Asymmetric homologation of boronic esters bearing azido and silyloxy substituents

Article abstract of DOI:10.1021/jo005522b

In the asymmetric homologation of boronic esters with a (dihalomethyl)lithium, substituents that can bind metal cations tend to interfere. Accordingly, we undertook the introduction of weakly basic oxygen and nitrogen substituents into boronic esters in order to maximize the efficiency of multistep syntheses utilizing this chemistry. Silyloxy boronic esters cannot be made efficiently by direct substitution, but a (hydroxymethyl)boronic ester has been silylated in the usual manner. Conversion of (α-halo boronic esters to α-azido boronic esters has been carried out with sodium azide and a tetrabutylammonium salt as phase-transfer catalyst in a two-phase system with water and either nitromethane or ethyl acetate. These are safer solvents than the previously used dichloromethane, which can form an explosive byproduct with azide ion. Boronic esters containing silyloxy or alkoxy and azido substituents have been shown to react efficiently with (dihalomethyl)-lithiums, resulting in efficient asymmetric insertion of the halomethyl group into the carbon-boron bond.

Full text of DOI:10.1021/jo005522b

6650
J . Org. Chem. 2000, 65, 6650-6653
Asym m etr ic Hom ologa tion of Bor on ic Ester s Bea r in g Azid o a n d
Silyloxy Su bstitu en ts
Rajendra Prasad Singh and Donald S. Matteson*
Department of Chemistry, Washington State University, Pullman, Washington 99164-4630
dmatteson@wsu.edu
Received May 24, 2000
In the asymmetric homologation of boronic esters with a (dihalomethyl)lithium, substituents that
can bind metal cations tend to interfere. Accordingly, we undertook the introduction of weakly
basic oxygen and nitrogen substituents into boronic esters in order to maximize the efficiency of
multistep syntheses utilizing this chemistry. Silyloxy boronic esters cannot be made efficiently by
direct substitution, but a (hydroxymethyl)boronic ester has been silylated in the usual manner.
Conversion of R-halo boronic esters to R-azido boronic esters has been carried out with sodium
azide and a tetrabutylammonium salt as phase-transfer catalyst in a two-phase system with water
and either nitromethane or ethyl acetate. These are safer solvents than the previously used
dichloromethane, which can form an explosive byproduct with azide ion. Boronic esters containing
silyloxy or alkoxy and azido substituents have been shown to react efficiently with (dihalomethyl)-
lithiums, resulting in efficient asymmetric insertion of the halomethyl group into the carbon-
boron bond.
In tr od u ction
conditions previously used for the azide substitution, a
phase-transfer reaction in dichloromethane/water,7,8 are
hazardous because of the possibility of generating diazi-
domethane.9 For masked hydroxyl functions, it appeared
likely that silyloxy groups would be ideal, but there had
never been a successful synthesis of an R-silyloxy boronic
ester.
It is well established that the highly stereoselective
homologation of chiral boronic esters with (dichlorom-
ethyl)lithium works best in the absence of highly polar
substituents.1 At the outset, it was found that the
reaction fails with tartrate boronates.2 Steps in a syn-
thesis of L-ribose proceeded efficiently in the presence of
up to three benzyloxy substituents, but the yield dropped
drastically after the fourth benzyloxy substituted carbon
had been introduced.3 An unexpected reaction in which
a benzyloxy group was cleaved in the presence of a
trityloxy group has been encountered.4 Failure of an
R-amido substituted boronic ester to undergo CHCl
insertion into the carbon-boron bond has thwarted an
attempted kainic acid synthesis.5 Silylated R-amido bo-
ronic esters are similarly resistant to the homologation,
though some success has been achieved with silylated
aminomethyl boronic esters.6
Resu lts
Silyloxy Su bstitu en ts. Treatment of 2-(bromom-
ethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1) with
lithiated tert-butyldimethylsilanol yielded a gross mix-
ture of isomers 3 and 4. The 1H NMR spectrum indicated
that the ratio was ∼70/30, based on the singlets at δ 1.24
and 3.11 attributed to the pinacol methyl groups and
B-methylene group, respectively, of 3 and the paired
singlets at δ 1.16 and 1.28 and the singlet at 4.20
attributed to the distinguishable pairs of pinacol methyl
groups and the B-methylene group of 4. An obvious
mechanism for production of 4 involves competing migra-
tion of the alkoxy and silyloxy groups from boron to the
bromomethyl carbon of intermediate 2.
The azido substituent has been found to be compatible
with the homologation process,7 and a synthesis of amino
acids via azido boronic esters has been reported.8 Thus,
the azido group appeared likely to be the most useful
masked amino group for this chemistry. However, the
(1) (a) Matteson, D. S. Tetrahedron 1998, 54, 10555-10607. (b)
Matteson, D. S. J . Organomet. Chem. 1999, 581, 51-65.
(2) Matteson, D. S.; Ray, R.; Rocks, R. R.; Tsai, D. J . S. Organome-
tallics 1983, 2, 1536-1543.
(3) Matteson, D. S.; Peterson, M. L. J . Org. Chem. 1987, 52, 5116-
5121.
(4) Matteson, D. S.; Soundararajan, R.; Ho, O. C.; Gatzweiler, W.
Organometallics 1996, 15, 152-163.
(5) Matteson, D. S.; Lu, J . Tetrahedron: Asymmetry 1998, 9, 2423-
2436.
(6) Matteson, D. S.; Singh, R. P.; Sutton, C. H.; Verheyden, J . D.;
Lu, J . Heteroat. Chem. 1997, 487-494.
(7) Matteson, D. S.; Sadhu, K. M.; Peterson, M. L. J . Am. Chem.
Soc. 1986, 108, 812-819.
(8) (a) Matteson, D. S.; Beedle, E. C. Tetrahedron Lett. 1987, 28,
4499-4502. (b) Matteson, D. S.; Beedle, E. C.; Christenson, E.; Dewey,
M. A.; Peterson, M. L. J . Labelled Cpd. Radiopharm. 1988, 25, 675-
683.
Alkoxy groups such as benzyloxy and even trityloxy
have invariably shown a strong migratory preference to
10.1021/jo005522b CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/08/2000

Asymmetric Azido and Silyl Boronic Esters
J . Org. Chem., Vol. 65, No. 20, 2000 6651
the apparent exclusion of ring expansion.3,4,10 Silyloxy
groups are evidently weaker competitors as a result of
their lower nucleophilicity.
We then turned to silylation of a 2-(hydroxymethyl)-
1,3,2-dioxaborolane. Hydrogenolysis of 2-(benzyloxy-
methyl)-1,3,2-dioxaborolane (5) to the hydroxymethyl
derivative 6 was followed immediately by silylation with
tert-butyldimethylsilyl chloride to form the 2-(trialkyl-
silyloxymethyl)-1,3,2-dioxaborolane 7a or with tert-butyl-
diphenylsilyl chloride to form the analogous derivative
7b.
Azid o Su bstitu en ts. Several attempts to make an
R-azido ester by reaction of an R-chloro boronic ester with
an alkali metal azide in DMSO have been unsuccessful.
The phase-transfer process between water and dichloro-
methane reported earlier has given excellent yields,7,8
though it can be hazardous.9 It was therefore appropriate
to test alternative solvents in the hope that one could be
found in which tetrabutylammonium salts would be
sufficiently soluble to provide useful reaction rates.
The R-chloro-â-trityloxy boronic ester 8d , which had
been used as the precursor to amido boronic esters
reported previously,6 as well as the analogous p-meth-
oxybenzyl boronic ester 8c, were used as the initial test
substrates. Tetrabutylammonium bromide proved insuf-
ficiently soluble in diethyl ether or diethoxymethane to
provide measurable reaction rates with sodium azide.
However, nitromethane was found to dissolve enough
tetrabutylammonium salt to provide slow but useful
reaction rates, comparable to those observed with dichloro-
methane, and efficient production of azido derivatives 9c
and d .
The availability of the silyloxy boronic esters 7a and
b from the route outlined above allowed the straightfor-
ward preparation of R-chloro boronic esters 8a and 8b.
Nitromethane was used as the organic phase with 8a ,
ethyl acetate with 8b, and efficient azide substitution to
form 9a or b was achieved in each case.
Homologation of azido boronic esters 9 with (dibromo-
methyl)lithium led to R-bromo boronic esters 10. Reaction
of 10 with lithioacetonitrile, assisted by magnesium
bromide as a catalyst/promoter,11 led to 11. This substi-
tution was slow and inefficient without the magnesium
bromide.
Discu ssion
The present investigation has provided efficient routes
to boronic esters bearing (trialkylsilyl)oxy and azido
substituents. Safe conditions have been found for intro-
ducing the azido group, allowing the reaction to be scaled
up. It has also been shown that homologation of boronic
esters with (dihalomethyl)lithiums can proceed efficiently
in the presence of these useful masked hydroxy and
amino substituents.
The most likely reason that polar substituents can
interfere with the rearrangement of (dihalomethyl)borate
anions to (R-haloalkyl)boronic esters is that they complex
with the required metal cation. Zinc chloride is well-
known to facilitate this rearrangement,1 and the most
likely mechanism involves a zinc or other metal cation
directly in the transition state.12 This interpretation is
consistent with previous observations that increasing
amounts of zinc chloride were required as the number of
benzyloxy substituents increased,3 and that homologation
of a δ-trityloxy-γ-benzyloxy boronic ester was accompa-
nied by debenzylation to benzyl chloride, though the trityl
group was not cleaved.4
A practical question of synthetic utility is whether the
silyl protecting groups offer sufficient advantage over
trityl or benzyl substituents to be worth the extra steps
required to introduce them. It appears that they do for
some multistep syntheses. The interference of multiple
benzyloxy substituents with the homologation has al-
ready been noted.3 The efficiency with which the reac-
tions described here proceeded is encouraging. Trityloxy
substituted boronic esters often yield some trityl alcohol
as a byproduct, perhaps from accidental acid cleavage
during workup. Cleavage of the TBDMS or TBDPS
groups was not noticeable, and the homologations ap-
peared to proceed particularly smoothly up through the
formation of 10a ,b. The one advantage of the trityloxy
compounds is their greater tendency to crystallize.
Beyond 11, erratic results were obtained in the homo-
logations and substitutions. Structures 12a ,b,d and 13a
are supported by mass spectral and NMR data but the
compounds were not fully purified and characterized.
(9) (a) Bretherick, L. Chem. Eng. News 1986, 64, 22 Dec, 2. (b)
Hassner, A. Angew. Chem., Int. Ed. Engl. 1986, 25, 478-479.
(10) Ho, O. C.; Soundararajan, R.; Lu, J .; Matteson, D. S.; Wang,
Z.; Chen, X.; Wei, M.; Willett; R. D. Organometallics 1995, 14, 2855-
2860.
(11) Man, H.-W.; Hiscox, W. C.; Matteson, D. S. Org. Lett. 1999, 1,
379-382.
(12) (a) Midland, M. M. J . Org. Chem. 1998, 63, 914-915. (b) Corey,
E. J .; Barnes-Seeman, D.; Lee, T. W. Tetrahedron: Asymmetry 1997,
8, 3711-3713.

6652 J . Org. Chem., Vol. 65, No. 20, 2000
Singh and Matteson
The azido group is the only known nitrogen functional-
ity that permits homologation chemistry to proceed in a
useful manner in its presence. It is remarkable that this
group is stable in the presence of boronic esters, inas-
much as any more acidic boron functionality will react
with organic azides with replacement of the carbon-
boron bond by a carbon-nitrogen bond.13 Although azido
boronic esters have been shown to undergo homologation
and substitution previously,7,8 the present substitution
of â-azido-R-bromo boronic ester 10 by (cyanomethyl)-
lithium in the presence of magnesium bromide to produce
11 represents a significant extension of this chemistry.
Preliminary evidence that further chain extension is
possible was obtained, but results were erratic in at-
tempted further homologation of 11 to 12 and 13, as
described further below.
The displacement of chloride by azide is inconveniently
slow at room temperature, usually requiring several days
to complete. Epimerization of R-chloro boronic esters by
chloride produced in the displacement process is a known
problem,7 and is largely overcome by using a large excess
of sodium azide. In the reactions reported here, no
evidence of epimerized product or other side products was
seen, but the evidence does not exclude the possibility of
a few percent. The solvent systems developed here would
permit acceleration of the reaction by heating, but the
question of whether epimerization or side reactions would
increase to significant levels at higher temperatures has
not been explored.
The trityl series proceeded as far as 12d but failed to
yield 13d . This failure was unexpected, inasmuch as
homologation of the analogue of 11d bearing a p-
methoxybenzyloxy substituent in place of the azido group
had proceeded without difficulty.14 The problems with the
trityl compounds provided the original motivation to
explore the silyl series. The silylated homologation
products 12a ,b and 13a ,b were obtained in highly
variable yields. These compounds were not purified or
fully characterized, but are strongly supported by HRMS
and NMR data. While it is apparent that not all of the
variables were understood and controlled, it does not
appear that the azido or silyloxy substituents were the
source of any problems. The cyanomethyl group has
acidic protons that may become involved if excess base
is present. The boronic ester intermediates were not
rigorously protected from air during storage. Autocata-
lytic autoxidation, to which boronic esters are about as
susceptible as aldehydes, may have occurred in some
cases.15
that any transformations possible with silyloxy substit-
uents are not possible with alkoxy substituents, but does
indicate that silyloxy substituents cause minimal inter-
ference.15 Practical means for producing azido and silyl-
oxy substituted boronic esters are described here for the
first time.
Exp er im en ta l Section
Gen er a l Meth od s. The usual procedures for handling
reactive organometallic reagents were followed, including the
use of an inert atmosphere (argon) and THF (tetrahydrofuran)
that had been rigorously dried over sodium benzophenone
ketyl. Detailed procedures for carrying out reactions of boronic
esters with (dichloromethyl)lithium or (dibromomethyl)lithium
have been reported previously.2,3,7
(4S,5S)-4,5-Dicycloh exyl-2-(ben zyloxy)m eth yl-1,3,2-d i-
oxa bor ola n e (5). The pinacol boronate, 2-(benzyloxy)methyl-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane, was prepared from
2-bromomethyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and so-
dium benzyl oxide in DMSO according to the procedure
described previously for 2-(trityloxy)methyl-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane; 90%.10 A solution of the pinacol
boronate (24.8 g, 100 mmol) and (S,S)-1,2-dicyclohexyl-1,2-
ethanediol (22.6 g, 100 mmol) in diethyl ether (400 mL) was
stirred at 20-25 °C for 20 h. The ether solution was extracted
with saturated aqueous ammonium chloride, dried over mag-
nesium sulfate, and concentrated under vacuum to viscous
liquid 5 (34.9 g, 98%): became low melting solid on storage;
1
[R]22 -32.42° (CHCl3, c 1.65); 300 MHz H NMR (CDCl3) δ
546
0.83-1.76 (m, 22H), 3.34 (s, 2H), 3.91 (m, 2H), 4.52 (m, 2H),
7.24 (m, 5H); 75 MHz 13C NMR (CDCl3) δ 25.9, 26.0, 26.4, 27.4,
28.3, 42.8, 56.6 (br, C-B), 75.7, 83.8, 127.5, 128.1, 128.3, 138.3;
HRMS calcd for C22H33BO3 (M+) 356.2523, found (El) 356.2540.
No further purification was required for the analytical sample.
Anal. Calcd for C22H33BO3: C, 74.16; H, 9.34; B, 3.03. Found:
C, 74.06; H, 9.42; B, 2.82.
(4S,5S)-4,5-Dicycloh exyl-2-h yd r oxym eth yl-1,3,2-d ioxa -
bor ola n e (6). A solution of 5 (17.81 g, 50 mmol) in ethyl
acetate (350 mL) was hydrogenated over 5% Pd/C (4 g) at 1
atm at 20-25 °C for 24 h. Concentration under vacuum yielded
analytically pure low melting solid 6 (12.77 g, 96%): [R]22
546
-48.21° (CHCl3, c 1.43); 300 MHz 1H NMR (CDCl3) δ 0.82-
1.79 (m, 22H), 2.08 (s, 1H), 3.58 (s, 2H), 3.93 (m, 2H); 75 MHz
13C NMR (CDCl3) δ 25.8, 26.0, 27.3, 28.4, 42.9, 49.2 (br, C-B),
84.2; HRMS calcd for C15H27BO3 (M+) 266.2053, found (EI)
266.2069. Anal. Calcd for C15H27BO3: C, 67.68; H, 10.22; B,
4.06. Found: C, 67.92; H, 10.24; B, 3.94.
(4S ,5S )-4,5-Dicycloh e xyl-2-[[(1,1-d im e t h yle t h yl)d i-
m eth ylsilyl]oxy]m eth yl-1,3,2-d ioxa bor ola n e (7a ). Solid
tert-butylchlorodiphenylsilane (17.2 g, 62.5 mmol) was added
to a solution of (hydroxymethyl)dioxaborolane 6 (15 g, 56.4
mmol) in ethyl acetate (400 mL). The stirred reaction mixture
was cooled with an ice bath, and a solution of imidazole (5.35
g, 78.8 mmol) in ethyl acetate (70 mL) was added dropwise
(exothermic). The mixture was stirred at 20-25 °C for 24 h
and then washed with ammonium chloride solution. The
organic phase was dried over magnesium sulfate and concen-
trated under reduced pressure to crude 7a containing some
tert-butyldiphenylsilanol. The product was dissolved in pen-
tane and passed through a short column of silica gel, then
concentrated to viscous liquid 7a (17.6 g, 82%): [R]22546 -42.31°
(CHCl3, c 1.35); 300 MHz 1H NMR (C6D6) δ 0.13 (s, 6H), 0.80-
1.83 (m, 22H + s, 9H at δ 1.03), 3.74 (s, 2H), 3.77 (m, 2H); 75
MHz 13C NMR (C6D6) δ -5.3, 18.8, 26.2, 26.3, 26.4, 26.8, 27.7,
28.7, 43.3, 50.1, 84.0; HRMS calcd for C17H32O3SiB (M - 57)
323.2201, found (EI) 323.2201. Anal. Calcd for C21H41BO3Si:
C, 66.30; H, 10.86; B, 2.84; Si, 7.38. Found: C, 66.20; H, 10.92;
B, 2.74; Si, 7.22.
It may be concluded that silyloxy and azido substitu-
ents are compatible with the reaction of boronic esters
with (dihalomethyl)lithium and subsequent substitution
of the resulting (R-haloalkyl)boronic esters. Azido sub-
stituents are the only useful protected amino functional-
ity known for this purpose. This work does not yet prove
(13) (a) J ego, J . M.; Carboni, B.; Vaultier, M.; Carrie´, R. J . Chem.
Soc., Chem. Commun. 1989, 142-143. (b) Brown, H. C.; Salunkhe, A.
M. Tetrahedron Lett. 1993, 34, 1265-1268. (c) Evans, D. A.; Weber,
A. E. J . Am. Chem. Soc. 1987, 109, 7151-7157.
(14) Matteson, D. S.; Yang, J .-J . Tetrahedron: Asymmetry 1997, 8,
3855-3861.
(15) The air oxidation hypothesis cannot be proved with the present
data, but in an ongoing investigation of closely analogous chemistry
involving multistep synthesis, NMR evidence of autoxidation of
samples during storage has been observed, and careful protection of
all intermediates from air exposure during storage has resulted in
significantly improved yields in later stages of the synthesis. The tert-
butyldiphenylsilyl protecting group has consistently given excellent
results. Matteson, D. S.; Pharazyn, P. S. Unpublished results.
[2(1R),4S,5S]-4,5-Dicycloh exyl-2-[1-ch lor o-2-[[(1,1-d i-
m e t h y le t h y l)d i m e t h y ls i ly l]o x y ]e t h y l]-1,3,2-d i o x a -
bor ola n e (8a ). (Dichloromethyl)lithium was prepared as
previously described7 by addition of butyllithium (29.0 mmol)
to dichloromethane (90 mmol) in THF (300 mL) at -100 °C
under argon. A solution of silyloxy boronic ester 7a (9.50 g,

Asymmetric Azido and Silyl Boronic Esters
J . Org. Chem., Vol. 65, No. 20, 2000 6653
25 mmol) in THF (25 mL) was added via cannula. Anhydrous
zinc chloride (6.8 g, 50 mmol) was added and the mixture was
allowed to warm to 20-25 °C and stirred for 24 h. The solution
was concentrated under vacuum. Diethyl ether was added, and
the mixture was extracted with saturated aqueous ammonium
chloride, dried over magnesium sulfate, and concentrated
[2(1R,2S),4S,5S]-4,5-Dicycloh exyl-2-[2-a zid o-1-cya n o-
m e t h yl-3-[[(1,1-d im e t h yle t h yl)d im e t h ylsilyl]oxy]p r o-
p yl]-1,3,2-d ioxa bor ola n e (11a ). Lithioacetonitrile was pre-
pared by dropwise addition of LDA (10 mmol, 1.5 M solution
in hexane) to a solution of acetonitrile (0.41 g, 0.52 mL, 10
mmol) in THF (150 mL) at -78 °C. After 5 min, a solution of
bromo boronic ester 10a (4.23 g, 8 mmol) in THF (10 mL) was
added via cannula. After an additional 5 min stirring at -78
°C, magnesium bromide (16 mmol, from magnesium metal and
1,2-dibromoethane) in THF was added via cannula. The bath
temperature was allowed to rise to 20-25 °C and stirring was
continued for 24 h. The solution was concentrated at reduced
pressure. Diethyl ether was added, and the solution was
extracted with saturated ammonium chloride. The organic
phase was dried over magnesium sulfate and concentrated to
a viscous liquid mixture of ∼80% 11a and ∼20% unchanged
bromo boronic ester 10a as estimated by 1H NMR analysis (3.6
g). Chromatography on silica with 1:20 ether/pentane yielded
colorless viscous liquid 11a (2.8 g, 72%): IR (KBr pellet) cm-1
2098 (CN3), 2197 (CN); 300 MHz 1H NMR (C6D6) δ 0.05 (s,
6H), 0.83-1.71 (m, 22H + s, 9H at δ 0.93), 2.05 (m, 2H), 3.58,
(m, 2H), 3.67 (m, 2H), 3.86 (m, 1H); 75 MHz 13C NMR (C6D6)
δ -5.4, 16.5, 18.3, 25.2, 26.0, 26.2, 26.3, 26.7, 27.6, 28.6, 43.1,
65.4, 66.0, 84.3, 119.1; HRMS calcd for C31H36BN4O3Si (M -
57) 431.2650, found (EI) 431.2657.
[2(1R,2R,3S),4S,5S]-4,5-Dicycloh exyl-2-[3-azido-l-br om o-
2-cya n om eth yl-4-[[(1,1-d im eth yleth yl)d im eth ylsilyl]oxy]-
bu tyl]-1,3,2-d ioxa bor ola n e (12a ). A solution of cyano boronic
ester 11a (2.92 g, 6 mmol) and dibromomethane (0.83 mL, 2.08
g, 12 mmol) in THF (60 mL) was stirred at -78 °C under argon
during the dropwise addition of LDA (6.0 mmol, 1.5 M in
hexane). Anhydrous zinc chloride (3.26 g, 24 mmol) was added,
and the mixture was allowed to warm to 20-25 °C and stirred
for 24 h. The solution was concentrated at reduced pressure.
Diethyl ether was added, and the solution was extracted with
saturated ammonium chloride. The organic phase was dried
over magnesium sulfate and concentrated to a viscous liquid
mixture of -65% bromo boronic ester 12a and ∼35% un-
changed 11a as estimated by 1H NMR analysis (3.1 g).
Chromatography on silica gel with 1:20 ether/pentane yielded
12a (1.2 g, 35%): [R]22546 -46.23° (c 1.7, CHCl3); IR (neat) cm-1
2098.8 (CN3), 2280.3 (CN); 1H NMR (C6D6) δ 0.02 (s, 6H), 0.92
(s, 9H), 0.71-1.78 (m, 23H), 2.20 (m, 2H) 3.48 (d, 1H), 3.57
(m, 2H), 3.70 (m, 1H), 3.83 (m, 2H); 75 MHz 13C NMR (C6D6)
δ -3.6, 16.4, 18.2, 26.0, 26.3, 26.4, 26.6, 27.7, 29.0, 32.0, 43.6,
64.7, 65.2, 65.3, 84.4, 117.6; HRMS calcd for C26H47BBrN4O3-
Si (M + 1), 581.2694, found, 581.2780.
under vacuum to colorless liquid 8a (10.4 g, 97%): [R]22
546
-47.37° (c 1.58, CHCl3); 300 MHz 1H NMR (C6D6) δ 0.01 (s,
6H), 0.87-1.80 (m, 22H + s, 9H at δ 0.95), 3.51 (t, 1H), 3.77
(d, 2H), 3.93 (m, 2); 75 MHz 13C NMR (C6D6); δ -5.3, 18.6,
26.0, 26.2, 26.3, 26.7, 27.6, 28.5, 43.3, 65.8, 84.3; HRMS calcd
for C18H33O3SiB (M - 57) 371.1981, found (EI) 371.1975. The
analytical sample was chromatographed on a silica gel plate
with 1:20 ether/pentane. Anal. Calcd for C22H42BClO3Si: C,
61.61; H, 9.87; B, 2.52; C1, 8.27; Si, 6.55. Found: C, 61.80; H,
9.74; B, 2.36; Cl, 8.00; Si, 6.38.
[2(1S),4S,5S]-4,5-Dicycloh exyl-2-[1-a zid o-2-[[(1,1-d i-
m e t h y le t h y l)d i m e t h y ls i ly l]o x y ]e t h y l]-1,3,2-d i o x a -
bor ola n e (9a ). A solution of chloro boronic ester 8a (9.43 g,
22 mmol) in nitromethane (500 mL) was stirred with a solution
of sodium azide (14.3 g, 220 mmol) and tetrabutylammonium
bromide (1.6 g, 5 mmol) in water (120 mL) for 10 days at 20-
25 °C. The organic phase was separated and concentrated
under vacuum. Diethyl ether was added, and the mixture was
extracted with saturated aqueous ammonium chloride. The
organic phase was dried over magnesium sulfate and concen-
trated at reduced pressure to colorless viscous liquid 9a (9.4
g, 98%): [R]22546 -38.15° (c 1.32, CHCl3); IR (KBr pellet): cm-1
1
2087.5 (CN3); 300 MHz H NMR (C6D6) δ 0.05 (s, 3H), 0.07 (s,
3H), 0.91-1.80 (m, 22H + s, 9H at δ 0.97), 2.82 (t, 1H), 3.76
(m, 2H), 3.86 (m, 2H); 75 MHz 13C NMR (C6D6) δ -5.5, 18.5,
25.9, 26.0, 26.2, 26.8, 27.7, 28.7, 43.3, 51.0 (br, C-B), 65.5,
84.5; HRMS calcd for C19H33BNO3Si (M - 85) 350.2323, found
(EI) 350.2317. The analytical sample was chromatographed
on a silica gel plate with 1:15 ether/pentane. Anal. Calcd for
C
22H42BN3O3Si: C, 60.68; H, 9.72; B, 2.48; N, 9.65; Si, 6.45.
Found: C, 60.52; H, 9.80; B, 2.36; N, 9.50; Si, 6.62.
[2(1S),4S,5S]-4,5-Dicycloh exyl-2-[1-a zid o-2-[[(1,1-d i-
m e t h y le t h y l)d i p h e n y ls i ly l]o x y ]e t h y l]-1,3,2-d i o x a -
bor ola n e (9b). The conditions were the same as for the
conversion of 8a to 9a except that 8b (12.16 g, 22 mmol) was
used in place of 8a and ethyl acetate (250 mL) was used in
place of nitromethane, yielding colorless low melting solid 9b
(12.1 g, 98%): [R]22 -34.83° (CHCl3, c 1.40); IR (KBr pellet)
546
2087 cm-1 (CN3); 300 MHz 1H NMR (C6D6) δ 0.84-1.87 (m,
22H + S, 9H at δ 1.21), 2.86 (t, 1H), 3.80 (m, 2H), 3.99 (m,
2H), 7.24 (m, 6H) 7.85 (m, 41); 75 MHz 13C NMR C6D6) δ 19.4,
26.1, 26.3, 26.7, 27.0, 27.8, 28.7, 43.3, 51.3 (broad, C-B), 66.1,
84.7, 128.2, 130.0, 130.1, 133.5, 133.7, 136.1; HRMS calcd for
[2(1S ,2R ,3S ),4S ,5S ]-4,5-D ic y c lo h e x y l-2-[3-a zid o -2-
c y a n o m e t h y l-4-[[(1,1-d im e t h y le t h y l)d im e t h y ls ily l]-
oxy]-1-p h en ylbu tyl]-1,3,2-d ioxa bor ola n e (13a ). Phenyl-
magnesium bromide (1.72 mmol, 1 M in THF) was added
dropwise to a stirred solution of bromo boronic ester 12a (1.0
g, 1.72 mmol) in THF (10 mL) at -78 °C. After being stirred
for 15 h at 20-25 °C, the solution was concentrated under
vacuum. Dimethyl sulfoxide (2 mL) was added and the solution
was stirred for 8 h at 20-25 °C. Diethyl ether was added, and
the solution was extracted with saturated ammonium chloride.
The organic phase was dried over anhydrous magnesium
sulfate and concentrated at reduced pressure to 13a (0.90 g,
C
32H46BNO3Si (M - 28) 531.3340, found (EI) 531.3346. The
analytical sample was chromatographed. Anal. Calcd for
32H46BN3O3Si: C, 68.68; H, 8.29; B, 1.93; N, 7.51; Si, 5.02.
C
Found: C, 68.68; H, 8.33; B, 1.80; N, 7.30; Si, 5.12.
[2(1R,2R),4S,5S]-4,5-Dicycloh exyl-2-[2-a zid o-l-br om o-
3-[[(1,1-d im eth yleth yl)d im eth ylsilyl]oxy]p r op yl]-1,3,2-d i-
oxa bor ola n e (10a ). A solution of LDA (11 mmol, 1.5 M in
hexane) was added dropwise to a stirred solution of azido
boronic ester 9a (7.83 g, 18 mmol) and dibromomethane (3.8
mL, 9.38 g, 54 mmol) in THF (200 mL) at -78 °C under argon.
Anhydrous zinc chloride (7.4 g, 54 mmol) was added. The
solutions was allowed to warm to 20-25 °C, stirred for 24 h,
and concentrated under vacuum. Diethyl ether (400 mL) was
added, the mixture was extracted with saturated ammonium
chloride (2 × 400 mL), and the organic phase was dried over
magnesium sulfate. Concentration under vacuum yielded
viscous liquid 10a (8.5 g, 95%): [R]22546 -51.62° (c 1.67, CHCl3);
1
90%): IR (neat) cm-1 2099 (CN3); H NMR (C6D6) δ 0.21 (s,
6H), 1.13 (s, 9H), 0.71-1.78 (m, 24H), 2.04 (m, 2H) 3.55 (m,
2H), 3.96 (m, 2H), 4.06 (m, 1H); 13C NMR (C6D6) δ -3.6, 1.4,
25.8, 26.3, 26.4, 26.4, 27.7, 29.1, 32.0, 44.2, 62.4, 65.5, 66.0,
82.3, 119.2; HRMS calcd for C28H42BN4O3Si (M - 57) 521.3119,
found 521.3107.
Ack n ow led gm en t. We thank the National Insti-
tutes of Health, Grant No. GM50298, and the National
Science Foundation, Grant No. CHE9613857, for sup-
port.
1
IR (KBr) cm-1 2099 (CN3); 300 MHz H NMR (C6D6) δ 0.02 (s,
6H), 0.82-1.75 (m, 22H + s, 9H at δ 0.90), 3.58, (d, 1H), 3.66
(m, 1H), 3.72 (m, 2H), 3.78 (m, 2H); 75 MHz 13C NMR (C6D6)
δ -5.4, 18.4, 26.0, 26.2, 26.3, 27.5, 28.5, 43.3, 65.3, 65.6, 84.5;
HRMS calcd for C19H34BBrNO3Si (M - 85) 442.1584, found
(EI) 442.1599. The analytical sample was chromatographed
on a silica gel plate with 1:14 ether/pentane. Anal. Calcd for
C23H43BBrN3O3Si: C, 52.28; H, 8.20; B, 2.05; Br, 15.12; N, 7.95;
Si, 5.32. Found: C, 52.50; H, 8.14; B, 1.88; Br, 15.16; N, 7.72;
Si, 5.48.
Su p p or tin g In for m a tion Ava ila ble: Preparative infor-
mation and physical properties of compounds 7b,c, 8b,c, 9c,d ,
10b,c,d , 11b,c,d , and 12b,d . This material is available free
of charge via the Internet at http://pubs.acs.org.
J O005522B