was dissolved in THF (9 mL) and
cooled to –30 °C. A 1 M solution of BH3·THF in THF (1.40 mL, 1.40
mmol) was added and the mixture was stirred for 3 h while being al-
lowed to warm to r.t. It was then cooled to 0 °C and subsequently 2 M
aq NaOH (2 mL) and H2O2 (30 weight% in H2O; 0.7 mL, 6.85 mmol)
were added dropwise and stirring was continued for 18 h. Sat. aq
Na2S2O3 (1.4 mL) was added and the mixture was extracted with Et2O
(3 × 20 mL). The combined organic extracts were dried (MgSO4) and
concentrated in vacuo. After column chromatography (silica gel,
hexanes/EtOAc 9:1 to 4:1 to 0:1), the product was isolated.
Yield: 54 mg (47%); colorless oil.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H32F3NO3NaSi: 442.2001;
found: 442.2009.
IR (film, ATR): 3380 (O-H), 2930–2850 (C-H), 1470 (C-C) cm–1
.
1H NMR (500 MHz, CDCl3):  = 0.09 (s, 6 H, SiMe2), 0.89 (s, 9 H, CMe3),
1.10–1.80*, 1.89–1.96, 2.05–2.60 (3 m, 13 H, 1-H, 4-H, CH, CH2, OH),
1.44* (s, 3 H, 5-Me), 3.56 (dd, J = 8.5, 11.1 Hz, 1 H, 4-H), 3.81 (mc, 1 H,
1-H), 3.86 (ddd, J = 3.4, 4.9, 8.5 Hz, 1 H, 3-H); * overlapping signals.
13C NMR (100 MHz, CDCl3):  = –4.7, –4.0 (2 q, SiMe2), 17.9, 25.8 (s, q,
CMe3), 21.4, 25.5 (2 t, CH2), 32.3 (q, 5-Me), 34.7, 35.7 (t, CH2), 40.5,
45.8 (2 d, C-4a, C-8a), 71.5, 73.1, 74.2 (3 d, C-1, C-3, C-4), 72.6 (s, C-5).
Methyl (1aR*,7R*,7aR*,7bS*)-1a-(tert-Butyldimethylsiloxy)-7-
hydroxy-7-methyl-1a,2,4,5,6,7,7a,7b-octahydro-1H-cyclopropa[a]-
naphthalene-1-carboxylate (34)
Cu(acac)2 (8.9 mg) was added to a solution of 21 (100 mg, 0.34 mmol)
in EtOAc (24 mL). The mixture was heated to reflux and a solution of
methyl diazoacetate (170 mg) in EtOAc (6 mL) was slowly added over
a period of 4.5 h. After 72 h and 79 h, both Cu(acac)2 (8.9 mg, 0.1
equiv at a time, in total 27 mg, 0.09 mmol) and a solution of methyl
diazoacetate (170 mg, 5 equiv at a time, in total 510 mg, 5.10 mmol)
in EtOAc (6 mL) were added. After 92 h of stirring at reflux, the sus-
pension was filtered and the filtrate was concentrated in vacuo. After
column chromatography (silica gel, hexanes/EtOAc 9:2), 34 was iso-
lated as a mixture of trans/cis-isomers (trans/cis refers to the posi-
tions of the OTBS and the CO2Me groups).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C14H34O4NaSi: 353.2119;
found: 353.2135.
(1R*,2R*,4R*,4aR*,8R*,8aS*)-8-Methyldecahydronaphthalene-
1,2,4,8-tetrol (31)
At 0 °C, 1 M TBAF in THF (207 L) was added to a solution of the prod-
uct obtained above (54 mg, 0.16 mmol) in THF (4 mL). The mixture
was stirred for 1 h at r.t.; then MeOH (0.1 mL) was added, all volatiles
were removed in a stream of argon, and the crude material was sub-
jected to column chromatography (silica gel, CH2Cl2/MeOH 4:1).
Yield: 39 mg (31%); trans/cis 5:1.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

I
A. Niermann, H.-U. Reissig
Paper
Synthesis
IR (film, ATR): 3430 (O-H), 2950–2860 (=C-H, C-H), 1730 (C=O), 1630
(C=C), 1170 (C-O), 1110 (C-O) cm–1
Funding Information
.
This work was supported by the Deutsche Forschungsgemeinschaft
1H NMR (700 MHz, C6D6):  (trans-34; major isomer) = 0.16*, 0.20 (2
s, 3 H each, SiMe2), 0.90 (s, 9 H, CMe3), 1.10 (s, 3 H, Me), 1.13 (tq, J =
4.2, 13.4 Hz, 1 H, 5-H1), 1.35 (dt, J = 4.5, 13.4 Hz, 1 H, 6-H1), 1.46 (mc, 1
H, 5-H2), 1.60 (mc, 1 H, 6-H2), 1.72* (mc, 1 H, 4-H1), 1.94 (mc, 1 H, 4-H2),
1.95 (d, J = 11.0 Hz, 1 H, 1-H), 2.07 (d, J = 11.0 Hz, 1 H, 7b-H), 2.45 (mc,
1 H, 2-H1), 2.58* (mc, 1 H, 7a-H), 2.89 (mc, 1 H, 2-H2), 3.31 (s, 3 H,
OMe), 5.02 (mc, 1 H, 3-H); * overlapping signals of both diastereo-
mers.
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Acknowledgment
We thank Dr. Reinhold Zimmer for help during preparation of the
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13C NMR (176 MHz, C6D6):  (trans-34; major isomer) = –3.7, –3.0 (2
q, SiMe2), 17.8 (s, CMe3), 20.9 (q, Me), 24.6 (d, C-7b), 25.6 (t, C-5), 25.8
(q, CMe3), 29.4 (d, C-1), 31.3 (t, C-2), 35.4 (t, C-4), 42.7 (t, C-6), 48.1 (d,
C-7a), 50.9 (q, OMe), 58.3 (s, C-1a), 74.5 (s, C-7), 116.9 (d, C-3), 136.5
(s, C-3a), 168.9 s, CO).
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707889.
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1H NMR (700 MHz, C6D6):  (cis-34; minor isomer) = 0.16*, 0.26 (2 s, 3
H each, SiMe), 1.00 (s, 9 H, CMe3, 1.05 (s, 3 H, Me), 1.26 (mc, 1 H, 6-H1),
1.56–1.58 (m, 1 H, 6-H2), 1.70–1.74* (m, 2 H, 4-H1, 1-H), 1.94 (mc, 1 H,
4-H2), 2.00 (mc, 1 H, 7a-H), 2.36 (mc, 1 H, 2-H1), 2.54–2.56* (m, 1 H, 2-H2),
2.73 (d, J = 6.0 Hz, 1H, 7b-H), 3.46 (s, 3 H, OMe), 4.88 (mc, 1 H, 3-H); *
overlapping signals of both diastereomers.
13C NMR (176 MHz, C6D6):  (cis-34; minor isomer) = –3.4, –2.6 (2 q,
SiMe2), 18.2 (s, CMe3), 21.1 (q, Me), 26.1 (t, C-5), 27.1 (d, C-7b), 30.0
(d, C-1), 33.5 (t, C-2), 35.2 (t, C-4), 51.3 (q, OMe), 51.6 (d, C-7a), 63.6
(s, C-1a), 74.5 (s, C-7), 116.5 (d, C-3), 135.6 (s, C-3a), 171.5 (s, CO); the
signal of CMe3 could not be identified.
References
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HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H34O4NaSi: 389.2119;
found: 389.2123.
Methyl (1R*,8R*,8aR*)-2′-(8-Hydroxy-8-methyl-2-oxo-
1,2,3,5,6,7,8,8a-octahydronaphthalen-1-yl)acetate (35)
TiCl4 (2 drops) was added to a solution of compound 34 (19 mg, 0.052
mmol, cis/trans mixture) in MeOH (5 mL) at –78 °C and the solution
was stirred at this temperature for 3 h. Due to incomplete conversion,
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54 h, allowing the mixture to reach r.t. H2O (10 mL) and brine (10 mL)
were added and the mixture was extracted with Et2O (3 × 20 mL). The
combined organic extracts were dried (MgSO4) and concentrated in
vacuo. After column chromatography (silica gel, hexanes/EtOAc 3:1),
35 was isolated.
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Yield: 8 mg (58%); colorless oil.
IR (film, ATR): 3375 (O-H), 3020–2870 (=C-H, C-H), 1720, 1685 (C=O),
1495 (C=C) cm–1
.
1H NMR (700 MHz, CDCl3):  = 1.12 (s, 3 H, 8-Me), 1.38 (tq, J = 4.2, 13.4
Hz, 1 H, 6-H1), 1.52–1.59 (m, 1 H, 7-H1), 1.73–1.79 (m, 1 H, 6-H2),
1.81–1.85 (m, 1 H, 7-H2), 1.87 (br s, 1 H, OH), 1.93–2.03 (m, 1 H, 5-H1),
2.27 (tdd, J = 1.9, 4.2, 13.3 Hz, 1 H, 5-H2), 2.38–2.41 (m, 1 H, 8a-H),
2.70, 2.74 (AB-part of ABX-system, JAB = 16.3 Hz, JAX = 6.7 Hz, JBX = 7.1
Hz, 1 H each, 2′-H), 2.84–2.94 (m, 2 H, 3-H), 3.20 (X-part of ABX-
system, JAX = 6.7 Hz, JBX = 7.1 Hz, additional couplings, J = 0.7, 3.8 Hz,
1 H, 1-H), 3.69 (s, 3 H, OMe), 5.43–5.50 (m, 1 H, 4-H).
13C NMR (176 MHz, CDCl3):  = 20.7 (q, Me), 24.3 (t, C-6), 34.0 (d, C-8a),
34.8 (t, C-5), 36.3 (t, C-2′), 37.9 (t, C-3), 42.8 (t, C-7), 43.7 (d, C-1), 51.7
(q, OMe), 74.9 (s, C-8), 116.9 (d, C-4), 137.5 (s, C-4a), 174.2 (s, C-1′),
209.9 (s, C-2).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C14H20O4Na: 275.1254;
found: 275.1256.
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A. Niermann, H.-U. Reissig
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Synthesis
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THF at an earlier stage of the multistep reaction is possible. See:
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