Synthesis of tricyclic precursors of cyclitols

Article abstract of DOI:10.1055/s-0033-1341266

Stereoselective syntheses of three tricyclic cyclohexenones are described. These compounds were conceived as novel precursors of synthetic conduritols, quercitols, and inositols because they allow diastereoselective C=O reductions, C=C osmylations, and C=C epoxidations to be performed. These functionalizations created up to three uniformly configured oxygen-bearing stereocenters. One of the follow-up products was a tricycle that was amenable to successive cleavages of its 1,4-dioxane and 1,3-dioxane rings. This rendered the pentaesters of neo-quercitol, which contain five stereogenic C-O bonds, with ds = 85:15. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1341266

1312▌
LETTER
lSetyternthesis of Tricyclic Precursors of Cyclitols
Tricyclic Precursors of Cyclitols
Johannes Aucktor, Chiara Anselmi,1 Reinhard Brückner,* Manfred Keller
Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany
Fax +49(761)2036100; E-mail: reinhard.brueckner@organik.chemie.uni-freiburg.de
Received: 21.02.2014; Accepted after revision: 27.03.2014
nones 8, endo-9, and exo-9. Their cyclohexenone moieties
stem from hydroquinone monoethers.
Abstract: Stereoselective syntheses of three tricyclic cyclohexe-
nones are described. These compounds were conceived as novel
precursors of synthetic conduritols, quercitols, and inositols be-
cause they allow diastereoselective C=O reductions, C=C os-
mylations, and C=C epoxidations to be performed. These
functionalizations created up to three uniformly configured oxygen-
bearing stereocenters. One of the follow-up products was a tricycle
that was amenable to successive cleavages of its 1,4-dioxane and
1,3-dioxane rings. This rendered the pentaesters of neo-quercitol,
which contain five stereogenic C–O bonds, with ds = 85:15.
cyclohexitols
OH
OH
HO
OH
OH
HO
OH
HO
HO
OH
OH
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
HO
OH
OH
quercitols (2)
OH
conduritols (1)
ref. 8: this work:
inositols (3)
this work: ref. 11:
Hal
ref. 9:
ref. 10:
Key words: α-hydroxy ketone, cyclohexadienones, diastereoselec-
OH
tivity, 1,2-diol, hypervalent iodine reagent, oxidative cyclization
HO
OH
OH
O
O
O
HO
O
O
4
5
6
7
Polyhydroxycyclohexenes and polyhydroxycyclohexanes
are important representatives of a family of compounds,
both natural and unnatural, which are collectively known
as cyclitols.2 As specified in Scheme 1 they encompass
tetrahydroxycyclohexenes [conduritols (1)], pentahy-
droxycyclohexanes [quercitols (2)], and hexahydroxycy-
clohexanes [inositols (3)].3 Their structures appear simple
but are markedly diverse because of an abundance of ste-
reostructures: Counting enantiomers as distinct, there are
ten stereoisomeric conduritols (1), 16 quercitols (2), and
nine inositols (3). These stereoisomers differ from their
carba-analogues, anhydrodeoxypentopyranoses, deoxy-
pentopyranoses, and pentopyranoses, by the inclusion of
meso-isomers; there are two meso-configured conduritols,
four meso-configured quercitols, and seven meso-config-
ured inositols.
OMe
= PMP
O
O
O
O
O
*
H
O
O
H
O
PMP = endo-9
PMP = exo-9
8
O
O
*
*
Scheme 1 Stereoselective syntheses of cyclitols such as conduritols
(1), quercitols (2) or inositols (3) from a pyranose (4),8 from cyclo-
hexa-1,4-diene (5),9 from p-benzoquinone (6),10 and from the aceton-
ide of enantiopure cis-3-halocyclohexa-3,5-diene-1,2-diols (7)11 (all
established) or from the tricyclic cyclohexenones 8, endo-9, and exo-
9 (suggested in the present study).
The tricyclic cyclohexenone 8 was obtained as shown in
Scheme 2. The enantiomerically pure ketal 1012 was ether-
ified under Mitsunobu conditions13 with hydroquinone
monoacetate (1114) giving ketal 12 (91% yield). Hydroly-
sis rendered 92% of the diol-containing hydroquinone
monoether 13. The latter cyclized when exposed to
PhI(O2CCF3)2.15 An inseparable 78:22 mixture of the ben-
zoquinone monoketal isomers 14 (97% ee)16 and 15 was
formed (85% yield). Their ketal moieties were six- and
seven-membered rings, respectively. When this mixture
was deprotonated with NaH, the major isomer (14) only
underwent an intramolecular oxa-Michael addition. This
led to 81% of the tricyclic cyclohexenone 8 (relative to the
fraction of ketal 14 in the 14/15 mixture).
The sp2-carbon atoms in the C=O and the C=C bond of the
tricyclic cyclohexenone 8 were transformed to oxygenat-
ed stereocenters with very high diastereocontrol (Scheme
3). LiAlH4 attacked exclusively the β-face of the C=O
bond, generating the cyclohexenol 16 with ds = 98:2.
Without prior purification, it was acetylated under the re-
action conditions. This allowed the isolation of the corre-
sponding acetate 17 as a pure diastereomer (88%). The
The strong interest in cyclitol chemistry is due to the im-
portance of the derived monophosphates and oligophos-
phates, plus notably diacylglycerol esters thereof, for
biological signaling.4 For accessing such compounds5 the
sole affordable source is synthesis, with or without the aid
of enzymes. Regioselectivity is a major issue when intro-
ducing the phosphate substituent(s)6 while a prime con-
cern in preparing the underlying cyclitol cores is
achieving stereocontrol.3b,7 As Scheme 1 indicates this has
been possible, inter alia, starting from pyranoses (4),8 cy-
clohexa-1,4-diene (5),9 p-benzoquinone (6)10 or enantio-
merically pure acetonides 711 of cis-configured 3-
halocyclohexa-3,5-diene-1,2-diols. The present publica-
tion describes the development of novel starting materials
for synthesizing cyclitols, namely the tricyclic cyclohexe-
SYNLETT 2014, 25, 1312–1318
Advanced online publication: 29.04.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1341266; Art ID: st-2014-b0150-l
© Georg Thieme Verlag Stuttgart · New York

LETTER
Tricyclic Precursors of Cyclitols
1313
Et
Et
homogenous triacetates 21 (95%) and 22 (90%), respec-
tively. The former compound, i.e., 21 was identical with
the triacetate obtained from the cyclohexanediol 18 by the
following treatment (Scheme 4, bottom): OH-directed re-
duction of the C=O bond with Me4N+ –BH(OAc)3;20 di-
acetylation and separation from a trace of triacetate 23 by
flash chromatography19 (ds = 98:2). The triacetate 23, in
turn, could be prepared from the cyclohexanediol 18 with
essentially complete diastereocontrol by reversing the or-
der of steps, that is, by a diacetylation followed by NaBH4
reduction.
OAc
a)
OR2
OH
R1O
O
O
+
R1O
b)
HO
O
12: R1–R2 = C(Et)2, R2 = Ac
11
10
13: R1 = R2 = H
c)
OH
O
O
O
O
O
d)
H
O
+
H
O
HO
O
O
O
8 (X-ray: Figure 1)
14a (78:22 mixture)
(97% ee)
15
Scheme 2 Synthesis of the unsubstituted tricyclic cyclohexenone 8.
Reagents and conditions: (a) 1012 (1.0 equiv), 1114 (1.1 equiv), Ph3P
(1.1 equiv), DEAD (1.1 equiv), CH2Cl2, r.t., 4 h, 91%; (b) Amberlyst-
15 (cat.), MeOH, r.t., 20 h, 92%; (c) PhI(O2CCF3)2 (1.1 equiv),
NaHCO3 (3.0 equiv), MeCN, r.t., 15 min, K2CO3 (2.2 equiv), 85%,
14/15 (78:22 mixture); (d) NaH (1.5 equiv), 18-crown-6 (0.5 equiv),
OAc
OAc
a)
OAc
O
O
O
O
O
O
+
H
H
H
ds =
93:7
OR
OR
O
O
O
OR
OR
20b R = H
22 R = Ac
(separated
chromato-
graphically)
20a R = H
21 R = Ac
17
a
c)
b)
toluene, 110 °C, 24 h, 81%. The drawing of compound 14 depicts
primarily constitution and configuration. Its dioxane moiety is drawn
in a conformation, which relates closely to the 3D structure of com-
pound 8 prepared therefrom. However, the major conformer of com-
pound 8 contains a dioxane chair with an equatorial α-hydroxymethyl
group. This follows from the J = 11.8 Hz coupling in the (HO)CH2–
CH–CHax motif; it is a trans-diaxial H,H coupling.
(separated
chromato-
graphically)
OAc
O
d)
O
O
ds = 98:2 (favoring 21)
H
O
H
O
OAc
OH
e),f) ds = 100:0
O
O
OAc
OH
23
18 (X-ray: Figure 1)
Scheme 4 Processing the tricyclic templates 17 and 18 from Scheme
3. Reagents and conditions: (a) K2OsO2(OH)4 (5 mol%), NMO (1.3
equiv), citric acid (2.0 equiv), t-BuOH–H2O (1:1), r.t., 15 h, 84.6%
20a, 6.8% 20b (separated by flash chromatograpy19); (b) Ac2O (4.0
equiv), DMAP (20 mol%), pyridine (5.0 equiv), CH2Cl2, r.t., 15 h,
95%; (c) Ac2O, pyridine, r.t., 20 h, 90%; (d) Me4N+ –BH(OAc)3 (3.0
equiv), AcOH (6.0 equiv), MeCN, r.t., 1.5 h; Ac2O (15 equiv), DMAP
(30 mol%), pyridine (18 equiv), THF, 40 °C, 20 h, 94% 21, 1.4% 23
(separated by flash chromatography19); (e) same as (c) but 18 h, 71%;
(f) NaBH4 (three-fold molar amount), MeOH, 0 °C, 1 h; Ac2O, pyri-
dine, r.t., 18 h, 53%.
C=C bond of the tricyclic cyclohexenone 8 was dihydrox-
ylated with exceptionally high diastereocontrol from the
β-face when subjected to a citric acid mediated os-
mylation.17 The tricyclic dihydroxycyclohexanone 18 re-
sulted in 92% yield. High stereocontrol was also observed
for the nucleophilic epoxidation of cyclohexenone 8 with
cumene hydroperoxide and Triton-B.18 If the reaction was
β-selective, like the previous transformations, the product
was the epoxycyclohexanone 19 (58% yield).
OH
OAc
At this point we had gained the stereouniform cyclohexa-
none-based diol 18 and epoxide 19 (Scheme 3), the cyclo-
hexene-based monoacetate 17 (Scheme 3), and the
cyclohexane-based triacetates 21 and 23 (Scheme 4) in
quite satisfactory manners. However, all efforts to trans-
form these compounds to a more cyclitol-like structure
met with failure. A plausible culpable was the 1,4-dioxane
subunit. It stemmed from the oxa-Michael addition step
(14 → 8, Scheme 2), had stayed since, but now refused to
ring-open. We felt, however, that exactly this ring-open-
ing was a prerequisite for having more promising attempts
at hydrolyzing the ketal group in any of the mentioned
‘building blocks’.21 As a consequence we chose to modify
the 1,4-dioxane moiety of the tricyclic cyclohexenone 8,
which we had studied so far; we introduced a predeter-
mined breaking point by a p-methoxyphenyl (PMP) sub-
stituent. It turned the hitherto ‘purely aliphatic ether’
moiety into a p-methoxybenzyl (PMB) ether moiety.
PMB ethers can be removed under a number of reaction
conditions, which leave aliphatic ethers unaffected.22
These considerations made either of the tricyclic cyclo-
hexenone diastereomers endo-9 or exo-9 (Scheme 5) a vi-
able second-generation cyclitol building block candidate
for our project.
O
O
O
O
a)
con-
tin-
ued
H
H
O
O
17
dr = 100:0
16 (X-ray: Figure 1)
a)
ds = 98:2
O
O
O
O
O
O
O
b)
c)
H
H
O
H
O
OH
O
O
O
O
OH
18 (X-ray: Figure 1)
ds = 100:0
ds = 98:2
19
8
Scheme 3 C=C and C=O bond functionalizations of the cyclohexe-
none moiety of the unsubstituted tricyclic cyclohexenone 8. Reagents
and conditions: (a) LiAlH4 (0.3-fold molar amount), THF, –78 °C, 1
h; Ac2O (7.0 equiv), DMAP (10 mol%), –78 °C → r.t., 6 h, 88%; (b)
K2OsO2(OH)4 (0.5 mol%), NMO (1.2 equiv), citric acid (2.0 equiv),
t-BuOH–H2O (1:1), r.t., 8 h, 92%; (c) cumene hydroperoxide (2.0
equiv), BnNMe3+ –OH (cat.), THF, 0 °C, 2 d, 58%.
Scheme 4 shows stereogenic follow-up transformations of
the cyclohexenyl acetate 17 and the cyclohexanediol 18,
prepared as shown in Scheme 3. The citric acid mediated
osmylation17 of cyclohexenyl acetate 17 (Scheme 4, top)
delivered the diastereomeric cis-1,2-diols 20a (85%) and
20b (7%) after separation by flash chromatography on sil-
ica gel.19 Diacetylations rendered the stereochemically
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1312–1318

1314
J. Aucktor et al.
LETTER
BzO
BzO
a)
PMP
+
HO
PMP
OH
O
24
25
26
b)
OH
HO
BzO
BzO
d)
HO
OH
OH
OH
e)
c)
PMP
PMP
PMP
PMP
O
O
O
O
ds > 99:1
OH
OH
OH
(>99.9% ee)
29
epi-27 (>99.9% ee)
O
28
27
f)
g)
O
HO
O
PMP
H
O
PMP
H
O
PMP
H
O
HO
O
PMP
H
O
O
O
O
i)
h)
ds = 100:0
ds = 100:0
O
O
O
O
epi-30a
30a
endo-9 (X-ray: Figure 1)
exo-9 (X-ray: Figure 1)
Scheme 5 Synthesis of the PMP-substituted tricyclic cyclohexenones endo-9 and exo-9. Reagents and conditions: (a) 2523 (1.00 equiv), 2424
(1.20 equiv), Ph3P (1.10 equiv), DIAD (1.15 equiv), THF, r.t., 12 h, 93%; (b) K2OsO2(OH)4 (1.0 mol%), (DHQD)2PHAL (2.0 mol%),
K3Fe(CN)6 (3.0 equiv), K2CO3 (3.0 equiv), MeSO2NH2 (1.0 equiv), t-BuOH–H2O (1:1), 0 °C, 6 d, 94%, 99.2% ee (≥99.9% ee after crystalli-
zation); (c) KOH (1.1 equiv), MeOH, r.t., 2 h, 99%; (d) DDQ (1.07 equiv), CH2Cl2, r.t., 8 d, 95%, >99.9% ee; (e) Zn(BH4)2 (0.5-fold molar
amount), THF, –30 °C, 14 h; NaOH (2.2 equiv), MeOH, 0 °C → r.t., 2 h, 96%, ds >99:1, >99.9% ee; (f) PhI(O2CCF3)2 (1.05 equiv), NaHCO3
(3.0 equiv), CH2Cl2, 0 °C, 20 min, 82%; (g) same as (f), 79%; (h) NaH (1.4 equiv), DME, 60 °C, 90 min, 62%; (i) NaH (1.2 equiv), THF, 65
°C, 100 min, 87%. [a]The drawings of compounds 30 and epi-30 depict primarily constitutions and configurations. The dioxane moieties are
drawn in conformations, which relate closely to the 3D structure of compounds endo-30 and exo-30 prepared therefrom. However, the major
conformers of compounds 30 and epi-30 contain dioxane chairs with an equatorial α-hydroxybenzyl group. This follows from the J = 11.8 Hz
coupling in the respective (HO)CH(PMP)–CH–CHax motif; it is a trans-diaxial H,H coupling. (DHQD)2PHAL = bis(dihydroquinidine)phthala-
zine-1,4-diyl diether.
Our routes to the second-generation cyclitol precursors The stereostructures of the novel cyclohexenones endo-9
endo-9 and exo-9 (Scheme 5) began with the E-configured and exo-9 were ascertained by X-ray monocrystal analy-
homocinnamylic alcohol 2523 and hydroquinone mono- ses (Figure 1). Their cyclohexenone rings possess half-
benzoate (24).24 The latter compound was alkylated by the chair conformations. The latter are folded such that they
former under Mitsunobu conditions.13 The resulting ether have two quasi-equatorial oxygen substituents and one
26 (93% yield) was dihydroxylated asymmetrically.25 quasi-axial oxygen substituent. The heterocycles in com-
This rendered the syn-configured diol 28 in 94% yield and pounds endo-9 and exo-9, i.e., the 1,4-dioxane and 1,3-di-
with 99.2% ee26 (→ ≥99.9% ee26 after recrystallization). It oxane (‘ketal’) rings, have chair conformations. The same
was transformed into the tricyclic cyclohexenone endo-9 half-chair/chair/chair scaffold was contained in our first-
retaining both stereocenters, and into the epimeric cyclo- generation tricyclic cyclohexenone 8 (Figure 1). Structur-
hexenone exo-9 inverting the benzylic stereocenter.
ally speaking, our second-generation tricyclic cyclohexe-
nones endo-9 and exo-9 differ from 8 only by their
respective PMP substituent. It is axially appended to the
1,4-dioxane moiety of tricycle endo-9 and equatorially in
exo-9. These differential PMP orientations let us expect
that C=C or C=O bond functionalizations in the tricycle
endo-9 would exhibit (even) higher β-selectivities than
analogous reactions of the tricycles exo-9 and 8. For rea-
sons unknown, these expectancies did not bear out fully
(vide infra): usually, C=C bond functionalizations were
more β-selective in scaffolds with an exo- rather than
endo-PMP substituent.
The retention-of-configuration pathway from diol 28 to
cyclohexenone endo-9 comprises three steps (Scheme 5,
lower left): (1) Alkaline benzoate cleavage (→ 99% hy-
droquinone monoether 27); (2) oxidation with
PhI(O2CCF3)215 (→ 82% benzoquinone monoketal 3027);
(3) NaH-induced oxa-Michael cyclization (→ 62% target
endo-9, ds = 100:0). The inversion-of-configuration path-
way from diol 28 to cyclohexenone exo-9 consists of five
steps, which were realized in four operations (Scheme 5,
lower right). We began by inverting the configuration of
the benzylic stereocenter through an oxidation/reduction
sequence. Other than in existing procedures28 this was re- The C=O and C=C bonds of the PMP-containing cyclo-
alized without protection in between. Diol 28 and DDQ29 hexenones endo-9 and exo-9 were turned into oxygenated
gave 95% α-hydroxy ketone 29 without racemization.30 stereocenters by the reactions shown in Scheme 6. In es-
31
Reduction with Zn(BH4)2
was completely anti- sence, these reactions exhibited similar or lesser diastereo-
selective32 so that an ensuing debenzoylation provided the selectivity, respectively, as the analogous reactions of the
desired hydroquinone monoether epi-27 exclusively.33 PMP-free cyclohexenone 8 (Scheme 3). Firstly, LiAlH4
15
Oxidation with PhI(O2CCF3)2 gave 79% of the benzo- reductions of the carbonyl group delivered the cyclohex-
quinone monoketal epi-30.34 Sodium hydride induced cy- enols endo-31 (ds >99:1) and exo-31 (ds = 98:2), respec-
clization delivered the tricycle exo-9 (87%, ds = 100:0).
tively.35 Secondly, citric acid mediated osmylations17 of
the cyclohexenones endo-9 and exo-9 gave the cis-1,2-
Synlett 2014, 25, 1312–1318
© Georg Thieme Verlag Stuttgart · New York

LETTER
Tricyclic Precursors of Cyclitols
1315
Figure 1 ORTEP plotsa of X-ray crystal structure analyses of compounds 8 (at 100 K45), 16 (at 100 K46), 18 (at 100 K47), endo-9 (at 294 K48),
exo-9 (at 294 K49), endo-33 (at 100 K50), exo-33 (at 173 K51), exo-32 (at 173 K52), and 39 (at 100 K53). The left-hand column depicts cyclohex-
enones (8, endo-9, and exo-9), the center column dihydroxycyclohexanones (18, endo-33, and exo-33), and the right-hand column a cyclohex-
enol (16), a related cyclohexenyl acetate (exo-32), and a corresponding epoxycyclohexyl acetate (39). [a] For easier recognizability the para-
methoxyphenyl (‘PMP’) rings are omitted except for their center C-1. The latter is shown in green color. Full representations of these X-ray
structures are included in the Supporting Informations.
diol endo-33 as an inseparable 89:11 mixture with a minor Scheme 7 shows the subsequent introduction of other ste-
diastereomer (90% combined yield) and the pure cis-1,2- reogenic centers into the cyclohexenyl acetate exo-32, the
diol exo-33 (92%) after purification by flash chromatog- cyclohexanediol exo-33, and the epoxycyclohexanone
raphy,19 respectively. Thirdly, nucleophilic epoxidation of exo-34 (all prepared as shown in Scheme 6). The cyclo-
cyclohexenones endo-9 and exo-9 with H2O2/DBU36 fur- hexenyl acetate exo-32 was cis-dihydroxylated by
nished the epoxycyclohexanone endo-34 in an insepara- Sharpless’ OsO4–NMO–citric acid procedure.17 The 1,2-
ble 62:38 mixture with its diastereomer (49% combined diols 35a and 35b resulted in a 87:13 ratio. They were sep-
yield) and the epoxycyclohexanone exo-34 (81%) with arated by flash chromatography19 and acetylated, which
ds = 96:4, respectively.
provided the corresponding triacetates 3637 and 37. A
100% diastereoselective route to the triacetate 3637 was
the triacetoxyborohydride reduction20 of the C=O-con-
taining cyclohexanediol exo-33. Yet another triacetate 38
was accessed with excellent stereocontrol (ds = 98:2), too.
To this end, the C=O-containing cyclohexanediol exo-33
was diacetylated and the resulting diacetoxy ketone re-
duced by LiAlH(Ot-Bu)3. Finally, we also prepared the
not yet mentioned triacetate 40 in a highly stereocon-
trolled manner. Starting with a Luche reduction38 of the
epoxycyclohexanone exo-34 we obtained the epoxycyclo-
hexanol with ds = 94:6. An esterification followed by pu-
rification by flash chromatography19 afforded the
epoxycyclohexyl acetate 39 as a single diastereomer.
Ring-opening of the epoxide moiety in 30:1 toluene/H2O
in the presence of BF3·OEt239 delivered two diaxial diols40
exclusively (not depicted in Scheme 7). The diacetylation
of these diols resulted in the already mentioned triacetate
40.40
R1
R2
R1
R2
HO
AcO
O
O
O
O
a)
endo: R1 = PMP, R2 = H
exo: R1 = H, R2 = PMP
H
H
O
O
endo-31 (dr > 99:1)
exo-31 (dr > 99:1)
endo-32
exo-32 (X-ray: Fig. 1)
b)
R1
R2
R1
R1
O
O
O
O
O
O
O
R2
O
O
R2
c)
d)
H
H
H
HO
O
O
O
O
OH
endo-33* (dr = 89:11)
exo-33* (dr = 98:2)
endo-9
exo-9
endo-34 (dr = 62:38)
exo-34 (dr = 96:4)
* X-rays: Figure 1
Scheme 6 C=C and C=O bond functionalizations of the cyclohexe-
none moiety of the PMP-substituted tricyclic cyclohexenones endo-9
and exo-9. Reagents and conditions: (a) for endo-32: Ac2O (2.0
equiv), DMAP (10 mol%), pyridine (3.0 equiv), CH2Cl2, r.t., 6 h,
97%; for exo-32: same as above but 12 h, 100%; (b) for endo-31:
LiAlH4 (0.3-fold molar amount), THF, –78 °C, 30 min, 99%; for exo-
31: same as above but 45 min, 100%, 98:2 mixture with the diastereo-
mer (dr >99:1 after recrystallization from Et2O); (c) for endo-33:
K2OsO2(OH)4 (1.2 mol%), citric acid (2.0 equiv), NMO (1.5 equiv),
MeCN–t-BuOH–H2O (4:1:1), r.t., 3 d, 90% of the 89:11 mixture with
the diastereomer; for exo-33: K2OsO2(OH)4 (0.5 mol%), citric acid
(2.0 equiv), NMO (1.5 equiv), t-BuOH–H2O (1:1), r.t., 30 h, 92%
pure exo-33 after flash chromatography;19 (d) for endo-34: H2O2 (8.0
equiv), DBU (3.0 equiv), THF, r.t., 15 h, 49%, 62:38 mixture with the
diastereomer; for exo-34: H2O2 (3.0 equiv), DBU (1.0 equiv), THF,
r.t., 2 h, 81% of the 96:4 mixture with the diastereomer (dr >99:1 after
recrystallization).
Scheme 8 presents a proof-of-concept sequence. It show-
cases how we degraded the tricyclic triacetate 36 to the
monocyclic cyclitol derivative 44a (along with two iso-
mers). Substrate 36 was chosen arbitrarily from our siz-
able collection of tricyclic templates. In step one we
cleaved its PMB–O bond by treatment with Et3SiH in
F3CCO2H.41 This broke the 1,4-dioxane moiety of sub-
strate 36 open in 94% yield. Thereby a transformation had
been turned into practice, for which we had found no so-
lution with respect to the PMP-free substrate 21 (Scheme
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1312–1318

1316
J. Aucktor et al.
LETTER
AcO
AcO
OR
O
AcO
AcO
PMP
a)
AcO
RO
PMP
H
PMP
a)
AcO
AcO
PMP
O
O
O
O
O
O
O
O
+
PMP
H
H
H
RO
O
O
O
O
O
ds =
87:13
separated
chromato-
graphically
AcO
OAc
RO
RO
36
41 R = H
AcO
c)
OBz Br
exo-32 (X-ray: Figure 1)
35a R = H
36 R = Ac
35b R = H
37 R = Ac
b)
b)
c)
O
42 R = Bz
PMP
AcO
O
ketal hydrolysis
separated
chromato-
graphically
AcO
43 (dr ~ 50:50)
d),e)
PMP
AcO
AcO
PMP
H
O
O
O
O
ds = 100:0
AcO
AcO
OBz
OAc
AcO
d)
OBz
O
e)
H
O
O
HO
f),g) (dr36/38 = 2:98)
O
ds = 85:15
AcO
AcO
OH
38
exo-33 (X-ray: Figure 1)
AcO
45
44a (separated
from the isomers
by HPLC)
AcO
+
AcO
AcO
PMP
H
AcO
PMP
O
PMP
H
O
O
O
O
AcO
AcO
OAc AcO
OBz
j)
h),i)
O
O
O
+
H
ds =
94:6
O
O
O
O
OBz AcO
OAc
46
AcO
39 (X-ray: Figure 1)
exo-34
40
AcO
AcO
44b
(dr = 100:0)
Scheme 8 Synthesis of the asymmetrically esterified neo-quercitol
44a after ether cleavage and ketal fragmentation of the tricyclic tem-
plate 36 from Scheme 7. Reagents and conditions: (a) Et3SiH (5
equiv), CF3CO2H, r.t., 3 h, 94%; (b) PhCOCl (1.5 equiv), DMAP (15
mol%), pyridine, r.t., 15 h, 98%; (c) NBS (1.05 equiv), AIBN (20
mol%), CCl4, reflux, hν (150 W tungsten lamp), 3 h, 71%; (d) Li-
AlH(Ot-Bu)3 (2.0 equiv), THF, r.t., 1 h; isolation of crude product,
Ac2O (≥8 equiv), pyridine (≥12 equiv), DMAP (≥30 mol%), CH2Cl2,
r.t., 30 min, 96% of a 77:8:15 mixture 44a/44b/46; 44a was separated
from its isomers by HPLC; (e) Zn (10 equiv), THF, r.t., 15 h, 27%.
Scheme 7 Processing the tricyclic templates exo-32, exo-33, and
exo-34 from Scheme 6. Reagents and conditions: (a) K2OsO2(OH)4
(5.0 mol%), citric acid (2.0 equiv), NMO (1.5 equiv), H2O–t-BuOH–
MeCN (2:2:1), r.t., 2 d, 85% 35a, 13% 35b (separated by flash
chromatograpy19); (b) Ac2O (4.0 equiv), DMAP (20 mol%), pyridine
(8.0 equiv), CH2Cl2, r.t., 15 h, 99%; (c) same as (b), 99%; (d) Me4N+
–BH(OAc)3 (4.0 equiv), AcOH (8.0 equiv), MeCN, r.t., 2 h, 100%; (e)
Ac2O (10 equiv), DMAP (30 mol%), pyridine (10 equiv), THF, r.t.,
16 h, 98%; (f) AcCl (4.0 equiv), DMAP (20 mol%), pyridine (5.4
equiv), CH2Cl2, r.t., 20 h, 89%; (g) LiAlH(Ot-Bu)3 (2.0 equiv), THF,
–30 °C, 15 h, → r.t. within 4 h; Ac2O (18 equiv), DMAP (15 mol%),
pyridine (20 equiv), THF, r.t., 3 d, 96% 38, 2% 36 (separated by flash
chromatograpy19); (h) NaBH4 (1.0-fold molar amount), CeCl3 (1.0
equiv), THF–MeOH (1:1), –78 °C → 0 °C, 3 h; (i) Ac2O (2.0 equiv),
DMAP (15 mol%), pyridine (3.0 equiv), CH2Cl2, r.t., 2 h, 88% (over
the 2 steps) pure 39 after flash chromatography;19 (j) BF3·OEt2 (1.1
equiv), toluene–H2O (30:1), 0 °C → r.t., 6 h; Ac2O (10 equiv), DMAP
(20 mol%), pyridine (15 equiv), CH2Cl2, r.t., 15 h, 82%.
reomer of the reduction product suffered no such ‘diver-
sion’ through acyl group migration.43 Our workup
procedure advanced it to the corresponding acetate 46
(14% yield). Our final products 44a (which was separated
by HPLC from its isomers and thereby isolated pure) and
44b represent unsymmetrically peracylated neo-querci-
tols. Compound 46 is a peracylated (–)-gala-quercitol.
Their preparation from the tricyclic cyclohexenone exo-9
via the tricyclic triacetate 36 is the first demonstration of
the viability of our approach to cyclitols.
4). The product of this ionic hydrogenolysis was the hy-
droxy ketal 41. Benzoylation gave the ester 42 in near-
quantitative yield. The ketal moiety in this compound,
however, was inert towards acid-mediated hydrolysis.
Therefore, we gave up on releasing the desired cyclohex-
anone 45 from the ester 42 in a single step.
The present study describes the synthesis of three tricyclic
cyclohexenone templates (8, endo-9, and exo-9). They are
designed as novel intermediates en route to synthetic con-
duritols (1), quercitols (2), and inositols (3). The four-step
sequence disclosed in Scheme 8 details how the tricyclic
triacetate 36, which was made from template exo-9 in
three steps (Schemes 6 and 7), was transformed into the
quercitol peresters 44a, 44b, and 46. If the sequence of
Scheme 8 can be improved and generalized it will be ap-
plicable for the selective syntheses of both unprotected
and protected cyclitols. It is conceivable that the synthetic
strategy delineated here can be extended to producing car-
basugars.44
A two-step detour route to the cyclohexanone 45 was fea-
sible, though. It began with a benzylic bromination of sub-
strate 42 with NBS–AIBN.42 This furnished 71% of a 1:1
mixture of the diastereomeric bromides 43. A solution of
this mixture in anhydrous THF was treated with 10 equiv-
alents of Zn powder (pretreated with Me3SiCl) at room
temperature for 15 hours. Via the respective alkylzinc
bromide as a plausible intermediate, its decay by a β-elim-
ination, and the decomposition of the resulting hemiketal
the cyclohexanone tetraester 45 was formed in 27% yield.
Its keto group was reduced chemoselectively in 96% yield
employing LiAlH(Ot-Bu)3. A 85:15 preference for an α-
attack was deduced from an outcome, which was compli-
cated by some benzoate migration43 in the major diaste-
reomer of the initially formed alkoxide. After acetylating
the crude product mixture, the interference of this benzoyl
shift had diverted some of the desired product 44a to the
regioisomer 44b (82% combined yield). The minor diaste-
Acknowledgment
The authors gratefully recognize financial support of this work by
the German Research Foundation (DFG; IRTG 1038).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnuIpofoiprmntgirStanoIuifpog
r
t
iornat
Synlett 2014, 25, 1312–1318
© Georg Thieme Verlag Stuttgart · New York

LETTER
Tricyclic Precursors of Cyclitols
1317
mL/min, n-heptane/i-PrOH (90:10); λdetection = 254 nm, tret,14
= 36.4 min, tret,ent-14 = 41.0 min].
(17) For the method, see: Dupau, P.; Epple, R.; Thomas, A. A.;
Fokin, V. V.; Sharpless, K. B. Adv. Synth. Catal. 2002, 344,
421.
(18) For the method, see: (a) With cumene hydroperoxide/
BnNMe3+ –OH: Devreese, A. A.; Demuynck, M.; De Clercq,
P. J.; Vandewalle, M. Tetrahedron 1983, 39, 3039. (b) With
t-BuOOH/BnNMe3+ –OH: Yang, N. C.; Finnegan, R. A.
J. Am. Chem. Soc. 1958, 80, 5845.
(19) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923.
(20) For the method, see: (a) Evans, D. A.; Chapman, K. T.
Tetrahedron Lett. 1986, 27, 5939. (b) Evans, D. A.;
Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc. 1988,
110, 3560.
References and Notes
(1) New Address: Istituto CNR di Scienza e Technologie
Molecolari, c/o Dipartimento di Chimica, Università degli
Studi di Perugia, via Elce di Sotto 8, 06123 Perugia, Italy.
(2) According to the definition by the IUPAC ‘cyclitols are
cycloalkanes containing one hydroxyl group on each of three
or more ring atoms’. See: IUPAC-IUBMB Joint
Commission on Biochemical Nomenclature, Liébec, C.,
Ed.; Biochemical Nomenclature and Related Documents;
Portland Press Ltd: London, 1992, 2nd ed. 149–155.
(3) (a) For reviews, see: Hudlicky, T.; Cebulak, M. Cyclitols
and Their Derivatives: A Handbook of Physical, Spectral,
and Synthetic Data; Verlag Chemie: Weinheim, 1993.
(b) Gueltekin, M. S.; Celik, M.; Balci, M. Curr. Org. Chem.
2004, 8, 1159.
(4) (a) For reviews, see: Billington, D. C. The Inositol
Phosphates: Chemical Synthesis and Biological
Significance; Verlag Chemie: Weinheim, 1993. (b) Potter,
B. V. L.; Lampe, D. Angew. Chem., Int. Ed. Engl. 1996, 34,
1933; Angew. Chem. 1995, 107, 2085 . (c) Best, M. D.;
Zhang, H.; Prestwich, G. D. Nat. Prod. Rep. 2010, 27, 1403.
(5) For a parallel interest in the chemistry, synthesis, and
biological evaluation of aminocyclitols, cf.: (a) Lysek, R.;
Vogel, P. Tetrahedron 2006, 62, 2733. (b) Delgado, A. Eur.
J. Org. Chem. 2008, 3893.
(6) (a) For reviews, see: Billington, D. C. Chem. Soc. Rev. 1989,
18, 83. (b) Prestwich, G. D. Acc. Chem. Res. 1996, 10, 503.
(c) Sureshan, K. M.; Shashidhar, M. S.; Praveen, T.; Das, T.
Chem. Rev. 2003, 103, 4477.
(7) For reviews, see: (a) Duchek, J.; Adams, D. R.; Hudlicky, T.
Chem. Rev. 2011, 111, 4223. (b) Kilbas, B.; Balci, M.
Tetrahedron 2011, 67, 2355. (c) Balci, M. Pure Appl. Chem.
1997, 69, 97. (d) Balci, M.; Sütbeyaz, Y.; Seçen, H.
Tetrahedron 1990, 46, 3715.
(21) At a later point of our investigation we would learn that such
ketal hydrolyses would not be facile even after the 1,4-
dioxane was gone [see our vain attempt to perform the 1,3-
dioxane cleavage 42 → 45 in one step (Scheme 8)].
(22) For example, DDQ/H2O, (NH4)2Ce(NO3)6/H2O,
Me2S/MgBr2·OEt2, NaI/CeCl3, Na/NH3, H2/Pd(C) or
Et3SiH/BF3·OEt2: Wuts, P. G. M.; Greene, T. W.
Greene’s Protective Groups in Organic Synthesis; Wiley-
Interscience: Hoboken, 2007, 4th ed. 23–30,120–135.
(23) (a) For a method for E-selective Wittig olefinations [(3-
hydroxypropyl)triphenylphosphoniumchloride (ref. 23b),
n-BuLi (2.0 equiv), THF, –20 °C, 2 h; 4-methoxybenzalde-
hyde (1.2 equiv), –20 °C → r.t., 4 h; 72% of pure E-isomer
after recrystallization from cyclohexane], see: Maryanoff,
B.; Reitz, A.; Duhl-Emswiler, B. J. Am. Chem. Soc. 1985,
107, 217. (b) For the preparation [PPh3, 3-chloropropan-1-ol
(1.05 equiv), toluene, reflux, 5 d; 87%], see: Dolle, R. E.; Li,
C.-S.; Novelli, R.; Kruse, L. I.; Eggleston, D. J. Org. Chem.
1992, 57, 128.
(8) For example, see: Pang, L.-J.; Wang, D.; Zhou, J.; Zhang,
L.-H.; Ye, X.-S. Org. Biomol. Chem. 2009, 7, 4252 and
references cited therein.
(9) For example, see: Aydin, G.; Savran, T.; Aktaş, F.; Baran,
A.; Balci, M. Org. Biomol. Chem. 2013, 11, 1511 and
references cited therein.
(24) (a) One-step preparation of monobenzoate 24 from
hydroquinone, benzoyl chloride (1.0 equiv), and NaOH (1.0
equiv) in H2O (0 °C, 1.5 h; 65%. Ref.24b 84%).
(b) Bredereck, H.; Heckh, H. Chem. Ber. 1958, 91, 1314.
(25) For the method, see: (a) Sharpless, K. B.; Amberg, W.;
Bennani, Y. L.; Crispino, G. A.; Hartung, J.; Jeong, K.-S.;
Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang,
X.-L. J. Org. Chem. 1992, 57, 2768. (b) Amberg, W.;
Bennani, Y. L.; Chadha, R. K.; Crispino, G. A.; Davies, W.
D.; Hartung, J.; Jeong, K.-S.; Ogino, Y.; Shibata, T.;
Sharpless, K. B. J. Org. Chem. 1993, 58, 844. (c) Corey, E.
J.; Guzman-Perez, A.; Noe, M. C. J. Am. Chem. Soc. 1995,
117, 10805.
(10) For example, see: Trost, B. M.; Dudash, J. Jr.; Hembre, E. J.
Chem. Eur. J. 2001, 7, 1619 and references cited therein.
(11) For example, see: Hudlicky, T.; Price, J. D.; Rulin, F.;
Tsunoda, T. J. Am. Chem. Soc. 1990, 112, 9439 and
references cited therein.
(12) For the synthesis of hydroxyketal 10 from L-malic acid, see:
(a) Reduction with BH3·SMe2/(B(OMe)3: Hanessian, S.;
Ugolini, A.; Dubé, D.; Glamyan, A. Can. J. Chem. 1984, 62,
2146. (b) Ketalization with 3-pentanone: Arth, H.-L.;
Sinerius, G.; Fessner, W.-D. Liebigs Ann. 1995, 2037.
(13) (a) For precedents, see: Etherification with DEAD:
Mitsunobu, O. Synthesis 1981, 1. (b) Mitsunobu
etherification of hydroquinone monobenzoate (24) with
DIAD: Amela-Cortés, M.; Heinrîch, B.; Donnio, B.; Evans,
K. E.; Smith, C. W.; Bruce, D. W. J. Mater. Chem. 2011, 21,
8427. (c) For Mitsunobu etherification of homoallylic
alcohols, see ref. 25c.
(14) (a) For the two-step preparation of monoacetate 11 from
hydroquinone, see: Tricotet, T. Dissertation; Universität
Freiburg: Germany, 2006, 220, 225. (b) For the one-step
preparation of 11 from hydroquinone, see: Dimroth, K.
Chem. Ber. 1939, 72, 2043.
(15) For the first respective application of this reagent, see:
Tamura, Y.; Yakura, T.; Haruta, J.; Kita, Y. J. Org. Chem.
1987, 52, 3927.
(26) The enantiomeric excess (ee) of the diol 28 was determined
by chiral HPLC [Chiralcel OD-H; 0.8 mL/min, n-heptane/
EtOH (80:20); λdetection = 275 nm, tret,ent-28 = 13.3 min, tret,28
15.3 min].
=
(27) The oxidation of the diol 27 delivered, besides the six-
membered-ring ketal 30, the isomeric seven-membered-ring
ketal (8%; not depicted in Scheme 5), i.e. a PMP-substituted
analogue of the seven-membered-ring ketal 15. It was
separated by flash chromatography on silica gel (ref. 19).
(28) The inversion of configuration of a benzylic C–O bond in a
syn-configured arylethane-1,2-diol was described if the non-
benzylic oxygen was incorporated in a OMEM group:
Ramachandran, P. V.; Liu, H.; Reddy, M. V. R.; Brown, H.
C. Org. Lett. 2003, 5, 3755.
(29) For the oxidation of benzylic alcohols to aromatic ketones by
DDQ, see: Peng, K.; Chen, F.; She, X.; Yang, C.; Cui, Y.;
Pan, X. Tetrahedron Lett. 2005, 46, 1217.
(30) The enantiomeric excess (ee) of the hydroxy ketone 29 was
determined by chiral HPLC [Chiralpak AD-3; 1.0 mL/min,
(16) The enantiomeric excess (ee) of benzoquinone monoketal 14
was determined by chiral HPLC [Chiralcel OB-H; 1.0
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1312–1318

1318
J. Aucktor et al.
LETTER
F3B–
O+
n-heptane/EtOH (25:75); λdetection = 275 nm, tret,29 = 28.3 min,
H
OH
O
t
ret,ent-29 = 34.2 min].
OR2
(31) Zn(BH4)2 in THF solution was prepared from Zn(OMe)2 and
BH3·THF as described by: Nöth, H.; Wiberg, E.; Winter, R.
P. Z. Anorg. Allg. Chem. 1969, 370, 209.
OAc
O
O
~Ac
OR1
H2O
O
O
O
(Fürst–Plattner
opening)
H
H
(32) (a) For anti-selective reductions of racemic α-hydroxy
ketones giving 1,2-diols, see: Nakata, T.; Tanaka, T.; Oishi,
T. Tetrahedron Lett. 1983, 24, 2653. (b) For anti-selective
reductions of enantiomerically pure aromatic α-hydroxy
ketones giving arylethane-1,2-diols, see: Husain, S. M.;
Stillger, T.; Dünkelmann, P.; Lödige, M.; Walter, L.;
Breitling, E.; Pohl, M.; Bürcher, M.; Krossing, I.; Müller,
M.; Romano, D.; Molinari, F. Adv. Synth. Catal. 2011, 353,
2359.
(33) The enantiomeric excess (ee) of the diol epi-27 was
determined by chiral HPLC [Chiralpak OD-3; 1.0 mL/min,
n-heptane/EtOH (85:15); λdetection = 275 nm, tret,ent-epi-27 = 11.8
min, tret,epi-27 = 14.4 min].
(34) The oxidation of the diol epi-27 delivered, besides the six-
membered-ring ketal epi-30, the isomeric seven-membered-
ring ketal (10%; not depicted in Scheme 5), i.e. another (ref.
27) PMP-substituted analogue of the seven-membered-ring
ketal 15. It was separated by flash chromatography on silica
gel (ref. 19).
(35) Acetylation of the cyclohexenols endo-31 and exo-31 gave
the corresponding acetates endo-32 and exo-32, respec-
tively. Both were isolated isomerically pure.
PMP
PMP
47a R1 = H, R2 = Ac
+
47b R1 = Ac, R2 = H
BF3
F3B–
H
O
O
OAc
BF3, H2O
O
O
O
O
H2O
O
+
O
H
O
O
H
OH
O
OH
PMP
PMP
39
(X-ray)
O
OAc
H
O
equatorial in a cyclohexene
oxide half-chair conformer
PMP
Ac2O
Ac2O
OAc OAc
H
OAc
H
H
3
3
H
OAc
O
O
2
1
2
1OAc
O
O
OAc
O
O
PMP
H
H
PMP
iso-40
40
(36) Procedure: Chae, H. I.; Hwang, G.-S.; Jin, M. Y.; Ryu, D. H.
Bull. Korean Chem. Soc. 2010, 31, 1047.
(37) The triacetate 36 was processed further as disclosed in
Scheme 8.
(38) Rücker, G.; Hörster, H.; Gajewski, W. Synth. Commun.
1980, 623.
J2-H
ax = 12.4 Hz (conceivable)
J2-H
ax = 12.4 Hz
,1-H
,1-H
ax
ax
J2-H
ax = 12.7 Hz
,3-H
J2-H
eq = 12.7 Hz (impossible)
,3-H
ax
ax
Scheme 9
(39) For the method, see: Mehta, G.; Pujar, S. R.; Ramesh, S. S.;
Islam, K. Tetrahedron Lett. 2005, 46, 3373.
(43) An analogous acetate migration in the initially formed
reduction product would have passed unnoticed. We never
worked up the reduction product properly, but subjected it to
an in-situ acetylation before we worked it up.
(44) (a) Arjona, O.; Gomez, A. M.; Lopez, J. C.; Plumet, J. Chem.
Rev. 2007, 107, 1919. (b) Leclerc, E.; Pannecoucke, X.;
Etheve-Quelquejeu, M.; Sollogoub, M. Chem. Soc. Rev.
2013, 42, 4270. (c) Lahiri, R.; Ansari, A. A.; Vankar, Y. D.
Chem. Soc. Rev. 2013, 42, 5102.
(45) The crystallographic data of the tricyclic cyclohexenone 8
are contained in CCDC 987664 (ref. 54).
(46) The crystallographic data of the tricyclic cyclohexenol 16
are contained in CCDC 987666 (ref. 54).
(47) The crystallographic data of the tricyclic dihydroxy-
cyclohexanone 18 are contained in CCDC 987665 (ref. 54).
(48) The crystallographic data of the tricyclic cyclohexenone
endo-9 are contained in CCDC 987667 (ref. 54).
(49) The crystallographic data of the tricyclic cyclohexenone
exo-9 are contained in CCDC 987668 (ref. 54).
(50) The crystallographic data of the tricyclic dihydroxy-
cyclohexanone endo-33 are contained in CCDC 987669 (ref.
54).
(51) The crystallographic data of the tricyclic dihydroxy-
cyclohexanone exo-33 are contained in CCDC 987670 (ref.
54).
(52) The crystallographic data of the tricyclic cyclohexenyl
acetate exo-32 are contained in CCDC 987671 (ref. 54).
(53) The crystallographic data of the tricyclic epoxycyclohexyl
acetate 39 are contained in CCDC 987672 (ref. 54).
(54) These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via the link
www.ccdc.cam.ac.uk/data_request/cif.
(40) (a) A neighboring participation of an acetate group is a
plausible inaugural step for carrying on the epoxide 39
towards the triacetate 40 (Scheme 9). The resulting
carboxonium ion picks up H2O at the dioxygenated C
atom (followed by decay of the dialkyl orthocarboxylate
intermediate to a mixture of two regioisomeric glycol
monoacetates 47a and 47b), not at the monooxygenated C
atom (by an SN2 attack). This chemoselectivity is known
from the carboxonium ion intermediate of the Woodward
(= aqueous) diacetoxylation as opposed to the Prevost
(= anhydrous) diacetoxylation of C=C bonds. The former is
a cis-diacetoxylation (while the latter is a trans-diacetoxylation;
it includes an SN2-opening by an acetate ion, not by H2O).
(b) All tricyclic compounds prepared in the present study,
which were not analyzed stereochemically by X-ray
crystallography (cf. Figure 1) were conceived as
cyclohexane-based chair conformers or as cyclohexene-
based half-chair conformers. Whether their substituents
were equatorially or axially disposed was inferred from the
magnitudes of the vicinal H,H coupling constants in the
respective substructures [similarly as exemplified in the
bottom-line of Scheme 9 for telling apart the diastereomers
40 (which we had obtained) and iso-40 (which we had not
obtained)].
(41) For the method, see: Ma, Z.; Hu, H.; Xiong, W.; Zhai, H.
Tetrahedron 2007, 63, 7523.
(42) (a) Floyd, D. M.; Moquin, R. V.; Atwal, K. S.; Ahmed, S. Z.;
Spergel, S. H.; Gougoutas, J. Z.; Malley, M. F. J. Org. Chem.
1990, 55, 5572. (b) Peschko, C.; Winklhofer, C.; Terpin, A.;
Steglich, W. Synthesis 2006, 3048.
Synlett 2014, 25, 1312–1318
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