(2R,3R)-1,4-Dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol: Chiral auxiliary and efficient protecting group for boronic acids

Article abstract of DOI:10.1021/jo0056601

(2R,3R)-1,4-Dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol (1) has been used as an efficient chiral auxiliary in the cyclopropanation of alkenylboronic esters. The stability of the obtained cyclopropylboronic esters allowed the chromatographic separation of the diastereoisomers. Furthermore, it enabled a variety of transformations in the side-chain, including oxidation, reduction, and reactions under acidic, basic, or radical conditions, that finally led to boron containing functionalized bicyclopropanes, e.g., 12 and 18. The absolute configurations of these building blocks were established by X-ray crystallography (compound 10) and by chemical correlation. The Matteson homologation led to a known advanced intermediate of the oligocyclopropane FR-900848.

Full text of DOI:10.1021/jo0056601

9194
J . Org. Chem. 2000, 65, 9194-9200
(2R,3R)-1,4-Dim eth oxy-1,1,4,4-tetr a p h en yl-2,3-bu ta n ed iol: Ch ir a l
Au xilia r y a n d Efficien t P r otectin g Gr ou p for Bor on ic Acid s
J oachim E. A. Luithle and J o¨rg Pietruszka*
Institut fu¨r Organische Chemie der Universita¨t Stuttgart,
Pfaffenwaldring 55, D-70569 Stuttgart, Germany
joerg.pietruszka@po.uni-stuttgart.de
Received September 25, 2000
(2R,3R)-1,4-Dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol (1) has been used as an efficient chiral
auxiliary in the cyclopropanation of alkenylboronic esters. The stability of the obtained cyclopro-
pylboronic esters allowed the chromatographic separation of the diastereoisomers. Furthermore,
it enabled a variety of transformations in the side-chain, including oxidation, reduction, and reactions
under acidic, basic, or radical conditions, that finally led to boron containing functionalized
bicyclopropanes, e.g., 12 and 18. The absolute configurations of these building blocks were
established by X-ray crystallography (compound 10) and by chemical correlation. The Matteson
homologation led to a known advanced intermediate of the oligocyclopropane FR-900848.
In tr od u ction
have usually been limited to simple model compounds.
This changed with the introduction of the new chiral
auxiliary 1.4,1g Due to the high stability of the boronic
esters, it was not only possible to separate the diaster-
eomeric cyclopropylboronic esters 2 for the first time,2d
but also to perform simple deprotections in the side-
chain.1g,2f An example is the simple desilylation5 of
alkenylboronic ester 3sobtained in one step by direct
hydroboration of the corresponding protected propargyl
alcohol in 91% yieldsgiving alcohol 4 in high yield
(Figure 1).1g,6 This sequence has been performed on a
multigram scale (30 g). In view of the high interest in
oligocyclopropanes in general,7 and in natural products
such as the antifungal compound FR-9008488 or the
cholesteryl ester transfer protein inhibitor U-1063059 in
particular, we thought to extend our method to bicyclo-
propanes. For a selective and general approach, the diol
1 (or its enantiomer) should guarantee two features: (a)
Cyclopropylboronic esters have frequently been re-
ported to be ideal building blocks for cyclopropane
chemistry. Especially the broad synthetic potential of the
boron moiety has been noted, although the focus has been
on Suzuki couplings1 and transformations to cyclopro-
panols.2 The use of chiral auxiliaries, first reported by
Imai et al.,2b finally led directly2d or indirectly2e to
enantiomerically pure 1,2-trans-disubstituted cyclopro-
panes. cis-Cyclopropylboronic esters were reported only
recently, thus closing a gap.2f Despite the dramatic
developments since the first successful reports about the
synthesis of these intermediates,1-3 most investigations
* To whom correspondence should be addressed.
(1) (a) Hildebrand, J . P.; Marsden, S. P. Synlett 1996, 893-894. (b)
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38, 2809-2812. (d) Pietruszka, J .; Widenmeyer, M. Synlett 1997, 977-
979. (e) Zhou, S.-M.; Deng, M.-Z.; Xia, L.-J .; Tang, M.-H. Angew. Chem.
1998, 110, 3061-3063. Angew. Chem., Int. Ed. 1998, 37, 2845. (f) Zhou,
S.-M.; Yan, Y.-L.; Deng, M.-Z. Synlett 1998, 198-200. (g) Luithle, J .
E. A.; Pietruszka, J . J . Org. Chem. 1999, 64, 8287-8297. (h) Chen,
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Org. Chem. 2000, 65, 5034-5036. (m) Soderquist, J . A.; Huertas, R.;
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M.; Deng, M.-Z. Tetrahedron Lett. 2000, 41, 3951-3954. For a recent
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(6) On a large scale a regioisomer 4a (see Supporting Information)
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alkenylboronic ester 3 was not completely regioselective.
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10.1021/jo0056601 CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/28/2000

Efficient Protecting Group for Boronic Acids
J . Org. Chem., Vol. 65, No. 26, 2000 9195
Sch em e 2a
F igu r e 1. Transformations in the side-chain of cyclopropyl-
boronic esters.
Sch em e 1a
a
Reagents: (a) cat. TPAP, NMO, CH2Cl2; (b) NaH, THF,
MeO2CCH2P(dO)(OMe)2; (c) DIBAL-H, THF, -78 °C to room
temperature; (d) i. cat. 13, Et2Zn, CH2Cl2; ii. ZnI2, CH2Cl2; iii.
CH2I2, Et2Zn, CH2Cl2.
a
Reagents: (a) cat. TPAP, NMO, CH2Cl2; (b) NaH, THF,
obtained by selective cyclopropanation of 4 using the
Denmark conditions.14,1g The absolute configuration had
been deduced by characteristic NMR data. At this stage
we could confirm, after oxidation to aldehyde 9 and reac-
tion with trimethyl phosphonoacetate to ester 10 (90%
over two steps), the assignment (Scheme 2): The X-ray
structure analysis (see supporting material) unambigu-
ously proved our prediction. The DIBAL-H reduction to
allyl alcohol 11 was again a high-yielding process. Obvi-
ously, these transformations were also possible for the
diastereoisomeric series (8a to 11a ; see Supporting In-
formation). Cyclopropanation led predominantly to bicy-
clopropane 12 (91% yield as a separable 92:8 diastereo-
isomeric mixture; minor diastereoisomer: 12a ) when
substoichiometric amounts of bis(sulfonamide) 13 were
used as a chiral ligand. A low selectivity (12:12a , 45:55)
was obtained in the mismatched case utilizing enanti-
omer ent-13.
MeO2CCH2P(dO)(OMe)2; (c) DIBAL-H, THF, -78 °C to room
temperature.
The chiral auxiliary should lead to high diastereomeric
ratios in the cyclopropanation step and (b) it should fulfill
all requirements of a good protecting group for boronic
acids. It is already known that the introduction of diol 1
and the cleavage of boronic esters such as 2 is possible,
and in this contribution we intend to answer the question
about the limits of possible transformations without
interfering with the boron moiety.
Resu lts a n d Discu ssion
First of all, we examined simple chain-elongations
starting with alkenylboronic ester 4 (Scheme 1). Oxida-
tion, either using the Dess-Martin conditions10 (64%) or,
in this case preferentially, with the Ley reagent,11 led to
smooth formation of aldehyde 5. No side-product was
detected. Horner-Wadsworth-Emmons reaction12 gave
a clean transformation to diene 6 in 74% overall yield.
The selectivity of the reduction is remarkable: Although
prolonged reaction time with an excess of DIBAL-H is
inadvisable since formation of diol 1 would be detected,
the carboxylic ester reacts much faster than this boronic
ester. By thoroughly following the reaction by TLC, we
found that alcohol 7 was the only product obtained. First
attempts to perform selective cyclopropanations failed.
Only complex, inseparable mixtures of mono- and dicy-
clopropanated diastereoisomers were detected. In view
of some recent work on Diels-Alder reactions of boron-
containing dienes,13 compounds 6 and 7 could be of
considerable interest.
(11) Ley, S. V.; Norman, J .; Griffith, W. P.; Marsden, S. P. Synthesis
1994, 639-668.
(12) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863-927.
(13) (a) Martinez-Fresneda, P.; Vaultier, M. Tetrahedron Lett. 1989,
30, 2929-2932. (b) Singleton, D. A.; Martinez, J . P. J . Am. Chem. Soc.
1990, 112, 7423-7424. (c) Wang, X. J . Chem. Soc., Chem. Commun.
1991, 1515-1517. (d) Guennouni, N.; Rasset-Deloge, C.; Carboni, B.;
Vaultier, M. Synlett 1992, 581-584. (e) Kamabuchi, A.; Miyaura, N.;
Suzuki, A. Tetrahedron Lett. 1993, 34, 4827-4828. (f) Singleton, D.
A.; Redman, A. M. Tetrahedron Lett. 1994, 35, 509-512. (g) Garnier,
L.; Plunian, B.; Mortier, J .; Vaultier, M. Tetrahedron Lett. 1996, 37,
6699-6700. (h) Bonk, J .; Avery, M. A. Tetrahedron: Asymmetry 1997,
8, 1149-1152. (i) Renard, P.-Y.; Six, Y.; Lallemand, J .-Y. Tetrahedron
Lett. 1997, 38, 6589-6590. (j) Lorvelec, G.; Vaultier, M. Tetrahedron
Lett. 1998, 39, 5185-5188. (k) Batey, R. A.; Thadani, A. N.; Lough, A.
J . Chem. Commun. 1999, 475-476. (l) Batey, R. A.; Thadani, A. N.;
Lough, A. J . J . Am. Chem. Soc. 1999, 121, 450-451. (m) Six, Y.;
Lallemand, J .-Y. Tetrahedron Lett. 1999, 40, 1295-1296. (n) Renaud,
J .; Graf, C.-D.; Oberer, L. Angew. Chem. 2000, 112, 3231-3234; Angew.
Chem., Int. Ed. 2000, 39, 3101.
Next, we followed the same sequence starting with the
enantiomerically pure cyclopropylboronic ester 8 that we
(14) Denmark, S. E.; O’Connor, S. P. J . Org. Chem. 1997, 62, 3390-
3401. On a large scale we improved the yield and selectivity for the
formation of cyclopropane 8: 94% yield, dr 91:9.
(10) Dess, D. B.; Martin, J . C. J . Org. Chem. 1983, 48, 4155-4156.

9196 J . Org. Chem., Vol. 65, No. 26, 2000
Luithle and Pietruszka
Sch em e 4a
Sch em e 3a
a
Reagents: (a) TPS-Cl, imidazole, CH2Cl2; (b) BnBr, NaH,
DMF; (c) i. LiAlH4, THF, ii. NH4Cl, iii. 1,3-propanediol; (d) i.
ClCH2Li, THF, -78 °C to room temperature, ii. 30% H2O2/KHCO3.
a
+
Reagents: (a) NaIO4, cat. RuCl3; (b) 2-mercaptopyridine
Yield over two steps starting from 14a .
N-oxide, DCC, DMAP, cyclohexene, CHI3, reflux; (c) PhB(OH)2,
Pd(PPh3)4, KOtBu, DME, reflux; (d) PhI, Pd(PPh3)4, KOtBu, DME,
reflux.
Although we were confident that the assignment of the
configuration for the second cyclopropane was correct, we
needed some proof, especially since the NMR data were
not very meaningful. We envisaged to perform a simple
Matteson homologation15 in order to synthesize a known
optically pure bicyclopropane. Not surprisingly, the direct
transformation of compound 12 was not successful. We
did only recover the starting material. Unfortunately, all
attempts to isolate the corresponding boronic acid also
failed when the hydroxy group was not protected. Intro-
duction of a silyl or a benzyl protecting group was
straightforward (Scheme 3), furnishing compounds 14a
and 14b, respectively. Again, the boronic ester remained
untouched. The following transesterifications to the
dioxaborinanes 15a (87%) and 15b (94%) were unprob-
lematic, when using our standard procedure: formation
of the corresponding alkylborohydride with LiAlH4, hy-
drolysis with aqueous NH4Cl, and condensation with 1,3-
propanediol.1g Homologation with chloromethyllithium
and subsequent oxidation with 30% H2O2/KHCO3 led
to the desired products 16a (60% over two steps) and
16b (72%; 68% over two steps), respectively. In full
agreement to the observation made by Ren and Crud-
den,16 we noted no sequential insertion with this re-
agent. In the case of the silyl-protected alcohol, we
could also isolate 13% of the corresponding cyclopropanol
16c as the only side-product. All analytical data of the
known optically pure bicyclopropane 16a were in full
agreement to reported data,8e thus confirming that the
diastereoselective cyclopropanation did not lead to the
anti compound.7a
stabilize the cyclopropylboronic ester during radical
reactions. In our hands, the thermal decarboxylation of
the corresponding Barton thiohydroxamic ester17 in the
presence of iodoform was the best condition. This fur-
nished the iodocyclopropane 18, albeit in relatively low
yield (42%; ∼10:1 mixture of trans:cis isomer). Neverthe-
less, our findings indicate that not the radical reaction
itself was problematic, but the formation of some uni-
dentified side-products during the synthesis of the Barton
ester. We further speculated that the difunctionalized
bicyclopropane 18 should be an ideal intermediate for a
variety of consecutive transformations. A Suzuki coupling
of the iodide with boronic acids followed by deprotection
of our boronic ester and, for example, another Suzuki
coupling with a halide, was an attractive goal. Unfortu-
nately, we did not yet succeed to find ideal conditions
for a useful protocol. Coupling with phenylboronic acid
led to an inseparable mixture of three compounds. Mass
spectrometry (FAB, NBA+NaI) showed the presence of
some starting material 18 (m/z 693 [(M + Na)+]), the
corresponding reduction product (m/z 567 [(M + Na)+],
presumably formed after the hydrolysis of the palladium
intermediate) and product 19 (m/z 643 [(M + Na)+]). The
phenylboronic acid was consumed (formation of product
and likely benzene). Obviously the oxidative addition of
palladium(0) proceeded, but was a very slow process in
the presence of the bulky boronic ester. With a less bulky
palladium intermediate, formed for instance during the
coupling of dioxaborinane 15a with phenyl iodide, the
desired product 20 was readily formed (79%). Although
these findings were not completely comparable, with the
boronic esters derived from 1,3-propanediol being more
reactive than the initial boronic acids,1c we believe that
the reductive elimination was the limiting step. We are
currently investigating whether, by changing the order
of events, the key intermediate 12 could become a more
Since the oxidation to aldehydes worked well and
without side-reaction at the boronic ester moiety, we were
optimistic that the ruthenium-catalyzed oxidation of
alcohol 12 to carboxylic acid 17 would be unproblematic.
Indeed, we obtained the desired compound in 79% yield
(Scheme 4). This was our starting material to test,
whether the protecting group (diol 1) would sufficiently
(15) (a) Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4,
1687-1689. (b) Matteson, D. S. Tetrahedron 1998, 54, 10555-10607.
Imai et al. reported a single example for a successful homologation of
a cyclopropylboronic ester (see ref 2b).
(16) Ren, L.; Crudden, C. M. Chem. Commun. 2000, 721-722.
(17) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron
1985, 41, 3901-3924.

Efficient Protecting Group for Boronic Acids
J . Org. Chem., Vol. 65, No. 26, 2000 9197
chromatography on silica gel, eluting with petroleum ether/
ethyl acetate (85:15), yielded a colorless foam (2.50 g, 4.35
mmol, 74%).
Softening range ) 80-86 °C; [R]20 ) +15 (c 0.3, CHCl3);
D
IR (film) 3080, 1719 cm-1; MS [FAB, NBA+NaI] m/z 597 (15)
[(M + Na)+], 197 (65) [(Ph2COCH3)+], 176 (100); 1H NMR
(CDCl3, 500 MHz) δ 2.98 (s, 6 H, OCH3), 3.69 (s, 3 H, CO2CH3),
5.35 (s, 2 H, 4-H/5-H), 5.83 (dd, J ) 17.6, 0.8 Hz, 1 H, 1′-H),
6.13 (dd, J ) 15.4, 0.8 Hz, 1 H, 4′-H), 6.88 (ddd, J ) 17.6,
11.0, 0.8 Hz, 1 H, 2′-H), 7.36 (ddd, J ) 15.4, 11.0, 0.8 Hz, 1 H,
3′-H), 7.24-7.32 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
δ 51.7 (CO2CH3), 51.8 (OCH3), 77.8 (C-4/C-5), 83.3 (CPh2-
OCH3), 123.6 (C-4′), 127.3, 127.4, 127.6, 127.9, 128.4, 129.7,
140.9, 141.1 (Ar-C), 145.4 (C-3′), 145.6 (C-2′), 167.1 (CO2CH3),
(C-1′ not detected). Anal. Calcd for C36H35BO6 (574.47): C,
75.27; H, 6.14. Found: C, 75.22; H, 6.28.
F igu r e 2. Diol 1: Chiral auxiliary and protecting group for
boronic acids.
general building block for the synthesis of bicyclopro-
panes.
P r ep a r a tion of (4R,5R)-2-[(1E,3E)-5-Hyd r oxy-1,3-p en -
ta d ien -1-yl]-4,5-bis(m eth oxyd ip h en ylm eth yl)-1,3,2-d iox-
a bor ola n e 7. DIBAL-H (4.2 mL of a 1 M solution in hexane,
4.2 mmol) was added to a stirred solution of ester 6 (804 mg,
1.40 mmol) in THF (14 mL) at -78 °C. The reaction mixture
was slowly (over 2 h) warmed to room temperature; at this
point TLC indicated complete consumption of the starting
material. Addition of H2O (0.5 mL), NaOH (1 mL of a 2 M
solution in H2O), and again H2O (0.5 mL) led to a precipitate
that was separated by filtration. The solid was thoroughly
washed with Et2O. The crude product was obtained after
evaporation of the solvent under reduced pressure. Flash-
column chromatography on silica gel, eluting with petroleum
ether/ethyl acetate (95:5 to 80:20), yielded a colorless foam (660
mg, 1.21 mmol, 87%).
Con clu sion
We demonstrated that diol 1 qualifies as an efficient
protecting group for boronic acids. Highly stable dienyl-
and bicyclopropylboronic esters have been synthesized
from readily available alkenylboronic ester 4 by a variety
of transformations (Figure 2) in the side-chain of the
boronic ester. Deprotection was achieved with LiAlH4,
followed by aqueous workup and condensation with 1,3-
propanediol. The 1,3,2-dioxaborinanes were successfully
used for CC-bond forming reactions such as the Suzuki
coupling or the Matteson homologation. This last reaction
also allowed the unambiguous assignment of the absolute
configuration of the synthesized bicyclopropanes by
comparison of our results with literature data.
Softening range ) 92-100 °C; [R]20 ) +43 (c 0.5, CHCl3);
D
IR (film) 3400, 3058 cm-1; MS [FAB, NBA+NaI] m/z 569 (12)
1
[(M + Na)+], 197 (100) [(Ph2COCH3)+]; H NMR (CDCl3, 500
MHz) δ 1.35 (br s, 1 H, OH), 2.92 (s, 6 H, OCH3), 4.06 (d, J )
5.4 Hz, 2 H, 5′-H), 5.09 (d, J ) 17.7 Hz, 1 H, 1′-H), 5.27 (s, 2
H, 4-H/5-H), 5.75 (dt, J ) 15.3, 5.4 Hz, 1 H, 4′-H), 6.06 (dd, J
) 15.3, 10.5 Hz, 1 H, 3′-H), 6.50 (dd, J ) 17.7, 10.5 Hz, 1 H,
2′-H), 7.17-7.33 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
δ 51.8 (OCH3), 63.0 (C-5′), 77.7 (C-4/C-5), 83.4 (CPh2OCH3),
∼121 (br, C-1′), 127.3, 127.5, 127.6, 127.8, 128.5, 129.7 (Ar-
C), 132.7 (C-3′), 135.5 (C-4′), 141.0, 141.4 (Ar-C), 148.3 (C-2′).
Anal. Calcd for C35H35BO5 (546.46): C, 76.93; H, 6.46. Found:
C, 76.47; H, 6.59.
Exp er im en ta l Section
Gen er a l. All reagents were used as purchased from com-
mercial suppliers without further purification. The reactions
were carried out using standard Schlenk techniques under a
dry nitrogen atmosphere. Glassware was oven-dried at 150 °C
overnight. Solvents were dried and purified by conventional
methods prior to use; diethyl ether and THF were freshly
distilled from sodium/benzophenone. Flash-column chroma-
tography: Merck silica gel 60, 0.040-0.063 mm (230-400
mesh). TLC: Precoated sheets, Alugram SIL G/UV254 Mach-
erey-Nagel; detection by UV extinction or by cerium molyb-
denium solution [phosphomolybdic acid (25 g), Ce(SO4)2‚H2O
(10 g), concentrated H2SO4 (60 mL), H2O (940 mL)]. Prepara-
tive MPLC: Packed column (49 × 500 mm), LiChroprep, Si60
(15-25 µm), and UV detector (259 nm). 1H and 13C signals
were assigned by means of C-H and H-H COSY spectra.
Microanalysis: Performed at the Institut fu¨r Organische
Chemie, Stuttgart.
P r ep a r a tion of (4R,5R)-2-[(1E,3E)-4-Meth oxyca r bon yl-
1,3-bu ta d ien -1-yl]-4,5-bis(m eth oxyd ip h en ylm eth yl)-1,3,2-
d ioxa bor ola n e 6. To a stirred solution of alkenylboronic ester
4 (3.05 g, 5.86 mmol) in CH2Cl2 (50 mL) at 0 °C was added
N-methylmorpholine N-oxide (872 mg, 6.45 mmol), 4 Å mo-
lecular sieves (5.0 g), and tetra-n-propylammonium perruth-
enate (103 mg, 0.29 mmol). Stirring was continued at room
temperature for 12 h (TLC indicated complete consumption
of the starting material). Filtration through Celite and silica
gel (CH2Cl2) followed by evaporation of the solvent under
reduced pressure gave the crude aldehyde 5 which was directly
used without further purification.
(1′R,2′R,4R,5R)-2-{2-[(E)-2-Meth oxyca r bon yleth en yl]-
cyclop r op yl}-4,5-b is[m et h oxyd ip h en ylm et h yl]-1,3,2-d i-
oxa bor ola n e 10. The same procedure was followed as de-
scribed above for the synthesis of diene 6. Starting from
cyclopropylboronic ester 8 (19.76 g, 36.99 mmol), we obtained
the product 10 as a colorless foam (19.56 g, 33.2 mmol, 90%).
Recrystallization from petroleum ether/diethyl ether at -20
°C yielded colorless crystals, suitable for X-ray analysis.
Mp ) 157 °C; [R]20D ) -83.0 (c 0.96, CHCl3); IR (film) 3058,
1720 cm-1; MS [EI, 70 eV] m/z 588 (<0.1) [M+], 556 (1.5) [(M
1
- CH3OH)+], 197 (100) [(Ph2COCH3)+]; H NMR (CDCl3, 500
MHz) δ -0.19 (ddd, J ) 10.2, 7.1, 5.1 Hz, 1 H, 1′-H), 0.47 (ddd,
J ) 7.5, 7.1, 3.7 Hz, 1 H, 3′-Htrans), 0.62 (ddd, J ) 10.2, 4.9,
3.7 Hz, 1 H, 3′-Hcis), 1.46 (dddd, J ) 10.0, 7.5, 5.1, 4.9 Hz, 1 H,
2′-H), 2.99 (s, 6 H, CPh2OCH3), 3.66 (s, 3 H, CO2CH3), 5.29 (s,
2 H, 4-H/5-H), 5.78 (d, J ) 15.4 Hz, 1 H, 2′′-H), 6.19 (dd, J )
15.4, 10.0 Hz, 1 H, 1′′-H), 7.25-7.32 (m, 20 H, Ar-H); 13C NMR
(CDCl3, 125 MHz) δ ∼4 (br, C-1′), 14.1 (C-3′), 21.1 (C-2′), 51.3
(CPh2OCH3), 51.8 (CO2CH3), 77.7 (C-4/C-5), 83.3 (CPh2OCH3),
117.7 (C-2′′), 127.4, 127.4, 127.6, 127.9, 128.4, 129.7, 141.0,
141.1 (Ar-C), 153.9 (C-1′′), 167.0 (CO2CH3). Anal. Calcd for
C
37H37BO6 (588.50): C, 75.51; H, 6.34. Found: C, 75.66; H,
6.52.
P r ep a r a tion of (1′R,2′R,4R,5R)-2-{2-[(E)-2-Hyd r oxy-
Trimethyl phosphonoacetate (1.17 g, 6.45 mmol) was added
to a suspension of NaH (258 mg, 6.45 mmol, 60% in paraffin)
in THF (50 mL) at 0 °C. After 1 h the mixture was treated
with a solution of aldehyde 5 in THF (10 mL). Stirring was
continued for 12 h at room temperature. The crude product
was obtained after addition of saturated aqueous NH4Cl
solution, extraction of the aqueous layer with Et2O, washing
of the combined organic layer with brine, drying over anhy-
drous MgSO4, and evaporation of the solvent. Flash-column
m et h ylet h en yl]cyclop r op yl}-4,5-b is[m et h oxyd ip h en yl-
m eth yl]-1,3,2-d ioxa bor ola n e 11. The same procedure was
followed as described above for the synthesis of alcohol 7.
Starting from cyclopropylboronic ester 10 (1.40 g, 2.38 mmol),
we obtained the product 10 as a colorless foam (1.29 g, 2.31
mmol, 97%).

9198 J . Org. Chem., Vol. 65, No. 26, 2000
Luithle and Pietruszka
Softening range ) 83-87 °C; [R]21D ) -83.5 (c 0.82, CHCl3);
IR (film) 3392 cm-1; MS [EI, 70 eV] m/z 560 (<0.1) [M+], 528
(1.5) [(M - CH3OH)+], 197 (100) [(Ph2COCH3)+]; 1H NMR
(CDCl3, 500 MHz) δ -0.44(ddd, J ) 10.1, 6.6, 5.3 Hz, 1 H,
1′-H), 0.32 (ddd, J ) 7.8, 6.6, 3.5 Hz, 1 H, 3′-Htrans), 0.41 (ddd,
J ) 10.1, 5.1, 3.5 Hz, 1 H, 3′-Hcis), 1.22 (t, J ) 7.0 Hz, 1 H,
OH), 1.35 (dddd, J ) 8.9, 7.8, 5.3, 5.1 Hz, 1 H, 2′-H), 3.01 (s,
6 H, CPh2OCH3), 3.98-4.03 (m, 2 H, CH2OH), 5.02 (ddt, J )
15.2, 8.9, 1.3 Hz, 1 H, 1′′-H), 5.28 (s, 2 H, 4-H/5-H), 5.62 (dt, J
) 15.2, 6.2 Hz, 1 H, 2′′-H), 7.25-7.32 (m, 20 H, Ar-H); 13C
NMR (CDCl3, 125 MHz) δ ∼2.2 (br, C-1′), 12.6 (C-3′), 20.5
(C-2′), 51.7 (CPh2OCH3), 63.6 (CH2OH), 77.5 (C-4/C-5), 83.2
(CPh2OCH3), 126.5, 127.2, 127.5, 127.8, 128.4, 128.7 (Ar-C),
126.5 (C-1′′), 137.0 (C-2′′), 141.1, 141.2 (Ar-C). Anal. Calcd for
brine, drying over MgSO4, and evaporation of the solvents
under reduced pressure, the crude product was obtained.
Purification by flash-column chromatography (petroleum ether/
diethyl ether, 95:5) yielded (1.04 g, 1.28 mmol, 98%) a colorless
foam.
Softening range ) 65-75 °C; [R]21D ) -91.2 (c 2.04, CHCl3);
IR (film) 3060, 1077 cm-1; MS [FAB, NBA+NaI] m/z 835 (4)
1
[(M + Na)+], 197 (100) [(Ph2COCH3)+]; H NMR (CDCl3, 500
MHz) δ -0.81 (ddd, J ) 9.9, 6.1, 5.9 Hz, 1 H, 1′-H), -0.26 (ddd,
J ) 7.9, 6.1, 3.4 Hz, 1 H, 3′-Htrans), 0.07 (ddd, J ) 9.9, 5.6, 3.4
Hz, 1 H, 3′-Hcis), 0.01-0.09 (m, 2 H, 3′′-Ha/3′′Hb), 0.53 (dddd,
J ) 8.5, 5.3, 4.5, 4.4 Hz, 1 H, 1′′-H), 0.63 (mc, 1 H, 2′′-H), 0.75
(dddd, J ) 7.9, 5.9, 5.6, 4.5 Hz, 1 H, 2′-H), 0.98 (s, 9 H,
(CH3)3C), 2.98 (s, 6 H, OCH3), 3.37 (dd, J ) 10.7, 6.2 Hz, 1 H,
1′′′-Ha), 3.46 (dd, J ) 10.7, 5.9 Hz, 1 H, 1′′′-Hb), 5.22 (s, 2 H,
4-H/5-H), 7.23-7.70 (m, 30 H, Ar-H); 13C NMR (CDCl3, 125
MHz) δ ∼ -2 (br, C-1′), 7.4 (C-3′′), 9.8 (C-3′), 18.5(C-1′′), 18.8
(C-2′′), 19.1 ((CH3)3C), 19.2 (C-2′), 26.9 ((CH3)3C), 51.7 (OCH3),
67.0 (C-1′′′), 77.4 (C-4/C-5), 83.4 (CPh2OCH3), 127.2, 127.2,
127.5, 127.6, 127.7, 127.8, 128.4, 129.5, 129.6, 129.7 134.8,
135.5, 134.1, 134.1, 141.3, 141.4 (Ar-C). Anal. Calcd for
C
36H37BO5 (560.49): C, 77.14; H, 6.65. Found: C, 77.18; H,
6.76.
P r ep a r a tion of (4R,5R,1′R,2′R,1′′S,2′′R)-2-{2-[2-Hy-
d r oxym e t h ylcyclop r op yl]cyclop r op yl}-4,5-b is[m e t h -
oxyd ip h en ylm eth yl]-1,3,2-d ioxa bor ola n e 12 a n d (4R,-
5R,1′R,2′R,1′′R,2′′S)-2-{2-[2-Hyd r oxym eth ylcyclop r op yl]-
cyclop r op yl}-4,5-b is[m et h oxyd ip h en ylm et h yl]-1,3,2-d i-
oxa bor ola n e 12a . To a stirred solution of alkenylboronic ester
11 (6.74 g, 12.0 mmol) and bis(sulfonamide) 13 (509 mg, 1.21
mmol) in CH2Cl2 (36 mL) was added diethyl zinc (12.0 mL of
a 1 M solution in hexane) at 0 °C. After 10 min, the mixture
was transferred to a second flask containing freshly prepared
ZnI2 (from 6.22 g iodine and 12.3 mL of diethyl zinc solution
[1 M in hexane]) in CH2Cl2 (120 mL). The suspension was
stirred for 5 min at 0 °C, and was then added to a third flask
with a preformed reagent [2.03 mL (24.1 mmol) CH2I2 dis-
solved in CH2Cl2 (265 mL) and treated with diethyl zinc
solution (12.0 mL of a 1 M solution in hexane) at 0 °C] for the
cyclopropanation. Stirring was continued for 12 h at room
temperature. After quenching the reaction with saturated
aqueous NH4Cl (120 mL), the aqueous layer was extracted
with diethyl ether. The combined organic layer was dried over
MgSO4, and the solvents were removed under reduced pres-
sure. The crude product was purified by flash-column chro-
matography (petroleum ether/ethyl acetate 80:20). Yield: 6.29
g (11.0 mmol, 91%), dr 12:12a , 92:8; with bis(sulfonamid) ent-
13 (instead of 13), a diastereomeric ratio of dr 12:12a , 45:55
was obtained. The desired diastereomer 12 could be isolated
and further purified by MPLC (petroleum ether/ethyl acetate
80:20). The first eluted minor diastereomer 12a could not be
fully purified; the 13C NMR data were obtained from the
mixture (1H NMR data were ambiguous).
C
53H57BO5Si (812.91): C, 78.31; H, 7.07. Found: C, 77.92; H,
7.23.
P r ep a r a tion of (4R,5R,1′R,2′R,1′′S,2′′R)-2-{2-[2-(Ben -
zyloxym et h yl)cyclop r op yl]cyclop r op yl}-4,5-b is(m et h -
oxyd ip h en ylm eth yl)-1,3,2-d ioxa bor ola n e 14b. NaH (251
mg, 6.26 mmol, 60% in paraffin) was slowly added to a stirred
solution of bicyclopropane 12 (3.00 g, 5.22 mmol) in DMF
(5 mL) at room temperature. Benzyl bromide (744 µL, 1.07 g,
6.26 mmol) was syringed into the reaction flask, and stir-
ring was continued for 48 h. The mixture was diluted with
Et2O, the aqueous layer separated, the organic layer washed
with brine and dried over MgSO4, and the solvents were
evaporated under reduced pressure. The crude product was
purified by flash-column chromatography (petroleum ether/
ethyl acetate, 95:5). Yield 2.62 g (3.94 mmol, 76%) of a colorless
foam.
Softening range ) 60-65 °C; [R]21D ) -118 (c 0.57, CHCl3);
IR (film) 3062, 1075 cm-1; MS [FAB, NBA+NaI] m/z 687 (4)
1
[(M + Na)+], 197 (100) [(Ph2COCH3)+]; H NMR (CDCl3, 500
MHz) δ -0.75 (ddd, J ) 9.8, 6.2, 5.8 Hz, 1 H, 1′-H), -0.07
(ddd, J ) 7.9, 6.2, 3.5 Hz, 1 H, 3′-Htrans), 0.10 (ddd, J ) 9.8,
5.4, 3.5 Hz, 1 H, 3′-Hcis), 0.16 (mc, 2 H, 3′′-Ha/3′′Hb), 0.56 (dddd,
J ) 7.0, 6.2, 4.6, 4.5 Hz, 1 H, 1′′-H), 0.71 (mc, 1 H, 2′′-H), 0.81
(dddd, J ) 7.9, 5.8, 5.4, 4.6 Hz, 1 H, 2′-H), 2.98 (s, 6 H, OCH3),
3.15 (dd, J ) 10.4, 7.0 Hz, 1 H, 1′′′-Ha), 3.25 (dd, J ) 10.4, 6.6
Hz, 1 H, 1′′′-Hb), 4.44 (s, 2 H, OCH2Ph), 5.23 (s, 2 H, 4-H/5-H),
7.23-7.34 (m, 25 H, Ar-H); 13C NMR (CDCl3, 125 MHz) δ ∼
-1.5 (br, C-1′), 8.0 (C-3′′), 9.7 (C-3′), 16.6 (C-2′′), 19.2 (C-1′′),
19.2 (C-2′), 51.7 (OCH3), 72.2 (OCH2Ph), 73.8 (C-1′′′), 77.4 (C-
4/C-5), 83.2 (CPh2OCH3), 127.2, 127.2, 127.4, 127.4, 127.6,
127.8, 128.3, 128.4, 129.7, 138.6, 141.2, 141.3 (Ar-C). Anal.
Calcd for C44H45BO5 (664.64): C, 79.51; H, 6.82. Found: C,
79.43; H, 6.87.
12: Softening range ) 83-86 °C; [R]21 ) -127 (c 0.76,
D
CHCl3); IR (film) 3384 cm-1; MS [FAB, NBA+NaI] m/z 597
1
(10) [(M + Na)+], 197 (100) [(Ph2COCH3)+]; H NMR (CDCl3,
500 MHz) δ -0.77 (ddd, J ) 9.9, 6.2, 5.7 Hz, 1 H, 1′-H), -0.06
(ddd, J ) 7.9, 6.2, 3.4 Hz, 1 H, 3′-Htrans), 0.09 (ddd, J ) 9.9,
5.4, 3.4 Hz, 1 H, 3′-Hcis), 0.16 (mc, 2 H, 3′′-Ha/3′′Hb), 0.56 (dddd,
J ) 8.5, 5.6, 4.5, 4.5 Hz, 1 H, 1′′-H), 0.69 (mc, 1 H, 2′′-H), 0.80
(dddd, J ) 7.9, 5.7, 5.4, 4.5 Hz, 1 H, 2′-H), 1.39 (br s, 1 H,
OH), 2.98 (s, 6 H, OCH3), 3.29 (dd, J ) 11.2, 7.1 Hz, 1 H, 1′′′-
Ha), 3.33 (dd, J ) 11.2, 7.1 Hz, 1 H, 1′′′-Hb), 5.23 (s, 2 H, 4-H/
5-H), 7.21-7.32 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
δ ∼ -1.5 (br, C-1′), 7.7 (C-3′′), 10.2 (C-3′), 19.09 (C-1′′), 19.1
(C-2′), 19.4 (C-2′′), 51.6 (OCH3), 66.8 (C-1′′′), 77.4 (C-4/C-5),
83.4 (CPh2OCH3), 127.2, 127.2, 127.4, 127.8, 128.4, 129.7,
141.2, 141.3 (Ar-C). Anal. Calcd for C37H39BO5 (574.51): C,
77.35; H, 6.84. Found: C, 76.99; H, 6.99.
P r ep a r a t ion of (1′R,2′R,1′′S,2′′R)-2-{2-[2-(ter t-Bu t yl-
d ip h en ylsiloxym eth yl)cyclop r op yl]cyclop r op yl}-1,3,2-d i-
oxa bor in a n e 15a . LiAlH4 (114 mg, 3 mmol) was slowly added
to a stirred solution of dioxaborolane 14a (813 mg, 1.00 mmol)
in THF (10 mL) at room temperature. After 2 h, the starting
material was consumed (as judged by TLC). The reaction was
carefully quenched with saturated aqueous NH4Cl solution (10
mL) and the reaction mixture filtered through silica gel. With
petroleum ether/ethyl acetate 80:20 the diol 1 was eluted first,
changing the solvent system to ethyl acetate allowed the
separation of the crude boronic acid. After evaporation of the
solvent under reduced pressure, pentane (5 mL) and 1,3-
propanediol (73 µL, 77 mg, 1.0 mmol) were added. After 12 h
at room temperature, the clear solution was dried over MgSO4.
Evaporation of the solvents under reduced pressure and finally
in a kugelrohr apparatus yielded 376 mg (0.87 mmol, 87%) of
product 15a as a colorless oil.
12a : 13C NMR (CDCl3, 125 MHz) δ ∼ -1.5 (br, C-1′), 7.9
(C-3′′), 10.5 (C-3′), 19.08 (C-1′′), 19.1 (C-2′), 19.2 (C-2′′), 51.57
(OCH3), 66.78 (C-1′′′), 77.4 (C-4/C-5), 83.4 (CPh2OCH3), 127.2,
127.2, 127.45, 127.75, 128.4, 129.7, 141.2, 141.3 (Ar-C).
P r ep a r a tion of (4R,5R,1′R,2′R,1′′S,2′′R)-2-{2-[2-(ter t-Bu -
tyld ip h en ylsiloxym eth yl)cyclop r op yl]cyclop r op yl}-4,5-
bis(m et h oxyd ip h en ylm et h yl)-1,3,2-d ioxa b or ola n e 14a .
Imidazole (97.0 mg, 1.41 mmol) and then t-BuPh2SiCl (373 mg,
1.36 mmol) were slowly added to a stirred solution of bicyclo-
propane 12 (740 mg, 1.29 mmol) in CH2Cl2 (5 mL) at 0 °C. A
voluminous precipitate formed. After 5 h, the reaction was
quenched with H2O, the organic layer separated, and the
aqueous layer extracted with pentane. After washing with
[R]21 ) -62.0 (c 0.43, CHCl3); IR (film) 3025, 1095 cm-1
;
D
MS [FAB, NBA+NaI] m/z 377 (4) [(M-C4H9)+]; 1H NMR
(CDCl3, 500 MHz) δ -0.56 (ddd, J ) 9.5, 6.2, 5.9 Hz, 1 H, 1′-
H), 0.18 (mc, 2 H, 3′′-H), 0.25 (ddd, J ) 9.5, 5.2, 3.2 Hz, 1 H,

Efficient Protecting Group for Boronic Acids
J . Org. Chem., Vol. 65, No. 26, 2000 9199
3′-Hcis), 0.27 (ddd, J ) 7.9, 6.2, 3.2 Hz, 1 H, 3′-Htrans), 0.65 (mc,
1 H, 1′′-H), 0.80 (mc, 1 H, 2′′-H), 0.93 (mc, 1 H, 2′-H), 1.09 (s,
9 H, (CH3)3C), 1.88 (q, J ) 5.5 Hz, 2 H, 5-H), 3.39 (t, J ) 5.5
Hz, 4 H, 4-H/6-H), 3.47 (dd, J ) 10.7, 6.3 Hz, 2 H, 1′′′-H), 7.23-
7.63 (m, 10 H, Ar-H); 13C NMR (CDCl3, 125 MHz) δ ∼ -4.0
(br, C-1′), 7.7 (C-3′′), 9.1 (C-3′), 18.6 (C-2′), 18.9 (C-1′′), 19.2
((CH3)3C), 19.3 (C-2′′), 26.9 ((CH3)3C), 27.4 (C-5), 61.6 (C-4/C-
6), 67.1 (C-1′′′), 127.5, 129.4, 135.6, 134.1 (2 x) (Ar-C). Anal.
Calcd for C26H35BO3Si (434.45): C, 71.88; H, 8.12. Found: C,
71.81; H, 8.08.
125 MHz) δ 8.0 (C-3′ or C-3′′), 8.3 (C-3′ or C-3′′), 17.0 (C-1′′ or
C-2′), 18.0 (C-1′ or C-2′′), 19.9 (C-1′′ or C-2′), 19.9 (C-1′ or C-2′′),
66.8 (C-1), 72.4 (OCH2Ph), 73.9 (C-1′′′), 127.50, 127.63, 128.3,
138.5 (Ar-C). Anal. Calcd for C15H20O2 (232.32): C, 77.55; H,
8.68. Found: C, 76.12; H, 8.62.
P r ep a r a tion of (4R,5R,1′R,2′R,1′′S,2′′R)-2-{2-[2-Iod ocy-
clopr opyl]cyclopr opyl}-4,5-bis[m eth oxydiph en ylm eth yl]-
1,3,2-d ioxa bor ola n e 18. RuCl3‚3H2O (16 mg, 61 µmol) was
added to a vigorously stirred mixture of alcohol 12 (690 mg,
1.20 mmol) and NaIO4 (771 mg, 3.60 mmol) in 7 mL of CCl4/
H2O/CH3CN (2:3:2) at room temperature. After 3 h, the
starting material was consumed (as judged by TLC).). The
reaction was quenched with saturated aqueous NH4Cl solution
(20 mL). Extraction with ethyl acetate, drying of the organic
layer with Na2SO4, filtration, and evaporation of the solvents
under reduced pressure furnished the crude product. Filtration
through a pad of silica gel (petroleum ether to ethyl acetate)
yielded a solid (556 mg, 0.95 mmol, 79%) that was directly
subjected to the next transformation.
P r ep a r a tion of (1′R,2′R,1′′S,2′′R)-2-{2-[2-(Ben zyloxy-
m eth yl)cyclopr opyl]cyclopr opyl}-1,3,2-dioxabor in an e 15b.
The same procedure as described for the synthesis of dioxa-
borinane 15a was followed: 3.13 g (4.71 mmol) dioxaborolane
14b gave 1.26 g (4.40 mmol, 94%) of product 15b as a colorless
oil.
[R]21 ) -89.1 (c 1.62, CHCl3); IR (film) 3064, 1098 cm-1
;
D
MS [EI, 70 eV] m/z 286 (1) [(M)+], 91 (100) [(C7H7)+]; 1H NMR
(CDCl3, 500 MHz) δ -0.56 (ddd, J ) 9.5, 6.2, 5.9 Hz, 1 H, 1′-
H), 0.26-0.37 (m, 3 H, 3′-Hcis/3′′-H), 0.50 (ddd, J ) 7.9, 6.4,
3.2 Hz, 1 H, 3′-Htrans), 0.71 (mc, 1 H, 1′′-H), 0.92 (mc, 1 H, 2′′-
H), 0.96 (mc, 1 H, 2′-H), 1.91 (q, J ) 5.5 Hz, 2 H, 5-H), 3.25
(dd, J ) 10.4, 7.0 Hz, 1 H, 1′′′-Ha), 3.36 (dd, J ) 10.4, 6.6 Hz,
1 H, 1′′′-Hb), 3.93 (t, J ) 5.5 Hz, 4 H, 4-H/6-H), 4.53 (m, 2 H,
OCH2Ph), 7.26-7.36 (m, 5 H, Ar-H); 13C NMR (CDCl3, 125
MHz) δ ∼ -4.0 (br, C-1′), 8.5 (C-3′′), 9.2 (C-3′), 17.3 (C-2′′),
18.9 (C-2′), 19.9 (C-1′′), 27.6 (C-5), 61.8 (C-4/C-6), 72.5 (OCH2-
Ph), 74.3 (C-1′′′), 127.6, 127.9, 128.6, 138.9 (Ar-C). Anal. Calcd
for C17H23BO3 (286.17): C, 71.35; H, 8.10. Found: C, 71.31;
H, 8.11.
Softening range ) 83-86 °C; [R]20D ) -136 (c 0.40, CHCl3);
IR (film) 3410 (br), 1725, 1358, 1060 cm-1; MS [FAB, NBA+NaI]
1
m/z 611 (14) [(M + Na)+], 197 (100) [(Ph2COCH3)+]; H NMR
(CDCl3, 500 MHz) δ -0.68 (ddd, J ) 10.0, 6.4, 5.6 Hz, 1 H,
1′-H), -0.04 (ddd, J ) 7.8, 6.4, 3.8 Hz, 1 H, 3′-Htrans), 0.15 (ddd,
J ) 10.0, 5.6, 3.8 Hz, 1 H, 3′-Hcis), 0.59 (ddd, J ) 8.2, 6.6, J
4.4 Hz, 1 H, 3′′-Htrans), 0.79 (dddd, J ) 7.8, 5.6, 5.6, 4.9 Hz, 1
H, 2′-H), 1.01 (ddd, J ) 9.2, 4.6, 4.4 Hz, 1 H, 3′′-Hcis), 1.24
(ddd, J ) 8.2, 4.6, 3.9 Hz, 1 H, 2′′-H), 1.34 (dddd, J ) 9.2, 6.6,
4.9, 3.9 Hz, 1 H, 1′′-H), 2.99 (s, 6 H, OCH3), 5.25 (s, 2 H, 4-H/
5-H), 7.24-7.47 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
δ ∼ -1 (br, C-1′), 9.4 (C-3′), 13.8 (C-3′′), 18.6 (C-2′), 19.0
(C-2′′), 26.0 (C-1′′), 51.6 (OCH3), 77.4 (C-4/C-5), 83.2 (CPh2-
OCH3), 127.2, 127.3, 127.5, 127.8, 128.3, 129.7, 141.2, 141.2
(Ar-C), 180.2 (COOH). Anal. Calcd for C37H39BO5 (574.51): C,
77.35; H, 6.84. Found: C, 76.99; H, 6.99.
P r ep a r a tion of (1′R,2′R,1′′S,2′′R)-2-{2-[2-(ter t-Bu tyld i-
p h e n ylsiloxym e t h yl)cyclop r op yl]cyclop r op yl}m e t h -
a n ol 16a . Dioxaborolane 14a (602 mg, 0.74 mmol) was con-
verted to dioxaborinane 15a . The crude product and CH2ClI
(163 µL, 391 mg, 2.23 mmol) in THF (5 mL) was cooled to -78
°C. t-BuLi (2.84 mL of a 1.5 M solution in Et2O, 4.26 mmol)
was slowly added, and the temperature kept for 30 min before
warming to room temperature. Stirring was continued for 48
h. The reaction was quenched with a mixture of a saturated
KHCO3 solution (10 mL) and H2O2 (2 mL of a 40% aqueous
solution). After 1 h, the mixture was extracted with Et2O. The
organic layer was separated and dried over MgSO4, and the
solvents were removed under reduced pressure. The pure
product 16a was isolated after flash-column chromatography
(petroleum ether/ethyl acetate 80:20) and MPLC (petroleum
ether/ethyl acetate 85:15). Yield 169 mg (0.44 mmol, 60%) as
a colorless oil.
Protected from light, a mixture containing the carboxylic
acid 17 (556 mg, 0.95 mmol), DCC (586 mg, 2.84 mmol), DMAP
(231 mg, 1.89 mmol), CHI3 (1.12 g, 2.84 mmol), 2-mercapto-
pyridine N-oxide (361 mg, 2.84 mmol), and cyclohexene (15
mL) was first stirred for 2 h at room temperature and then
refluxed for 14 h. The solids were filtered off and washed with
Et2O. The organic layer was washed with saturated aqueous
NH4Cl solution, dried over MgSO4, and filtered, and the
solvents were removed under reduced pressure. Purification
by flash-column chromatography (petroleum ether/ethyl ac-
etate, 98:2) and MPLC (petroleum ether/ethyl acetate, 99:1)
furnished 264 mg (0.39 mmol, 42%) of the slightly impure title
compound 18.
[R]20 ) -41.2 (c 2.82, CHCl3); IR (film) 3336, 3069 cm-1
;
D
MS [CI, NH3] m/z 398 (25) [(M + NH4)+], 363 (100) [(M -
OH)+]; 1H NMR (CDCl3, 500 MHz) δ 0.17-0.24 (m, 2 H, 3′-H),
0.25-0.31 (m, 2 H, 3′′-H), 0.64 (m, 1H, 1′′-H), 0.69 (m, 1H,
2′-H), 0.77 (mc, 1H, 2′′-H), 0.81 (mc, 1 H, 1′-H), 1.02 (s, 9 H,
C(CH3)3), 1.19 (t, J ) 5.8 Hz, 1H, OH), 3.33-3.42 (m, 2 H,
1-Ha/1-Hb), 3.38 (dd, J ) 10.7, 6.8 Hz, 1H, 1′′′-Ha), 3.57 (dd, J
) 10.7, 5.8 Hz, 1H, 1′′′-Hb), 7.34-7.66 (m, 10 H, Ar-H); 13C
NMR (CDCl3, 125 MHz) δ 8.0 (C-3′), 8.2 (C-3′′), 17.7 (C-1′′),
18.1 (C-2′), 19.2 (C(CH3)3), 19.3 (C-2′′), 19.7 (C-1′), 26.8
(C(CH3)3), 66.9 (C-1), 67.0 (C-1′′′), 127.5, 129.5, 135.6, 134.0,
134.0 (Ar-C). Anal. Calcd for C24H32O2Si (380.59): C, 75.74;
H, 8.47. Found: C, 75.96; H, 8.54.
Softening range ) 75-85 °C; [R]20D ) -98.5 (c 0.96, CHCl3);
IR (film) 3059, 1076 cm-1; MS [FAB, NBA+NaI] m/z 693 (10)
[(M + Na)+], 197 (100) [(Ph2COCH3)+]; HRMS: calcd. for
C
36H36BINaO4 [(M + Na)+] 693.1646; found: 693.1646. 1H
NMR (CDCl3, 500 MHz) δ -0.71 (ddd, J ) 9.9, 6.3, 5.8 Hz, 1
H, 1′-H), -0.07 (ddd, J ) 7.9, 6.3, 3.7 Hz, 1 H, 3′-Htrans), 0.06
(ddd, J ) 9.9, 5.3, 3.7 Hz, 1 H, 3′-Hcis), 0.59 (ddd, J ) 7.8, 6.2,
6.2 Hz, 1 H, 3′′-Htrans), 0.65 (ddd, J ) 9.2, 6.2, 4.6 Hz, 1 H,
3′′-Hcis), 0.78 (dddd, J ) 7.9, 5.8, 5.3, 4.8 Hz, 1 H, 2′-H), 1.07
(dddd, J ) 9.2, 6.2, 4.8, 3.9 Hz, 1 H, 1′′-H), 1.93 (ddd, J ) 7.8,
4.6, 3.9 Hz, 1 H, 2′′-H), 2.97 (s, 6 H, OCH3), 5.23 (s, 2 H, 4-H/
5-H), 7.21-7.29 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
-16.4 (C-2′′), ∼ -2 (br, C-1′), 9.2 (C-3′), 14.3 (C-3′′), 18.7
(C-2′), 25.6 (C-1′′), 51.7 (OCH3), 77.6 (C-4/C-5), 83.2 (CPh2-
OCH3), 127.2, 127.6, 127.8 (2 x), 128.4, 129.7, 141.2, 141.2 (Ar-
C). Anal. Calcd for C36H36BIO4 (670.38): C, 64.50; H, 5.41.
Found: C, 65.49; H, 5.89.
P r epar ation of (1′R,2′R,1′′S,2′′R)-2-{2-[2-(Ben zyloxym eth -
yl)cyclop r op yl]cyclop r op yl}m eth a n ol 16b. The same pro-
cedure as described for the synthesis of bicyclopropane 16a
was followed: 1.21 g (4.23 mmol) dioxaborinane 15b gave 710
mg (3.06 mmol, 72%) of slightly impure product 16b as a
colorless oil after a single chromatographic separation (silica
gel, petroleum ether/ethyl acetate 80:20).
P r ep a r a tion of (1′R,2′R,1′′S,2′′R)-2-[2-(ter t-Bu tyld i-
p h en ylsiloxym eth yl)cyclop r op yl]cyclop r op ylben zol 20.
Dioxaborinane 15a (265 mg, 0.61 mmol) was dissolved in DME
(7 mL). After addition of Pd(PPh3)4 (70 mg, 61 µmol) and
KOtBu (1.22 mL of a 1 M solution in tBuOH), the mixture
was carefully deoxygenated by freeze technique. Phenyliodide
(68.0 mL, 124 mg, 0.61 mmol) was added. After 50 h at 80 °C,
the mixture was treated with H2O and extracted with diethyl
ether. The organic layer was washed with brine and dried
(MgSO4), the solvent removed under reduced pressure, and
[R]19 ) -73.4 (c 0.37, CHCl3); IR (film) 3388, 3064 cm-1
;
D
MS [FAB, NBA+NaI] m/z 255 (100) [(M + Na)+]; HRMS:
Calcd for C15H20NaO2 [(M + Na)+] 255.1361; found: 255.1357.
1H NMR (CDCl3, 500 MHz) δ 0.30-0.38 (m, 4 H, 3′-H/3′′-H),
0.76-0.82 (m, 2 H, 1′′-H/2′-H), 0.86-0.93 (m, 1H, 1′-H/2′′-H),
1.39 (br, 1H, OH), 3.28-3.33 (m, 2 H, 1′′′-Ha/1′′′-Hb or 1-Ha/
1-Hb), 3.40-3.47 (m, 2 H, 1′′′-Ha/1′′′-Hb or 1-Ha/1-Hb), 4.53 (m,
2 H, OCH2Ph), 7.27-7.35 (m, 5 H, Ar-H); 13C NMR (CDCl3,

9200 J . Org. Chem., Vol. 65, No. 26, 2000
Luithle and Pietruszka
the crude product purified (after filtration through silica gel)
by means of MPLC (petroleum ether/ethyl acetate 95:5). The
product 20 (205 mg, 0.48 mmol, 79%) was obtained as color-
less oil.
Ack n ow led gm en t. Financial support by the Fonds
der Chemischen Industrie (Liebig-fellowship to J .P. and
doctoral fellowship to J .E.A.L.) and the Deutschen
Forschungsgemeinschaft (fellowship for J .P.) is grate-
fully acknowledged. We also thank the Institut fu¨r
Organische Chemie der Universita¨t Stuttgart (Prof. Dr.
Dr. h. c. F. Effenberger and Prof. Dr. V. J a¨ger), the
Bayer AG (Wuppertal), Aventis Pharma Deutschland
GmbH (Frankfurt/Main), Novartis AG (Basel), the Boe-
hringer Ingelheim KG (Biberach), the Degussa AG
(Hanau), and the Clariant GmbH (Frankfurt/Main) for
their support.
[R]20 ) -93.3 (c 0.61, CHCl3); IR (film) 2980, 1065 cm-1
;
D
MS [EI, 30 eV] m/z 426 (35) [(M)+], 369 (100) [(M - C4H9)+];
1H NMR (CDCl3, 500 MHz) δ 0.26 (ddd, J ) 8.4, 5.2, 4.9 Hz,
1 H, 3′-Ha), 0.28 (ddd, J ) 8.2, 5.3, 4.9 Hz, 1 H, 3′-Hb), 0.72
(ddd, J ) 8.8, 5.8, 4.9 Hz, 1 H, 3-Hcis), 0.77 (mc, 1 H, 1′-H),
0.78 (ddd, J ) 8.6, 5.1, 4.9 Hz, 1 H, 3-Htrans), 0.89 (mc, 1 H,
2′-H), 1.03 (s, 9 H, (C(CH3)3), 1.08 (dddd, J ) 8.6, 5.1, 5.1, 4.6
Hz, 1 H, 2-H), 1.60 (ddd, J ) 8.8, 5.1, 5.1 Hz, 1 H, 1-H), 3.42
(dd, J ) 10.7, 6.7 Hz, 1 H, 1′′-Ha), 3.62 (dd, J ) 10.7, 5.8 Hz,
1 H, 1′′-Hb), 6.98-7.66 (m, 10 H, Ar-H); 13C NMR (CDCl3, 125
MHz) δ 7.8 (C-3′), 14.1 (C-3), 18.4 (C-1′), 19.2 (C(CH3)3), 19.5
(C-2′), 22.0 (C-1), 24.8 (C-2), 26.9 (C(CH3)3), 67.1 (C-1′′), 125.2,
125.6, 127.2, 127.6, 129.5, 135.6, 134.0, 134.1, 143.6 (Ar-C).
Anal. Calcd for C29H34OSi (426.67): C, 81.64; H, 8.03. Found:
C, 81.55; H, 8.06.
Su p p or tin g In for m a tion Ava ila ble: Crystallographic
data for compound 10; NMR spectra of 7, 16b, and 18; full
data for 4a , 10a , 11a , and 16c. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O0056601