Synthesis of enantiomerically pure cyclopropanes from cyclopropylboronic acids

Article abstract of DOI:10.1021/jo9910278

A general method for the stereocontrolled synthesis of cyclopropanes is described. Various, highly stable, enantiomerically pure alkenylboronic esters 13 have been conveniently synthesized by the direct hydroboration of alkynes 11 using the new chiral 1,3,2-dioxaborolane 15. The high stability was also demonstrated by the selective deprotection of a tert- butyldimethylsilyl protecting group without hydrolyzing the boronic ester. The diastereoselective cyclopropanation of the olefins was achieved by the palladium(II) acetate catalyzed decomposition of diazomethane. This process was optimized giving cyclopropylboronic esters 20/21 in high yield (89-99%) and with good to excellent diastereomeric ratios (up to 95:5). The diastereomers were separated by means of MPLC and their configurations determined by X-ray crystallography (compound 21c), by transformation to known cyclopropanols, and by correlation of NMR data. Treatment with LiAlH₄ followed by acidic hydrolysis yielded the enantiomerically pure cyclopropylboronic acid 27 for the first time and allowed the nearly quantitative recovery of the chiral auxiliary 3. Different protocols for the Suzuki coupling reaction of compound 27 were investigated.

Full text of DOI:10.1021/jo9910278

J . Org. Chem. 1999, 64, 8287-8297
8287
Syn th esis of En a n tiom er ica lly P u r e Cyclop r op a n es fr om
Cyclop r op ylbor 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
Received J une 28, 1999
A general method for the stereocontrolled synthesis of cyclopropanes is described. Various, highly
stable, enantiomerically pure alkenylboronic esters 13 have been conveniently synthesized by the
direct hydroboration of alkynes 11 using the new chiral 1,3,2-dioxaborolane 15. The high stability
was also demonstrated by the selective deprotection of a tert-butyldimethylsilyl protecting group
without hydrolyzing the boronic ester. The diastereoselective cyclopropanation of the olefins was
achieved by the palladium(II) acetate catalyzed decomposition of diazomethane. This process was
optimized giving cyclopropylboronic esters 20/21 in high yield (89-99%) and with good to excellent
diastereomeric ratios (up to 95:5). The diastereomers were separated by means of MPLC and their
configurations determined by X-ray crystallography (compound 21c), by transformation to known
cyclopropanols, and by correlation of NMR data. Treatment with LiAlH4 followed by acidic hydrolysis
yielded the enantiomerically pure cyclopropylboronic acid 27 for the first time and allowed the
nearly quantitative recovery of the chiral auxiliary 3. Different protocols for the Suzuki coupling
reaction of compound 27 were investigated.
In tr od u ction
A major setback has been the relative lability of this class
of compounds; separation of diastereomers was not
Cyclopropanes have attracted considerable interest in
recent years. They are also increasingly incorporated into
pharmaceuticals due to their well-defined three-dimen-
sional structure.1 From the point of view of new synthetic
targets, it is especially noteworthy that a growing
number of natural products containing a cyclopropyl
group have been isolated.2 Elegant, highly selective
methods for the synthesis of optically active cyclopro-
panes have consequently been developed in recent years.3
Nevertheless, new, more general approaches to a wide
variety of enantiomerically pure cyclopropane derivatives
are still highly desirable.4 Alkenylmetal compounds (B,
Al, Si, Sn) are versatile intermediates, since after cyclo-
propanation they can potentially react with a variety of
electrophiles.5 Cyclopropyl boron derivatives are ideal:
the starting materials are not only readily available in a
stereodefined manner, but by utilizing the whole poten-
tial of boron compounds,6 the synthesis of a plethora of
different cyclopropanes should be feasible. Cyclopropyl-
boronic esters are most convenient,7-9 since the only
carbon substituent on boron is easily displaced. In
addition, boronic esters allow for the introduction of
chiral auxiliaries, thus enabling diastereoselective cyclo-
propanations of alkenylboronic esters, a method first
employed by Imai et al.8a and later adopted by others.8b,c
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* To whom correspondence should be addressed. E-mail:
joerg.pietruszka@po.uni-stuttgart.de.
† This paper is dedicated to Prof. Dr. W. A. Ko¨nig on the occasion of
his 60th birthday.
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10.1021/jo9910278 CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/08/1999

8288 J . Org. Chem., Vol. 64, No. 22, 1999
Luithle and Pietruszka
possible, and after workup and/or further transformation
only partially enantiomerically enriched cyclopropanes
were isolated.
Recently,9 we demonstrated that alkenylboronic esters
1, which are stable on silica gel, are conveniently cyclo-
propanated by the Pd(II)-catalyzed decomposition of
diazomethane to furnish cyclopropylboronic esters 2
(Figure 1). Bulky substituents appear ideally adapted to
stabilize these dioxaborolanes.9a Previously, we reported9b
that the synthesis of cyclopropylboronic esters of diol 310
proved to be superior (higher diastereoselectivity; readily
separable diastereomers) to the corresponding esters of
pinanediol 411 and 1,1,2-triphenyl-1,2-ethanediol 5.12 We
now present a detailed account of the synthesis of a
variety of enantiomerically pure cyclopropanes, demon-
F igu r e 1. Synthesis of cyclopropylboronic esters 2 from
enantiomerically pure alkenylboronic esters 1 (derived from
diols 3-5).9
Sch em e 1. Syn th esis a n d Str u ctu r e (As
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boranes; Hafner, K., Rees, C. W., Trost, B. M., Lehn, J .-M., von Rague´
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strating that cyclopropylboronic esters 2 are highly
desirable key intermediates.
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Resu lts a n d Discu ssion
To serve as a good and reliable protecting group for
boronic esters, the chiral auxiliary 3 needs to meet the
following requirements: (a) diol 3 must be available on
a multigram scale; (b) synthesis of alkenylboronic esters
2 should be straightforward; (c) the cyclopropanation
should be highly diastereoselective; (d) the cyclopropyl-
boronic esters 3 should be sufficiently stable so as to allow
separation of the diastereomers, but (e) not so stable as
to prevent further transformations; and (f) as an ideal
protecting group, the recovery of diol 3 is the ultimate
prerequisite.
(10) Nakayama, K.; Rainier, J . D. Tetrahedron 1990, 46, 4165-4170.
(11) (a) Matteson, D. S.; Sadhu, K. M.; Peterson, M. L. J . Am. Chem.
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Soc. 1982, 59, 119-123.
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406.
Syn th esis of Ch ir a l Au xilia r y 3. For the synthesis
of diol 3, we followed a procedure described by Nakayama
and Rainier (Scheme 1).10 Starting from dimethyl L-
tartrate 6, we first formed acetal 7 (87%) by the acid-

Synthesis of Cyclopropanes from Cyclopropylboronic Acids
J . Org. Chem., Vol. 64, No. 22, 1999 8289
Sch em e 2
catalyzed transacetalization with anisaldehyde dimethyl
acetal (PMP: p-methoxyphenyl). Addition of phenylmag-
nesium bromide gave diol 8 (83%), with minor amounts
(<2%) of monoester 9 and biphenyl, side products that
were easily separated. Sequential methylation (giving
diether 10 in 98% yield) followed by oxidative cleavage
of the acetal with 2,3-dichloro-4,5-dicyano-1,4-benzo-
quinone (DDQ) and subsequent reduction of the inter-
mediate with LiAlH4 furnished diol 3 (87%). Upon
crystallization, suitable crystals for an X-ray structure
analysis were obtained, revealing the highly stabilizing
hydrogen bonds between the methoxy groups at C-1/C-4
and the hydroxy groups at C-3/C-2. Although we opti-
mized the whole sequence by minimizing the amounts
of solvents and reagents in each step and thus increasing
the yield of every reaction (62% overall), the workup
procedures, especially the chromatographic purifications
of the intermediates, were much too time-, solvent-, and
silica gel-consuming to make multigram quantities of
product available. Since the amounts of side products
were also minimized, starting from diester 7 (which was
isolated by crystallization), all laborious purifications
could be omitted and a single chromatographic separation
gave diol 3. This four-step sequence (70% yield from 7;
61% overall) was regularly performed giving up to 35 g
of product 3. Unfortunately, we were not yet able to
directly crystallize the desired diol 3 from the crude
reaction mixture.
Sch em e 3
Hyd r obor a tion w ith En a n tiom er ica lly P u r e 1,3,2-
Dioxa bor ola n es. Alkenylboronic esters were regularly
synthesized starting from alkynes 11 by a hydroboration
(with HBBr2-SMe2 complex13 or catecholborane14) hy-
drolysis sequence to form alkenylboronic acids that were
condensed with diols. The reaction with diol 3 to ester
13 proved to be rather sluggish. One problem was the
known difficulty in obtaining boronic acids (white solids)
analytically pure, because of their tendency to form
boroxines (oils, slightly off color).3i,9b Another obvious
reason could be the steric bulk of diol 3; however,
similarly sterically demanding auxiliaries had not been
observed to cause a problem.9a Finally, the highly stable
hydrogen bonds that were also observed in solution might
prevent the otherwise fast reaction. Surprisingly, treat-
ment of the reagents with 1 equiv of water prior to the
condensation was found to be advantageous when mix-
tures of boronic acid and boroxines were used. This
process is still not understood, since NMR investigations
at room temperature showed neither a change of the
boronic acid/boroxine equilibrium nor an influence on the
hydrogen bonds of diol 3. An alternative approach that
would omit the isolation of boronic acids was the employ-
ment of alkenyl iodides, e.g., 14, that were obtained from
alkynes utilizing a hydroalumination, iodination se-
quence.15 By a metal-halide-exchange reaction with 2
equiv of tert-butyllithium followed by triisopropyl borate,
an ate complex was formed16 that was directly treated
with diol 3, giving the desired alkenylboronic ester 13a
in 79% yield (Scheme 2).
This was still an indirect, two-step synthesis of 13 from
alkynes 11, and the overall efficiency was moderate.
Arguably, the most convenient method would be a direct
hydroboration of alkynes to give alkenylboronic esters.
Although this is established when performing the trans-
formation with catechol-14 or pinacolborane,17 other ex-
amples, especially with chiral hydroborating reagents,
are scarce.18,19 The 1,3,2-dioxaborolane derived from
pinanediol attracted considerable interest in the past, but
no convenient conditions for the reaction with alkynes
were reported.17,19 Recently,9b we reported that the new
reagent 15 was obtained by treatment of diol 3 with
BH3-SMe2 complex in dichloromethane. However, its
formation required a higher temperature than expected;
the relatively sensitive 1,3,2-dioxaborolane 15 was only
formed after refluxing for 4 h (Scheme 3). The hydro-
boration of alkynes 11 was not straightforward, since no
reaction occurred at room temperature or in refluxing
dichloromethane. After hydrolysis, the hydroxy com-
pound 16 was the only isolated product whose structure
was confirmed by X-ray crystallography (recrystallization
from methanol gave the 1-methoxy-1,3,2-dioxaborolane
17). The first success was achieved when the alkyne 11
was heated with the neat reagent 15 at 80 °C giving
alkenylboronic esters 13, products that are neither ther-
molabile20 nor sensitive to oxidation,21 albeit in low yield
with major amounts of product 16. Further increasing
the temperature (Table 1) improved the yield of 13
(13) (a) Brown, H. C.; Campbell, J . B., J r. J . Org. Chem. 1980, 45,
389-395. (b) Brown, H. C.; Bhat, N. G.; Somayaji, V. Organometallics
1983, 2, 1311-1316.
(14) (a) Brown, H. C.; Gupta, S. K. J . Am. Chem. Soc. 1971, 93,
1816-1819. (b) Brown, H. C.; Gupta, S. K. J . Am. Chem. Soc. 1972,
94, 4370-4371. (c) Brown, H. C.; Gupta, S. K. J . Am. Chem. Soc. 1975,
97, 5249-5255. (d) Brown, H. C.; Chandrasekharan, J . J . Org. Chem.
1983, 48, 5080-5082.
(17) Tucker, C. E.; Davidson, J .; Knochel, P. J . Org. Chem. 1992,
57, 3482-3485.
(18) Woods, W. G.; Strong, P. L. J . Am. Chem. Soc. 1966, 88, 4667-
4671.
(15) (a) Stille, J . K.; Simpson, J . H. J . Am. Chem. Soc. 1987, 109,
2138-2152. (b) Zweifel, G.; Whitney, C. C. J . Am. Chem. Soc. 1967,
89, 2753-2754.
(19) (a) Ray, R.; Matteson, D. S. J . Ind. Chem. Soc. 1982, 59, 119-
123. (b) Matteson, D. S.; J esthi, P. K.; Sadhu, K. M. Organometallics
1984, 3, 1284-1288. (c) Matteson, D. S.; Sadhu, K. M.; Peterson, M.
L. J . Am. Chem. Soc. 1986, 108, 810-819.
(16) Dieck, H. A.; Heck, R. F. J . Org. Chem. 1975, 40, 1083-1090.

8290 J . Org. Chem., Vol. 64, No. 22, 1999
Luithle and Pietruszka
Ta ble 1. Hyd r obor a tion of Alk yn es 11 w ith
1,3,2-Dioxa bor ola n e 15
Sch em e 4
product
R
yield (%)
T (°C)
13a
13b
13c
13d
13e
13
13g
13h
13i
n-Pe
n-Bu
t-Bu
Ph
TPSO(CH2)3
BzOCH2
MOMOCH2
BnOCH2
TBSOCH2
68
70
90
90
40-90
120
82
83
135
100-120
100-120
120
(31)
91
120
Sch em e 5
F igu r e 2. Esters 18 and 19 formed by direct hydroboration
using enantiomerically pure 1,3,2-dioxaborolanes.9b
dramatically with only traces (<1%) of the regioisomers
detectable. The limiting factor is the boiling point of some
alkynes; e.g., to form n-pentyl- or n-butyl-substituted
products 13a or 13b, respectively, the reaction temper-
ature should not exceed 90 °C. In addition, it is advanta-
geous to use 2 equiv of the low-boiling alkynes for the
transformations, whereas usually 1.3-1.5 equiv was
used. Unfortunately, we were not able to obtain the ester
13c, probably due to the low boiling point of 3,3-
dimethylbutyne 11c. On the other hand, if temperatures
between 100 and 135 °C were used for the transforma-
tion, e.g., alkynes 11d or 11e, this one-pot reaction gave
alkenylboronic esters 13 in high yield and purity. Al-
though protected propargylic alcohols were also success-
fully employed in this sequence, it is obvious that the
choice of protecting group is crucial. Whereas the benzoyl
(Bz) group or ether protecting groups (MOM, methoxy-
methyl; Bn, benzyl) that could easily serve to complex
the reagent, thus further decreasing its reactivity, were
not suitable for this transformation, silyl groups proved
to be compatible. The microanalytically pure ester 13i
was isolated in high yield (91%). The benzyl-protected
product 13h was obtained as a complex, inseparable
mixture of isomers and undefined side products. How-
ever, the general concept can be employed for a variety
of 1,3,2-dioxaborolanes as long as the starting diol does
not show any side reactions. It proved to be versatile for
the transformation of pinanediol 411 and 1,1,2-triphenyl-
1,2-ethanediol 5,12 giving stable alkenylboronic esters 18
and 19 (81% and 67% yield), respectively (Figure 2).
Cyclop r op a n a tion of Alk en ylbor on ic Ester s. Next
we focused on the improvement of the diastereoselectivity
of the cyclopropanation step. First we optimized the
transformation of the n-pentyl-substituted olefin 13a to
the diastereomeric cyclopropylboronic esters 20a and 21a
(Scheme 4). We found that neither Simmons-Smith
conditions nor reactions with sulfur or phosphorus ylides
would yield the desired cyclopropanes. Pd(OAc)2-cata-
lyzed decomposition of diazomethane in the presence of
Ta ble 2. Dia ster eoselective Cyclop r op a n a tion of
Alk en ylbor on ic Ester 13a w ith Dia zom eth a n e
Pd(OAc)2
(mol %)
CH2N2
(mL/h)
dr
entry
T (°C)
(20a :21a )
1
2
3
4
5
6
7
-15
2
2
5
10
30
50
5a
60
2
60
2
2
60
2
72:28
83:17
88:12
91:9
92:8
97:3
-15
0
0
0
0
0
93:7
a
Catalyst was pretreated in an ultrasonic bath.
the olefin was the method of choice. To get high diaster-
eomeric ratios (dr), it was observed that the important
requirement was a fast decomposition of diazomethane.
Conditions favoring this fast reaction, relatively high
reaction temperature (0 °C), high concentration of
Pd(OAc)2 (up to 50 mol %), and slow addition of diazo-
methane (2 mL/h) would lead to an increased selectivity
(Table 2). Instead of using more than reasonable amounts
of “catalyst” (Table 2, entry 6), it was advantageous to
pretreat it in an ultrasonic bath, guaranteeing a fine
distribution (Table 2, entry 7). These conditions did not
only give a high selectivity (93:7, compared to 72:28
(Table 2, entry 1) as previously reported9a), but it also
minimized the formation of polymethylene, a side product
that regularly led to deactivation of the catalysts. The
strong influence of temperature and amount of catalyst
are in contrast to our observations made with the more
reactive alkenylboronic esters derived from tartric acid
derivatives.8b
With these conditions, we performed all cyclopropan-
ations of alkenylboronic esters 13a -e,i (Scheme 5 and
Table 3) and obtained the desired cyclopropanes 20 and
21 in high yield (89% to 99%) and with good selectivity
(up to 95:5). The diastereoisomers were purified by flash-
column chromatography to yield analytically pure com-
pounds, and the diastereomers were separated by means
of MPLC (the minor diastereomer 21e could not be fully
separated). The only exception was the transformation
of the silyl-protected boronic ester 13i. The combination
of low selectivity and difficulty in diastereomer separa-
tion presented a problem.
(20) (a) Matteson, D. S. J . Am. Chem. Soc. 1960, 82, 4228-4233.
(b) Matteson, D. S.; Schaumberg, G. D. J . Org. Chem. 1966, 31, 726-
731.
(21) (a) J ohnson, J . R.; Van Campen, M. G., J r. J . Am. Chem. Soc.
1938, 60, 121-124. (b) Korcek, S.; Watts, G. B.; Ingold, K. U. J . Chem.
Soc., Perkin Trans. 2 1972, 242-248.

Synthesis of Cyclopropanes from Cyclopropylboronic Acids
J . Org. Chem., Vol. 64, No. 22, 1999 8291
Ta ble 3. Cyclop r op a n a tion of Alk en es 13
Ta ble 4. Cyclop r op a n a tion of Alk en e 13j
starting
material
yield (%)
(20 + 21)
dr
(20:21)
yield (%)
(20j + 21j) (20j:21j)
dr
product
conditions
13a
13b
13c9a
13d
13e
13i
20a + 21a
20b + 21b
20c + 21c
20d + 21d
20e + 21e
20i + 21i
99
98
95
93
89
90
93:7
CH2N2, Pd(OAc)2, Et2O, 0 °C
98
94
90
91
a
80:20
36:64
20:80
60:40
60:40
30:70
89:11
87:13
86:14
95:5
Et2Zn, CH2I2, ZnI2, CH2Cl2, 0 °C
Et2Zn, CH2I2, ZnI2, 22, CH2Cl2, 0 °C
Et2Zn, CH2I2, ZnI2, ent-22, CH2Cl2, 0 °C
Et2Zn, CH2I2, 23, CH2Cl2, 0 °C
70:30
Et2Zn, CH2I2, ent-23, CH2Cl2, 0 °C
b
a
b
50% conversion of alkenylboronic ester 13j. 78% conversion
of alkenylboronic ester 13j.
Sch em e 6
Ta ble 5. Dia gn ostic 1H NMR Ch em ica l Sh ifts of
Cycloclop r op ylbor on ic Ester s 20 a n d 21 (500 MHz,
CDCl3)
major diastereomer
minor diastereomer
entry
2′-H
3′-Htrans
entry
2′-H
3′-Htrans
20a
20b
20c
20d
20e
20i
20j
0.26
0.26
0.49
1.36
0.25
0.65
0.64
0.31
0.31
0.20
0.80
0.30
0.43
0.41
21a
21b
21c
21d
21e
21i
21j
0.57
0.57
0.59
1.74
0.58
0.99
1.00
-0.06
-0.06
-0.26
0.43
-0.05
0.08
0.06
and 21j, providing a good access to these versatile
building blocks.
In the preceding tables, the absolute configuration of
the major or minor diastereomers was assigned without
any comment. Previously,9a a chemical correlation via the
synthesis of the corresponding, known cyclopropanols
unequivocally allowed the assignment. With these results
and the characteristic, diagnostic 1H NMR shifts for the
2′-H and the 3′-Htrans protons of the cyclopropane moiety,
new cyclopropylboronic esters 20 or 21 were easily
classified (Table 5). Whereas in all major diastereomers
20, the 2′-H protons show a distinct high-field shift
relative to the minor diastereomer 21, the 3′-Htrans
protons show a (relative) downfield shift. A last proof was
the X-ray structure of the minor diastereomer 21c
(Figure 3), confirming the assignment.
The X-ray structures of 21c and especially of the
corresponding alkenylboronic ester 13c are not only good
evidence for the identity of the compounds, but also
served as a tool for rationalizing the stereochemical
outcome of the cyclopropanation step. It is obvious that
the conformation of the 1,3,2-dioxaborolane ring with its
bulky substituents is always very similar, and it is
reasonable to assume that the same holds true for the
reactive conformation. With the substituents blocking
three quadrants, one face of attack should be favored.
However, this cannot directly explain the difference of
selectivity when ester 13j is cyclopropanated under
different conditions. A simple MM2 calculation23 starting
with the X-ray data from olefin 13c and replacing the
tert-butyl group with a hydroxymethyl group was per-
formed (Figure 3, bottom). From these calculations, it was
obvious that the depicted conformation is approximately
8 kJ /mol more stable than a different conformer with the
hydroxyalkyl chain showing up. We believe that the
conformation of the side chain is essential for the
selectivity, with the cyclopropanating reagent derived
from diazomethane attacking the double bond from the
opposite face (broad arrow, major diastereomer). On the
other hand, it is well established that the Simmons-
In view of the high synthetic potential of cyclopropyl-
boronic esters derived from propargylic alcohols, we
looked for an alternative. The high stability of our boronic
esters allowed us to easily desilylate ester 13i, using
either hydrofluoric acid in acetonitrile or concentrated
hydrochloric acid in ethanol (Scheme 6). This deprotec-
tion furnished alkenylboronic ester 13j in 98% or 76%
yield, respectively. Cyclopropanation (Table 4) using the
usual conditions gavesrelative to the silylated compound
13isan increased selectivity (20j/21j 80:20; 98% yield).
For the first time, we were also able to perform a
diastereoselective Simmons-Smith-type (Et2Zn, CH2I2)
cyclopropanation (94% yield) of one of our highly steri-
cally demanding alkenylboronic esters, demonstrating
the importance of a free hydroxy group for this type of
reaction. Although the selectivity was low, it was inter-
esting to note that it was reversed (20j/21j 36:64). With
these results, we next investigated whether a matched/
mismatched interaction could be observed when a chiral
ligand 22 or ent-2222 was added. Indeed, when performing
the cyclopropanation as described by Denmark et al.,3c
we got in good yield (90-91%) the products 20j and 21j,
with bissulfonamide 22 in a 20:80 ratio and with the
enantiomeric ligand ent-22 as a 60:40 mixture. Although
the Charette protocol3k using the chiral modifier 23 or
ent-23 could not be successfully employedsafter 72 h the
conversion was not completesthe results in Table 4
indicate that a matched/mismatched interaction is ob-
served. Summing up, we found two complementary,
selective approaches to either of the diastereomers 20j
(22) Takahashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.; Koba-
yashi, S. Tetrahedron 1992, 48, 5691-5700.
(23) The MM2 tool in CS Chem3D Pro 4.0 1997 from CambridgeSoft
Corp. was used.

8292 J . Org. Chem., Vol. 64, No. 22, 1999
Luithle and Pietruszka
Sch em e 8
Ta ble 6. Cyclop r op ylbor on ic Acid 25 (or r a c-25) in
Su zu k i Rea ction sa
T
(°C)
yieldb
(%)
entry product
halide
PhI
PhI
PhI
PhI
PhBr
solvent
base
1
2
3
4
5
26a
26a
26a
26a
26a
THF
THF
10% KOH
10% KOH
50 - (<10)
70 51 (>98)
50 - (66)
F igu r e 3. (Top) structures of 13c and 21c by X-ray diffraction.
(Bottom) Chem3D23 projection of 13j, rationalizing the major
reaction pathway (see text).
hexane 10% KOH
toluene 10% KOH 100 71 (>98)
DME
2 equiv of
KO-t-Bu
10% KOH
80 74 (>98)
70 66 (>98)
Sch em e 7
6
7
8
9
26b
26b
26b
26c
1-naphthyl THF
bromide
1-naphthyl toluene 3 equiv of 100 48 (70)
bromide
1-naphthyl DME
bromide
K3PO4
2 equiv of
KOtBu
80 77 (>98)
ethyl (Z)-3- toluene 3 equiv of 100 65 (>98)
bromo
K3PO4
acrylate
a
All reactions were performed with Pd(PPh3)4 as catalyst; the
b
mixtures were left for 36 h at the temperature given. Isolated
product; turnover of reaction given in parentheses was determined
by GLC.
proceed well, we found it more convenient to use LiAlH4.
The reaction to give compound 24 was fast, and subse-
quent hydrolysis with diluted sulfuric acid gave the
boronic acid 25. A fast filtration through a pad of silica
was essential to separate boronic acid 25 from diol 3,
allowing the diol to be recovered in near-quantitative
yield (always >90%). The crude boronic acid was directly
used for the Suzuki coupling, employing the conditions
described by Deng et al.7f Surprisingly, the yield was
relatively low (65%), although monitoring of all our
reactions by GLC indicated complete conversion of phenyl
bromide.
For a more detailed investigation, we synthesized
racemic cyclopropylboronic acid rac-25 from ester 277e
(Scheme 8). We then compared the different coupling
protocols to form cyclopropanes rac-26 and later repeated
the “best conditions” with enantiomerically pure acid 25
(Table 6). It was obvious to us that even when a complete
conversion of the phenyl halide (Table 6, entries 1-5)
was possible (temperatures at 70 °C or above; entries 2,
4, and 5, 26a in up to 74% yield), another side product
was formed. Changing to 1-naphthyl bromide (Table 6,
entries 6-8) not only underlined the superiority of the
Smith reagent will first form a complex between the
hydroxy group (dotted arrow) and the carbenoid being
delivered. This would obviously give a totally different
conformation since an attack from the lower face would
be more likely.
Su zu k i-Typ e Cou p lin gs of Cyclop r op ylbor on ic
Ester 20a . One of the most important transformations
of cyclopropylboronic esters is their potential in C-C
bond formations. Apart from the one-carbon homologa-
tion developed by Matteson et al.,8a,24 the Suzuki coupling
is the most prominent method to achieve the coupling
between cyclopropyl boron compounds and aryl,7e-f,8b
alkenyl,7h,8c or cyclopropyl halides.7g We were not sur-
prised to find that under various reported conditions the
direct coupling of our stable cyclopropylboronic ester 20a
did not succeed (Scheme 7). In analogy to our previously
reported results,9a it was necessary to first form an ate
complex before further transformations were possible.
Although reactions with methyllithium are possible and
(24) Luithle, J . E. A.; Pietruszka, J . Unpublished results.

Synthesis of Cyclopropanes from Cyclopropylboronic Acids
J . Org. Chem., Vol. 64, No. 22, 1999 8293
conditions developed by Marsden7e (Table 6, entry 8, 26b
in 77% yield), but also allowed the isolation of naphtha-
lene as the only side product in 10-30% yield, thus
explaining the relatively low yield obtained before. Potas-
sium phosphate remained the base of choice for relatively
labile olefins such as ethyl (Z)-3-bromoacrylate (Table 6,
entry 9, 26c in 65% yield).
phy (2 kg silica gel, petroleum ether/ethyl acetate 15:1 to 7:1)
could give diol 8 in 83% yield and compound 9 in traces (<2%);
however, the crude product could also be directly converted
to ether 10.
A solution of the yellow oil in DMSO (100 mL) was treated
with 20 mL of a solution of dimsyl anion (prepared from 0.3
mol of NaH and 60 mL of DMSO) at room temperature. To
the resulting brown mixture was added methyl iodide (7.5 mL,
0.12 mmol) after 30 min. Within 30 min, the solution had
changed to pale yellow. This procedure was repeated (in some
cases twice when TLC indicated the incomplete conversion to
product 10). Addition of diethyl ether and H2O was followed
by repeated extraction of the aqueous layer with diethyl ether.
The etheral layer was washed with water and brine to remove
remaining DMSO. After the mixture was dried over anhydrous
MgSO4, the solvent was removed under reduced pressure to
give a yellow oil. Again, flash-column chromatography (1000
g of silica gel per 20 mmol of product; petroleum ether/ethyl
acetate 19:1) could give product 10 in 99% yield (starting from
pure diol 8), but we prefer to perform the final deprotection
with the crude product.
Crude dioxolane 10 was dissolved in CH2Cl2/H2O (17:1),
DDQ (30.47 g, 0.11 mol) was added in portions at room
temperature, and immediate formation of DDQH was observed
(color change to orange/red and formation of precipitate). After
2 h, TLC indicated complete consumption of starting material.
The mixture was diluted with CH2Cl2 and filtered through a
pad of Celite. The filtrate was washed with saturated aqueous
NaHCO3, and the combined aqueous layers were extracted
with CH2Cl2. The extracts were dried (MgSO4), and the solvent
was removed under reduced pressure. The yellow oil was
dissolved in dry diethyl ether (120 mL) and slowly added to a
stirred suspension of LiAlH4 (8.38 g, 0.22 mol) in diethyl ether
(120 mL) at room temperature. The mixture was kept at
ambient temperature by cooling with a water bath. After 2 h,
the suspension was diluted with diethyl ether (100 mL) and
the reaction quenched by sequential addition of H2O (10 mL),
NaOH (15%, 10 mL), and H2O (30 mL). The precipitate was
filtered off and the solid thoroughly washed with diethyl ether.
The filtrate was dried over MgSO4 and the solution concen-
trated in vacuo. The resulting yellow oil was purified by flash-
column chromatography (1500 g of silica gel, petroleum ether/
ethyl acetate 93:7). Diol 3 (31.67 g, 70 mmol) was obtained in
70% yield (from diester 7) as a colorless, analytically pure solid.
Crystallization from petroleum ether/MeOH at -20 °C gave
colorless crystals, sufficient for X-ray analysis.
Con clu sion
Highly stable, enantiomerically pure cyclopropyl-
boronic esters 20 and 21 have been synthesized by a
simple two-step protocol from alkynes 11 in high yield,
utilizing the new hydroborating reagent 15 and the
palladium-catalyzed decomposition of diazomethane in
the cyclopropanation step. The high stability was dem-
onstrated by a selective silyl group protection without
decomposition of the boronic ester moiety. A rationale for
the selectivity based on X-ray crystal structures has been
proposed. In addition, by employing Suzuki conditions
we were able to transform cyclopropylboronic ester 20a
into enantiomerically pure cyclopropanes 26, showing
that these stable boronic esters are ideal, general inter-
mediates for cyclopropane chemistry.
Exp er im en ta l Section
Gen er a l Meth od s. The silyl-protected alkynes 11e and 11i
were prepared according to literature procedures.25 All re-
agents were used as purchased from commercial 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. Ca u tion : The generation and handling
of diazomethane requires special precaution.26 Flash-column
chromatography: Merck silica gel 60, 0.040-0.063 mm (230-
400 mesh). Preparative MPLC: packed column (49 × 500 mm),
LiChroprep, Si60 (15-25 µm), and UV detector (259 nm). 13C
NMR signals were assigned by means of C-H and H-H COSY
spectra. Microanalysis: performed at the Institut fu¨r Or-
ganische Chemie, Universita¨t Stuttgart.
P r epar ation of (2R,3R)-1,4-Dim eth oxy-1,1,4,4-tetr aph en -
yl-2,3-bu ta n d iol (3). For the synthesis of acetal 7 we followed
the procedure described previously,10 starting from dimethyl
tartrate 6 (111.4 g, 0.625 mol), anisaldehyde dimethyl acetal27
(120.8 g, 0.663 mol), and p-toluenesulfonic acid (130 mg, 0.75
mmol) in toluene (320 mL). The product was recrystallized
from petroleum ether/diethyl ether, giving product 7 as a
colorless solid in 87% yield (137.1 g, 0.463 mol).
(2R,3R)-1,4-Dim et h oxy-1,1,4,4-t et r a p h en yl-2,3-b u t a n -
d iol (3): mp ) 76-79 °C; [R]21 ) +66.6 (c 1.5, CHCl3); IR
D
(film) 3554, 3427 cm-1; 1H NMR (CDCl3, 500 MHz) δ 2.74 (br,
2 H, OH), 3.16 (s, 6 H, OMe), 4.71 (d, J ) 3.7 Hz, 2 H, 2-H/
3-H), 7.20-7.31 (m, 16 H, Ar-H), 7.41-7.44 (m, 4 H, Ar-H);
13C NMR (CDCl3, 125 MHz) δ 53.5 (OMe), 71.1 (C-2/C-3), 85.2
(C-1/C-4), 127.2, 127.3, 127.8, 127.9, 128.0, 128.7, 141.2, 142.5
(Ar-C). Anal. Calcd for C30H30O4 (454.56): C, 79.27; H, 6.65.
Found: C, 78.98; H, 6.60.
The phenylmagnesium bromide was prepared in the con-
ventional manner in 2 L three-neck round-bottom flask from
Mg turnings (24.3 g, 1.0 mol) and phenyl bromide (105 mL,
1.0 mol) in THF (280 mL). After the mixture was cooled to
-15 °C, the diester 7 (29.62 g, 0.1 mol) in THF (180 mL) was
carefully added. The reaction mixture was allowed to warm
to room temperature. After TLC indicated consumption of the
starting material, the mixture was diluted with diethyl ether
and hydrolyzed with aqueous NH4Cl solution. Separation of
the organic layer followed by extraction of the aqueous layer
with diethyl ether, washing the combined organic extracts with
saturated aqueous NaHCO3, drying over anhydrous MgSO4,
and removing of the solvent under reduced pressure gave a
yellow oil (83.5 g). Purification by flash column chromatogra-
(4R,3R)-5-(Hydr oxy(diph en yl)m eth yl)-4-m eth yloxycar -
bon yl-2-(4-m eth oxyp h en yl)-1,3-d ioxola n e (9): mp ) 119-
121 °C; [R]21 ) +45.5 (c 2.0, CHCl3); IR (film) 3456, 3027,
D
1748 cm-1
;
1H NMR (CDCl3, 500 MHz) δ 2.99 (s, 1 H, OH),
3.37 (s, 3 H, OMe), 3.80 (s, 3 H, OMe), 4.64 (d, J ) 6.9 Hz, 1
H, 5-H or 4-H), 5.35 (d, J ) 6.9 Hz, 1 H, 4-H or 5-H), 6.00 (s,
1 H, 2-H), 6.91 (d, J ) 8.6 Hz, 2 H, Ar-H), 7.20-7.57 (m, 12
H, Ar-H); 13C NMR (CDCl3, 125 MHz) δ 52.3 (OMe), 55.3
(OMe), 76.4, 78.1 (C-4/C-5), 82.9 (CPh2OH), 106.7 (C-2), 113.7,
126.2, 127.3, 127.4, 127.6, 128.2, 128.3, 129.3, 142.3, 144.6,
160.6 (Ar-C), 169.8 (CdO). Anal. Calcd for C25H24O6 (420.46):
C, 71.42; H, 5.75. Found: C, 71.51; H, 5.80.
P r ep a r a tion of Alk en ylbor on ic Ester 13a fr om Vin yl
Iod id e 14. Under an atmosphere of nitrogen vinyl iodide,15
14 (224 mg, 1.00 mmol) was dissolved in diethyl ether (1 mL)
and cooled to -78 °C. After addition of t-BuLi (1.35 mL of a
1.5 M solution in hexane, 2 mmol), a white precipitate formed.
Stirring was continued, and after 30 min triisopropyl borate
(188 mg, 231 µL, 1.00 mmol) was syringed into the mixture,
which was then allowed to warm to room temperature. The
(25) Toshima, K.; Ohta, K.; Ohashi, A.; Nakamura, T.; Nakata, M.;
Tatsuta, K.; Matsumura, S. J . Am. Chem. Soc. 1995, 117, 4822-4831.
(26) (a) Lombardi, P. Chem. Ind. (London) 1990, 708. (b) Moss, S.
Chem. Ind. (London) 1994, 122. (c) Moore, J . A.; Reed, D. E. Organic
Syntheses; Wiley: New York, 1973; Collect. Vol. V, pp 351-355.
(27) Evans, M. E. Carbohydr. Res. 1972, 21, 473-475.

8294 J . Org. Chem., Vol. 64, No. 22, 1999
Luithle and Pietruszka
ate complex was quenched with diol 3 (340 mg, 0.75 mmol),
and the reaction mixture was left at ambient temperature for
18 h. Diethyl ether was added, and the organic layer was
washed with saturated aqueous NH4Cl, H2O, and brine and
dried over MgSO4. The solution was concentrated under
reduced pressure and the residue subjected to flash-column
chromatography on silica gel, eluting with pentane/diethyl
ether (10:1 to 4:1), yielding product 13a (330 mg, 0.59 mmol,
79%). All data were in full agreement to those previously
published.9a
127.6, 127.8, 128.2, 129.6, 140.9, 141.0 (Ar-C). Anal. Calcd for
C30H29BO5 (480.36): C, 75.01; H, 6.09. Found: C, 74.87; H,
6.21.
(4R,5R)-2-Meth oxy-4,5-bis[m eth oxy(d ip h en yl)m eth yl]-
1,3,2-d ioxa bor ola n e (17): colorless crystals obtained by the
attempted crystallization of compound 16 from MeOH; mp )
129-130 °C; [R]20 ) -106.0 (c 1.8, CHCl3); IR (film) 3058,
D
1405, 1076 cm-1; MS (CI, CH4) m/z 494 (0.3) [M+], 462 (0.7)
[(M - MeOH)+], 197 (100) [(Ph2COMe)+]; 1H NMR (CDCl3, 500
MHz) δ 2.95 (s, 6 H, OMe), 3.18 (s, 3 H, BOMe), 5.21 (s, 2 H,
4-H and 5-H), 7.18-7.35 (m, 20 H, Ar-H); 13C NMR (CDCl3,
125 MHz) δ 51.8 (OMe), 52.3 (BOMe), 76.1 (C-4/C-5), 83.4
(CPh2OMe), 127.3, 127.4, 127.5, 127.8, 128.2, 129.6, 141.0,
Gen er a l P r oced u r e for th e P r ep a r a tion of Alk en yl-
bor on ic Ester s 13 via Dir ect Hyd r obor a tion of Alk yn es
11. Diol 3 (1 equiv) was carefully dried at 50 °C under reduced
pressure for 1 h. Under an atmosphere of nitrogen, CH2Cl2 (1
mL/2 mmol of diol 3) was added and the solution cooled to 0
°C. BH3-SMe2 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 °C, and alkyne 11 (1.5 equiv)
slowly added. The flask was closed with a septum, slowly
heated to the temperature indicated (Table 1), and kept at this
temperature for 12 h. After the mixture was cooled to room
temperature, standard workup (see above or ref 9) followed,
giving analytically pure alkenylboronic esters 13. Yields for
compounds 13a , 13b, and 13d are given in Table 1; all
analytical data are in full agreement to those previously
published.9a
141.1, 141.2, 141.3 (Ar-C). Anal. Calcd for
C31H31BO5
(494.39): C, 75.31; H, 6.32. Found: C, 75.25; H, 6.35.
(4R ,5R )-2-[(E )-2-{H yd r oxym e t h yl}e t h e n yl]-4,5-b is-
[m eth oxy(diph en yl)m eth yl]-1,3,2-dioxabor olan e (13j). (A)
HF (0.25 mL in 5 mL of MeCN) was slowly added to a stirred
solution of alkenylboronic ester 13i (200 mg, 0.32 mmol) in
MeCN (5 mL) at room temperature. After 20 min, TLC
indicated complete conversion of starting material. The crude
product was obtained after dilution with H2O, extraction with
CH2Cl2, washing the organic layer with brine, drying over
anhydrous MgSO4, and evaporation of the solvent. Flash-
column chromatography on silica gel, eluting with petroleum
ether/diethyl ether (10:1 to 3:1), yielded a colorless foam (161
mg, 0.31 mmol, 98%).
(B) Alkenylboronic ester 13i (5.67 g, 8.74 mol) was dissolved
in EtOH (100 mL), concentrated HCl (1.45 mL) in EtOH (20
mL) was slowly added, and the solution was stirred at room
temperature for 2 h. The mixture was diluted with diethyl
ether and H2O, the aqueous layer was extracted with diethyl
ether, and the combined organic layer was washed with
saturated aqueous NaHCO3. After being dried over MgSO4,
the mixture was filtered, the solvent evaporated, and the crude
product subjected to flash-column chromatography (see
above): yield 3.44 g (6.62 mmol, 76%); softening range ) 80-
86 °C; [R]20D ) -85.8 (c 1.0, CHCl3); IR (film) 3420, 3042, 3010,
1361, 1063 cm-1; MS (EI, 70 eV) m/z 520 (>1) [M+], 488 (2)
[(M - MeOH)+], 197 (100) [(Ph2COMe)+]; 1H NMR (CDCl3, 500
MHz) δ 1.21 (t, J ) 6.0 Hz, 1 H, OH), 2.97 (s, 6 H, OMe), 4.03
(ddd, J ) 6.0, 4.2, 1.9 Hz, 2 H, 1′′-H), 5.27 (dt, J ) 18.1, 1.9
Hz, 1 H, 1′-H), 5.32 (s, 2 H, 4-H and 5-H), 6.29 (dt, J ) 18.1,
4.2 Hz, 1 H, 2′-H), 7.21-7.35 (m, 20 H, Ar-H); 13C NMR (CDCl3,
125 MHz) δ 51.8 (OMe), 64.4 (C-1′′), 77.7 (C-4/C-5), 83.3 (CPh2-
OMe), 116.2 (C-1′), 127.2, 127.3, 127.5, 127.8, 128.4, 129.7,
141.1, 141.3 (Ar-C), 151.2 (C-2′). Anal. Calcd for C33H33BO5
(520.42): C, 76.16; H, 6.39. Found: C, 75.84; H, 6.41.
Gen er a l P r oced u r e for th e Cyclop r op a n a tion of Al-
k en ylb or on ic E st er s 13 w it h Dia zom et h a n e. Alkenyl-
boronic ester 13 (1 equiv) was dissolved in diethyl ether (1
mL/mmol 13) and 5 mol % Pd(OAc)2 added. The suspension
was treated for 2 min in an ultrasonic bath. After the mixture
was cooled to 0 °C, diazomethane26 (50 mL/mmol 13 of an
approximately 0.5 M solution in diethyl ether) was slowly (2
mL/min) added by means of a syringe pump.29 Unreacted
diazomethane was destroyed by stirring the reaction mixture
vigorously. Filtration through Celite and evaporation of the
solvent under reduced pressure, followed by chromatographic
purification, led to analytically pure cyclopropylboronic esters
20/21. The diastereomeric ratios and yields are given in Table
3. Analytical data for cyclopropanes 20a -d /21a -d were in full
agreement with those previously published.9a
(4R,5R)-2-[(E)-2-[3-ter t-Bu tyl(d ip h en yl)siloxyp r op yl]-
eth en yl]-4,5-bis[m eth oxy(d ip h en yl)m eth yl]-1,3,2-d ioxa -
bor ola n e (13e):28 yield 83%; white foam; softening range )
60-75 °C; [R]20 ) -46.6 (c 1.1, CHCl3); IR (film) 3056, 3027,
D
1380, 1077 cm-1; MS (EI, 70 eV) m/z 786 (<0.1) [M+], 754 (0.8)
[(M - MeOH)+], 197 (100) [(Ph2COMe)+]; 1H NMR (CDCl3, 500
MHz) δ 0.94 (s, 9 H, Me3C), 1.46 (mc, 2 H, 2′′-H), 1.98 (mc, 2
H, 1′′-H), 2.92 (s, 6 H, OMe), 3.49 (t, J ) 6.5 Hz, 2 H, 3′′-H),
4.95 (dt, J ) 17.9, 1.5 Hz, 1 H, 1′-H), 5.24 (s, 2 H, 4-H and
5-H), 6.10 (dt, J ) 17.9, 6.5 Hz, 1 H, 2′-H), 7.12-7.33 (m, 26
H, Ar-H), 7.54 (mc, 4 H, Ar-H); 13C NMR (CDCl3, 125 MHz) δ
18.9 (Me3C), 26.6 (Me3C), 30.7 (C-2′′), 31.5 (C-1′′), 51.5 (OMe),
62.8 (C-3′′), 77.2 (C-4/C-5), 83.2 (CPh2OMe), 117.9 (C-1′), 127.0
(2×), 127.2, 127.3 (2×), 127.4, 127.5, 128.2, 129.3, 129.5, 133.7,
135.0, 135.2, 140.9, 141.2 (Ar-C), 153.2 (C-2′). Anal. Calcd for
C
51H55BO5Si (786.88): C, 77.85; H, 7.05. Found: C, 77.72; H,
7.13.
(4R,5R)-2-[(E)-2-[3-ter t-Bu tyl(d im eth yl)siloxym eth yl]-
eth en yl]-4,5-bis[m eth oxy(d ip h en yl)m eth yl]-1,3,2-d ioxa -
bor ola n e (13i): yield 91%; white foam; softening range ) 59-
65 °C; [R]20D ) -60.2 (c 2.6, CHCl3); IR (film) 3048, 3010, 1351,
1063 cm-1; MS (EI, 70 eV) m/z 602 (0.8) [(M - MeOH)+], 197
(100) [(Ph2COMe)+]; 1H NMR (CDCl3, 500 MHz) δ -0.07 (s, 6
H, Me2Si), 0.80 (s, 9 H, Me3C), 2.93 (s, 6 H, OMe), 4.01 (dd, J
) 3.6, 2.0 Hz, 2 H, 1′′-H), 5.27 (dt, J ) 17.9, 2.0 Hz, 1 H, 1′-
H), 5.27 (s, 2 H, 4-H and 5-H), 6.18 (dt, J ) 17.9, 3.6 Hz, 1 H,
2′-H), 7.18-7.30 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
δ -5.3 (Me2Si), 18.4 (Me3C), 25.9 (Me3C), 51.8 (OMe), 64.5 (C-
1′′), 77.6 (C-4/C-5), 83.4 (CPh2OMe), 115.3 (C-1′), 127.2, 127.3
(2×), 127.4, 127.8, 128.4, 128.5, 129.7, 141.1, 141.5 (Ar-C),
151.6 (C-2′). Anal. Calcd for C39H47BO5Si (634.68): C, 73.80;
H, 7.46. Found: C, 73.54; H, 7.61.
(4R,5R)-2-Hyd r oxy-4,5-bis[m eth oxy(d ip h en yl)m eth yl]-
1,3,2-d ioxa bor ola n e (16): white foam; softening range )
120-135 °C; [R]20 ) -125.7 (c 0.56, CHCl3); IR (film) 3437,
D
(4R,5R,1′S,2′S)-2-[2-{3-ter t-Bu tyl(diph en yl)siloxypr opyl}-
cyclop r op yl]-4,5-bis[m eth oxy(d ip h en yl)m eth yl]-1,3,2-d i-
oxa bor ola n e (20e) a n d (4R,5R,1′R,2′R)-2-[2-{3-ter t-Bu tyl-
(d ip h en yl)siloxyp r op yl}cyclop r op yl]-4,5-bis[m eth oxy(d i-
p h en yl)m eth yl]-1,3,2-d ioxa bor ola n e (21e). After flash-
column chromatography (petroleum ether/diethyl ether 10:1)
a white foam (yield 89%) was isolated; by MPLC (1% EtOAc
in petroleum ether) only the major, second eluted diastereomer
3089, 3059, 1384, 1077 cm-1; MS (CI, CH4) m/z 462 (4) [(M -
1
H2O)+], 197 (100) [(Ph2COMe)+]; H NMR (CDCl3, 500 MHz)
δ 2.91 (s, 6 H, OMe), 3.31 (s, 1 H, OH), 5.19 (s, 2 H, 4-H and
5-H), 7.17-7.34 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
δ 51.8 (OMe), 76.5 (C-4/C-5), 83.3 (CPh2OMe), 127.4, 127.5,
(28) The attempted crystallization from the crude mixture failed;
the only product isolated was (4R,5R)-2-tert-butyldimethylsiloxy-4,5-
bis[methoxy(diphenyl)methyl]-1,3,2-dioxaborolane 27 as single crystals
(suitable for X-ray crystallographic analysis), probably derived by the
deprotection of alkyne 11i with the boric acid derivative 16.
(29) For the safe handling of diazomethane with the help of a
syringe-pump, all tubing, fittings, and joints were made from Teflon;
metals must be omitted.

Synthesis of Cyclopropanes from Cyclopropylboronic Acids
J . Org. Chem., Vol. 64, No. 22, 1999 8295
1
20e could be obtained in pure form (the H NMR data for the
127.8, 128.4, 129.7, 141.2, 141.2 (Ar-C). 21j (minor, first eluted
cyclopropyl group of compound 21e in Table 5 were determined
from the mixture): softening range ) 55-60 °C; [R]20D ) -34.9
(c 1.1, CHCl3); IR (film) 3067, 1370, 1077 cm-1; MS (EI, 70
eV) m/z 768 (<1) [(M - MeOH)+], 743 (<1) [(M - t-Bu)+], 197
(100) [(Ph2COMe)+]; 1H NMR (CDCl3, 500 MHz) δ -0.88 (ddd,
J ) 9.2, 6.0, 5.4 Hz, 1 H, 1′-H), 0.07 (ddd, J ) 9.2, 5.0, 3.0 Hz,
1 H, 3′-Hcis), 0.25 (mc, 1 H, 2′-H), 0.30 (ddd, J ) 9.1, 6.0, 3.0
Hz, 1 H, 3′-Htrans), 0.89-0.97 (m, 1 H, 1′′-Ha), 0.96 (s, 9 H,
Me3C), 1.19-1.27 (m, 1 H, 1′′-Hb), 1.45 (tt, J ) 7.5, 6.5 Hz, 2
H, 2′′-H), 2.93 (s, 6 H, OMe), 3.54 (mc, 2 H, 3′′-H), 5.18 (s, 2 H,
4-H and 5-H), 7.18-7.34 (m, 26 H, Ar-H), 7.57-7.59 (m, 4 H,
Ar-H); 13C NMR (CDCl3, 125 MHz) δ ∼-0.4 (C-1′), 11.5 (C-3′),
18.0 (C-2′), 18.9 (Me3C), 26.7 (Me3C), 31.3 (C-1′′), 32.4 (C-2′′),
51.5 (OMe), 63.5 (C-3′′), 76.5 (C-4/C-5), 83.0 (CPh2OMe), 122.9,
127.0, 127.2, 127.3, 127.5, 128.2, 129.2, 129.5, 133.8, 135.3,
141.0, 141.2 (Ar-C). Anal. Calcd for C52H57BO5Si (800.90): C,
77.98; H, 7.17. Found: C, 77.90; H, 7.36.
diastereomer): softening range ) 85-88 °C; [R]20 ) -117.7
D
1
(c 0.9, CHCl3); H NMR (CDCl3, 500 MHz) δ -0.72 (ddd, J )
9.7, 6.0, 5.6 Hz, 1 H, 1′-H), 0.06 (ddd, J ) 7.7, 6.0, 3.6 Hz, 1 H,
3′-Htrans), 0.20 (ddd, J ) 9.7, 5.2, 3.6 Hz, 1 H, 3′-Hcis), 0.98-
1.03 (m, 2 H, 2′-H and OH), 2.94 (s, 6 H, OMe), 3.08-3.13 (m,
1 H, 1′′-Ha), 3.23-3.27 (m, 1 H, 1′′-Hb), 5.21 (s, 2 H, 4-H and
5-H), 7.17-7.28 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz)
δ ∼-2.0 (C-1′), 9.6 (C-3′), 20.9 (C-2′), 51.7 (OMe), 67.8 (C-1′′),
77.5 (C-4/C-5), 83.3 (CPh2OMe), 127.2, 127.3, 127.5, 127.8,
128.4, 129.7, 141.2, 141.2 (Ar-C).
Cyclop r op a n a tion of Alk en ylbor on ic Ester 13j Utiliz-
in g Mod ified Sim m on s-Sm ith Con d ition s. (A) To a stirred
solution of alkenylboronic ester 13j (100 mg, 0.19 mmol) in
CH2Cl2 (2 mL) was added diethylzinc (211 µL 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 97.5
mg iodine and 192 µL diethyl zinc solution (1 M in hexane))
in CH2Cl2 (4 mL). The suspension was stirred for 5 min at 0
°C and was then added to a third flask with a preformed
reagent [31 µL (0.38 mmol) CH2I2 dissolved in CH2Cl2 (8 mL)
and treated with diethylzinc solution (192 µL of a 1 M solution
in hexane) at 0 °C] for the cyclopropanation. Stirring was
continued for 12 h at room temperature. After the reaction
was quenched with saturated aqueous NH4Cl, the aqueous
layer was extracted with diethyl ether. The combined organic
layer was dried over MgSO4 and the solvents were removed
under reduced pressure. The crude product was purified by
flash-column chromatography (see above): yield 97 mg (0.18
mmol, 94%), dr 20j/21j 36:64.
(4R,5R,1′S,2′S)-2-[2-[ter t-Bu tyl(dim eth yl)siloxym eth yl]-
cyclop r op yl]-4,5-bis[m eth oxy(d ip h en yl)m eth yl]-1,3,2-d i-
oxabor olan e (20i) an d (4R,5R,1′R,2′R)-2-[(E)-2-[ter t-Bu tyl-
(dim eth yl)siloxym eth yl]cyclopr opyl]-4,5-bis[m eth oxy(di-
p h en yl)m et h yl]-1,3,2-d ioxa b or ola n e (21i). After flash-
column chromatography (petroleum ether/diethyl ether 10:1),
a white foam (yield 90%) was isolated; by MPLC (1% EtOAc
in petroleum ether) the diastereoisomers 20i and 21i could
be partially separated. The analytical data for the minor
diastereoisomer 21i were obtained from the mixture: IR (film)
3059, 3026, 1387, 1077 cm-1; MS (FAB, NBA + NaI) m/z 671
(5) [(M + Na)+], 197 (100) [(Ph2COMe)+]. Anal. Calcd for
C
7.70.
40H49BO5 (648.71): C, 74.06; H, 7.61. Found: C, 73.90; H,
(B) The same protocol was followed, but bis(sulfonamide)
2222 (8.1 mg, 0.02 mmol) was added to the alkenylboronic ester
13j before addition of diethylzinc: yield 92 mg (0.17 mmol,
90%), dr 20j/21j 20:80.
20i (major diastereomer): softening range ) 54-60 °C;
[R]21 ) -44.3 (c 1.1, CHCl3); 1H NMR (CDCl3, 500 MHz) δ
D
-0.64 (ddd, J ) 9.5, 6.0, 5.4 Hz, 1 H, 1′-H), -0.01 (s, 3 H,
Me), 0.00 (s, 3 H, Me), 0.34 (ddd, J ) 9.5, 5.2, 3.4 Hz, 1 H,
3′-Hcis), 0.43 (ddd, J ) 7.9, 6.0, 3.4 Hz, 1 H, 3′-Htrans), 0.65 (mc,
1 H, 2′-H), 0.84 (s, 9 H, Me3C), 2.99 (s, 6 H, OMe), 3.08 (dd, J
) 10.5, 7.0 Hz, 1 H, 1′′-Ha), 3.59 (dd, J ) 10.5, 4.7 Hz, 1 H,
1′′-Hb), 5.25 (s, 2 H, 4-H and 5-H), 7.23-7.34 (m, 20 H, Ar-H);
13C NMR (CDCl3, 125 MHz) δ -5.3 (Me), -5.2 (Me), -3.2 (C-
1′), 9.6 (C-3′), 18.4 (Me3C), 20.0 (C-2′), 26.0 (Me3C), 51.7 (OMe),
66.9 (C-1′′), 77.6 (C-4/C-5), 83.3 (CPh2OMe), 127.2, 127.4,
127.7, 128.4, 129.7, 141.2, 141.4 (Ar-C). 21i (minor diaster-
eomer): 1H NMR (CDCl3, 500 MHz) δ -0.63 (ddd, J ) 9.8,
5.9, 5.7 Hz, 1 H, 1′-H), -0.03 (s, 3 H, Me), -0.02 (s, 3 H, Me),
0.08 (mc, 1 H, 3′-Htrans), 0.27 (ddd, J ) 9.8, 5.2, 3.4 Hz, 1 H,
3′-Hcis), 0.84 (s, 9 H, Me3C), 0.99 (mc, 1 H, 2′-H), 3.00 (s, 6 H,
OMe), 3.07 (dd, J ) 10.6, 7.0 Hz, 1 H, 1′′-Ha), 3.57 (dd, J )
10.6, 4.9 Hz, 1 H, 1′′-Hb), 5.26 (s, 2 H, 4-H and 5-H), 7.24-
7.37 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125 MHz) δ -5.6 (Me),
-5.5 (Me), -3.2 (C-1′), 9.8 (C-3′), 18.4 (Me3C), 20.0 (C-2′), 26.0
(Me3C), 51.7 (OMe), 67.1 (C-1′′), 77.7 (C-4/C-5), 83.3 (CPh2-
OMe), 127.1, 127.3, 127.4, 128.3, 129.7, 141.2, 141.4 (Ar-C).
(4R,5R,1′S,2′S)-2-[2-(Hyd r oxym eth yl)cyclop r op yl]-4,5-
bis[m eth oxy(d ip h en yl)m eth yl]-1,3,2-d ioxa bor ola n e (20j)
a n d (4R,5R,1′R,2′R)-2-[2-(Hyd r oxym eth yl)cyclop r op yl]-
4,5-b is[m et h oxy(d ip h en yl)m et h yl]-1,3,2-d ioxa b or ola n e
(21j). After flash-column chromatography (petroleum ether/
ethyl acetate 4:1) a white foam (yield 98%) was isolated: IR
(film) 3392, 3058, 1387, 1076 cm-1; MS (FAB, NBA + NaI)
m/z 557 (35) [(M + Na)+], 197 (100) [(Ph2COMe)+]. Anal. Calcd
for C34H55BO5 (534.45): C, 76.41; H, 6.60. Found: C, 76.31;
H, 6.72.
(C) Same protocol as above (B), but with bis(sulfonamide)
en t-22: yield 93 mg (0.17 mmol, 91%), dr 20j/21j 60:40.
(D) Dioxaborolane 23 was prepared from butylboronic acid
(6.2 mg, 0.06 mmol) and l-(+)-N,N,N′,N′-tetramethyltar-
tramide30 (14.7 mg, 0.07 mmol) in CH2Cl2 (1 mL) in the
presence of MgSO4 (200 mg). The resulting solution was
filtered under an atmosphere of nitrogen into a flask contain-
ing alkenylboronic ester 13j (26.4 mg, 0.05 mmol). The
resulting solution was syringed into a third flask with the
freshly prepared Simmons-Smith reagent (from 26 µL of
CH2I2 dissolved in 1 mL of CH2Cl2 and 160 µL of 1 M
diethylzinc solution) at 0 °C. After 72 h at room temperature,
NMR indicated only 50% conversion to the product (dr 20j/
21j 60:40).
(E) Same protocol as above (D), but with D-(-)-N,N,N′,N′-
tetramethyltartramide. Conversion after 72 h: 78% (dr 20j/
21j 30:70).
Syn th esis of Cyclop r op ylbor on ic Acid r a c-25. A stirred
solution of 1-heptyne (8.53 mL, 65 mmol) in CH2Cl2 (20 mL)
was cooled to 0 °C. Dibromoborane-dimethyl sulfide complex
(13.55 g, 58 mmol) in CH2Cl2 (24 mL) was slowly added. After
4 h at room temperature, the green solution was carefully
transferred into a cooled solution of 10% aqueous NaOH (90
mL) and the mixture stirred for 15 min at 0 °C. Saturated
aqueous NH4Cl (150 mL) was added, and a voluminous white
precipitate formed. CH2Cl2 was removed under reduced pres-
sure. The boronic acid 12a was filtered with suction and
washed extensively with ice-water. The colorless solid was
directly used without any further purification. To a slurry of
the boronic acid in pentane (40 mL) was added 1,3-propanediol
(4.33 mL, 60 mmol). After 48 h, the aqueous layer was
separated. The organic layer was dried over MgSO4 and the
product distilled to yield a colorless oil (9.19 g, 50 mmol, 87%).
By MPLC (20% EtOAc in petroleum ether) the diaster-
eomers 20j and 21j could be separated. 20j (major, second
eluted diastereomer): mp ) 135-136 °C; [R]20D ) -89.8 (c 2.1,
CHCl3); 1H NMR (CDCl3, 500 MHz) δ -0.72 (ddd, J ) 9.6,
6.2, 5.4 Hz, 1 H, 1′-H), 0.24 (ddd, J ) 9.6, 5.2, 3.6 Hz, 1 H,
3′-Hcis), 0.41 (ddd, J ) 7.7, 6.2, 3.6 Hz, 1 H, 3′-Htrans), 0.64 (mc,
1 H, 2′-H), 1.04 (br, 1 H, OH), 2.93 (s, 6 H, OMe), 3.13-3.18
(m, 1 H, 1′′-Ha), 3.19-3.25 (m, 1 H, 1′′-Hb), 5.21 (s, 2 H, 4-H
and 5-H), 7.17-7.28 (m, 20 H, Ar-H); 13C NMR (CDCl3, 125
MHz) δ ∼-2.0 (C-1′), 9.4 (C-3′), 20.4 (C-2′), 51.7 (OMe), 67.8
(C-1′′), 77.5 (C-4/C-5), 83.3 (CPh2OMe), 127.2, 127.3, 127.5,
(30) (a) Seebach, D.; Kalinowski, H.-O.; Bastani, B.; Crass, G.;
Daum, H.; Do¨rr, H.; DuPreez, N. P.; Ehrig, V.; Langner, W.; Nu¨ssler,
C.; Oei, H.-A.; Schmidt, M. Helv. Chim. Acta 1977, 60, 301-325. (b)
Seebach, D.; Kalinowski, H.-O.; Langer, W.; Crass, G.; Wilka, E.-M.
Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, pp 41-
50.

8296 J . Org. Chem., Vol. 64, No. 22, 1999
Luithle and Pietruszka
2-[(E)-1-Hep ten -1-yl]-1,3,2-d ioxa bor in a n e: bp ) 105 °C
(15 Torr); IR (film) 2928, 2857, 1325 cm-1; MS (EI, 70 eV) m/z
182 (17) [M+], 154 (10) [(M - C2H4)+], 139 (17) [(M - C3H7)+],
126 (100) [(M - C4H8)+]; 1H NMR (CDCl3, 500 MHz) δ 0.85 (t,
J ) 6.9 Hz, 3 H, 7′-H), 1.21-1.31 (m, 4 H, 5′-H and 6′-H), 1.35-
1.61 (m, 2 H, 3′-H), 1.93 (mc, 2 H, 5-H), 2.07-2.11 (m, 2 H,
3′-H), 4.00 (mc, 4 H, 4-H and 6-H), 5.29 (dt, J ) 17.8, 1.2 Hz,
1 H, 1′-H), 6.47 (dt, J ) 17.8, 6.5 Hz, 1 H, 2′-H); 13C NMR
(CDCl3, 125 MHz) δ 14.0 (C-7′), 22.5 (C-5′ or C-6′), 27.4 (C-5),
28.2 (C-4′), 31.4 (C-6′ or C-5′), 35.5 (C-3′), 61.6 (C-4 and C-6),
∼124.9 (br, C-1′), 151.7 (C-2′). Anal. Calcd for C10H19BO2
(182.07): C, 65.97; H, 10.52. Found: C, 65.87; H, 10.67.
The olefin (6.66 g, 36.6 mmol) was dissolved in diethyl ether
(10 mL), and Pd(OAc)2 (165 mg, 0.74 mmol) was added. A
solution of diazomethane in diethyl ether (600 mL) was
carefully added. The excess diazomethane was destroyed by
vigorously stirring the mixture. The suspension was filtered
through a pad of Celite, the solvent removed under reduced
pressure, and the residue distilled. The product (4.70 g, 24.0
mmol, 65%) was obtained as a colorless oil.
2-(t r a n s-2-P e n t ylcyclop r op yl)-1,3,2-d ioxa b or in a n e
(27): bp ) 117-119 °C (15 Torr); IR (film) 2924, 2854, 1347
cm-1; MS (EI, 70 eV) m/z 196 (17) [M+], 168 (26) [(M - C2H4)+],
139 (51) [(M - C4H9)+], 126 (100) [(M -C5H10)+]; 1H NMR
(CDCl3, 500 MHz) δ -0.61 (ddd, J ) 9.3, 6.0, 5.4 Hz, 1 H, 1′-
H), 0.24 (ddd, J ) 9.3, 5.0, 3.0 Hz, 1 H, 3′-Hcis), 0.52 (ddd, J )
9.2, 6.0, 3.0 Hz, 1 H, 3′-Htrans), 0.79 (mc, 1 H, 2-H′), 0.85 (t, J
) 7.3 Hz, 3 H, 5′′-H), 1.11 (mc, 1 H, 1′′-Ha), 1.20-1.30 (m, 5 H,
1′′-Hb, 3′′-H and 4′′-H), 1.31-1.38 (m, 2 H, 2′′-H), 1.87 (mc, 2
H, 5-H), 3.90 (mc, 4 H, 4-H and 6-H); 13C NMR (CDCl3, 125
MHz) δ 3.4 (br, C-1′), 11.0 (C-3′), 14.1 (C-5′′), 17.8 (C-2′), 22.6
(C-5′ or C-6′), 27.4 (C-5), 29.4 (C-2′′), 31.7 (C-3′′ or C-4′′), 35.3
After 36 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 the crude product purified by means of
MPLC (petroleum ether). (B) Syn th esis of Cyclop r op a n e
26c. Cyclopropylboronic acid 25 (1.1 equiv) was dissolved in
toluene (10 mL/mmol 25). After addition of Pd(PPh3)4 (3 mol
%) and K3PO4 (4 equiv), the mixture was carefully deoxygen-
ated. Ethyl (Z)-3-bromoacrylate (1 equiv) was added. After 36
h at 100 °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 pres-
sure, and the crude product purified by means of MPLC
(petroleum ether).
(1S,2S)-1-P h en yl-2-pen tylcyclopr opan e (26a): yield 74%;
colorless oil; [R]20D ) +73.9 (c 1.0, CHCl3); IR (film) 3048, 3023
cm-1; MS (EI, 70 eV) m/z 188 (31) [M+], 117 (59) [(M -
C5H11)+], 104 (100) [(M - C6H12)+], 91 (20) [(C7H7)+]; 1H NMR
(CDCl3, 500 MHz) δ 0.77 (ddd, J ) 8.5, 5.7, 4.6 Hz, 1 H, 3-Hcis),
0.89 (ddd, J ) 8.5, 4.8, 4.6 Hz, 1 H, 3-Htrans), 0.91 (t, J ) 7.0
Hz, 3 H, 5′-H), 1.07 (dtdd, J ) 8.5, 6.5, 5.7, 4.4 Hz, 1 H, 2-H),
1.29-1.34 (m, 4 H, 3′-H and 4′-H), 1.35-1.41 (m, 2 H, 1′-H),
1.41-1.52 (m, 2 H, 2′-H), 1.62 (ddd, J ) 8.5, 4.8, 4.4 Hz, 1 H,
1-H), 7.06 (mc, 2 H, Ar-H), 7.14 (mc, 1 H, Ar-H), 7.26 (mc, 2 H,
Ar-H); 13C NMR (CDCl3, 125 MHz) δ 14.1 (C-5′), 16.2 (C-3),
22.7 (C-3′ or C-4′), 23.2 (C-1), 23.9 (C-2), 29.1 (C-2′), 31.7 (C-4′
or C-3′), 34.4 (C-1′), 125.1, 125.5, 128.2, 144.1 (Ar-C). Anal.
Calcd for C14H20 (188.31): C, 89.29; H, 10.71. Found: C, 89.38;
H, 10.71.
(1S,2S)-1-(1-Naph th yl)-2-pen tylcyclopr opan e (26b): yield
77%; colorless oil; [R]20D ) +31.3 (c 1.5, CHCl3); IR (film) 3048
cm-1; MS (EI, 70 eV) m/z 238 (72) [M+], 167 (100) [(M -
C5H11)+], 154 (35) [(M - C6H12)+], 141 (19) [(C11H10)+]; 1H NMR
(CDCl3, 500 MHz) δ 0.82 (ddd, J ) 8.5, 5.4, 4.4 Hz, 1 H, 3-Hcis),
0.85 (t, J ) 7.0 Hz, 3 H, 5′-H), 0.95 (ddd, J ) 8.4, 5.2, 4.4 Hz,
1 H, 3-Htrans), 1.08 (dtdd, J ) 8.4, 6.5, 5.4, 4.8 Hz, 1 H, 2-H),
1.24-1.38 (m, 4 H, 3′-H and 4′-H), 1.40 (mc, 1 H, 1′-Ha), 1.46-
1.54 (m, 2 H, 2′-H), 1.68 (mc, 1 H, 1′-Hb), 2.07 (ddd, J ) 8.5,
5.2, 4.8 Hz, 1 H, 1-H), 7.19 (mc, 1 H, Ar-H), 7.34 (mc, 1 H, Ar-
H), 7.48 (mc, 2 H, Ar-H), 7.65 (mc, 1 H, Ar-H), 7.82 (mc, 1 H,
Ar-H), 8.43 (mc, 1 H, Ar-H); 13C NMR (CDCl3, 125 MHz) δ 13.7
(C-3), 14.1 (C-5′), 20.8 (C-1), 21.1 (C-2), 22.7 (C-3′ or C-4′), 29.2
(C-2′), 31.8 (C-4′ or C-3′), 34.5 (C-1′), 123.4, 124.4, 125.5, 125.8,
126.3, 127.9, 128.5, 133.3, 133.4, 139.4 (Ar-C). Anal. Calcd for
(C-1′′), 61.5 (C-4 and C-6). Anal. Calcd for
C11H21BO2
(196.09): C, 67.37; H, 10.79. Found: C, 67.33; H, 10.94.
The cyclopropyl boronic ester 27 (1.25 g, 6.38 mmol) was
added dropwise to a cooled solution of 10% aqueous NaOH (50
mL). The mixture stirred for 15 min at 0 °C. Saturated aqueous
NH4Cl (100 mL) was added, and a voluminous white precipi-
tate formed. The boronic acid r a c-25 was filtered with suction
and washed extensively with ice-water. The colorless solid
r a c-25 (940 mg) was directly used for further transformations
without purification.
tr a n s-2-P en tylcyclop r op ylbor on ic a cid (r a c-25): MS
(EI, 70 eV) m/z 414 (3) [(3M - 3H2O)+] (cyclic trimer), 156 (5)
1
[M+], 138 (8) [(M - H2O)+], 86 (46) [(M - C5H10)+]; H NMR
C
18H22 (238.37): C, 90.70; H, 9.30. Found: C, 90.71; H, 9.42.
(THF-d8, 500 MHz) δ -0.65 (dt, J ) 9.3, 6.0, 5.4 Hz, 1 H, 1-H),
0.20 (ddd, J ) 9.3, 5.0, 2.8 Hz, 1 H, 3-Hcis), 0.57 (ddd, J ) 7.6,
6.0, 2.8 Hz, 1 H, 3-Htrans), 0.83 (mc, 1 H, 2-H), 0.89 (t, J ) 7.2
Hz, 3 H, 5′-H), 1.19-1.24 (m, 2 H, 1′-H), 1.28-1.34 (m, 4 H,
3′-H and 4′-H), 1.37-1.43 (m, 2 H, 2′-H), 6.40 (s, 2 H, OH);
13C NMR (THF-d8, 125 MHz) δ 4.8 (br, C-1), 11.9 (C-3), 14.7
(C-5′), 18.8 (C-2), 23.9 (C-3′ or C-4′), 30.8 (C-2′), 33.1 (C-3′ or
C-4′), 36.9 (C-1′); HRMS (EI, 70 eV) calcd for C24H45B3O3
414.3648 [M+], found 414.3648.
(1S,2S)-2-P en tylcyclop r op ylbor on ic Acid (25). Cyclo-
propylboronic ester 20a (2.03 g, 3.53 mmol) in THF (5 mL)
was stirred at 0 °C. LiAlH4 (402 mg, 10.6 mmol) was carefully
added and the mixture kept at 0 °C for 1 h, after which time
TLC indicated the complete consumption of starting material.
Dilution with diethyl ether (25 mL) was followed by treatment
with 10% sulfuric acid (20 mL). The aqueous layer was quickly
extracted with petroleum ether. The combined organic layer
was washed with brine, and the solution was directly subjected
to flash-column chromatography (silica gel, eluting with
petroleum ether/diethyl ether 4:1-1:1). The diol 3 (1.57 g, 3.45
mmol, 98%) was recovered, and the crude boronic acid 25 (460
mg) was used for Suzuki couplings without further purifica-
tion.
E t h yl
(1S,2S)-(Z)-3-(2-p en t ylcyclop r op yl)a cr yla t e
(26c): yield 65%; colorless oil; [R]20 ) -64.9 (c 1.7, CHCl3);
D
IR (film) 2958, 2926, 2856, 1717, 1632, 1184 cm-1; MS (EI, 70
eV)) m/z 210 (4) [M+], 181 (1) [(M - C2H5)+], 165 (9) [(M -
C2H5O)+], 125 (19) [(M - C2H5) - (C4H8)+], 111 (100) [(M -
C2H5) - (C4H8)+]; 1H NMR (CDCl3, 500 MHz) δ 0.70 (ddd, J )
8.5, 4.5, 4.4 Hz, 1 H, 11-Ha), 0.79 (ddd, J ) 8.1, 5.9, 4.4 Hz, 1
H, 11-Hb), 0.87 (t, J ) 7.1 Hz, 3 H, 10-H), 0.85-0.94 (m, 1 H,
5-H), 1.22-1.41 (m, 8 H, 6-H, 7-H, 8-H, and 9-H), 1.28 (t, J )
7.0 Hz, 3 H, CH3CH2O), 2.63 (dddd, J ) 11.2, 8.1, 4.5, 4.1 Hz,
1 H, 4-H), 4.17 (mc, 2 H, CH3CH2O), 5.47 (t, J ) 11.2 Hz, 1 H,
3-H), 5.62 (d, J ) 11.2 Hz, 1 H, 2-H); 13C NMR (CDCl3, 125
MHz) δ 14.1 (C-10), 14.3 (CH3CH2O), 16.4 (C-11), 19.9 (C-4),
22.6 (C-8 or C-9), 23.7 (C-5), 28.9 (C-7), 31.6 (C-8 or C-9), 33.3
(C-6), 59.6 (CH2O), 116.1 (C-2), 155.1 (C-3), 167.3 (C-1). Anal.
Calcd for C13H22O2 (210.31): C, 74.24; H, 10.54. Found: C,
74.05; H, 10.65.
Ack n ow led gm en t . We thank the Deutsche For-
schungsgemeinschaft (fellowship to J .P.) and the Fonds
der Chemischen Industrie (Liebig fellowship to J .P. and
doctoral fellowship to J .E.A.L.) for generous support of
this work. Donations from the Boehringer Ingelheim KG
(Biberach, Germany), the Degussa AG (Hanau, Ger-
many), the Bayer AG (Leverkusen/Monheim, Germany),
and the Novartis AG (Basel, Switzerland) were greatly
appreciated. We are grateful to the Institut fu¨r Or-
ganische Chemie der Universita¨t Stuttgart (Prof. Dr.
Su zu k i Cou p lin gs: “Best Con d ition s” for th e P r ep a r a -
tion of Cyclop r op a n es 26. (A) Syn th esis of 1-Ar yl-2-
p en tylcyclop r op a n es 26a ,b. Cyclopropylboronic acid 25 (1.1
equiv) was dissolved in DME (10 mL/mmol 25). After addition
of Pd(PPh3)4 (3 mol %) and KO-t-Bu (2 mL/mmol 25 of a 1 M
solution in t-BuOH), the mixture was carefully deoxygenated
by a freeze technique. Phenyl bromide (1 equiv) was added.

Synthesis of Cyclopropanes from Cyclopropylboronic Acids
J . Org. Chem., Vol. 64, No. 22, 1999 8297
V. J a¨ger and Prof. Dr. Dr. h. c. F. Effenberger) for their
ongoing support. Special thanks to our analytical de-
partment for their assistance and contributions that
enabled the preparation of this manuscript (X-ray
structure analysis: Dr. W. Frey; NMR-service: PD Dr.
P. Fischer, J . Rebell, H.-U. Ho¨hn; MS-service: Dr. J .
Opitz, F. Bender, J . Trinkner). We also gratefully
acknowledge the help of Prof. Dr. R. F. W. J ackson
during the preparation of the manuscript. Finally, we
thank our collegue and co-worker Dipl.-Chem. A. Witt
for preliminary experiments.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR data for
compounds 7, 8, and 10; analytical data for compounds 11e,
18, 19, and 27; crystallographic data for compounds 3, 13c,
21c, and 27; 1H/13C NMR spectra of compounds 13a ,j, 20a ,
21a , 20j, 21j, and 26a -c. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O9910278