Enantiomerically pure cyclopropylboronic esters: Auxiliary-versus substrate-control

Article abstract of DOI:10.1039/b006970l

Stable, enantiomerically pure cyclopropylboronic esters are synthesized from alkynes by a hydroboration-cyclopropanation sequence. The direct hydroboration-utilizing 1,3,2-dioxaborolane 4-is most convenient, however, with more functionalized side-chains it failed to give the desired intermediates. Using the more reactive dicyclohexylborane, followed by oxidation and transesterification, is a good alternative one-pot conversion. Cyclopropanations were performed either following a Simmons-Smith protocol or with diazomethane-palladium(II) acetate. The influence on the diastereoselectivity of the auxiliary 1 is compared with the influence of an additional stereogenic center in the side-chain.

Full text of DOI:10.1039/b006970l

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Enantiomerically pure cyclopropylboronic esters: auxiliary- versus
substrate-control
Jörg Pietruszka* and Andreas Witt
1
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart,
Germany
Received (in Cambridge, UK) 29th August 2000, Accepted 19th October 2000
First published as an Advance Article on the web 1st December 2000
Stable, enantiomerically pure cyclopropylboronic esters are synthesized from alkynes by a hydroboration–
cyclopropanation sequence. The direct hydroboration—utilizing 1,3,2-dioxaborolane 4—is most convenient,
however, with more functionalized side-chains it failed to give the desired intermediates. Using the more reactive
dicyclohexylborane, followed by oxidation and transesterification, is a good alternative one-pot conversion.
Cyclopropanations were performed either following a Simmons–Smith protocol or with diazomethane–palladium()
acetate. The influence on the diastereoselectivity of the auxiliary 1 is compared with the influence of an additional
stereogenic center in the side-chain.
anhydrous trimethylamine N-oxide22–24 and transesterification
of the intermediates 7 with diol 1 to the alkenylboronic esters
5c–e (Scheme 1). Although branched alkynes could also be
Introduction
Cyclopropylboronic esters have attracted considerable interest
as general building blocks for cyclopropanes. Since the first
reports of their successful synthesis,1–4 various groups proved
the versatility of this approach, e.g. by demonstrating that the
Suzuki coupling of these boron intermediates is possible.5–15
Furthermore, after the first diastereoselective cylopropanations
by Imai et al.,16 new auxiliaries, e.g. 1, were developed that
would increase the stability of the cyclopropylboronic esters 2
thus allowing chromatographic separations of the diastereo-
isomers giving enantiomerically pure cis-17 or trans-
disubstituted11,18,19 cyclopropanes. A major set-back was the
lack of substrate generality; all model reactions with cyclopro-
pylboronic esters were usually performed with substrates with
no additional functional group or stereogenic centers in the
side-chain. We now present a detailed account closing this gap.
Results and discussion
We chose different protected propargyl alcohols 3 as model
compounds for this study. Direct hydroboration of alkynes with
1,3,2-dioxaborolane 4 is usually the method of choice to form
alkenylboronic esters, however, with functionalized alkynes 3
this changed. Whereas silyl protecting groups (compounds 3a/
b) did not interfere and the synthesis of the corresponding
alkenylboronic esters 5a/b was straightforward (route 1), ethers,
acetals and esters (compounds 3c–e) would not allow the
convenient formation of olefins 5c–e. In order to achieve
the desired transformations we chose a three-step, one-pot
sequence using the more reactive dicyclohexylborane (route 2),
a protocol that was first employed for various diols by Vaultier
et al.20 and Hoffmann and Dresely.21 The hydroboration to
vinylboranes 6 was followed by the selective oxidation with
Scheme 1 Synthesis of alkenylboronic esters 5.
successfully transformed, the diastereomeric products 8 could
not be obtained in pure form. We succeeded in separating
neither the common side-product 9—which was presumably
DOI: 10.1039/b006970l
J. Chem. Soc., Perkin Trans. 1, 2000, 4293–4300
This journal is © The Royal Society of Chemistry 2000
4293

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formed after incomplete consumption of dicyclohexylborane
in the first step—nor the diastereoisomers.
The cyclopropanation was performed with diazomethane–
palladium() acetate using our optimized reaction conditions
(Scheme 2).11 The yields were usually high (88–98%) and the
Scheme 3 Synthesis and hydroboration of alkyne 16.
Scheme 2 Synthesis of cyclopropanes 10 and 11.
diastereomeric ratios moderate to good (dr 66:34 to 86:14).
When starting with alkenylboronic ester 5b, we were surprised
to isolate not only the desired separated diastereoisomers
10b/11b, but also another unprecedented isomer 12. This is
explained by the presence of an additional compound in the
starting material whose structure could now be assigned to
regioisomer 13.
Next, we addressed the question of the influence of an
additional stereogenic center in the side-chain. Starting from
2,3-O-isopropylidene--glyceraldehyde 14,25–27 we first followed
a modified28 Corey–Fuchs29 sequence via the dibromoalkene 15
to alkyne 16 (Scheme 3). We found that the yields were poor,
but—even worse—we observed (not surprisingly) partial
racemization during the first step.28 This was proved by measur-
ing the optical rotation of all intermediates, and later by the
formation of diastereomeric hydroboration products. The most
convenient synthesis of alkyne 16 utilizes the Bestmann–Ohira
reagent 17.30–35 In a single step aldehyde 14 was converted (69%)
without racemization of the starting material.
The following hydroboration was performed by both routes
outlined in Scheme 1. Again, we found that the three-step,
one-pot sequence—introducing diol 1, ent-1 and pinacol in the
last step—was superior to the direct hydroboration, furnishing
alkenylboronic esters 18–20 in 50–80% yield. The only
side-product isolated was the cyclohexylboronic ester 9 (and
ent-9, when diol ent-1 was used; the corresponding pinacol
derivative was also detected, but could not be obtained).
All three alkenylboronic esters 18–20 were cyclopropanated
using our standard conditions (diazomethane–palladium()
acetate; method A) and the Simmons–Smith reaction,36–38 in
particular the Furukawa protocol (method B).39,40 Generally
speaking, method A led to higher yields (A: 88–95%; B: 58–
72%), but it was less selective as compared to method B (Fig. 1).
The influence of the additional stereogenic center in the
side-chain on the diastereomeric ratio depends on the method
used. Simplifying, the cyclopropanation with diazomethane
can be regarded as predominantly auxiliary-controlled, whereas
the Simmons–Smith reactions are substrate-controlled. It is
Fig. 1 Diastereoselective cyclopropanation of alkenylboronic esters
18–20.
important to note that just by changing the reaction conditions
for the transformation of olefin 18, the ratio of cyclopropyl-
boronic esters 21:22 could be reversed. Unfortunately, only the
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Table 1 Characteristic NMR data of cyclopropylboronic esters; assignment of their absolute configuration
R
Compound
2Ј-H
3Ј-Htrans
C-2Ј
C-3Ј
Compound
2Ј-H
3Ј-Htrans
C-2Ј
C-3Ј
TBSOCH2
TPSOCH2
BnOCH2
MOMOCH2
BzOCH2
Bun
10a11
10b
0.65
0.59
0.64
0.66
0.68
0.26
0.26
0.49
1.36
0.64
0.25
0.55
0.43
0.33
0.46
0.50
0.38
0.31
0.31
0.20
0.80
0.41
0.30
0.35
20.0
20.2
17.4
17.3
16.4
18.3
18.4
29.4
22.1
20.4
18.0
19.4
9.6
9.5
10.1
10.0
9.9
11.7
11.7
7.7
15.5
9.4
11a11
11b
0.99
0.91
1.00
1.01
1.00
0.57
0.57
0.59
1.74
1.00
0.58
0.81
0.08
Ϫ0.01
0.10
0.14
0.00
Ϫ0.06
Ϫ0.06
Ϫ0.26
0.43
0.06
Ϫ0.05
0.11
20.0
20.4
17.7
17.5
16.7
18.6
18.6
29.6
22.7
20.9
ndc
9.8
10.1
10.1
10.0
10.0
11.8
11.8
7.9
10c
11c
10d
10e
11d
11e
10f11
10g11
10h11
10i11
10j11
10k11
21
11f11
11g11
11h11
11i11
11j11
11k11
22
n-Pentyl
But
Ph
15.1
9.6
nd
HOCH2
TPSO(CH2)3
11.5
7.6
19.7
9.8
a
b
0.59
0.48
19.5
9.4
0.79
Ϫ0.04
19.9
7.7
a Obtained when the hydroboration–cyclopropanation sequence was performed with partially racemized alkyne 16; the NMR data are identical with
the enantiomeric compound 23. b Obtained when the hydroboration–cyclopropanation sequence was performed with partially racemized alkyne 16;
the NMR data are identical with the enantiomeric compound 24. c nd: not determined.
boronic esters 21–24 could be separated into the pure diastereo-
isomers; we were not able to perform this purification with the
pinacol-derived compounds 25/26.
Up to this point we took the assignment of the absolute
Conclusion
A sequence for the synthesis of a variety of enantiomerically
pure cyclopropylboronic esters 10/11 has been established. The
flexible approach allowed the isolation not only of products
with more functionalized side-chains, but also enabled the
investigation of the influence of additional stereogenic centers
in the substrate (18–20) on the diastereoselectivity. The
investigation proved that depending on the cyclopropanation
condition the reaction was either predominantly substrate-
configurations for granted. In fact, we have already shown that
1
the H NMR shifts for the 2Ј-H and the 3Ј-Htrans protons of
the cyclopropane moiety are diagnostic.11 As can be seen from
Table 1, all new compounds match perfectly in the series. Apart
from these characteristic relative high-field shifts of the 2Ј-H
protons and down-field shifts of the 3Ј-Htrans protons (major
controlled (Simmons–Smith protocol) or auxiliary-controlled
relative to minor diastereoisomer), the 13C NMR data are also
(diazomethane–palladium() acetate). The absolute configur-
to a certain extent diagnostic. In particular the C-2Ј carbons are
ations of all products were confirmed by means of characteristic
NMR data of the boronic esters or by chemical correlation.
As a consequence, an advanced intermediate 27 for the total
synthesis of solandelactones was isolated.
all shifted to high fields for the major diastereomers; the data
for the C-3Ј carbons are less reliable and depend on the nature
of the side-chain.
For the diastereoisomers 25 (26) we had no precedent to
establish the absolute configuration via the NMR data. Con-
sequently, we performed a chemical correlation. Transform-
Experimental
ation of boronic ester 25 by a Matteson homologation41 yielded
All reagents were used as purchased from commercial suppliers
without further purification. The alkynes 3 were synthesized
using standard procedures and the spectroscopic data were in
agreement with published data.46–49 Aldehyde 1425–27 and the
Bestmann–Ohira reagent 1730–35 were prepared according to the
references given. The reactions were carried out using standard
Schlenk techniques under a dry nitrogen atmosphere. Glass-
ware was oven-dried at 150 ЊC overnight. Solvents were dried
and purified by conventional methods prior to use; diethyl
ether, 1,2-dimethoxyethane, and tetrahydrofuran were freshly
distilled from sodium–benzophenone. Petroleum ether refers to
the fraction with a boiling point between 40 and 60 ЊC. Caution:
The generation and handling of diazomethane requires special
precautions.50–52 Flash-column chromatography: Merck silica
gel 60, 0.040–0.063 mm (230–400 mesh). TLC: Pre-coated
sheets, Alugram SIL G/UV254 Macherey–Nagel; detection by
UV extinction or by cerium molybdenum solution [phosphomo-
lybdic acid (25 g), Ce(SO4)2ؒH2O (10 g), conc. H2SO4 (60 mL),
H2O (940 mL)]. Preparative MPLC: Gilson (Spectrochrom),
with a packed column (49 × 500 mm), LiChroprep, Si60 (15–25
µm), and UV detector (259 nm). 1H and 13C NMR spectra were
recorded—at room temperature in CDCl3 unless otherwise
the primary alcohol 27, a product whose enantiomer had
Scheme 4 Determination of the absolute configuration of cyclopro-
pylboronic ester 25.
previously been reported (Scheme 4).42 No sequential insertion
was observed.43 The cyclopropane derivative 27 itself was pro-
posed to be a key intermediate for the construction of the
right hand fragment of solandelactones, e.g. solandelactone
E.44,45
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indicated—on a Bruker A 500. Chemical shifts δ are given in
ppm relative to resonances of the solvent (1H: CHCl3, 7.25
ppm; 13C: CDCl3, 77.0 ppm), coupling constants J are given in
hertz; in spectra of higher order δ and J values were not
corrected. 13C signals were assigned by means of C–H- and H–
H-COSY spectra. Microanalysis: performed at the Institut für
Organische Chemie, Stuttgart. Melting points (Büchi 510) were
not corrected. Specific rotations were measured at 21 ЊC unless
in CHCl3) (Found: C, 78.44; H, 6.45. C40H39BO5 requires C,
78.69; H, 6.44%); IR (film)/cmϪ1 3039, 3005, 1344 and 1061;
NMR δH (500 MHz; CDCl3) 2.92 (6 H, s, OMe), 3.86 (2 H, dd,
J 4.8 and 1.5, 1Љ-H), 4.33 (2 H, s, PhCH2O), 5.27 (1 H, dt, J 18.1
and 1.5, 1Ј-H), 5.28 (2 H, s, 4-H and 5-H), 6.17 (1 H, dt, J 18.1
and 4.8, 2Ј-H), 7.17–7.53 (25 H, m, ArH); δC (125 MHz;
CDCl3) 51.8 (OMe), 71.6 (C-1Љ), 71.9 (PhCH2O), 77.7 (C-4/C-
5), 83.8 (CPh2OMe), ~119 (br, C-1Ј), 127.3 (Ar), 127.3 (Ar),
127.5 (Ar), 127.6 (Ar), 127.6 (Ar), 127.8 (Ar), 128.3 (Ar),
128.5 (Ar), 129.7 (Ar), 138.2 (Ar), 141.1 (Ar), 141.4 (Ar), 148.7
(C-2Ј); m/z (FAB ϩ NaI) 633 (3%) [(M ϩ Na)ϩ] and 197 (100).
otherwise stated; [α]D values are given in 10Ϫ1 deg cm2 gϪ1
.
Preparation of alkenylboronic esters
General procedure A (route 1). Diol 1 (1 equiv.) was carefully
dried at 50 ЊC under reduced pressure for 1 h. Under an atmos-
phere of nitrogen, dichloromethane (1 mL per 2 mmol diol 1)
was added and the solution cooled to 0 ЊC. BH3ؒSMe2 complex
(1.2 equiv. of a 12 M solution in dimethyl sulfide) was added
dropwise with vigorous stirring, followed by refluxing the
mixture for 4 h. The solvent was removed, the reagent cooled
to 0 ЊC, and the alkyne (1.5 equiv.) slowly added. The flask
was closed with a septum, slowly heated to 120 ЊC and kept at
this temperature for 12 h. After cooling to room temperature
standard work-up followed,11,18,19 giving alkenylboronic esters.
The yields are given in Scheme 1; the reaction was typically
performed on a 1–2 mmol scale.
(4R,5R)-4,5-Bis[methoxydiphenylmethyl]-2-[(E)-2-(methoxy-
methoxymethyl)ethenyl]-1,3,2-dioxaborolane (5d). Yield 38%
(route 2), white foam; softening range = 52–59 ЊC; [α]D Ϫ54.9
(c 1.10 in CHCl3) (Found: C, 74.52; H, 6.72. C35H37BO6 requires
C, 74.47; H, 6.66%); IR (film)/cmϪ1 3059, 3024, 1348 and 1077;
NMR δH (500 MHz; CDCl3) 2.92 (6 H, s, OMe), 3.23 (3 H,
s, CH2OMe), 3.90 (2 H, complex m, 1Љ-H), 4.46 (2 H, s, CH2-
OMe), 5.24 (1 H, dt, J 18.1 and 1.8, 1Ј-H), 5.27 (2 H, s, 4-H and
5-H), 6.13 (1 H, dt, J 18.1 and 4.7, 2Ј-H), 7.18–7.28 (20 H, m,
ArH); δC (125 MHz; CDCl3) 51.8 (OMe), 55.2 (CH2OMe), 68.4
(C-1Љ), 77.7 (C-4/C-5), 83.3 (CPh2OMe), 95.5 (CH2OMe),
~118.5 (br, C-1Ј), 127.2 (Ar), 127.3 (Ar), 127.5 (Ar), 127.8 (Ar),
128.5 (Ar), 129.7 (Ar), 141.1 (Ar), 141.4 (Ar), 148.2 (C-2Ј); m/z
(EI) 528 (0.1%), 519 (0.1) and 197 (100).
General procedure B (route 2).21 Under an atmosphere of dry
nitrogen BH3ؒSMe2 complex (1.0 equiv. of a 12 M solution
in dimethyl sulfide) in 1,2-dimethoxyethane (1 mL per mmol
borane) was cooled to 0 ЊC. After addition of cyclohexene (2.0
equiv.) and removal of the cooling bath, a colourless precipitate
formed. After 2 h the reaction mixture was cooled to 0 ЊC,
followed by the addition of the appropriate alkyne (1.3–1.5
equiv.). The mixture was stirred at this temperature for 15 min,
then allowed to warm to room temperature. Stirring was con-
tinued for 2–4 h, during which time a clear solution formed.
Trimethylamine N-oxide22–24 (2 equiv.) was carefully added at
a rate keeping the reaction under gentle reflux. After 2 h at
room temperature the diol 1 (1 equiv.) was added. The reaction
mixture was stirred until complete consumption (as judged by
TLC) of diol 1 was indicated. The solvent was removed under
reduced pressure and the crude product subjected to flash-
column chromatography on silica gel, eluting with petroleum
ether–diethyl ether (12:1 to 4:1). The yields are given in
Scheme 1; the reaction was typically performed on a 1–40 mmol
scale.
(4R,5R)-2-[(E)-2-(Benzoyloxymethyl)ethenyl]-4,5-bis[meth-
oxydiphenylmethyl]-1,3,2-dioxaborolane (5e). Yield 60% (route
2), white foam; softening range = 71–76 ЊC; [α]D Ϫ47.3 (c 1.50
in CHCl3) (Found: C, 76.72; H, 6.09. C40H37BO6 requires C,
76.93; H, 5.97%); IR (film)/cmϪ1 3059, 3031, 1723, 1348 and
1076; NMR δH (500 MHz; CDCl3) 2.96 (6 H, s, OMe), 4.72
(2 H, dd, J 4.5 and 1.6, 1Љ-H), 5.36 (2 H, s, 4-H and 5-H), 5.40
(1 H, dt, J 18.1 and 1.6, 1Ј-H), 6.29 (1 H, dt, J 18.1 and 4.5,
2Ј-H), 7.25–7.36 (20 H, m, ArH), 7.41–7.44 (2 H, m, ArH),
7.53–7.56 (1 H, m, ArH), 8.01–8.03 (2 H, m, ArH); δC (125
MHz; CDCl3) 51.8 (OMe), 65.6 (C-1Љ), 77.7 (C-4/C-5), 83.3
(CPh2OMe), ~119 (br, C-1Ј), 127.3 (Ar), 127.3 (Ar), 127.5 (Ar),
127.8 (Ar), 128.3 (Ar), 128.4 (Ar), 129.6 (Ar), 129.7 (Ar), 130.0
(Ar), 133.0 (Ar), 141.0 (Ar), 141.3 (Ar), 145.4 (C-2Ј), 165.9
(C᎐O); m/z (EI) 624 (<0.3%) and 197 (100).
᎐
(4R,5R)-4,5-Bis(methoxydiphenylmethyl)-2-cyclohexyl-1,3,2-
dioxaborolane (9). White foam; softening range = 95–100 ЊC;
[α]D Ϫ120 (c 1.30 in CHCl3) (Found: C, 78.98; H, 7.30.
C36H39BO4 requires C, 79.12; H, 7.19%); IR (film)/cmϪ1 3059,
2924, 1336 and 1076; NMR δH (500 MHz; CDCl3) 0.33 (1 H, tt,
J 12.3 and 3.3, 1Ј-H), 0.68–1.47 (10 H, m, -CH2-), 2.93 (6 H, s,
OMe), 5.18 (2 H, s, 4-H and 5-H), 7.18–7.28 (20 H, m, ArH); δC
(125 MHz; CDCl3) 22.7 (C-1Ј), 27.1 (-CH2-), 27.7 (-CH2-), 27.8
(-CH2-), 27.9 (-CH2-), 28.2 (-CH2-), 52.1 (OMe), 83.8
(CPh2OMe), 127.5 (Ar), 127.6 (Ar), 127.8 (Ar), 128.1 (Ar),
128.9 (Ar), 130.2 (Ar), 141.8 (Ar), 141.9 (Ar); m/z (EI) 514 (1%)
and 197 (100).
(4R,5R)-2-[(E)-2-(tert-Butyldiphenylsiloxymethyl)ethenyl]-
4,5-bis[methoxydiphenylmethyl]-1,3,2-dioxaborolane (5b). Yield
60% (route 1), white foam; softening range = 69–75 ЊC; [α]D
Ϫ30.5 (c 0.40 in CHCl3) (Found: C, 77.38; H, 6.89.
C49H51BO5Si requires C, 77.56; H, 6.77%); IR (film)/cmϪ1 2932,
2857, 2360, 1341 and 1077; NMR δH (500 MHz; CDCl3) 0.93 (9
H, s, Me3C), 2.92 (6 H, s, OMe), 4.02 (2 H, dd, J 3.5 and 1.8, 1Љ-
H), 5.28 (2 H, s, 4-H and 5-H), 5.43 (1 H, dt, J 18.0 and 1.8, 1Ј-
H), 6.16 (1 H, dt, J 18.0 and 3.5, 2Ј-H), 7.17–7.53 (30 H, m,
ArH); δC (125 MHz; CDCl3) 19.7 (Me3C), 27.2 (Me3C), 52.3
(OMe), 65.5 (C-1Љ), 78.1 (C-4/C-5), 83.8 (CPh2OMe), ~118 (br,
C-1Ј), 127.7 (Ar), 127.9 (Ar), 128.0 (Ar), 128.2 (Ar), 128.7 (Ar),
128.9 (Ar), 129.9 (Ar), 130.0 (Ar), 134.0 (Ar), 135.8 (Ar), 141.5
(Ar), 141.9 (Ar), 151.4 (C-2Ј); m/z (EI) 758 (0.3%), 726 (10) and
197 (100). The NMR spectra indicated that the sample was a
mixture of the title compound containing minor amounts
(<10%) of boronic ester 13. Separation was not possible at this
stage; the structure of compound 13 was indirectly elucidated
by isolating the corresponding cyclopropanation product.
Cyclopropanation of alkenylboronic esters
General procedure C (method A). The alkenylboronic ester
(1 equiv.) was dissolved in diethyl ether (1 mL per mmol
boronic ester) and 5 mol% palladium() acetate added. The
suspension was treated for 2 min in an ultrasonic bath. After
cooling the mixture to 0 ЊC, diazomethane50–52 (25 mL per
mmol boronic ester of an approx. 0.5 M solution in diethyl
ether) was slowly (1 mL minϪ1) added by means of a syringe-
pump.53 Unreacted diazomethane was destroyed by stirring
the reaction mixture vigorously. Filtration through Celite,
evaporation of the solvent under reduced pressure, followed by
chromatographic purification led to analytically pure cyclo-
propylboronic esters. The diastereomeric ratios and yields are
(4R,5R)-2-[(E)-2-(Benzyloxymethyl)ethenyl]-4,5-bis[meth-
oxydiphenylmethyl]-1,3,2-dioxaborolane (5c). Yield 47% (route
2), white foam; softening range = 65–72 ЊC; [α]D Ϫ46.1 (c 0.90
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J. Chem. Soc., Perkin Trans. 1, 2000, 4293–4300

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given in Scheme 2; the reaction was typically performed on a
(4R,5R,1ЈS,2ЈS)-2-[2-(Benzyloxymethyl)cyclopropyl]-4,5-bis-
0.3–3 mmol scale.
[methoxydiphenylmethyl]-1,3,2-dioxaborolane (10c) and (4R,5R,
1ЈR,2ЈR)-2-[2-(benzyloxymethyl)cyclopropyl]-4,5-bis[methoxy-
diphenylmethyl]-1,3,2-dioxaborolane (11c). Yield 88% (general
procedure C), white foam (Found: C, 78.49; H, 6.75. C41H41BO5
requires C, 78.84; H, 6.62%); IR (film)/cmϪ1 3039, 3002, 1352
and 1061; m/z (FAB ϩ NaI) 647 (0.1%) [(M ϩ Na)ϩ] and 197
(100). The diastereoisomers 10c and 11c were separated by
means of MPLC (2% ethyl acetate in petroleum ether).
Major diastereoisomer 10c (second eluted): softening
range = 68–71 ЊC; [α]D Ϫ48.5 (c 1.00 in CHCl3); NMR δH (500
MHz; CDCl3) Ϫ0.69 (1 H, ddd, J 9.5, 6.3, and 5.3 Hz, 1Ј-H),
0.29 (1 H, ddd, J 9.5, 5.2, and 3.5 Hz, 3Ј-Hcis), 0.46 (1 H, ddd,
J 8.4, 6.3, and 3.5 Hz, 3Ј-Htrans), 0.64 (1 H, ddddd, J 8.4,
7.8, 5.3, 5.2 and 5.2 Hz, 2Ј-H), 2.85 (1 H, dd, J 10.2 and 7.8, 1Љ-
Ha), 2.95 (6 H, s, OMe), 3.38 (1 H, dd, J 10.2 and 5.2, 1Љ-Hb),
4.37 (1 H, d, J 12.1, PhCHaHbO), 4.43 (1 H, d, J 12.1,
PhCHaHbO), 5.21 (2 H, s, 4-H and 5-H), 7.18–7.31 (25 H, m,
ArH); δC (125 MHz; CDCl3) Ϫ3 (br, C-1Ј), 10.1 (C-3Ј), 17.4
(C-2Ј), 51.7 (OMe), 72.3 (PhCH2O), 74.6 (C-1Љ), 77.5 (C-4/C-5),
83.2 (CPh2OMe), 127.2 (Ar), 127.4 (Ar), 127.5 (Ar), 127.5 (Ar),
127.7 (Ar), 127.9 (Ar), 128.3 (Ar), 128.3 (Ar), 129.7 (Ar), 138.6
(Ar), 141.2 (Ar), 141.3 (Ar).
Minor diastereoisomer 11c (first eluted): softening
range = 79–83 ЊC; [α]D Ϫ89.0 (c 0.60 in CHCl3); NMR δH (500
MHz; CDCl3) Ϫ0.69 (1 H, ddd, J 9.9, 6.2, and 5.4 Hz, 1Ј-H),
0.10 (1 H, ddd, J 8.5, 6.2, and 3.5 Hz, 3Ј-Htrans), 0.23 (1 H,
ddd, J 9.9, 5.2, and 3.5 Hz, 3Ј-Hcis), 1.00 (1 H, ddddd, J 8.5, 7.6,
5.4, 5.2 and 5.2 Hz, 2Ј-H), 2.92 (1 H, dd, J 10.2 and 7.6, 1Љ-Ha),
2.95 (6 H, s, OMe), 3.27 (1 H, dd, J 10.2 and 5.2, 1Љ-Hb), 4.35
(1 H, d, J 12.0, PhCHaHbO), 4.38 (1 H, d, J 12.0, PhCHaHbO),
5.21 (2 H, s, 4-H and 5-H), 7.17–7.39 (25 H, m, ArH); δC
(125 MHz; CDCl3) Ϫ2 (br, C-1Ј), 10.1 (C-3Ј), 17.7 (C-2Ј), 51.7
(OMe), 72.4 (PhCH2O), 74.8 (C-1Љ), 77.5 (C-4/C-5), 83.3
(CPh2OMe), 127.2 (Ar), 127.3 (Ar), 127.4 (Ar), 127.5 (Ar),
127.6 (Ar), 127.8 (Ar), 128.3 (Ar), 128.4 (Ar), 129.7 (Ar), 138.5
(Ar), 141.2 (Ar), 141.3 (Ar).
General procedure D (method B). The alkenylboronic ester
(1.0 equiv.) in dichloromethane (1 mL per mmol boronic ester)
was added to a pre-formed cyclopropanating reagent [5.0 equiv.
diiodomethane dissolved in dichloromethane (10 mL per mmol
boronic ester), treated with diethylzinc solution (2.5 equiv. of a
1 M solution in hexane) at 0 ЊC]. Stirring was continued for 12 h
at room temperature. After quenching the reaction with satur-
ated aqueous ammonium chloride, the aqueous layer was
extracted with dichloromethane (3×). The combined organic
layer was dried over magnesium sulfate and the solvents
removed under reduced pressure. The crude product was puri-
fied by flash-column chromatography; the reaction was typi-
cally performed on a 0.3–6 mmol scale.
(4R,5R,1ЈS,2ЈS)-2-[2-{tert-Butyl(diphenyl)siloxymethyl}-
cyclopropyl]-4,5-bis[methoxydiphenylmethyl]-1,3,2-dioxa-
borolane (10b), (4R,5R,1ЈR,2ЈR)-2-[2-{tert-butyl(diphenyl)sil-
oxymethyl}cyclopropyl]-4,5-bis[methoxydiphenylmethyl]-1,3,2-
dioxaborolane (11b), and (4R,5R)-2-[1-{tert-butyl(diphenyl)-
siloxymethyl}cyclopropyl]-4,5-bis(methoxydiphenylmethyl)-
1,3,2-dioxaborolane (12). Yield 90% (general procedure C),
white foam (Found: C, 77.39; H, 7.26. C50H53BO5Si requires C,
77.70; H, 6.91%); IR (film)/cmϪ1 2931, 2856, 2360, 1388
and 1076; m/z (EI) 772 (0.1%), 740 (0.1) and 197 (100). The
diastereoisomers 10b and 11b, and the regioisomer 12 were
separated by means of MPLC (0.3% ethyl acetate in petroleum
ether).
Major diastereoisomer 10b (second eluted): softening
range = 69–71 ЊC; [α]D Ϫ26.7 (c 0.60 in CHCl3); NMR δH (500
MHz; CDCl3) Ϫ0.66 (1 H, ddd, J 9.5, 6.4, and 5.4 Hz, 1Ј-H),
0.28 (1 H, ddd, J 9.5, 5.3, and 3.3 Hz, 3Ј-Hcis), 0.33 (1 H, ddd,
J 7.7, 6.5, and 3.3 Hz, 1 H, 3Ј-Htrans), 0.59 (1 H, complex m, 2Ј-
H), 0.91 (9 H, s, Me3C), 2.91 (6 H, s, OMe), 3.16 (1 H, dd, J 10.5
and 6.2, 1Љ-Ha), 3.54 (1 H, dd, J 10.5 and 4.6, 1Љ-Hb), 5.17 (2 H,
s, 4-H and 5-H), 7.16–7.55 (30 H, m, ArH); δC (125 MHz;
CDCl3) Ϫ3 (br, C-1Ј), 9.5 (C-3Ј), 19.6 (Me3C), 20.2 (C-2Ј), 27.2
(Me3C), 52.2 (OMe), 67.3 (C-1Љ), 78.0 (C-4/C-5), 83.7
(CPh2OMe), 127.6 (Ar), 127.6 (Ar), 127.8 (Ar), 127.9 (Ar),
128.0 (Ar), 128.2 (Ar), 128.8 (Ar), 129.9 (Ar), 130.0 (Ar), 134.3
(Ar), 136.0 (Ar), 141.6 (Ar), 141.8 (Ar).
Minor diastereoisomer 11b (third eluted): softening
range = 67–70 ЊC; [α]D Ϫ77.7 (c 1.20 in CHCl3); NMR δH (500
MHz; CDCl3) Ϫ0.75 (1 H, ddd, J 9.9, 5.8, and 5.6 Hz, 1Ј-H),
Ϫ0.01 (1 H, ddd, J 7.7, 6.0, and 3.4 Hz, 1 H, 3Ј-Htrans), 0.20
(1 H, ddd, J 9.9, 5.2, and 3.4 Hz, 3Ј-Hcis), 0.81 (1 H, complex m,
2Ј-H), 0.93 (9 H, s, Me3C), 2.93 (6 H, s, OMe), 3.05 (1 H, dd,
J 10.7 and 7.2, 1Љ-Ha), 3.53 (1 H, dd, J 10.7 and 4.8, 1Љ-Hb), 5.17
(2 H, s, 4-H and 5-H), 7.16–7.54 (30 H, m, ArH); δC (125 MHz;
CDCl3) Ϫ3 (br, C-1Ј), 10.1 (C-3Ј), 19.6 (Me3C), 20.4 (C-2Ј), 27.3
(Me3C), 52.1 (OMe), 68.2 (C-1Љ), 77.9 (C-4/C-5), 83.7
(CPh2OMe), 127.5 (Ar), 127.6 (Ar), 127.8 (Ar), 127.9 (Ar),
128.2 (Ar), 128.8 (Ar), 128.9 (Ar), 129.9 (Ar), 130.1 (Ar), 134.3
(Ar), 136.0 (Ar), 141.6 (Ar), 141.8 (Ar).
Regioisomer 12 (first eluted): colourless oil; [α]D Ϫ55.5
(c 0.70 in CHCl3); NMR δH (500 MHz; CDCl3) Ϫ0.14 (1 H,
ddd, J 8.9, 5.8, and 2.8 Hz, cyclopropyl-Ha), 0.24 (1 H, ddd,
J 8.9, 5.8, and 2.8 Hz, cyclopropyl-Hb), 0.29 (1 H, ddd, J
8.9, 5.8, and 3.2 Hz, cyclopropyl-Hc), 0.34 (1 H, ddd, J 8.9, 5.8,
and 3.2 Hz, cyclopropyl-Hd), 0.80 (9 H, s, Me3C), 2.91 (6 H, s,
OMe), 3.09 (1 H, d, J 10.1, 1Љ-Ha), 3.13 (1 H, d, J 10.1, 1Љ-Hb),
5.19 (2 H, s, 4-H and 5-H), 7.14–7.49 (30 H, m, ArH); δC (125
MHz; CDCl3) Ϫ9.5 (br, C-1Ј), 9.7 (C-2Ј), 18.3 (Me3C), 19.6
(C-3Ј), 27.2 (Me3C), 52.2 (OMe), 66.9 (C-1Љ), 78.1 (C-4/C-5),
83.8 (CPh2OMe), 127.6 (Ar), 127.7 (Ar), 127.8 (Ar), 127.9 (Ar),
128.2 (Ar), 128.8 (Ar), 129.7 (Ar), 130.2 (Ar), 136.0 (Ar), 136.1
(Ar), 141.8 (Ar), 142.0 (Ar).
(4R,5R,1ЈS,2ЈS)-4,5-Bis[methoxydiphenylmethyl]-2-
[2-{methoxymethoxymethyl}cyclopropyl]-1,3,2-dioxaborolane
(10d) and (4R,5R,1ЈR,2ЈR)-4,5-bis[methoxydiphenylmethyl]-2-
[2-{methoxymethoxymethyl}cyclopropyl]-1,3,2-dioxaborolane
(11d). Yield 98% (general procedure C), white foam (Found: C,
74.60; H, 6.90. C36H39BO6 requires C, 74.74; H, 6.80%); IR
(film)/cmϪ1 3058, 2983, 1386 and 1076; m/z (EI) 578 (0.1%), 546
(1) and 197 (100). Only the major diastereoisomers 10d could be
separated by means of MPLC (2% ethyl acetate in petroleum
ether) and fully characterized; the NMR data of boronic ester
11d (in Table 1) were obtained from the mixture.
Major diastereoisomer 10d (second eluted): softening
range = 100–102 ЊC; [α]D Ϫ52.8 (c 1.00 in CHCl3); NMR δH
(500 MHz; CDCl3) Ϫ0.64 (1 H, ddd, J 9.5, 6.3, and 5.3 Hz, 1Ј-
H), 0.34 (1 H, ddd, J 9.5, 5.2, and 3.5 Hz, 3Ј-Hcis), 0.50 (1 H,
ddd, J 8.5, 6.3, and 3.5 Hz, 3Ј-Htrans), 0.66 (1 H, ddddd,
J 8.5, 7.9, 5.3, 5.3 and 5.2 Hz, 2Ј-H), 2.95 (1 H, dd, J 10.4 and
7.9, 1Љ-Ha), 3.00 (6 H, s, OMe), 3.31 (3 H, s, CH2OMe), 3.46 (1
H, dd, J 10.4 and 5.3, 1Љ-Hb), 4.55 (2 H, complex m, CH2OMe),
5.26 (2 H, s, 4-H and 5-H), 7.24–7.35 (20 H, m, ArH); δC (125
MHz; CDCl3) Ϫ2 (br, C-1Ј), 10.0 (C-3Ј), 17.5 (C-2Ј), 51.7
(OMe), 55.0 (CH2OMe), 71.8 (C-1Љ), 77.5 (C-4/C-5), 83.3
(CPh2OMe), 95.7 (CH2OMe), 127.5 (Ar), 127.6 (Ar), 127.8
(Ar), 128.0 (Ar), 128.4 (Ar), 129.7 (Ar), 141.2 (Ar), 141.3 (Ar).
(4R,5R,1ЈS,2ЈS)-2-[2-(Benzoyloxymethyl)cyclopropyl]-4,5-
bis[methoxydiphenylmethyl]-1,3,2-dioxaborolane (10e) and (4R,
5R,1ЈR,2ЈR)-2-[2-(benzoyloxymethyl)cyclopropyl]-4,5-bis[meth-
oxydiphenylmethyl]-1,3,2-dioxaborolane (11e). Yield 96%
(general procedure C), white foam (Found: C, 76.95; H, 6.31.
C41H39BO6 requires C, 77.12; H, 6.16%); IR (film)/cmϪ1 3039,
J. Chem. Soc., Perkin Trans. 1, 2000, 4293–4300
4297

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3005, 1358 and 1060; m/z (FAB ϩ NaI) 661 (47%) [(M ϩ Na)ϩ]
and 197 (100). The diastereoisomers 10e and 11e could not
be separated by means of MPLC. The following data were
obtained from the mixture.
(4R,5R,4ЉS)-2-[(E)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethenyl]-
4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane (18)
Following the general procedure A, the product 18 was isolated
in 30% yield; general procedure B: yield 80% (route 2), white
foam; softening range = 76–79 ЊC; [α]D Ϫ41.5 (c 1.40 in CHCl3)
(Found: C, 75.45; H, 6.80. C37H39BO6 requires C, 75.26; H,
6.66%); IR (film)/cmϪ1 3058, 2937, 1379 and 1075; NMR δH
(500 MHz; CDCl3) 1.27 (3 H, s, Me), 1.28 (3 H, s, Me), 2.92 (6
H, s, OMe), 3.38 (1 H, dd, J 8.1 and 7.4 Hz, 5Љ-Ha), 3.93 (1 H,
dd, J 8.1 and 6.5 Hz, 5Љ-Hb), 4.30 (1 H, dddd, J 7.4, 6.5, 5.8 and
1.3 Hz, 4Љ-H), 5.25 (1 H, dd, J 18.1 and 1.3, 1Ј-H), 5.28 (2 H, s,
4-H and 5-H), 6.03 (1 H, dd, J 18.1 and 5.8, 2Ј-H), 7.16–7.36
(20 H, m, ArH); δC (125 MHz; CDCl3) 25.8 (Me), 26.5 (Me),
51.8 (OMe), 69.0 (C-5Љ), 77.6, 77.7 (C-4Љ and C-4/C-5), 83.3
(CPh2OMe), 110.9 (C-2Љ), ~120 (br, C-1Ј), 127.3 (Ar), 127.3
(Ar), 127.5 (Ar), 127.8 (Ar), 128.4 (Ar), 129.7 (Ar), 141.0 (Ar),
141.3 (Ar), 149.2 (C-2Ј); m/z (EI) 590 (0.1%), 575 (2), 558 (2)
and 197 (100).
Major diastereoisomer 10e: NMR δH (500 MHz; CDCl3)
Ϫ0.62 (1 H, ddd, J 9.6, 6.4, and 5.3 Hz, 1Ј-H), 0.28 (1 H,
ddd, J 9.6, 5.1, and 3.7 Hz, 3Ј-Hcis), 0.38 (1 H, ddd, J 8.2, 6.4,
and 3.7 Hz, 3Ј-Htrans), 0.68 (1 H, ddddd, J 8.2, 7.6, 6.1,
5.3 and 5.1 Hz, 2Ј-H), 2.81 (6 H, s, OMe), 3.71 (1 H, dd,
J 11.4 and 7.6, 1Љ-Ha), 3.94 (1 H, dd, J 11.4 and 6.1, 1Љ-Hb), 5.10
(2 H, s, 4-H and 5-H), 7.17–7.39 (25 H, m, ArH); δC (125 MHz;
CDCl3) Ϫ2 (br, C-1Ј), 9.9 (C-3Ј), 16.4 (C-2Ј), 51.7 (OMe),
69.3 (C-1Љ), 77.6 (C-4/C-5), 83.3 (CPh2OMe), 127.2 (Ar), 127.3
(Ar), 127.5 (Ar), 127.6 (Ar), 127.8 (Ar), 128.3 (Ar), 128.4 (Ar),
129.5 (Ar), 129.7 (Ar), 132.5 (Ar), 141.2 (Ar), 141.3 (Ar), 166.5
(C᎐O).
᎐
Minor diastereoisomer 11e: NMR δH (500 MHz; CDCl3)
Ϫ0.62 (1 H, ddd, J 10.0, 6.2, and 5.4 Hz, 1Ј-H), 0.00 (1 H,
ddd, J 7.6, 6.3, and 3.7 Hz, 3Ј-Htrans), 0.22 (1 H, ddd,
J 10.0, 5.1, and 3.7 Hz, 3Ј-Hcis), 1.00 (1 H, ddddd, J 7.6, 7.4,
6.6, 5.4 and 5.1 Hz, 2Ј-H), 2.81 (6 H, s, OMe), 3.75 (1 H, dd,
J 11.4 and 7.4, 1Љ-Ha), 3.85 (1 H, dd, J 11.4 and 6.6, 1Љ-Hb),
5.10 (2 H, s, 4-H and 5-H), 7.17–7.39 (25 H, m, ArH); δC (125
MHz; CDCl3) Ϫ2 (br, C-1Ј), 10.0 (C-3Ј), 16.7 (C-2Ј), 51.7
(OMe), 69.3 (C-1Љ), 77.6 (C-4/C-5), 83.3 (CPh2OMe), 127.1
(Ar), 127.2 (Ar), 127.3 (Ar), 127.7 (Ar), 128.0 (Ar), 128.2 (Ar),
128.6 (Ar), 129.4 (Ar), 129.5 (Ar), 130.3 (Ar), 141.2 (Ar), 141.3
(4S,5S,4ЉS)-2-[(E)-2-(2,2-Dimethyl-1,3-dioxolan-4-yl)ethenyl]-
4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane (19)
Following the general procedure A, the product 18 was isolated
in 27% yield; general procedure B: yield 50% (route 2), white
foam; softening range = 77–80 ЊC; [α]D ϩ67.9 (c 1.10 in CHCl3)
(Found: C, 74.98; H, 6.87. C37H39BO6 requires C, 75.26; H,
6.66%); IR (film)/cmϪ1 3058, 2937, 1379 and 1075; NMR δH
(500 MHz; CDCl3) 1.34 (3 H, s, Me), 1.43 (3 H, s, Me), 2.97
(6 H, s, OMe), 3.42 (1 H, dd, J 8.1 and 7.4 Hz, 5Љ-Ha), 3.98 (1 H,
dd, J 8.1 and 6.5 Hz, 5Љ-Hb), 4.37 (1 H, dddd, J 7.4, 6.5, 5.8 and
1.3 Hz, 4Љ-H), 5.32 (1 H, dd, J 18.1 and 1.3, 1Ј-H), 5.35 (2 H, s,
4-H and 5-H), 6.10 (1 H, dd, J 18.1 and 5.8, 2Ј-H), 7.24-7.37
(20 H, m, ArH); δC (125 MHz; CDCl3) 26.2 (Me), 26.9 (Me),
52.2 (OMe), 69.4 (C-5Љ), 78.0, 78.1 (C-4Љ and C-4/C-5), 83.7
(CPh2OMe), 110.0 (C-2Љ), ~120 (br, C-1Ј), 127.7 (Ar), 127.7
(Ar), 127.9 (Ar), 128.2 (Ar), 128.8 (Ar), 130.1 (Ar), 141.4 (Ar),
141.7 (Ar), 149.6 (C-2Ј); m/z (EI) 590 (0.1%), 575 (2), 558 (2)
and 197 (100).
(Ar), 166.7 (C᎐O).
᎐
(S)-(؊)-4-(2,2-Dibromoethenyl)-2,2-dimethyl-1,3-dioxolane (15)
By following the procedure as described by Jiang and Ma,28
partially racemized product 15 was obtained. Yield 61%, bp
50 ЊC (0.35 torr); [α]D Ϫ2.6 [c 1.1 in MeOH; lit.54 Ϫ3.6 (c 3.8 in
MeOH)] (Found: C, 29.39; H, 3.51; Br, 55.74. C7H10O2Br
requires C, 29.40; H, 3.52; Br, 55.88%); IR (film)/cmϪ1 2980,
2936, 1370 and 1040; NMR δH (500 MHz; CDCl3) 1.37 (3 H,
s, Me), 1.41 (3 H, s, Me), 3.67 (1 H, dd, J 8.4 and 6.5 Hz,
5-Ha), 4.19 (1 H, dd, J 8.4 and 6.3 Hz, 5-Hb), 4.71 (1 H, ddd,
J 7.6, 6.5 and 6.3 Hz, 4-H), 6.52 (1 H, d, J 7.6 Hz, 1Ј-H); δC
(125 MHz; CDCl3) 26.0 (Me), 27.9 (Me), 68.4 (C-5), 76.5 (C-4),
93.0 (C-1Ј), 110.4 (C-2), 137.5 (C-2Ј); m/z (EI) 284 (2%), 286 (4)
and 288 (2).
(4SЉ)-2-[(E)-2-(2,2-Dimethyl-1,3-dioxolan-4-yl)ethenyl]-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (20)
Yield 56% (route 2, lit.55 90%), colourless solid: mp 35 ЊC; [α]D
ϩ35.2 (c 1.10 in CHCl3) (Found: C, 61.47; H, 9.08. C13H23BO4
requires C, 61.44; H, 9.12%); IR (film)/cmϪ1 2982, 2935, 1372
and 1062; NMR δH (500 MHz; CDCl3) 1.23 (6 H, s, Me), 1.24
(6 H, s, Me), 1.36 (3 H, s, Me), 1.40 (3 H, s, Me), 3.61 (1 H, dd,
J 8.2 and 7.5 Hz, 5Љ-Ha), 4.08 (1 H, dd, J 8.2 and 6.4 Hz, 5Љ-Hb),
4.37 (1 H, dddd, J 7.5, 6.4, 6.4 and 1.2 Hz, 4Љ-H), 5.64 (1 H, dd,
J 18.0 and 1.2, 1Ј-H), 6.52 (1 H, dd, J 18.0 and 6.4, 2Ј-H); δC
(125 MHz; CDCl3) 24.7 (2 × Me), 24.8 (2 × Me), 25.9 (Me),
26.5 (Me), 69.0 (C-5Љ), 78.0 (C-4Љ), 83.4 (2 × Me2CO), 109.6
(C-2Љ), ~121 (br, C-1Ј), 149.5 (C-2Ј); m/z (EI) 253 (21%), 197
(49) and 101 (100).
(S)-(؉)-4-Ethynyl-2,2-dimethyl-1,3-dioxolane (16)
By following the procedure as described by Jiang and Ma,28
partially racemized product 16 was obtained. Yield 43%; [α]D
21.1 [c 1.10 in CHCl3; lit.54 43.0 (c 1.00 in CCl4) or lit.28 33.8
(c 1.00 in CHCl3)].
A solution of aldehyde 1425–27 (1.03 g, 7.90 mmol) and the
Bestmann–Ohira reagent 1730–35 (2.42 g, 12.6 mmol) in metha-
nol (50 mL) was cooled to 0 ЊC. Potassium carbonate (2.33 g,
16.8 mmol) was gradually added (30 min). The mixture was
stirred for 12 h, allowing it to warm to room temperature.
Saturated aqueous ammonium chloride (50 mL) was added
and the aqueous solution extracted with pentane (2 × 250 mL).
The organic layer was separated, dried over magnesium sulfate,
and the solvent carefully evaporated under reduced pressure.
After purification by flash-column chromatography (eluent
pentane–diethyl ether 10:1), alkyne 16 (700 mg, 5.50 mmol;
69%) was isolated as a colourless liquid, [α]D 40.6 (c 1.1 in
CHCl3) (Found: C, 66.12; H, 8.02. C7H10O2 requires C, 66.65;
H, 7.99%); IR (film)/cmϪ1 3290, 2990, 2940, 2120, 1370 and
1065; NMR δH (500 MHz; CDCl3) 1.35 (3 H, s, Me), 1.47 (3 H,
s, Me), 2.47 (1 H, d, J 2.3 Hz, 2Ј-H), 3.92 (1 H, dd, J 8.1 and 6.2
Hz, 5-Ha), 4.14 (1 H, dd, J 8.1 and 6.4 Hz, 5-Hb), 4.67 (1 H,
ddd, J 6.4, 6.2 and 2.3 Hz, 4-H); δC (125 MHz; CDCl3) 26.3
(Me), 26.5 (Me), 65.6 (C-5), 70.2 (C-2Ј), 74.3 (C-4), 81.8 (C-1Ј),
110.9 (C-2); m/z (EI, AUTO -CI) 127.0754 [(M ϩ H)ϩ. C7H11O2
requires 127.0759]; 127 (20%) and 111 (100).
(4R,5R,1ЈS,2ЈS,4ЉS)-2-[2-(2,2-Dimethyl-1,3-dioxolan-4-yl)-
cyclopropyl]-4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxa-
borolane (21) and (4R,5R,1ЈR,2ЈR,4ЉS)-2-[2-(2,2-dimethyl-1,3-
dioxolan-4-yl)cyclopropyl]-4,5-bis(methoxydiphenylmethyl)-
1,3,2-dioxaborolane (22)
Following the general procedure C, the product 21/22 was
isolated in 93% yield as a 83:17 mixture; general procedure D:
yield 58% (dr 11:89), white foam (Found: C, 75.59; H, 7.03.
C38H41BO6 requires C, 75.50; H, 6.84%); IR (film)/cmϪ1 3058,
2937, 1369 and 1076; m/z (EI) 604.2996 [(M)ϩ. C38H41BO6
requires 604.2996]; 604 (0.1%) and 197 (100). The diastereo-
isomers 21 and 22 were separated by means of MPLC (2% ethyl
acetate in petroleum ether).
Compound 21 (first eluted): mp 142 ЊC; [α]D Ϫ35.1 (c 1.00 in
CHCl3); NMR δH (500 MHz; CDCl3) Ϫ0.48 (1 H, ddd, J 9.6,
4298
J. Chem. Soc., Perkin Trans. 1, 2000, 4293–4300

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6.4, and 5.1 Hz, 1Ј-H), 0.24 (1 H, ddd, J 9.6, 5.2, and 3.6 Hz, 3Ј-
Hcis), 0.35 (1 H, ddd, J 8.0, 6.4, and 3.6 Hz, 3Ј-Htrans), 0.55
(1 H, dddd, J 8.0, 7.4, 5.2 and 5.1 Hz, 2Ј-H), 1.21 (3 H, s, Me),
1.34 (3 H, s, Me), 2.92 (6 H, s, OMe), 3.32 (1 H, ddd, J 7.8, 7.4
and 6.0 Hz, 4Љ-H), 3.42 (1 H, dd, J 7.8 and 7.8 Hz, 5Љ-Ha), 3.86
(1 H, dd, J 7.8 and 6.0 Hz, 5Љ-Hb), 5.17 (2 H, s, 4-H and 5-H),
7.16–7.29 (20 H, m, ArH); δC (125 MHz; CDCl3) Ϫ2 (br, C-1Ј),
7.6 (C-3Ј), 19.4 (C-2Ј), 25.6 (Me), 26.8 (Me), 51.7 (OMe), 69.0
(C-5Љ), 77.7 (C-4/C-5), 80.0 (C-4Љ), 83.3 (CPh2OMe), 108.7
(C-2Љ), 127.1 (Ar), 127.4 (Ar), 127.5 (Ar), 127.7 (Ar), 128.3
(Ar), 129.7 (Ar), 141.2 (Ar), 141.4 (Ar).
Compound 22 (second eluted): mp 130 ЊC; [α]D Ϫ75.1 (c 1.10
in CHCl3); NMR δH (500 MHz; CDCl3) Ϫ0.68 (1 H, ddd, J 9.9,
6.1, and 5.5 Hz, 1Ј-H), 0.11 (1 H, ddd, J 7.5, 6.2, and 3.7 Hz,
3Ј-Htrans), 0.33 (1 H, ddd, J 9.9, 5.0, and 3.7 Hz, 3Ј-Hcis), 0.81
(1 H, dddd, J 8.4, 7.5, 5.5 and 5.0 Hz, 2Ј-H), 1.20 (3 H, s, Me),
1.30 (3 H, s, Me), 2.92 (6 H, s, OMe), 3.26 (1 H, ddd, J 8.4, 7.4
and 6.1 Hz, 4Љ-H), 3.63 (1 H, dd, J 7.8 and 7.8 Hz, 5Љ-Ha), 3.82
(1 H, dd, J 7.8 and 6.0 Hz, 5Љ-Hb), 5.20 (2 H, s, 4-H and 5-H),
7.19–7.25 (20 H, m, ArH); δC (125 MHz; CDCl3) Ϫ2 (br, C-1Ј),
9.8 (C-3Ј), 19.7 (C-2Ј), 25.6 (Me), 26.8 (Me), 51.7 (OMe), 69.2
(C-5Љ), 77.5 (C-4/C-5), 81.2 (C-4Љ), 83.3 (CPh2OMe), 108.9
(C-2Љ), 127.3 (Ar), 127.3 (Ar), 127.5 (Ar), 127.8 (Ar), 128.4
(Ar), 129.7 (Ar), 141.2 (Ar), 141.2 (Ar).
isolated in 69% yield as a 60:40 mixture; general procedure
D: yield 60% (dr 95:5), colourless oil. The diastereoisomers 25
and 26 could not be separated and fully purified; all data were
obtained from the mixtures. IR (film)/cmϪ1 2982, 2935, 1380
and 1067; m/z (EI, AUTO-CI) 269.1928 [(M ϩ H)ϩ. C14H26BO4
requires 269.1924]; 269 (25%) and 253 (100).
Compound 25: NMR δH (500 MHz; CDCl3) Ϫ0.28 (1 H,
ddd, J 9.8, 6.3, and 5.4 Hz, 1Ј-H), 0.67 (1 H, ddd, J 9.8, 5.0, and
3.7 Hz, 3Ј-Hcis), 0.79 (1 H, ddd, J 7.6, 6.3, and 3.7 Hz, 3Ј-
Htrans), 1.13 (1 H, complex m, 2Ј-H), 1.18 (12 H, br s, 4 × Me),
1.31 (3 H, s, Me), 1.41 (3 H, s, Me), 3.38 (1 H, dddd, J 8.4, 7.2,
6.1 and 1.2 Hz, 4Љ-H), 3.67 (1 H, dd, J 8.2 and 7.2 Hz, 5Љ-Ha),
4.03 (1 H, dd, J 8.2 and 6.1 Hz, 5Љ-Hb); δC (125 MHz; CDCl3)
Ϫ3.5 (br, C-1Ј), 9.2 (C-3Ј), 19.9 (C-2Ј), 24.6 (4 × Me), 25.7
(Me), 26.8 (Me), 69.6 (C-5Љ), 81.1 (C-4Љ), 83.1 (2 × Me2CO),
109.0 (C-2Љ).
Compound 26: NMR δH (500 MHz; CDCl3) Ϫ0.02 (1 H,
ddd, J 9.8, 6.3, and 5.1 Hz, 1Ј-H), 0.54 (1 H, ddd, J 9.8, 5.1, and
3.7 Hz, 3Ј-Hcis), 0.63 (1 H, ddd, J 8.0, 6.3, and 3.7 Hz,
3Ј-Htrans), 1.11–1.16 (1 H, m, 2Ј-H), 1.17 (6 H, s, 2 × Me), 1.18
(6 H, s, 2 × Me), 1.23 (3 H, s, Me), 1.38 (6 H, s, Me), 3.51
(1 H, ddd, J 7.5, 6.0 and 6.0 Hz, 4Љ-H), 3.64 (1 H, dd, J 8.0 and
7.5 Hz, 5Љ-Ha), 4.01 (1 H, dd, J 8.0 and 6.0 Hz, 5Љ-Hb); δC (125
MHz; CDCl3) Ϫ1.5 (br, C-1Ј), 7.4 (C-3Ј), 19.5 (C-2Ј), 24.5
(4 × Me), 24.7 (Me), 25.8 (Me), 69.2 (C-5Љ), 80.3 (C-4Љ), 83.0
(2 × Me2CO), 108.9 (C-2Љ).
(4S,5S,1ЈR,2ЈR,4ЉS)-2-[2-(2,2-Dimethyl-1,3-dioxolan-4-yl)cyclo-
propyl]-4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxaborolane
(23) and (4S,5S,1ЈS,2ЈS,4ЉS)-2-[2-(2,2-dimethyl-1,3-dioxolan-4-
yl)cyclopropyl]-4,5-bis(methoxydiphenylmethyl)-1,3,2-dioxa-
borolane (24)
(1ЈR,2ЈR,4ЉS)-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)cyclopropyl]-
methanol (27)
Cyclopropylboronic ester 25 (287 mg, 1.00 mmol) and chloro-
iodomethane (0.15 mL, 2.00 mmol) were dissolved in tetra-
hydrofuran and the solution cooled to Ϫ78 ЊC. Butyllithium
(1.25 mL of a 1.6 M solution in hexane, 2.00 mmol) was slowly
added, the reaction mixture warmed up to room temperature
and stirred for 2 d. A 1:1 mixture of 30% hydrogen peroxide
and 3 M aqueous sodium hydroxide (5 mL) was carefully added
and stirring continued until TLC indicated complete consump-
tion of the intermediate. Dilution with diethyl ether (10 mL)
was followed by the addition of a saturated aqueous ammo-
nium chloride solution (5 mL). After extraction of the aqueous
layer, drying with magnesium sulfate and evaporation of the
organic solvents under reduced pressure, the crude product was
subjected to flash-column chromatography (petroleum ether–
ethyl acetate 4:1 to 1:1). Yield 67% (dr >95:5), colourless oil.
The spectroscopic data were in full agreement with published
data.42 [α]D Ϫ13 (c 1.7 in CHCl3); IR (film)/cmϪ1 3424, 2987,
1372 and 1064; m/z (EI, AUTO-CI) 173.1172 [(M ϩ 1)ϩ.
C9H16O3 requires 173.1178]; 173 (15%) and 157 (100); NMR
δH (500 MHz; CDCl3) 0.53 (1 H, ddd, J 8.3, 5.1, and 5.0 Hz,
3Ј-Htrans), 0.60 (1 H, ddd, J 8.5, 5.1, and 5.0 Hz, 3Ј-Hcis), 0.84
(1 H, dddd, J 8.3, 7.8, 5.1, and 4.3 Hz, 2Ј-H), 0.99 (1 H, ddddd,
J 8.5, 6.9, 6.8, 5.1, and 4.3 Hz, 1Ј-H), 1.27 (3 H, s, Me), 1.37
(3 H, s, Me), 1.79 (1 H, br s, OH), 3.40 (1 H, dd, J 11.2 and 6.9
Hz, 1-Ha), 3.46 (1 H, dd, J 11.2 and 6.8 Hz, 1-Hb), 3.57 (1 H,
ddd, J 7.8, 7.2, and 5.9 Hz, 4Љ-H), 3.64 (1 H, dd, J 8.0 and 7.2
Hz, 5Љ-Ha), 4.04 (1 H, dd, J 8.0 and 5.9 Hz, 5Љ-Hb); δC (125
MHz; CDCl3) 7.9 (C-3Ј), 17.8 (C-3Ј), 19.0, 19.1 (C-1Ј/C-2Ј),
25.6 (Me), 26.7 (Me), 65.8 (C-1), 69.1 (C-5Љ), 79.0 (C-4Љ), 108.02
(C-2Љ).
Following the general procedure C, the product 23/24 was isol-
ated in 95% yield as a 50:50 mixture; general procedure D:
yield 72% (dr 94:6), white foam (Found: C, 75.18; H, 7.07.
C38H41BO6 requires C, 75.50; H, 6.84%); IR (film)/cmϪ1 3058,
2937, 1370 and 1076; m/z (EI) 604.2996 [(M)ϩ. C38H41BO6
requires 604.2996]; 604 (0.1%), 572 (0.1) and 197 (100). The
diastereoisomers 23 and 24 were separated by means of MPLC
(2% ethyl acetate in petroleum ether).
Compound 23 (second eluted): mp 120 ЊC; [α]D 40.0 (c 1.00 in
CHCl3); NMR δH (500 MHz; CDCl3) Ϫ0.68 (1 H, ddd, J 9.8,
6.3, and 5.4 Hz, 1Ј-H), 0.40 (1 H, ddd, J 9.8, 5.0, and 3.6 Hz, 3Ј-
Hcis), 0.48 (1 H, ddd, J 7.5, 6.3, and 3.6 Hz, 3Ј-Htrans), 0.59
(1 H, dddd, J 8.1, 7.5, 5.4 and 5.0 Hz, 2Ј-H), 1.21 (3 H, s, Me),
1.32 (3 H, s, Me), 2.92 (6 H, s, OMe), 3.16 (1 H, ddd, J 8.1, 7.2
and 6.1 Hz, 4Љ-H), 3.49 (1 H, dd, J 8.0 and 7.2 Hz, 5Љ-Ha), 3.86
(1 H, dd, J 8.0 and 6.1 Hz, 5Љ-Hb), 5.20 (2 H, s, 4-H and 5-H),
7.16–7.25 (20 H, m, ArH); δC (125 MHz; CDCl3) Ϫ4 (br, C-1Ј),
9.4 (C-3Ј), 19.5 (C-2Ј), 25.6 (Me), 26.8 (Me), 51.7 (OMe), 69.3
(C-5Љ), 77.6 (C-4/C-5), 80.9 (C-4Љ), 83.3 (CPh2OMe), 108.8
(C-2Љ), 127.3 (Ar), 127.3 (Ar), 127.5 (Ar), 127.8 (Ar), 128.4
(Ar), 129.7 (Ar), 141.3 (Ar), 141.3 (Ar).
Compound 24 (first eluted): mp 100–102 ЊC; [α]D 88.3 (c 1.00
in CHCl3); NMR δH (500 MHz; CDCl3) Ϫ0.51 (1 H, ddd,
J 10.0, 6.2, and 5.6 Hz, 1Ј-H), Ϫ0.04 (1 H, ddd, J 8.0, 6.2, and
3.6 Hz, 3Ј-Htrans), 0.21 (1 H, ddd, J 10.0, 5.2, and 3.6 Hz,
3Ј-Hcis), 0.79 (1 H, complex m, 2Ј-H), 1.20 (3 H, s, Me), 1.25
(3 H, s, Me), 2.93 (6 H, s, OMe), 3.36–3.38 (2 H, m, 4Љ-H and
5Љ-Ha), 3.82–3.84 (1 H, m, 5Љ-Hb), 5.17 (2 H, s, 4-H and 5-H),
7.16–7.27 (20 H, m, ArH); δC (125 MHz; CDCl3) Ϫ2 (br, C-1Ј),
7.7 (C-3Ј), 19.9 (C-2Ј), 25.6 (Me), 26.7 (Me), 51.7 (OMe),
68.8 (C-5Љ), 77.5 (C-4/C-5), 79.5 (C-4Љ), 83.2 (CPh2OMe), 108.6
(C-2Љ), 127.2 (Ar), 127.4 (Ar), 127.5 (Ar), 127.7 (Ar), 128.3
(Ar), 129.7 (Ar), 141.2 (Ar), 141.3 (Ar).
Acknowledgements
Financial support by the Fonds der Chemischen Industrie
(Liebig-fellowship for J. P.) and the Deutschen Forschungsge-
meinschaft (fellowship for J. P.) is gratefully acknowledged.
We also thank the Institut für Organische Chemie der
Universität Stuttgart (Professor Dr Dr h. c. F. Effenberger
and Professor Dr V. Jäger), the Bayer AG (Wuppertal), Aventis
Pharma Deutschland GmbH (Frankfurt/Main), Novartis AG
(Basel), the Boehringer Ingelheim KG (Biberach), the Degussa
(1ЈR,2ЈR,4ЉS)-2-[2-(2,2-Dimethyl-1,3-dioxolan-4-yl)cyclo-
propyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (25) and
(1ЈS,2ЈS,4ЉS)-2-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)cyclopropyl]-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (26)
Following the general procedure C, the product 25/26 was
J. Chem. Soc., Perkin Trans. 1, 2000, 4293–4300
4299

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