Enantioselective total synthesis of (-)-diversonol

Article abstract of DOI:10.1002/chem.201204037

For the synthesis of (-)-diversonol (ent-1), an enantioselective domino-Wacker/carbonylation/methoxylation reaction and an enantioselective Wacker oxidation were used to give the chroman in high yield and 96 % and 93 % ee, respectively. Dihydroxylation at the vinyl moiety using the Sharpless procedure and a Wittig-Horner reaction followed by hydrogenation, benzylic oxidation, and an intramolecular acylation provided the tetrahydroxanthenone, from which ent-1 is accessible in a few steps. Furthermore, the synthesis of the diastereomeric diversonol rac-1,9 a-epi-diversonol (rac-41) is also described. Domino at its best: An enantioselective domino-Wacker/carbonylation/ methoxylation reaction was performed in the total synthesis of the fungal metabolite diversonol (see scheme). Furthermore, synthesis of diastereomeric rac-1,9a-epi-diversonol is also described. Copyright

Full text of DOI:10.1002/chem.201204037

DOI: 10.1002/chem.201204037
Enantioselective Total Synthesis of (ꢀ)-Diversonol
Lutz F. Tietze,* Stefan Jackenkroll, Christian Raith, Dirk A. Spiegl,
Johannes R. Reiner, and Maria Claudia Ochoa Campos[a]
Dedicated to Professor George M. Sheldrick on the occasion of his 70th birthday
Abstract: For the synthesis of (ꢀ)-di-
the Sharpless procedure and a Wittig–
Horner reaction followed by hydroge-
nation, benzylic oxidation, and an in-
tramolecular acylation provided the
versonol (ent-1), an enantioselective
domino-Wacker/carbonylation/methox-
ylation reaction and an enantioselec-
tive Wacker oxidation were used to
give the chroman in high yield and
96% and 93% ee, respectively. Dihy-
droxylation at the vinyl moiety using
tetrahydroxanthenone, from which ent-
1 is accessible in a few steps. Further-
more, the synthesis of the diastereo-
meric diversonol rac-1,9a-epi-diverso-
nol (rac-41) is also described.
Keywords: asymmetric catalysis
·
domino reactions · palladium · total
synthesis · Wacker oxidation
Introduction
diversonol (1) seems to be not very pronounced, since publi-
cations on that topic are missing. In contrast, the related di-
meric secalonic acids such as 2, also containing a functional-
ized tetrahydroxanthenone skeleton,[2a] are of high pharma-
cological interest due to their antibacterial, cytostatic, and
anti-HIV properties.[3]
These compounds were originally isolated from Claviceps
purpurea[4] and their structure was determined by Franck
et al.[5] In the corresponding monomeric unit called blenno-
lide C (3), which was isolated from Blennoria sp.,[6] a me-
thoxycarbonyl moiety at C-4a exists instead of a methyl
group as in 1. However, dimeric compounds as the diceran-
drols[7] and phomoxanthones[8] containing a hydroxymethyl
or acetoxymethyl group at C-4a are also known.
Diversonol (1) is a fungal metabolite and has been isolated
from different fungi such as Penicillium diversum[1a] and Mi-
crodiplodia sp.[1b] Its absolute configuration was determined
by Krohn et al. using CD-spectroscopy combined with
TDDFT ECD calculations[1b] and the first total syntheses of
the racemic as well as the enantiopure compound were de-
scribed by Brꢀse et al.;[2a,b,c] another access to rac-1 was pub-
lished by Nicolaou and Li (Figure 1).[2d] The bioactivity of
We have recently published a synthesis of enantiopure 4-
dehydroxydiversonol[9] (4) by using an enantioselective
domino-Wacker/carbonylation/methoxylation reaction. This
domino process[10] has also been used for the synthesis of
chromans, dioxins and oxazins.[11] Here we describe the total
synthesis of enantiopure (ꢀ)-diversonol (ent-1) based on
this procedure, which was followed by the introduction of
the hydroxyl group at C-4 (numbering as in 1) employing a
Sharpless dihydroxylation. Moreover, also the synthesis of
diastereomeric rac-1,9a-epidiversonol rac-41 is presented.
Figure 1. Diversonol (1), secalonic acid (2), blennolide C (3), and 4-dehy-
droxydiversonol (4).
Results and Discussion
The retrosynthetic analysis of ent-1 (Scheme 1) leads to the
chroman 7 by using the tetrahydroxanthenone 5 and the
chromanone 6. It was assumed by our group that chroma-
none 6 might be accessible from 7 by hydroxylation at C-2,
chain elongation, hydrogenation, and benzylic oxidation.
For the synthesis of 7, we wanted to use the enantioselective
domino-Wacker/carbonylation/methoxylation reaction of 8
developed by our group.[9]
[a] Prof. Dr. L. F. Tietze, S. Jackenkroll, Dr. C. Raith, Dr. D. A. Spiegl,
J. R. Reiner, M. C. Ochoa Campos
Institute of Organic and Biomolecular Chemistry
Georg-August-University Gçttingen
Tammannstrasse 2, 37077 Gçttingen (Germany)
Fax : (+49)551-39-9476
E-mail: ltietze@gwdg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201204037.
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Chem. Eur. J. 2013, 19, 4876 – 4882

FULL PAPER
give the intermediate 18. Thus,
condensation of aldehyde 10
with the sulfinyl acetate 12 and
piperidine as base probably
gives 15, which stays in an
equilibrium with 16 and 18
leading to (2-R,S)-17; 2,3-sig-
matropic rearrangement of (2-
R,S)-17 then affords rac-13 and
rac-14.[14] All attempts to avoid
the ring-opening by using dif-
ferent bases and solvents were
not successful.
Due to these unexpected dif-
ficulties, we revised our syn-
thetic strategy and introduced
the necessary hydroxyl group
Scheme 1. Retrosynthetic analysis of (ꢀ)-diversonol (ent-1).
by
a Sharpless dihydroxyla-
tion[15] of the vinyl chroman
19[16] (Scheme 4). Compound 19 is accessible from 7 by
LiAlH4 reduction of the ester moiety to give the corre-
sponding alcohol with ꢁ99% ee after purification on a
chiral IA phase. It followed an elimination using o-NO2-
C6H4SeCN/meta-chloroperbenzoic acid (mCPBA).[17] Com-
pound 19 can also be prepared directly by an enantioselec-
tive Wacker oxidation of 20 in the presence of the BOXAX
Thus, reaction of 8, which is easily accessible from orcinol
(9), with catalytic amounts of palladium(II) trifluoroacetate
[PdACHTUNGTRENNUNG
(tfa)2] and the Bn-BOXAX ligand[12] (11) under a carbon
monoxide atmosphere and methanol as solvent gave 7 in
80% yield and with an enantiomeric excess (ee) of 96%
(Scheme 2). In this process, p-benzoquinone was used to oxi-
dize the formed Pd0 into PdII needed for the Wacker oxida-
tion.
For the installation of the
hydroxy group at C-4 (num-
bering as in 1), we first investi-
gated a direct transformation
employing
Knoevenagel
a
hydroxylating
condensation
(Scheme 3).[13] For this pur-
pose, ester 7 was reduced by
using diisobutylaluminum hy-
dride (DIBAL) in toluene at
ꢀ788C to yield aldehyde 10 in
86% yield, which was then
treated with racemic as well as
enantiopure sulfinyl acetate 12
and piperidine as base in ace-
tonitrile at room temperature.
The reaction proceeded very
well to give the two diastereo-
meric hydroxyl compounds 13
and 14 in a ratio of almost 1:1,
in nearly quantitative yield,
which could easily be separat-
ed by chromatography. Un-
fortunately, the steric integrity
of the stereogenic center in 10
is lost in this process leading to
the racemic products rac-13
and rac-14. We explain this
result by assuming an opening
of the chroman ring-system to
Scheme 2. Synthesis of 10: a) [PdACTHNURTGNENG(U tfa)2] (3 mol%), (S,S)-Bn-BOXAX (11) (12 mol%), p-benzoquinone, CO
(1 atm), MeOH, RT, 15 h, 80%, 96% ee; b) DIBAL, toluene, ꢀ788C, 45 min, 86%.
Scheme 3. Synthesis of rac-13 and rac-14 and proposed pathway for the racemization by a retro 1,6-Michael
addition. a) piperidine, acetonitrile, RT, 7 h, 91%.
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L. F. Tietze et al.
followed by selective removal of the primary TBS group
with HF·pyridine, afforded alcohol 25 in 70% yield (2 steps,
93% based on recovered starting material (brsm)). The
requisite side-chain was introduced through the correspond-
ing aldehyde by oxidation of 25 with DMP followed by a
Wittig–Horner reaction with (MeO)2P(O)CH2CO2Me to
provide a 5:1 mixture of the a,b-unsaturated esters (deter-
1
mined by H NMR spectroscopy), which was hydrogenated
in the presence of Pd/C to yield chroman 29 in 90% yield
over three steps.
Chroman 29 was then oxidized at the benzylic position
upon treatment with excess tert-butylhydroperoxide and cat-
alytic amounts of [MnACHTUNTRGNEUNG(OAc)3] to give the corresponding
chromanone 31 in 51% yield.[18] A similar method employ-
ing dirhodium-tetrakiscaprolactamate as the catalyst was
less suitable.[19] The preparation of the chromanone 31 could
also be performed in a three-step procedure. Starting from
29, dehydrogenation with 2,3-dichloro-5,6-dicyanobenzoqui-
none (DDQ) led to the corresponding chromene, which was
hydroxylated in the presence of PhSiH3, O2 and catalytic
amounts of [MnACTHNUTRGNEUNG
(dpm)3],[20] and further oxidized with MnO2
to give 31 in 84% overall yield. For the intramolecular acy-
lation to provide the desired tetrahydroxanthenone 33, the
chromanone 31 was treated with TiCl4 and NEt3 in dichloro-
methane at 08C; however, a modest yield of 65% was ob-
tained. Fortunately, the use of TiACTHNUTRGNEG(NU iPrO)Cl3 increased the
Scheme 4. Synthesis of 33 and 34: a) LiAlH4, Et2O, 0 8C!RT, 2 h, 98%;
b) 1) nBu3P, o-NO2-C6H4SeCN, THF, RT, 1 h; 2) mCPBA, CH2Cl2,
yield to 84%; this could be explained by the formation of a
more nucleophilic Ti-enolate.[21] Comparison of 33 with race-
mic rac-33 by chromatography on a chiral phase gave an ee
value of ꢁ99%.
ꢀ408C, 1 h, iPr2NH, ꢀ408C!RT, 12 h, 98% (2 steps); c) [Pd
ACHTUNGERTN(NUNG tfa)2]
(10 mol%), (S,S)-Bn-BOXAX (11) (20 mol%), p-benzoquinone, MeOH,
RT, 22 h, for (E)-20: 75%, 93% ee; for (Z)-20: 79%, 83% ee; for the E/
Z-mixture (E/Z=1:2.4): 78%, 87% ee; d) AD-mix a, MeSO2NH2,
tBuOH/H2O, RT, 5 d, 93%, d.r.=3.8:1; e) TBSOTf, 2,6-lutidine, CH2Cl2,
08C!RT, 2.5 h, 99%; f) HF·py, RT, 60 h, 70% (93% brsm); g) DMP,
CH2Cl2, 08C!RT, 2 h, 95%; h) 1) (MeO)2P(O)CH2CO2Me, NaH, THF,
08C, 1.5 h; 2) H2 (4 bar), 10 mol% Pd/C, EtOAc, RT, 15 h, 95% (2
For an entry to the C-4-epimer of (ꢀ)-diversonol (ent-4-
epi-1), we transformed 22, obtained as the minor diaster-
eomer in the Sharpless dihydroxylation of 19, into the tetra-
hydroxanthenone 34 through the intermediates 22, 24, 26,
30, and 32 by using the procedures as described in the syn-
thesis of 33 (Scheme 4).
steps); i) method A: tBuOOH, [Mn
MS 3 ꢂ, RT, 4 d, 51%; method B: 1) DDQ, benzene, heat at reflux, 2 h;
2) [Mn(dpm)3] (10 mol%), PhSiH3, O2 (1 atm), EtOH, RT, 4.5 h;
3) MnO2, CH2Cl2, reflux, d, 84% (3 steps); j) Ti(iOPr)Cl3, NEt3,
ACHTUGNRTEN(NUGN OAc)3]·2H2O (40 mol%), EtOAc,
ACHTUNGTRENNUNG
The relative configuration of the stereogenic centers in 33
and 34 was determined by comparison of the coupling con-
stants. For the trans-compound 33, the coupling constants
J=1.8 and 3.9 Hz of the signal at d=4.02 ppm for 4-H show
that 4-H has an almost synclinal orientation to both hydro-
gen atoms at C-3; this requires an axial orientation of the
OTBS-group. Similar spectroscopic investigations were per-
formed with 34. From the coupling constants J=12.1 and
4.6 Hz of the signal for 4-H at d=4.11 ppm, it can be de-
duced that the OTBS group in the cis-epimer 34 has an
equatorial orientation. These results were confirmed by
NOE experiments (Scheme 5).
4
ACHTUNGTRENNUNG
CH2Cl2, 08C, 1 h, 84%; k) TBSOTf, 2,6-lutidine, CH2Cl2, 08C!RT, 2.5 h,
quant.; 1) HF·pyridine, THF/pyridine, RT, 52 h, 73% (98% brsm);
m) DMP, CH2Cl2, 08C!RT, 2.5 h, 89%; n) 1) (MeO)2P(O)CH2CO2Me,
NaH, THF, 08C, 1.5 h; 2) H2 (4 bar), 10 mol% Pd/C, EtOAc, RT, 15 h,
98% (2 steps); o) tBuOOH, [Mn
ACHTUGNRTEN(NUGN OAc)3]·2H2O (40 mol%), EtOAc, MS
3 ꢂ, RT, 4 d, 42%; p) Ti(iOPr)Cl3, NEt3, CH2Cl2, 08C, 2.5 h, 69%.
ACHTUNGTRENNUNG
ligand[12] (11), but with an ee value of only 87% by using the
E/Z mixture of 20 (E/Z=1:2.4) as a substrate, the procedure
was less suitable. The enantioselectivity of the Wacker oxi-
dation could be improved to 93% by employing the pure E
compound, whereas the Z compound gave an ee value of
83%. However, the separation of the E/Z-mixture of 20 by
chromatography is rather tedious and not practicable for
larger amounts.
The Sharpless dihydroxylation of vinyl chroman 19 using
AD-mix a and methane sulfonamide as additive furnished
the diols 21 and 22 as a 3.8:1 mixture of separable diaster-
eomers in 93% yield. Silylation of 21 with (tert-butyldime-
thylsilyl)methanesulfonate (TBSOTf) to give 23, which was
Scheme 5. NOE experiments of 33 and 34. The excited methyl group is
depicted in italic.
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Chem. Eur. J. 2013, 19, 4876 – 4882

Enantioselective Total Synthesis of (ꢀ)-Diversonol
FULL PAPER
the other enantiomeric form,
the described procedure also
allows the synthesis of (+)-di-
versonol (1).
Following up our initial ob-
servations on the hydroxyla-
tion step of 33 and having sub-
stantial amounts of the racemic
compound rac-33 in hand, we
also performed the synthesis of
rac-41, a diastereomer of diver-
sonol (1) (Scheme 7). For this
Scheme 6. Synthesis of (ꢀ)-diversonol (ent-1): a) IBX, DMSO/H2O, 60 8C, 12 h, 32%; b) HF·pyridine, THF,
308C, 5 d, 72% (94% brsm); c) MMPP, EtOH, 08C, 2 h, d.r.=5:1, 46%; d) NaBH4, MeOH/CH2Cl2, ꢀ788C,
2 h, 62%; e) BBr3, CH2Cl2, ꢀ788C!RT, 5.5 h, 75%.
Having the enantiopure tetrahydroxanthenone 33 in hand,
the stage was set for the introduction of the quaternary hy-
droxyl group at C-9a to give (ꢀ)-diversonol (ent-1)
(Scheme 6). However, hydroxylation of 33 employing mag-
nesium monoperoxyphthalate (MMPP), dimethyldioxirane
(DMDO) or meta-chloroperbenzoic acid (mCPBA) were
not successful, whereas the oxidation of 33 with o-iodoxy-
benzoic acid (IBX) in DMSO/water[22] at 608C furnished
32% of the undesired compound 35. The stereochemical
outcome of the transformation seems to be due to the steric
bulk of the OTBS group, which forces the oxidation to take
place anti to the OTBS-group. Therefore, we removed the
TBS group in 33 by desilylation using HF·pyridine in THF
at 308C for 5 d to give 36 in 72% yield (94% brsm). Under
these conditions, a structural isomerization[2d] of the skeleton
was not observed. The obtained compound 36 with a free
hydroxyl group at C-4 was then oxidized by using magnesi-
um monoperoxyphthalate (MMPP) in EtOH at 08C for 2 h
to give the desired dihydroxy compound 37 along with its C-
9a epimer in a 5:1 ratio. The reduction of the C-1 carbonyl
moiety with NaBH4 in a mixture of MeOH/CH2Cl2 to give
38 and cleavage of the aryl methyl ether using BBr3 at 08C
in CH2Cl2 for 5.5 h afforded the desired enantiopure (ꢀ)-di-
versonol (ent-1) in 21% yield over three steps.[2b] The spec-
troscopic data (1H NMR, 13C NMR and MS) match with
those published for the natural diversonol (1). Moreover,
the structure of the final product has been confirmed by a
crystal structure analysis. However, the measured optical ro-
tation with [a]2D2 =ꢀ62 (c=0.16, MeOH) is slightly lower
than the published value of [a]2D9 = +70 (c=0.33, MeOH).
Since the BOXAX ligand 11 used in the enantioselective
domino Wacker/carbonylation/methoxylation reaction of 8
and in the Wacker oxidation of 20 is easily accessible also in
purpose, rac-33 was subjected to an IBX oxidation in
DMSO/water at 608C for 4 h to yield the a-configured hy-
droxyl compound rac-35 in 49% yield.[22,23] Since the neces-
sary reduction of the carbonyl group at C-1 in rac-35 was
not possible, probably due to a steric shielding of both of its
faces, we removed the TBS group by using HF·pyridine,
which was followed by the reduction of the carbonyl moiety
with NaBH4 in a mixture of MeOH/CH2Cl2; by this method
rac-40 was obtained in 31% yield over two steps. The final
cleavage of the aryl methyl ether using BBr3 in dichlorome-
thane at 08C for 48 h afforded rac-1,9a-epi-diversonol (rac-
41) in 47% yield (Scheme 7).
Conclusion
We have developed a new enantioselective procedure for
the total synthesis of (ꢀ)-diversonol (ent-1) and its diaster-
eomer rac-41. Key steps are an enantioselective Pd-cata-
lyzed domino Wacker/cabonylation/methoxylation reaction
of 8 and an enantioselective Wacker oxidation of 20, respec-
tively.
Experimental Section
Synthesis of 19, 31, 33, 35, 41 and (ꢀ)-1: The syntheses of all other new
compounds including spectroscopic data can be found in the Supporting
Information.
(S)-5-Methoxy-2,7-dimethyl-2-vinylchroman (19): A solution of [PdACHTUNGTRENNUNG(tfa)2]
(7.8 mg, 23.6 mmol, 10 mol%) and (S,S)-Bn-BOXAX (11) (27.0 mg,
47.2 mmol, 20 mol%) in MeOH (0.5 mL) was stirred at room temperature
for 15 min. After addition of a solution of phenol (E)-20 (52.0 mg,
0.236 mmol, 1.00 equiv) in MeOH (1 mL) and p-benzoquinone (102 mg,
0.944 mmol, 4.00 equiv) stirring was continued at room temperature for
22 h. The mixture was poured into 1n HCl (20 mL) and extracted with
methyl tert-butyl ether (MTBE) (4ꢃ10 mL). The combined extracts were
washed with 1N NaOH (3ꢃ10 mL) and dried over Na2SO4. After evapo-
ration of the solvent in vacuo and column chromatography on silica gel
(petroleum ether/EtOAc=100:1!70:1) vinylchroman 19 was obtained as
a yellowish oil (38.4 mg, 0.176 mmol, 75%, 93% ee). Analytical HPLC
(column: Daicel Chiralcel OD): 250ꢃ4.6 mm, 5 mm, l=275 nm, flow:
0.8 mLminꢀ1, eluent: n-hexane/isopropanol 99.5:0.5, tR =10.1 ((ꢀ)-19),
11.9 min ((+)-19). Z-20 and the E/Z-mixture of 20 (E/Z=1:2.4) were
also converted to 19 using the described procedure. For Z-20: (79%,
83% ee) and for the E/Z-mixture of 20: (78%, 87% ee). [a]2D3 =ꢀ55.7
(c=0.50, CHCl3). 1H NMR (300 MHz, CDCl3): d=1.40 (s, 3H, 2’-CH3),
1.76 (ddd, J=13.5, 9.8, 5.9 Hz, 1H, 3’-Ha), 1.90 (ddd, J=13.5, 6.1, 5.0 Hz,
Scheme 7. Synthesis of rac-epi-1,9a-diversonol rac-41: a) IBX, DMSO/
H2O, 60 8C, 4 h, 49%; b) HF·pyridine, THF/pyridine, 508C, 60 h, 43%;
c) NaBH4, MeOH/CH2Cl2, ꢀ788C, 2 h, 71%; d) BBr3, CH2Cl2, ꢀ788C!
08C, 48 h, 47%.
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L. F. Tietze et al.
1H, 3’-Hb), 2.28 (s, 3H, 7’-CH3), 2.44 (ddd, J=16.7, 9.8, 6.0 Hz, 1H, 4’-
Ha), 2.65 (dt, J=17.0, 5.4 Hz, 1H, 4’-Hb), 3.78 (s, 3H, 5’-OCH3), 5.05 (dd,
J=10.8, 1.3 Hz, 1H, 2-Hcis), 5.17 (dd, J=17.3, 1.3 Hz, 1H, 2-Htrans), 5.85
(dd, J=17.3, 10.8 Hz, 1H, 1-H), 6.22 (s, 1H, 6’-H), 6.36 (s, 1H, 8’-
H) ppm; 13C NMR (125 MHz, CDCl3): d=16.7 (C-4’), 21.6 (7’-CH3), 26.8
(2’-CH3), 31.3 (C-3’), 55.3 (5’-OCH3), 76.2 (C-2’), 102.7 (C-8’), 107.3 (C-
4a’), 110.1 (C-6’), 113.6 (C-2), 136.9 (C-7’), 141.4 (C-1), 154.4, 157.5 (C-5’,
C-8a’) ppm. IR (film): n˜ =3082, 2952, 2927, 1615, 1583, 1459, 1409, 1350,
1261, 1229, 1209, 1126, 1091, 1023, 1013, 923, 814, 583 cmꢀ1; UV/Vis
(CH3CN): lmax (lg e)=208 (4.6293), 273 (2.9367), 280 (2.9163), 333 nm
(2.247); MS (ESI): m/z (%): 241.1 (33) [M+Na]+, 219.1 (100) [M+H]+;
HRMS (ESI): m/z calcd for C14H18O2 (218.29): 219.1380 [M+H]+; found:
219.1378 (ESI-HRMS).
(286 mL, 272 mg, 0.95 mmol, 0.87 equiv) in CH2Cl2 (5 mL) at 08C and the
resulting mixture stirred for 15 min at 08C; on the other hand, NEt3
(426 mL, 311 mg, 3.08 mmol, 2.8 equiv) was added to a solution of chro-
manone 31 (480 mg, 1.10 mmol) in CH2Cl2 (22 mL) at 08C. Subsequently,
the solution of TiACHTNURGTNEUNG(OiPr)Cl3 was transferred slowly through a transfer can-
nula to the solution of 31, and the resulting solution was stirred at 08C
for further 60 min (TLC monitoring) before being quenched with water
(100 mL). The aqueous layer was extracted with EtOAc (6ꢃ50 mL). The
combined organic layers were dried (MgSO4) and concentrated in vacuo.
Column chromatography on silica gel (n-hexane/EtOAc 9:1 ! 5:1) yield-
ed tetrahydroxanthenone 33 as a pale yellow solid (373 mg, 0.92 mmol,
84%). Optical rotation: [a]2D5 =ꢀ78.8 (c=0.50, CHCl3). 1H NMR
(600 MHz, CDCl3): d=0.00 (s, 3H, Si
ACHTUNTGRENNGU(CH3)a), 0.13 (s, 3H, SiACHTUNGTRENNUNG(CH3)b),
0.83 (s, 9H, SiC(CH3)3), 1.37 (s, 3H, 4a-CH3), 1.87–1.96 (m, 2H, 3-Ha, 3-
AHCTUNGTRENNUNG
Methyl (R)-4-(tert-butyldimethylsilyloxy)-4-[(S)-5-methoxy-2,7-dimethyl-
4-oxochroman-2-yl]butanoate (31): Method A: A mixture of chroman 29
(1.32 g, 3.12 mmol, 1.00 equiv), tert-butyl hydroperoxide (2.95 mL of a
5.5m solution in decane, 16.2 mmol, 5.20 equiv) and powdered molecular
sieves 3 ꢂ (1.2 g) in EtOAc (20 mL) was stirred at room temperature for
Hb), 2.24 (ddd, J=18.7, 5.8, 1.9 Hz, 1H, 2-Ha), 2.30 (s, 3H, 6-CH3), 2.74
(ddd, J=18.9, 11.0, 8.0 Hz, 1H, 2-Hb), 3.91 (s, 3H, 8-OCH3), 4.03 (dd, J=
3.8, 1.9 Hz, 1H, 4-H), 6.28 (s, 1H, Ar-H), 6.30 (s, 1H, Ar-H), 16.22 (s,
1H, 1-OH) ppm; 13C NMR (125 MHz, CDCl3): d=ꢀ5.0, ꢀ4.2 (Si
ACHTUNGTRENNUNG(CH3)2),
18.3 (SiCACHTNURGTENN(UG CH3)3), 22.4 (6-CH3), 25.7 (4a-CH3), 25.8 (C-3, SiCACHTUGNTRENN(UNG CH3)3), 26.4
30 min. Then [Mn
ACHTUNGTRENNUNG
(C-2), 56.1 (8-OCH3), 71.3 (C-4), 80.1 (C-4a), 105.1, 111.0 (C-5, C-7),
105.6 (C-9a), 107.0 (C-8a), 146.8 (C-6), 159.8, 160.4 (C-8, C-10a), 180.6
(C-9), 182.2 (C-1) ppm; IR (film) n˜ =2953, 2926, 2851, 1604, 1460, 1406,
1356, 1245, 1225, 1199, 1110, 1085, 995, 877, 834, 818, 772, 723, 683,
638 cmꢀ1; UV/Vis (CH3CN): lmax (lg e)=198 nm (4.2799), 281 (3.4838),
332 (4.0611); MS (ESI): m/z (%): 1235.6 (46) [3M+Na]+, 831.4 (100)
[2M+Na]+, 427.2 (36) [M+Na]+, 405.2 (14) [M+H]+; HRMS (ESI): m/z
calcd for C22H32O5Si (404.57): 427.1911 [M+Na]+; found: 427.1911.
added and stirring continued for four days; additional MnAHCTUNGTRENNUNG
(86 mg, 0.312 mmol, 10 mol%) and tert-butyl hydroperoxide (0.57 mL,
3.12 mol, 1.00 equiv) were added after 24, 48, and 72 h. Thereafter, the
mixture was filtered over silica gel (eluting with EtOAc). Concentration
in vacuo and column chromatography on silica gel (petroleum ether/
EtOAc 30:1!1:1) furnished chromanone 31 as a yellow oil (701 mg,
1.60 mmol, 51%).
Method B: A solution of 29 (107 mg, 0.253 mmol, 1.00 equiv) in benzene
(10 mL) was treated with DDQ (115 mg, 0.507 mmol, 2.00 equiv) and
heated at 808C for 2 h. The reaction mixture was cooled to room temper-
ature and filtrated over silica gel (eluting with EtOAc). Evaporation of
the solvent in vacuo and column chromatography on silica gel (petroleum
ether/EtOAc=30:1!10:1) furnished the corresponding chromene as a
colorless oil (101 mg, 0.240 mmol, 95%). A solution of the chromene
(103 mg, 0.245 mmol, 1.00 equiv) in CH2Cl2 (6.1 mL) was treated with
(ꢀ)-Diversonol (ent-1):
A
solution of enantiopure 36 (33.0 mg,
0.114 mmol, 1.00 equiv) in EtOH (6.5 mL) was treated with MMPP
(80%, 39.0 mg, 63.1 mmol, 0.55 equiv) at 08C and stirred for 2 h at 08C.
The reaction was quenched by addition of silica gel (1.5 g) at 08C before
being concentrated in vacuo at 08C. Filtration over silica gel (eluting
with petroleum ether/EtOAc=1:4) and purification by RP-HPLC with
water (A), MeOH (B) as the eluent (Jasco Kromasil 100 C18, 250ꢃ
20 mm, 7 mm, gradient: 0–30 min: 70A/30B!50A/50B, 30–40 min: 50A/
50B! 0 A/B100, 40–50 min: 0A/100B!70 A/30B, flow: 18 mLminꢀ1, l=
284 nm, tR =20.4 min) yielded diketone 37 as a white solid (16.0 mg,
[MnACHTUNGTRENNUNG(dpm)3] (15 mg, 24.8 mmol, 10 mol%) and PhSiH3 (125 mL, 106 mg,
0.98 mmol, 4.00 equiv). Oxygen was passed through the resulting mixture
for 5 min before being stirred under an O2 atmosphere at room tempera-
ture for further 4.5 h. Addition of silica gel, evaporation of the solvent
and column chromatography on silica gel (n-hexane/EtOAc=9:1!1:1)
provided chromanone 31 and the corresponding diastereomeric alcohols,
which were oxidized by adding MnO2 (48 mg, 0.49 mmol, 2.00 equiv) to
the alcohol mixture in CH2Cl2 (12 mL). The resulting mixture was heated
at reflux for four days (not at night). Additional MnO2 (48 mg,
0.49 mmol, 2.00 equiv) was added every 3 h (4 additions per day) with a
total amount of 1.92 g (19.6 mmol, 80 equiv) of MnO2. After filtration
over silica gel (eluting with EtOAc), evaporation of the solvent and
column chromatography on silica gel (n-hexane/EtOAc=9:1!1:1),
(94.7 mg, 0.217 mmol, 88%) of the combined chromanone 31 were ob-
52.2 mmol, 46%, diastereomeric ratio (d.r.)=5:1).
A solution of 37
(15.3 mg, 49.9 mmol, 1.00 equiv) in CH2Cl2 (0.5 mL) and MeOH (0.5 mL)
was treated with powdered NaBH4 (1.9 mg, 49.9 mmol, 1.00 equiv) at
ꢀ788C for 1.5 h. Additional NaBH4 (0.6 mg, 15.9 mmol, 0.32 equiv) was
added at ꢀ788C and stirring continued for 30 min at ꢀ788C. The reaction
was quenched with saturated aqueous NH4Cl (2 mL) at ꢀ788C and the
mixture poured into EtOAc (10 mL). The aq. layer was extracted with
EtOAc (5ꢃ4 mL) and the combined organic layers were dried over
Na2SO4. Purification by RP-HPLC with water (A), MeOH (B) as the
eluent (Jasco Kromasil 100 C18, 250ꢃ20 mm, 7 mm, gradient: 0–30 min:
70A/30B!50A/50B, 30–40 min: 50A/50B!0 A/B100, 40–50 min: 0A/
100B!70 A/30B, flow: 18 mLminꢀ1, l=284 nm, tR =23.1 min) yielded 38
as a white solid (9.5 mg, 30.8 mmol, 62%). BBr3 (0.31 mL of a 1m solution
in CH2Cl2, 0.31 mmol, 10.1 equiv) was added slowly to a solution of 38
(9.5 mg, 30.8 mmol, 1.00 equiv) in CH2Cl2 (2 mL) at ꢀ788C. The resulting
red solution was stirred for 30 min at ꢀ788C, 1.5 h at 08C and 3.5 h at
room temperature before being quenched with water (10 mL) at 08C.
The aqueous layer was extracted with CH2Cl2 (3ꢃ10 mL), the combined
organic layers were dried over Na2SO4 and the solvent was evaporated in
vacuo. Purification by RP-HPLC with water (A), MeOH (B) as the
eluent (Jasco Kromasil 100 C18, 250ꢃ20 mm, 7 mm, gradient: 0–30 min:
70 A/30B!50A/50B, 30–40 min: 50A/50B!0A/B100, 40–50 min: 0A/
100B!70A/30B, flow: 18 mLminꢀ1, l=284 nm, tR =29.9 min) furnished
tained as
a
colourless oil. [a]D25 =ꢀ19.4 (c=0.49, CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.04 (s, 3H, SiACTHUNRTGENN(GU CH3)a), 0.10 (s, 3H, SiACHTUNTGREN(NNGU CH3)b),
0.84 (s, 9H, SiCACHTUNGTRENNUNG(CH3)3), 1.27 (s, 3H, 2’-CH3), 1.50–1.63 (m, 1H, 3-Ha),
1.82–1.93 (m, 1H, 3-Hb), 2.28 (s, 3H, 7’-CH3), 2.31 (d, J=16.1 Hz, 1H, 3’-
Ha), 2.29–2.57 (m, 2H, 2-Ha, 2-Hb), 3.11 (d, J=16.0 Hz, 1H, 3’-Hb), 3.66
(s, 3H, 1-OCH3), 3.82 (dd, J=9.3, 3.0 Hz, 1H, 4-H), 3.86 (s, 3H, 5’-
OCH3), 6.25 (s, 1H, Ar-H), 6.27 (s, 1H, Ar-H) ppm; 13C NMR (125 MHz,
CDCl3): d=ꢀ4.5, ꢀ3.6 (Si
ACHUTNGTNERNU(G CH3)2), 18.4 (SiCAHCTUNGTREN(NGUN CH3)3), 19.9 (2’-CH3), 22.5
(7’-CH3), 26.1 (SiC(CH3)3), 27.4 (C-3), 30.8 (C-2), 43.1 (C-3’), 51.6 (1-
ACHTUNGTRENNUNG
OCH3), 56.0 (5’-OCH3), 76.5 (C-4), 83.7 (C-2’), 104.4, 110.8 (C-6’, C-8’),
108.3 (C-4a’), 147.3 (C-7’), 160.0, 160.7 (C-5’, C-8a’), 173.6 (C-1), 190.9
(C-4’) ppm; IR (film): n˜ =2953, 2930, 2855, 1737, 1682, 1613, 1568, 1463,
1416, 1351, 1250, 1221, 1169, 1142, 1104, 1081, 996, 833, 776 cmꢀ1; UV/Vis
(CH3CN): lmax (lg e)=194 (4.3426), 221 (4.2539), 269 (3.9905), 325 nm
(3.5392); MS (ESI): m/z (%)=895.4 (100) [2M+Na]+, 459.2 (17)
[M+Na]+; HRMS (ESI): m/z calcd for C23H36O6Si (436.61): 459.2173
[M+Na]+; found: 459.2168.
(ꢀ)-diversonol (ent-1) as a white solid (6.8 mg, 23.1 mmol, 75%). [a]D22
=
ꢀ62.0 (c=0.16, CHCl3); 1H NMR (600 MHz, [D6]DMSO): d=1.40 (s,
3H, 4a-CH3), 1.46 (d, J=14.2 Hz, 1H, 2-Ha), 1.69 (d, J=14.2 Hz, 1H, 3-
Ha), 1.97 (tdd, J=14.2, 4.4, 2.4 Hz, 1H, 3-Hb), 2.17 (ddd, J=17.2, 8.7,
3.4 Hz, 1H, 2-Hb), 2.25 (s, 3H, 6-CH3), 3.99 (brs, 1H, 1-H), 4.29 (brs,
1H, 4-H), 4.95 (brs, 1H, OH), 6.29 (s, 1H, 5-H), 6.31 (s, 1H, 7-H), 6.59
(brs, 1H, OH), 11.29 (brs, 1H, OH) ppm; 13C NMR (125 MHz,
[D6]DMSO): d=19.4 (4a-CH3), 21.9 (6-CH3), 22.6 (C-2), 24.8 (C-3), 66.2
(C-4), 73.3 (C-1), 75.5 (C-4a), 81.0 (C-9a), 104.4 (C-8a), 108.5 (C-5),
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
4880
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 4876 – 4882

Enantioselective Total Synthesis of (ꢀ)-Diversonol
FULL PAPER
108.8 (C-7), 149.1 (C-6), 158.3 (C-10a), 161.5 (C-8), 194.0 (C-9) ppm; IR
(film): n˜ =3554, 3358, 2978, 2942, 2879, 1655, 1630, 1570, 1439, 1387,
1352, 1327, 1252, 1197, 1093, 1056, 1022, 998, 883, 850, 829, 722, 675, 606,
575, 529 cmꢀ1; UV/Vis (CH3CN): lmax (lg e)=196 (4.2362), 210 (4.1737),
282 (3.9576), 379 nm (4.3401); MS (ESI): m/z (%)=611.2 (100)
[2M+Na]+, 317.1 (100) [M+Na]+, 295.1 (13) [M+H]+; HRMS (ESI): m/
z calcd for C15H18O6 (294.30): 317.0995 [M+Na]+; found: 317.0996.
Acknowledgements
The work was supported by Deutsche Forschungsgemeinschaft (DFG),
Land Niedersachsen and Volkswagenstiftung. We thank Prof. A. M.
Echavarren for valuable discussions. S.J. thanks the CaSuS Program for a
Ph.D. scholarship. C.R. thanks the Stiftung Stipendienfonds des Ver-
bandes der Chemischen Industrie (VCI) for a Ph.D. scholarship. J.R.R
thanks the Konrad Adenauer Stiftung for a Ph.D. scholarship. Generous
gifts of chemicals by Bayer AG, BASF SE, and Wacker Chemie AG are
greatly appreciated.
(4R,4aR,9aS)-4-(tert-Butyldimethylsilyloxy)-9a-hydroxy-8-methoxy-4a,6-
dimethyl-2,3,4,4a-tetrahydro-1H-xanthene-1,9
35): Synthesis of 35: Water (1.2 mL) and tetrahydroxanthenone 33
(325 mg, 0.803 mmol, 1.00 equiv) was added to solution of IBX
ACHTUNGERTN(NUNG 9aH)-dione (35) and (rac-
a
(536 mg, 2.01 mmol, 2.50 equiv) in DMSO (3.8 mL) and the resulting
mixture heated at 608C for 9 h. Additional IBX (112 mg, 0.402 mmol,
0.50 equiv) was added at room temperature and stirring was continued
for 3 h at 608C. The reaction mixture was cooled to room temperature,
diluted with CH2Cl2 (20 mL) and stirred vigorously for 30 min. The pre-
cipitate was removed by filtration, washed with CH2Cl2 (4ꢃ50 mL) and
the combined organic phases were treated with saturated aqueous
NaHCO3 (50 mL). The aqueous layer was extracted with CH2Cl2 (3ꢃ
25 mL) and the combined organic phases were washed with brine (1ꢃ
100 mL) and dried over Na2SO4. Evaporation of the solvent in vacuo and
column chromatography on silica gel (petroleum ether/EtOAc=4:1) fur-
nished 35 as a white solid (109 mg, 0.259 mmol, 32%).
[1] a) W. B. Turner, J. Chem. Soc. Perkin Trans. 1 1978, 1621; b) I. N.
Siddiqui, A. Zahoor, H. Hussain, I. Ahmed, V. U. Ahmad, D.
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Li, Angew. Chem. 2008, 120, 6681–6684; Angew. Chem. Int. Ed.
2008, 47, 6579–6582.
Synthesis of rac-35: Compound rac-35 was prepared according to the pro-
cedure described for enantiopure 35 by using freshly prepared IBX[23]
with 49% yield and a decreased reaction time of 4 h. Optical rotation of
35: [a]2D3 = +5.9 (c=0.50, CHCl3); 1H NMR (600 MHz, CDCl3): d=
[3] a) A. Stoll, J. Renz, A. Brack, Helv. Chim. Acta 1952, 35, 2022–
2034; b) I. Kurobane, S. Iwahashi, A. Fukuda, Drugs Exp. Clin. Res.
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[4] F. Kraft, Arch. Pharm. 1906, 244, 336–359.
ꢀ0.07 (s, 3H, Si
ACHTUNGTRENNUNG(CH3)a), 0.07 (s, 3H, SiAHCTUNRGTENN(GNU CH3)b), 0.80 (s, 9H, SiCACHTUNGTRENN(UNG CH3)3),
[5] a) B. Franck, E. M. Gottschalk, U. Ohnsorge, F. Hꢅper, Chem. Ber.
1966, 99, 3842–3862; b) B. Franck, E. M. Gottschalk, U. Ohnsorge,
G. Baumann, Angew. Chem. 1964, 76, 438–439; Angew. Chem. Int.
Ed. Engl. 1964, 3, 441–442.
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S. Antus, T. Kurtꢄn, J. Rheinheimer, S. Draeger, B. Schulz, Chem.
Eur. J. 2008, 14, 4913–4923.
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[8] a) M. Isaka, A. Jaturapat, K. Rukseree, K. Danwisetkanjana, M.
Tanticharoen, Y. Thebtaranoth, J. Nat. Prod. 2001, 64, 1015–1018;
b) B. Elsꢀsser, K. Krohn, U. Flçrke, N. Root, H.-J. Aust, S. Draeger,
B. Schulz, S. Antus, T. Kurtꢄn, Eur. J. Org. Chem. 2005, 4563–4570.
[9] L. F. Tietze, D. A. Spiegl, F. Stecker, J. Major, C. Raith, C. Grosse,
Chem. Eur. J. 2008, 14, 8956–8963.
1.26 (s, 3H, 4a-CH3), 1.91–1.96 (m, 1H, 3-Ha), 2.12–2.20 (m, 1H, 3-Hb),
2.28 (s, 3H, 6-CH3), 2.67 (mc, 1H, 2-Ha), 2.74 (mc, 1H, 2-Hb), 3.86 (s, 3H,
8-OCH3), 4.18 (dd, J=7.8, 3.6 Hz, 1H, 4-H), 4.65 (s, 1H, OH), 6.27 (s,
1H, Ar-H), 6.35 (s, 1H, Ar-H) ppm; 13C NMR (125 MHz, CDCl3): d=
ꢀ5.0, ꢀ4.6 (Si
ACHTUNGTRENNUNG(CH3)2), 17.0 (6-CH3), 18.1 (SiCCAHTUNGTRENN(GUN CH3)3), 22.5 (6-CH3), 25.7
(SiC(CH3)3), 28.8 (C-2), 34.2 (C-2), 56.0 (8-OCH3), 73.1 (C-4), 79.7 (C-
ACHTUNGTRENNUNG
4a), 86.6 (C-9a), 104.5, 110.6 (C-5, C-7), 107.1 (C-8a), 148.0 (C-6), 160.2,
161.0 (C-8, C-10a), 187.7 (C-9), 206.7 (C-1) ppm; IR (film): n˜ =3432,
2928, 2852, 1718, 1683, 1618, 1575, 1466, 1414, 1387, 1360, 1248, 1224,
1128, 1088, 992, 892, 859, 834, 816, 783, 710, 595 cmꢀ1; UV/Vis (CH3CN):
lmax (lg e)=195 (4.3334), 221 (4.1939), 276 (3.9978), 330 nm (3.4935); MS
(ESI): m/z (%): 863.5 (100) [2M+Na]+, 443.2 (74) [M+Na]+, 421.3 (12)
[M+H]+; HRMS (ESI): m/z calcd for C22H32O6Si (420.57): 443.1860
[M+Na]+; found: 443.1859.
[10] For domino reactions, see: a) L. F. Tietze, U. Beifuss, Angew. Chem.
1993, 105, 137–170; Angew. Chem. Int. Ed. Engl. 1993, 32, 131–163;
b) L. F. Tietze, Chem. Rev. 1996, 96, 115–136; c) L. F. Tietze, N.
Rackelmann, Pure Appl. Chem. 2004, 76, 1967–1983; d) L. F. Tietze,
N. Rackelmann, Multicomponent Reactions (Ed.: J. Zhu), Wiley-
VCH, Weinheim, 2005, p. 121–168; e) L. F. Tietze, G. Brasche,
K. M. Gericke, Domino Reactions in Organic Synthesis Wiley-VCH,
Weinheim, 2006; f) L. F. Tietze, L. Levy, The Mizoroki-Heck Reac-
tion (Ed.: M. Oestreich), Wiley-VCH, Weinheim, 2009, p. 281–344;
g) L. F. Tietze, A. Dꢅfert, Catalytic Asymmetric Conjugate Reactions
2010, p. 321–350; h) L. F. Tietze, A. Dꢅfert, Pure Appl. Chem. 2010,
82, 1375–1392; i) L. F. Tietze, S. Stewart, A. Dꢅfert Modern Tools
for the Synthesis of Complex Bioactive Molecules (Eds.: J. Cossy, S.
Arseniyades), Wiley, Hoboken, New Jersey 2012.
[11] a) L. F. Tietze, A. Heins, M. Soleiman-Beigi, C. Raith, Heterocycles
2009, 77, 1123–1146; b) L. F. Tietze, J. Zinngrebe, D. A. Spiegl, F.
Stecker, Heterocycles 2007, 74, 473–489.
[12] a) H. Hocke, Y. Uozumi, Tetrahedron 2003, 59, 619–630; b) T. D.
Nelson, A. I. Meyers, J. Org. Chem. 1994, 59, 2655–2658.
[13] a) R. Tanikaga, Y. Nozaki, T. Tamura, A. Kaji, Synthesis 1983, 134–
135; b) J. Nokami, T. Mandai, Y. Imakura, K. Nishiuchi, M.
Kawada, S. Wakabayashi, Tetrahedron Lett. 1981, 22, 4489–4490;
c) S. Yamagiwa, H. Sato, N. Hoshi, K. Kosugi, H. Uda, J. Chem. Soc.
Perkin Trans. 1 1979, 570–583.
(1S,4R,4aR,9aR)-1,4,8,9a-Tetrahydroxy-4a,6-dimethyl-2,3,4,4a-tetrahy-
dro-1H-xanthen-9ACHTUNGTRENNUNG(9aH)-one (rac-41): BBr3 (0.26 mL of a 1.0m solution
in CH2Cl2, 260 mmol, 10 equiv) was added slowly to a solution of methyl
ether rac-40 (8.0 mg, 26 mmol, 1.00 equiv) in CH2Cl2 (2 mL) at ꢀ788C.
The resulting orange solution was stirred for 45 min at ꢀ788C and for
48 h at 08C before being quenched with water (10 mL). The organic
layer was separated and the aqueous layer was extracted with EtOAc
(3ꢃ10 mL). The combined extracts were dried (Na2SO4) and the solvent
was evaporated in vacuo. Column chromatography on silica gel (CH2Cl2/
EtOAc 1:1) provided pure rac-41 (3.6 mg, 47%). 1H NMR (600 MHz,
[D6]DMSO): d=1.46 (dq, J=12.4, 3.7 Hz, 1H, 3-Ha), 1.54 (dq, J=13.7,
2.8 Hz, 1H, 2-Ha), 1.87 (tt, J=14.0, 3.3 Hz, 1H, 2-Hb), 2.11 (dq, J=14.3,
3.1 Hz, 1H, 3-Hb), 2.22 (s, 3H, 6-CH3), 3.56 (ddd, J=11.7, 7.2, 4.1 Hz,
1H, 4-H), 3.61 (dt, J=5.4, 2.8 Hz, 1H, 1-H), 4.64 (d, J=5.2 Hz, 1H, 1-
OH), 4.67 (d, J=7.4 Hz, 1H, 4-OH), 5.67 (s, 1H, 9a-OH), 6.20 (s, 1H, 5-
H), 6.22 (s, 1H, 7-H), 11.49 (s, 1H, 8-OH) ppm; 13C NMR (125 MHz,
[D6]DMSO): d=16.9 (4a-CH3), 21.9 (6-CH3), 24.4 (C-3), 27.9 (C-2), 70.6
(C-4), 71.4 (C-1), 76.4, 83.0 (C-4a, C-9a), 106.9 (C-8a), 107.7, 108.6 (C-5,
C-7), 149.1 (C-6), 159.8, 160.2 (C-8, C-10a), 201.8 (C-9) ppm; IR (film):
n˜ =3311, 2945, 2921, 1643, 1569, 1449, 1358, 1193, 1141, 1104, 1068, 1014,
983, 939, 876, 837, 717, 661, 585 cmꢀ1; UV/Vis (CH3CN): lmax (lg e)=195
(4.2831), 210 (4.2455), 282 (4.0008), 348 nm (3.4131); MS (ESI): m/z (%):
611.2 (31) [2M+Na]+, 317.1 (100) [M+Na]+; HRMS (ESI): C16H20O6
(294.30): calcd: 317.0996; found: 317.1001 [M+Na]+.
[14] a) B. M. Trost, S. Mallart, Tetrahedron Lett. 1993, 34, 8025–8028;
b) K. Burgess, I. Henderson, Tetrahedron 1991, 47, 6601–6616; c) K.
Chem. Eur. J. 2013, 19, 4876 – 4882
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4881

L. F. Tietze et al.
Burgess, J. Cassidy, I. Henderson, J. Org. Chem. 1991, 56, 2050–
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[22] A. Duschek, S. F. Kirsch, Chem. Eur. J. 2009, 15, 10713–10717.
[23] The yield depends on the quality of IBX used; see for its prepara-
tion: L. F. Tietze, T. Eicher, U. Diederichsen, A. Speicher, in Reac-
tions and Syntheses in the Organic Chemistry Laboratory, Wiley-
VCH, Weinheim, 2007, p. 218.
[18] T. K. M. Shing, Y.-Y. Yeung, P. L. Su, Org. Lett. 2006, 8, 3149–3151.
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Received: November 11, 2012
Published online: February 18, 2013
4882
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 4876 – 4882