(Alkoxyalkyl)boronic ester intermediates for asymmetric synthesis

Article abstract of DOI:10.1021/om950574q

The use of boronic ester chemistry in the construction of synthetic intermediates containing two or three chiral centers corresponding to steric relationships in the macrolide leuconolide has been explored. A four-carbon chain with a substituent at each carbon has been built from each end, and the effects of different chiral directors and masking groups have been compared. Exceptionally facile debenzylation of a benzyloxy group separated by four carbon atoms from a boronic ester function has been observed and may account for the failure of earlier attempts to synthesize sugars via analogous chemistry. A novel method of reducing a-chloro boronic esters to alkylboronic esters with sodium hydride in DMSO has been found.

Full text of DOI:10.1021/om950574q

152
Organometallics 1996, 15, 152-163
(Alk oxya lk yl)bor on ic Ester In ter m ed ia tes for
Asym m etr ic Syn th esis
Donald S. Matteson,* Raman Soundararajan, Oliver Chenpu Ho, and
Winfried Gatzweiler
Department of Chemistry, Washington State University, Pullman, Washington 99164-4630
Received J uly 25, 1995X
The use of boronic ester chemistry in the construction of synthetic intermediates containing
two or three chiral centers corresponding to steric relationships in the macrolide leuconolide
has been explored. A four-carbon chain with a substituent at each carbon has been built
from each end, and the effects of different chiral directors and masking groups have been
compared. Exceptionally facile debenzylation of a benzyloxy group separated by four carbon
atoms from a boronic ester function has been observed and may account for the failure of
earlier attempts to synthesize sugars via analogous chemistry. A novel method of reducing
R-chloro boronic esters to alkylboronic esters with sodium hydride in DMSO has been found.
In tr od u ction
steric properties of 2 to other similar fragments. How-
ever, the present study has uncovered and solved some
of the general problems in applying the boronic ester
chain extension method to functionalized systems of
intermediate complexity and has provided insight into
the nature of the difficulties encountered previously3
with increasing chain length and numbers of alkoxy
substituents.
Chain extension of boronic esters of chiral 1,2-diols
(1,3,2-dioxaborolanes) to the homologous R-halo boronic
esters provides an efficient, highly stereoselective ap-
proach to asymmetric synthesis.1,2 It was shown previ-
ously that benzyloxy or (p-methoxybenzyl)oxy substit-
uents are compatible with this process, though there
appeared to be a limit to the number or perhaps the
spacing of these substituents.3,4
Resu lts
The present investigation was undertaken with the
antibiotic aglycone leuconolide5,6 (1) in mind as a target
Substituted butylboronic esters having the stereo-
chemistry of the C(7)-C(10) segment of leuconolide (1)
have been constructed from both directions. Opposite
chiral directors are required. Otherwise, the essential
difference is whether the methyl group at C(8) or the
benzyloxy group at C(9) is installed first, and consid-
eration must be given to what groups might be incor-
porated at C(7) and C(10) for purposes of subsequent
connections.
Both routes begin from a (halomethyl)boronic ester,
which is converted to an (alkoxymethyl)boronic ester
before the first chain extension. The discovery of an
efficient preparation of diisopropyl (bromomethyl)bor-
onate via addition of butyllithium to a solution of
dibromomethane and triisopropyl borate7 has greatly
simplified the bulk preparation of starting materials.8
Three different chiral directors and two cleavable alkoxy
substituents have been tested in this work.
Rou tes fr om C(7). The correct absolute configura-
tion may be provided by the use of either “(R)-pi-
nanediol” or a C2-symmetrical (S,S)-diol as chiral di-
rector.1,9 Both were tested, but the most extensive work
was done with boronic esters of the (S,S)-diol, 1,2-
diisopropylethanediol,10 abbreviated here to “(S,S)-
DIPED”. In order to introduce the chiral director as late
and has proceeded as far as the C(6)-C(10) segment
represented by 2. Further progress toward this target
does not appear feasible until methods are developed
for connecting boronic esters of the general size and
X Abstract published in Advance ACS Abstracts, November 1, 1995.
(1) (a) Matteson, D. S. Chem. Rev. 1989, 89, 1535-1551. (b)
Matteson, D. S.; Sadhu, K. M.; Peterson, M. L. J . Am. Chem. Soc. 1986,
108, 812-819.
(2) Tripathy, P. B.; Matteson, D. S. Synthesis 1990, 200-206.
(3) (a) Matteson, D. S.; Peterson, M. L. J . Org. Chem. 1987, 52,
5116-5121. (b) Matteson, D. S.; Kandil, A. A. J . Org. Chem. 1987, 52,
5121-5124.
(4) Matteson, D. S.; Kandil, A. A.; Soundararajan, R. J . Am. Chem.
Soc. 1990, 112, 3964-3969.
(5) (a) Omura, S.; Katagiri, M.; Hata, T. J . Antibiot. 1968, 21, 199-
203; 272-278. (b) Omura, S.; Nakagawa, A.; Katagiri, M.; Hata, T.;
Hiramatsu, M.; Kimura, T.; Naya, K. Chem. Pharm. Bull. 1970, 18,
1501-1508. (c) Review: Masamune, S.; McCarthy, P. A. Macrolide
Antibiotics; Omura, S., Ed.; Academic Press: New York, 1984; pp 127-
198.
(6) (a) Tatsuta, K.; Amemiya, Y.; Maniwa, S.; Kinoshita, M. Tetra-
hedron Lett. 1980, 21, 2837-2840. (b) Nicolaou, K. C.; Seitz, S. P.;
Pavia, M. R. J . Am. Chem. Soc. 1981, 103, 1222-1224. (c) Nicolaou,
K. C.; Pavia, M. R.; Seitz, S. P. J . Am. Chem. Soc. 1981, 103, 1224-
1226.
(7) Michnick, T. J .; Matteson, D. S. Synlett. 1991, 631-632.
(8) Ho, O. C.; Soundararajan, R.; Lu, J .; Matteson, D. S.; Wang, Z.;
Chen, X.; Wei, M.; Willett, R. D. Organometallics 1995, 14, 2855-2860.
(9) (a) Sadhu, K. M.; Matteson, D. S.; Hurst, G. D.; Kurosky, J . M.
Organometallics 1984, 3, 804-806. (b) Matteson, D. S.; Kandil, A. A.
Tetrahedron Lett. 1986, 27, 3831-3834.
(10) Matteson, D. S.; Beedle, E. C.; Kandil, A. A. J . Org. Chem. 1987,
52, 5034-5036.
0276-7333/96/2315-0152$12.00/0 © 1996 American Chemical Society

(Alkoxyalkyl)boronic Ester Intermediates
Organometallics, Vol. 15, No. 1, 1996 153
Sch em e 1. Ser ies a a n d b In ter m ed ia tesa
benzyl, the hydroxyl R2 was tritylated with trityl
chloride to form 11a , which with DDQ was deprotected
to alcohol 12a and converted via the unstable mesylate
to iodo compound 13a . Where R1 was trityl, R2
)
p-methoxybenzyl was prepared via treatment of 10 with
sodium hydride followed by p-methoxybenzyl chloride
to form 11b. Cleavage of R1 ) trityl by formic acid11
readily yielded alcohol 12b, together with a small
amount of its formate ester. After chromatography, 12b
with oxalyl chloride/DMF12 yielded chloride 13b, which
1
was characterized by elemental analyses, H, 13C and
2D COSY NMR. The last few steps were all efficient,
and the overall yield of 13b from 4b was 40-45%.
1
The H NMR spectrum of 13b was too complicated to
allow interpretation of the five protons (CHaHbCl, CHc-
OBn, and OCHdHe), which all overlapped in the 3.48-
3.81 ppm region. This problem was solved by other
NMR experiments. First, homodecoupling by irradia-
tion of Hf at δ 2.22 caused the doublet at δ 1.01 (CH3)
to collapse to a singlet, the multiplet at δ 3.48-3.54 to
become a less complicated multiplet, the multiplet at δ
3.59-3.67 to collapse to a broad singlet and a set of less
complicated multiplets, and the multiplet at δ 3.76-
3.81 to collapse to a broad singlet. The unchanged
peaks had to be Hd and He (two sets of doublet of
doublets at δ 3.51 and 3.65). Second, the 2D COSY
experiment shows that region 1 (δ 3.48-3.54) is coupled
with region 2 (δ 3.59-3.67 ppm) and region 2 (δ 3.59-
3.67) is coupled with region 3 (δ 3.76-3.81). The above
data prove HaHb is in regions 2 and 3, Hc is in region 1
and HdHe is in regions 1 and 2.
Detritylation of (S,S)-DIPED (2S,3R)-[(2-(benzyloxy)-
3-methyl-4-(triphenylmethoxy)butyl]boronate (9b) with
formic acid11 followed by workup under basic conditions
apparently resulted in cyclization to a six-membered
1,2-oxaborin (14), which was characterized only by 200
a
Series a : R1 ) p-methoxybenzyl, R2 ) trityl. Series b: R1
) trityl, R2 ) p-methoxybenzyl. Key: (a) NaOR1 in DMSO;8
transesterify with corresponding diol. (b) CH2Br2 + 4 in THF,
-78 °C, add LDA; ZnCl2.3 (c) CH3MgCl. (d) LiOCH2Ph. (e)
ClCH2I, BuLi.7 (f) H2O2, OH-. (g) R2Cl, base. (h) (a ) DDQ or
(b) HCO2H. (i) (a ) MeSO2Cl/Et3N, NaI, or (b) (COCl)2/DMF.
as possible, pinacol (bromomethyl)boronate was first
converted to pinacol [((p-methoxybenzyl)oxy)methyl]-
boronate (series a ) (Scheme 1) or pinacol [(trityloxy)-
methyl]boronate8 (series b) and subsequently trans-
esterified with (S,S)-DIPED to form the (alkoxymethyl)-
boronic ester (4).
The reaction of bromo boronic ester 5a with methyl-
magnesium chloride resulted in formation of a small
amount (5-10%) of the cleavage product, (S,S)-DIPED
methylboronate, and the analogue 5b yielded a some-
what larger amount (10-15%) of the methylboronate,
with the remainder of the product being mainly 6 in
each case. Chain extension of 6 to 8 proceeded ef-
ficiently in both series. In order to avoid contamination
of 8 by its butoxy analogue, accidentally derived from
partially oxidized butyllithium, it was found preferable
to use sodium benzyl oxide prepared from sodium
hydride and benzyl alcohol in DMSO for the conversion
of 7b to 8b. The last extension to 9 with (chloromethyl)-
lithium was nearly quantitative. (Bromomethyl)lithium
proved less effective for conversion of 8 to 9, and similar
inefficiency of (bromomethyl)lithium with alkoxy-sub-
stituted boronic esters has been reported previously.7
Deboronation of the final boronic esters in the se-
quence (9) with hydrogen peroxide to form the corre-
sponding alcohols (10) was routine and nearly quanti-
tative. At this point a differentially protected pair of
hydroxyl functions at opposite ends of the butane chain
was desired. Where the first group R1 was p-methoxy-
and 500 MHz 1H NMR.15 A small proportion of the
alcohol initially formed was esterified under the reaction
conditions to the formate ester (9, R1 ) CHO). At-
tempted reactions of pinacol and pinanediol with (4R,5R)-
2-oxy-4-(benzyloxy)-5-methyl-1,2-oxaborin (14) to break
the B-O bond were unsuccessful.
(11) Bessodes, M.; Komiotis, D.; Antonakis, K. Tetrahedron Lett.
1986, 27, 579-580.
(12) Ireland, R. E.; Norbeck, D. W.; Mandel, G. S.; Mandel, N. S. J .
Am. Chem. Soc. 1985, 107, 3285-3294.
(13) 1,2-Diphenylethane-1,2-diol: (a) Wang, Z.-M.; Sharpless, K. B.
J . Org. Chem. 1994, 59, 8302-8303. (b) Sharpless, K. B.; Amberg, W.;
Bennani, Y. L.; Crispino, G. A.; Hartung, J .; J eong, K.-S.; Kwong, H.-
L.; Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L. J . Org. Chem.
1992, 57, 2768-2771.
(14) Hydrogenation to DICHED: (a) Hoffmann, R. W.; Ditrich, K.;
Ko¨ster, G.; Stu¨rmer, R. Chem. Ber. 1989, 122, 1783. (b) Matteson, D.
S.; Man, H.-W. J . Org. Chem. 1993, 58, 6545-6547.

154 Organometallics, Vol. 15, No. 1, 1996
Matteson et al.
Sch em e 3. P in a n ed iol Ester Ser iesa
Sch em e 2. Ser ies c In ter m ed ia tesa
a
Series c: R1 ) p-methoxybenzyl; R2 ) tert-BuMe2Si; (R)-
pinanediol esters. Key: (f) and preceding steps, same as series
a and b. (j) tert-BuMe2SiCl; DDQ.
An analogous series of intermediates was made with
the pinanediol boronic ester series c (Scheme 2). A close
analogy to the route as far as (R)-pinanediol [(1R)-1-
bromo-2-[(p-methoxybenzyl)oxy]ethyl]boronate (5c) via
(R)-pinanediol [((p-methoxybenzyl)oxy)methyl]boronate
(4c) had already been established,4 with (S)-pinanediol
(chloromethyl)boronate used in place of the bromo-
methyl ester 3 and the enantiomer en t-4c prepared in
place of 4c. Subsequent compounds in this series were
obtained up through the monosilylated alcohol 12c. The
structures are not illustrated in detail because all of the
steps were essentially the same as with series a . The
ultimate product was the p-methoxybenzyl-substituted
alcohol identical with 10a , which was silylated and
treated with DDQ to yield the TBDMSO-substituted
alcohol 12c. A sample of 12c was also converted to the
iodo derivative 13c (same as 13a with TBDMS in place
of trityl), but this compound was unstable to storage
a
(a) LiCHBr2.4 (b) CH3MgBr. (c) ICH2Cl or CH2Br2 + 17 in
THF, -78 °C, add BuLi.
1,2-dicyclohexyl-1,2-ethanediol13,14 [“(R,R)-DICHED”] bo-
ronic esters and the trityl blocking group for the
terminal oxygen. (R,R)-DICHED ((trityloxy)methyl)-
boronate8 (22) was prepared in an analogous manner
to 4, described above. Chain extension to the (1-
(benzyloxy)-2-(trityloxy)ethyl)boronic ester 23 was car-
ried out efficiently with (dichloromethyl)lithium followed
by sodium benzyl oxide. The second chain extension to
chloroboronic ester 24 and C-methylation to 25 was
carried out in the usual manner. When the direct
homologation of 25 to 27 was attempted with (chloro-
methyl)lithium or (bromomethyl)lithium, it appeared
that considerable elimination analogous to that seen in
the conversion of 17 to 19 and byproducts 20 and 21
could not be avoided, but the reaction of 25 with
(dichloromethyl)lithium to form 26 proved efficient.
Reduction of R-chloro boronic esters with various
borohydride reagents is well-known.4,16,17 However,
observation of such reduction by sodium hydride in
DMSO as a side reaction18 prompted us to try this
reagent for synthetic purposes, and it proved convenient
and efficient for conversion of 26 to 27.
Chain extension of 27 with (dichloromethyl)lithium
and reaction of the resulting R-chloro boronic ester with
allylmagnesium chloride yielded ∼60% 2. A major side
reaction was debenzylation to benzyl chloride, which
was positively identified by GC-mass spectrometry,
apparently during the zinc chloride promoted rear-
rangement of the adduct of 27 with (dichloromethyl)-
1
and was characterized only by H NMR.
Rou tes fr om C(10). The synthesis starting from
C(7) provides intermediates most likely to be useful if
the next operations are to be carried out at the boronic
ester terminus, C(10), since extra protection and depro-
tection steps are required in order to reach a structure
having a reactive C(7) terminus such as 13. To provide
the opposite pattern of active functionality, the C(10)
terminus was used as a starting point.
The first study was made with the pinanediol ester
series (Scheme 3). The (1,2-dialkoxyethyl)boronic ester
15 had been synthesized previously via en t-4c,4 the
route to which was modified in the present work to
utilize (S)-pinanediol (bromomethyl)boronate in place
of the chloro analogue and sodium p-methoxybenzyl
oxide in DMSO in place of the lithium alkoxide in THF.
Conversion of 15 via bromo boronic ester 16 to the (1-
methyl-2,3-dialkoxypropyl)boronic ester 17 was routine,
but reaction of 17 with (chloromethyl)lithium or (bro-
momethyl)lithium yielded mixtures of the homologous
boronic ester 19 with substantial amounts of the
elimination products crotyl p-methoxybenzyl ether (20)
and pinanediol [(benzyloxy)methyl]boronate (21).
The second study (Scheme 4) was made with (R,R)-
(15) The ring proton NMR signals in 14 are all well separated and
can be assigned on the basis of chemical shifts and splittings. The
observed couplings (in Hz) are as follows: J 34 ) 6, 5.5; J 45 ) ∼3; J 56
) 4.5, 7. These may be compared with results of a PC Model MMX
calculation on (4R,5R)-2-oxy-4-methoxy-5-methyl-1,2-oxaborin (ana-
logue of 14 having Me in place of Bn) using boron-oxygen parameters
reflecting strong π-bonding.8 The weighted average of the 5-methyl
(16) (a) Brown, H. C.; Naik, R. G.; Singaram, B.; Pyun, C. Organo-
metallics 1985, 4, 1925-1929. (b) Brown, H. C.; Imai, T.; Perumal, P.
T.; Singaram, B. J . Org. Chem. 1985, 50, 4032-4036.
(17) Matteson, D. S.; Beedle, E. C.; Christenson, E.; Dewey, M. A.;
Peterson, M. L. J . Labelled Compd. Radiopharm. 1988, 25, 675-683.
(18) We thank Hon-Wah Man for this observation. Reaction of an
R-chloro boronic ester with sodium benzyl oxide prepared from benzyl
alcohol and excess sodium hydride in DMSO resulted in some replace-
ment of Cl by H.
equatorial/axial conformers (∆E° ) 0.15 kcal mol-1) yielded J 34cis
6.2, J 34trans ) 5.1, J 45 ) 2.2, J 56cis ) 3.1, and J 56trans ) 7.3.
)

(Alkoxyalkyl)boronic Ester Intermediates
Organometallics, Vol. 15, No. 1, 1996 155
Sch em e 4a
Sch em e 5a
a
Key: (a) CH2dCHCH2MgCl. (b) CH2Br2 + 29 in THF, -78
°C, add LDA; ZnCl2. (c) LiOBn.
Discu ssion
In accord with previous work,1-4 1H NMR data have
indicated that all of the products of asymmetric reac-
tions in the present series are formed in high enantio-
meric and diastereomeric purity. No quantitative es-
timates of diastereomer content were attempted in the
present work, but products generally appeared to be
single compounds, consistent with the previous
findings1-4 of diastereomer levels below 1%. One cau-
tionary note is the recent discovery that unhindered
R-bromo boronic esters, for example, DICHED 1-bro-
mopentylboronate, epimerize extremely easily.20 How-
ever, the (R-bromohomoallyl)boronic ester 30 yielded
benzyloxy derivative 32 which, after chromatography,
showed no evidence of diastereomer above the ∼1%
noise level near the CHOBn triplet at δ 3.42 in the 300
MHz 1H NMR. The possibility that ∼10% contaminant
apparent at δ ∼3.33 in another sample could have been
diastereomer was not ruled out.
a
Key: (a) LiCHCl2, -100 °C; ZnCl2, -100 f 25 °C; LiOBn.
(b) LiCHCl2, -100 °C; ZnCl2, -100 f +25 °C. (c) CH3MgCl.
(d) NaH, DMSO. (e) LiCHCl2, -100 °C; ZnCl2, -100 f 25 °C;
CH2dCHCH2MgCl.
lithium. Two attempts to carry out chain extension of
2 failed, but the amount of available compound and
other resources had dwindled to the point where further
work was not feasible.
The chain extension of the one-carbon synthon 4a to
four-carbon synthon 9a and the analogous conversion
of 4b to 9b both proceeded in approximately 60% yields
over all. The pinanediol series 4c to 9c yielded 49%,
with the largest difference being in the last step, 8c to
9c. Because yields in these reactions are highly sensi-
tive to experimental technique, there is no clear evi-
dence that one route is inherently any more efficient
than another.
The unexpected debenzylation of 27 to form benzyl
chloride in the reaction with (dichloromethyl)lithium
presumably involves 1,2-oxaborin or perhaps 1,2-oxa-
borolane formation somewhat analogous to the genera-
tion of oxaborin 14. The presumed 3-chloro-1,2-oxaborin
or tetrahydrofurylboronic ester from ring contraction or
alternative oxaborolane was not observed, but may have
been adsorbed strongly on silica. Earlier attempts to
synthesize sugars via related chemistry failed inexpli-
cably at introduction of the fifth carbon atom,3a and
Allylbor on ic Ester Ch a in Exten sion . This work
was undertaken with the C(1)-C(6) segment of leu-
conolide in mind but was not completed very far
(Scheme 5). (S,S)-DICHED (R)-[bromoallylmethyl]bo-
ronate (30) was prepared in a conventional manner via
allylation of (S,S)-DICHED methoxyboronate (28) to the
allylboronic ester 29 and chain extension with (dibro-
momethyl)lithium. Although reasonable yields of 30
were obtained, substantial amounts of the allyl transfer
product 31 were also present. This kind of transfer of
an allyl group from a borate intermediate to an (R-
haloalkyl)boronic ester product has been reported previ-
ously in the 2,3-butanediol boronic ester series.19 Pi-
nanediol esters do not have this problem,19 and it was
not anticipated that the DICHED ester would behave
like the relatively unhindered butanediol ester. Con-
version of the crude 30 to the benzyloxy derivative 32
was carried out in the usual manner.
(19) Matteson, D. S.; Campbell, J . D. Heteroatom Chem. 1990, 1,
109-115.
(20) Matteson, D. S.; Man, H.-W. J . Org. Chem. 1994, 59, 5734-
5741.

156 Organometallics, Vol. 15, No. 1, 1996
Matteson et al.
in hexane (1.6 M, 194 mL, 0.31 mol) was added slowly to a
solution of p-methoxybenzyl alcohol (43 g, 0.31 mol) and
(optionally) a few crystals of 1,10-phenanthroline indicator in
anhydrous THF (250 mL) stirred at 0 °C. The resulting
solution of lithium p-methoxybenzyl oxide was stirred at 0 °C
during the addition of 2-(bromomethyl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane [pinacol (bromomethyl)boronate] via can-
nula. Dimethyl sulfoxide (24.2 g, 0.31 mol) was added, and
the mixture was stirred overnight at 20-25 °C. Water (150
mL) was added, followed by light petroleum ether (bp 35-60
°C), and the phases were separated. Saturated aqueous
sodium chloride (100 mL) was added to the aqueous phase,
which was then extracted with light petroleum ether (25-40
mL). The combined organic phase was washed with water (2
× 100 mL), dried over magnesium sulfate, filtered, and
concentrated under vacuum. Distillation yielded 2-((p-meth-
oxybenzyl)oxy)methyl-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane as a clear oil: bp 128-129 °C (0.25 Torr), 49-60 g (70-
86%); 200 MHz 1H NMR (CDCl3) δ 1.27 (s, 12), 3.24 (s, 2), 3.80
(s, 3), 4.45 (s, 2), 6.85-7.35 (m, 4). This intermediate was not
further characterized but was transesterified to 4a or 4c.
similar debenzylation is a plausible explanatory hy-
pothesis. The use of alternative masking groups in such
situations remains to be investigated.
It was anticipated that the (R-bromohomoallyl)boronic
ester 30 could be connected to a lithio derivative of
C(7)-C(10) fragment 13a to form a compound identical
with 2 except for the opposite chirality of the DICHED.
Indeed, 200 MHz 1H NMR data indicated that this
analogue of 2 was formed and underwent chain exten-
sion with (dibromomethyl)lithium, though further char-
acterization of these intermediates was not accom-
plished. It was hoped that the resulting C(10)-C(5)
fragment could be converted to an R-lithio ether,21 which
might then be joined to a C(1)-C(4) fragment in the
form of an R-halo-â-alkoxy boronic ester. However, this
approach was abandoned when we observed no coupling
of model compound (1-methoxy-2-methylpropyl)lithi-
um21 with an appropriate, though incompletely charac-
terized, R-halo-â-alkoxy boronic ester.22 Several other
attempts to extend carbon chains of boronic esters
beyond the final compounds in the series reported here
yielded encouraging 200 MHz 1H NMR spectra, but
attempts to characterize them definitively were ulti-
mately defeated by our inability to obtain satisfactory
mass spectra or sufficiently definitive NMR spectra with
the equipment available to us at the time the work was
done.
2-(((p -Met h oxyb en zyl)oxy)m et h yl)-4,5-b is(1-m et h yl-
eth yl)-1,3,2-d ioxa bor ola n e {(S,S)-DIP ED [((p-Meth oxy-
ben zyl)oxy)m eth yl]bor on a te} (4a ). (3S,4S)-2,5-Dimethyl-
3,4-hexanediol [(S,S)-DIPED] (36.5 g, 0.25 mol) was added to
a solution of 2-(((p-methoxybenzyl)oxy)methyl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (69.5 g, 0.25 mol) in pentane (150
mL) and stirred 15 min (until the solid dissolved). Water (200
mL) was added, the mixture was shaken vigorously in a
separatory funnel, and the phases were separated. The
organic phase was washed with water (3 × 100 mL) in order
to remove the pinacol and then dried over magnesium sulfate
and concentrated under vacuum. The viscous oily 2-(((p-
methoxybenzyl)oxy)methyl)-4,5-bis(1-methylethyl)-1,3,2-dioxa-
borolane was pure enough to use directly in the next step but
could be distilled, bp 149-151 °C (0.35 Torr), 74 g (97%), or,
for small batches, purified by chromatography on silica (230-
400 mesh) with 5% ethyl acetate in light petroleum ether: 300
Con clu sion s
(1) Several potentially useful boronic ester synthons
for differentially protected (2R,3R)-3-methyl-1,2,4-bu-
tanetriol and related compounds have been synthesized
efficiently in high diastereomeric and enantiomeric
purity. Because the opposite chiral directors are readily
available, the (2S,3S)-enantiomers could be made equally
easily.
(2) Compounds bearing benzyloxy and boronic ester
groups separated by a chain of four intervening carbon
atoms are unexpectedly susceptible to benzylic cleavage.
(3) Reduction of an R-chloro boronic ester, RCHClB-
(OR′)2, with sodium hydride in dimethyl sulfoxide has
provided an efficient route to an R-unsubstituted boronic
ester, RCH2B(OR′)2.
1
MHz H NMR (CDCl3) δ 0.92 (d, J ) 6.8 Hz, 12), 1.70 (m, 2),
3.32 (AB, 2), 3.79 (s, 3), 3.89 (m, 2), 4.45 (s, 2), 6.86 (d, J ) 8.7
Hz, 2), 7.28 (d, J ) 8.4 Hz, 2); 75 MHz 13C NMR (CDCl3) δ
16.73, 17.81, 32.88, 55.18, 75.20, 84.46, 113.60, 129.65, 130.32,
159.11. Anal. Calcd for C17H27BO4: C, 66.68; H, 8.89; B, 3.53.
Found: C, 66.11; H, 8.96; B, 3.14.
(1′R)-2-(2-((p-Meth oxyben zyl)oxy)-1-m eth yleth yl)-4,5-
bis(1-m eth yleth yl)-1,3,2-dioxabor olan e {(S,S)-DIP ED (1R)-
[(2-((p-Meth oxyben zyl)oxy)-1-m eth yleth yl]bor on ate} (6a).
In a 250-mL three-neck round bottom flask was placed 2-(((p-
methoxybenzyl)oxy)methyl)-4,5-bis(1-methylethyl)-1,3,2-dioxa-
borolane (4a ) (30.6 g, 0.1 mol) and dibromomethane (52.2 g,
0.3 mol) in anhydrous tetrahydrofuran (THF) (150 mL) under
an argon atmosphere. This mixture was stirred vigorously at
∼78 °C while lithium diisopropylamide (0.12 mol) was added
dropwise so that the internal temperature did not rise unduly.
(Overheated mixtures showed evidence of decomposition by
turning brown.) Powdered anhydrous (fused) zinc chloride was
added (53 g, 0.49 mol), and the solution was allowed to warm
to room temperature and stirred 12-16 h. The mixture was
treated with petroleum ether (bp 35-60 °C) (150 mL) followed
by saturated aqueous ammonium chloride (100 mL). The
aqueous phase was separated together with the small amount
of emulsion and, to facilitate phase separation, was treated
with saturated aqueous sodium chloride (∼50 mL) and then
extracted with a second portion of petroleum ether (25 mL).
The combined organic phase was washed with water (2 × 100
mL) and dried over anhydrous magnesium sulfate. The
solution was concentrated on a rotary evaporator and finally
under higher vacuum (0.1-1 Torr). The resulting crude (1′R)-
2-(2-((p-methoxybenzyl)oxy)-1-bromoethyl)-4,5-bis(1-methyl-
ethyl)-1,3,2-dioxaborolane (5a ) was dissolved in THF (100 mL)
and cooled to -78 °C under argon. The solution was stirred
and methylmagnesium chloride in THF (3 M, 35 mL, 0.105
Exp er im en ta l Section
Gen er a l Meth od s. Procedures similar to those used in this
work have been described previously.1-4 All procedures in-
volving carbanions and other air- or moisture-sensitive inter-
mediates were carried out under an atmosphere of argon.
P in a col (Br om om eth yl)bor on a te. Diisopropyl (bromo-
methyl)boronate7 (226 g, 1.19 mol) and pinacol (155 g, 1.31
mol) in diethyl ether (1 L) were stirred overnight, concentrated,
and distilled to yield pinacol (bromomethyl)boronate: bp 35
°C (0.3 Torr) or 72-75 °C (4.5-5 Torr); 239 g (90%); 200 MHz
1H NMR (CDCl3) δ 1.29 (s, 12), 2.59 (s, 2); HRMS (M+) calcd
for C7H14BBrO2, m/ e 222.0250; found m/ e 222.0257.
2-((p-Meth oxyben zyl)oxy)m eth yl-4,4,5,5-tetr a m eth yl-
1,3,2-d ioxa bor ola n e {P in a col [((p-Meth oxyben zyl)oxy)-
m eth yl]bor on a te}. Under argon, a solution of butyllithium
(21) Matteson, D. S.; Tripathy, P. B.; Sarkar, A.; Sadhu, K. M. J .
Am. Chem. Soc. 1989, 111, 4399-4402.
(22) The boronic esters tested were (S,S)-DIPED (1R,2S)-1-bromo-
2-(benzyloxy)-4-[(p-methoxybenzyl)oxy]butylboronate and its 1-chloro
analogue. These compounds were prepared by straightforward ap-
plication of known reactions and characterized only by 200 MHz 1H
NMR.

(Alkoxyalkyl)boronic Ester Intermediates
Organometallics, Vol. 15, No. 1, 1996 157
mol) was added dropwise. The mixture was stirred 12-15 h
at 20-25 °C. Light petroleum ether (150 mL) was added,
followed by 100 mL of water and a small amount of dilute
hydrochloric acid to clear up any emulsion present. The
phases were separated, and the aqueous phase was washed
with water (2 × 50 mL), dried over magnesium sulfate, filtered,
and concentrated under vacuum. Chromatography on silica
gel (230-400 mesh) with 5% ethyl acetate in light petroleum
ether separated a small amount of 2-methyl-4,5-bis(1-meth-
ylethyl)-1,3,2-dioxaborolane (0.85-1.7 g, 5-10%) from the
colorless oily (1′R)-2-(2-((p-methoxybenzyl)oxy)-1-methylethyl)-
4,5-bis(1-methylethyl)-1,3,2-dioxaborolane (6a ) (23.0-31.0 g,
69-93%): 300 MHz 1H NMR (CDCl3) δ 0.89 (d, J ) 6.8 Hz,
6), 0.90 (d, J ) 6.8 Hz, 6), 1.06 (d, J ) 7.4 Hz, 3), 1.50 (m, 1),
1.67 (m, 2), 3.43 (t, J ) 8.6 Hz, 1), 3.58 (dd, J ) 6.15 Hz, J )
8.9 Hz, 1), 3.80 (s, 3), 3.83 (m, 2), 4.44 (AB, J ) 11.7 Hz, 2),
6.86 (d, J ) 8.7 Hz, 2), 7.26 (d, J ) 8.6 Hz, 2). The use of a
larger than normal amount of zinc chloride (53 g, 0.39 mol,
3.9 equiv, instead of 39.4 g, 0.29 mol, 2.9 equiv) resulted in
formation of less of the byproduct, 2-methyl-4,5-bis(1-methyl-
ethyl)-1,3,2-dioxaborolane. Anal. Calcd for C19H31BO4: C,
68.27; H, 9.35; B 3.23. Found: C, 67.98; H, 9.30; B 2.55.
zyloxy)-4-((p-methoxybenzyl)oxy)-3-methylbutyl)-4,5-bis(1-
methylethyl)-1,3,2-dioxaborolane (9a ) (23.4 g, 50 mmol) in THF
(140 mL) was stirred in an ice bath. Water (60 mL) and
aqueous sodium hydroxide (3 M, 18.6 mL, 56 mmol) were
added. Hydrogen peroxide (30%, 6.3 mL, 55 mmol) was added
dropwise. The mixture was stirred for an additional 2 h at
20-25 °C. Water (100 mL) was added, and the mixture was
extracted with light petroleum ether (100 mL). The phases
were separated, the aqueous phase was extracted with light
petroleum ether (30 mL), and the combined organic phase was
washed with water (2 × 50 mL) and then dried over magne-
sium sulfate and concentrated under vacuum. The residue
was put into a sublimation apparatus and kept in an oil bath
at 65-75 °C under vacuum (0.1 Torr) for 2-3 days. The (S,S)-
DIPED sublimed, leaving an oily residue of ∼98% (2R,3R)-2-
(benzyloxy)-4-((p-methoxybenzyl)oxy)-3-methyl-1-butanol
1
(10a ): 16.2 g (98%); 200 MHz H NMR (CDCl3) δ 0.99 (d, J )
7 Hz, 2), 2.1 (m, 1), 2.5 (1, br) 3.40-3.56 (m, 5), 4.43 (s, 2),
4.55 (AB, 2), 6.85-7.34 (m, 9). Anal. Calcd for C20H26O4: C,
72.70; H, 7.93. Found: C, 72.71; H, 8.08.
(2R ,3R )-2-(Be n zyloxy)-4-((p -m e t h oxyb e n zyl)oxy)-3-
m eth yl-1-(tr ip h en ylm eth oxy)bu ta n e (11a ). A solution of
(2R,3R)-2-(benzyloxy)-4-((p-methoxybenzyl)oxy)-3-methyl-1-bu-
tanol (3.3 g, 10 mmol) in THF (25 mL) was treated with
triphenylmethyl chloride (3.06 g, 11 mmol), triethylamine (5
mL), and 4-(dimethylamino)pyridine (0.12 g, 1 mmol) and
stirred at 40 °C for 2 days. The mixture was treated with
water (30 mL) and extracted with light petroleum ether (30
mL). The aqueous phase was extracted with a second portion
of petroleum ether (10 mL). The combined organic phase was
washed with water (2 × 10 mL), dried over magnesium sulfate,
filtered, and concentrated under vacuum. The viscous liquid
(2R,3R)-2-(benzyloxy)-4-((p-methoxybenzyl)oxy)-3-methyl-1-
(triphenylmethoxy)butane (11a ) was chromatographed on
silica gel (230-400 mesh) with 5:1 hexane/ethyl acetate: 4.4
(4S,5S,1′S,2′R)-2-(1′-(Ben zyloxy)-3′-((p -m et h oxyb en -
zyl)oxy)-2′-m eth ylp r op yl)-4,5-bis(1-m eth yleth yl)-1,3,2-d i-
oxa bor ola n e {(S,S)-DIP ED (1S,2R)-[(1-(Ben zyloxy)-3-((p-
m eth oxyben zyl)oxy)-2-m eth ylpr opyl]bor on ate} (8a). The
reaction of (1′R)-2-(2-((p-methoxybenzyl)oxy)-1-methylethyl)-
4,5-bis(1-methylethyl)-1,3,2-dioxaborolane (6a ) (33.4 g, 0.1 mol)
with (dibromomethyl)lithium was carried out according to the
procedure described above for conversion 4a to 5a , except that
the amount of zinc chloride used was 39.4 g (0.29 mol). The
crude (1′R,2′R)-2-(1-bromo-3-((p-methoxybenzyl)oxy)-2-meth-
ylpropyl)-4,5-bis(1-methylethyl)-1,3,2-dioxaborolane (7a ) was
treated with excess lithium benzyl oxide (0.15 mol) under
conditions similar to those used for the preparation of 2-((p-
methoxybenzyl)oxy)methyl)-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane (4a ). Chromatography and concentration yielded clear
viscous liquid (1′S,2′R)-2-(1-benzyloxy)-3-((p-methoxybenzyl)-
oxy)-2-methylpropyl)-4,5-bis(1-methylethyl)-1,3,2-dioxaboro-
1
g (79%); 300 MHz H NMR (CDCl3) δ 0.88 (d, J ) 6.9 Hz, 3),
2.20 (m, 1), 3.16-3.59 (m, 5), 3.80 (s, 3); 4.38 (AB, 2), 4.63
(AB, 2), 6.84-7.53 (m, 24).
(2S,3R)-3-(Ben zyloxy)-4-(tr ip h en ylm eth oxy)-2-m eth yl-
1-iod obu ta n e (13a ). (2R,3R)-2-(Benzyloxy)-4-((p-methoxy-
benzyl)oxy)-3-methyl-1-(triphenylmethoxy)butane (2.79 g, 5
mmol) was oxidized with dichlorodicyanoquinone, and the
resulting alcohol 12a was treated with methanesulfonyl
chloride and triethylamine according to the procedure de-
scribed previously for the preparation of mesylates.9b The
resulting mesylate was formed quantitatively but was unstable
toward storage or purification. The mesylate was treated with
sodium iodide (∼4 equiv) in acetone at 20-25 °C for 2 days.
The organic phase was dried over magnesium sulfate, filtered,
and concentrated under vacuum. The 1H NMR spectrum
indicated complete conversion of the mesylate to (2S,3R)-3-
(benzyloxy)-4-(t riph enylm et h oxy)-2-m et hyl-1-iodobu t a n e
1
lane (8a ) (29.5-34 g, 65-75%): 200 MHz H NMR (CDCl3) δ
0.90 (d, J ) 6.7 Hz, 6), 0.92 (d, J ) 6.7 Hz, 6), 1.01 (d, J ) 6.8
Hz, 3), 1.62 (m, 2), 2.24 (m, 1), 3.31 (d, J ) 6.4 Hz, 1), 3.33 (t,
J ) 6.4 Hz, 1), 3.51 (dd, J ) 6.0 Hz, J ) 6.2 Hz, 1), 3.79 (s, 3),
3.83 (m, 2), 4.41 (s, 2), 4.52 (AB, 2), 6.81-7.32 (m, 9); HRMS
C
27H39BO5 (M+) calcd m/ e 454.2890, found m/ e 454.2903.
Anal. Calcd for
C27H39BO5: C, 71.37; H, 8.65; B, 2.38.
Found: C, 70.98; H, 8.67; B, 2.46.
(4S,5S,2′S,3′R)-2-(2′-(Ben zyloxy)-4′-((p -m et h oxyb en -
zyl)oxy)-3′-m eth ylbu tyl)-4,5-bis(1-m eth yleth yl)-1,3,2-d i-
oxa bor ola n e {(S,S)-DIP ED (2S,3R)-[(2-(Ben zyloxy)-4-((p-
m eth oxyben zyl)oxy)-3-m eth ylbu tyl]bor on a te} (9a ).
A
solution of (1′S,2′R)-2-(1-(benzyloxy)-3-((p-methoxybenzyl)oxy)-
2-methylpropyl)-4,5-bis(1-methylethyl)-1,3,2-dioxaborolane (8a)
(22.7 g, 50 mmol) and chloroiodomethane (9.7 g, 55 mmol) in
THF (50 mL) was stirred at -78 °C during the dropwise
addition of butyllithium (1.6 M in hexane, 34.4 mL, 55 mmol).
At the end of the addition the mixture turned into a slurry.
Stirring was continued for 10-12 h at 20-25 °C. The mixture
was diluted with light petroleum ether (75 mL) and extracted
with water (3 × 50 mL). The organic phase was dried over
magnesium sulfate, filtered, and concentrated under vacuum.
The 1H NMR spectrum of this crude product indicated <5%
remaining unchanged (1′S,2′R)-2-(1-benzyloxy)-3-((p-methoxy-
benzyl)oxy)-2-methylpropyl)-4,5-bis(1-methylethyl)-1,3,2-dioxa-
borolane in the (2′S,3′R)-2-(2-(benzyloxy)-4-((p-methoxybenzyl)-
oxy)-3-m et h ylbu t yl)-4,5-bis(1-m et h ylet h yl)-1,3,2-dioxa -
borolane (9a ) (22-23 g, 95-98%): 300 MHz 1H NMR (CDCl3)
δ 0.91 (m, 12), 1.02 (d, J ) 6.9 Hz, 3), 1.65 (m, 2), 2.25 (m, 1),
3.31-3.55 (m, 3), 3.75 (m, 2), 3.80 (s, 3), 4.41 (s, 2), 4.51 (AB,
J ) 11.5 Hz, 2), 6.84-7.31 (m, 9).
1
(13a ): 2.65 g (95%); 300 MHz H NMR (CDCl3) δ 0.83 (d, J )
6.7 Hz, 3), 1.90 (m, 1), 3.03-3.61 (m, 5), 4.61 (AB, 2), 7.21-
7.51 (m, 20). HRMS (C31H31IO2): calcd, m/ e 562.1369; found,
m/ e 562.1349.
(S,S)-DIP ED (1R)-[1-m eth yl-2-tr ip h en ylm eth oxy)eth -
yl]bor on a te (6b). LDA (lithium diisopropylamide) (129 mL,
1.43 M, 185 mmol) was added dropwise to a well-stirred
solution of (S,S)-DIPED [(triphenylmethoxy)methyl]boronate8
(5) (65.99 g, 154 mmol) and dibromomethane (80.42 g, 462
mmol) in THF (600 mL) at -78 °C. After the addition,
anhydrous (freshly fused) zinc chloride (63 g, 463 mmol) was
added. The solution was allowed to warm to room temperature
and kept for 18 h. The solution was poured into saturated
ammonium chloride (500 mL) and ether/hexane (1:1, 600 mL).
The organic layer was dried over magnesium sulfate and
filtered through a short pad of magnesium sulfate. Removal
of solvent gave a mixture of unchanged (S,S)-DIPED [(tri-
phenylmethoxy)methyl]boronate (4b) (∼13%) and (S,S)-DIPED
[(1R)-1-bromo-2-(triphenylmethoxy)ethyl]boronate (5b). The
crude 5b was dissolved in THF (600 mL) and cooled to -78
(2R ,3R )-2-(Be n zyloxy)-4-((p -m e t h oxyb e n zyl)oxy)-3-
m et h yl-1-bu t a n ol (10a ). A solution of (2′S,3′R)-2-(2-(ben-

158 Organometallics, Vol. 15, No. 1, 1996
Matteson et al.
°C under argon. The solution was stirred, and methylmag-
nesium chloride (2.68 M, 57.5 mL, 154 mmol) in THF was
added dropwise. The mixture was stirred 12-15 h at 20-25
°C. Ether/hexane (1:1, 600 mL) was added, followed by
saturated ammonium chloride (500 mL) to clear up any
emulsion present. The phases were separated, and the aque-
ous phase was washed with water (2 × 300 mL), dried over
magnesium sulfate, filtered, and concentrated under vacuum.
Chromatography on silica gel (230-400 mesh) with 10%
diethyl ether in hexane separated a small amount of (S,S)-
DIPED methylboronate (10-15%) from the colorless oily (S,S)-
DIPED (1R)-[1-methyl-2-(triphenylmethoxy)ethyl]boronate
(S,S)-DIP E D (2S,3R)-[2-(b en zyloxy)-3-m et h yl-4-(t r i-
p h en ylm eth oxy)bu tyl]bor on a te (9b). A solution of (S,S)-
DIPED (1S,2R)-[1-(benzyloxy)-2-methyl-3-(triphenylmethoxy)-
propyl]boronate (8b) (13.8 g, 24 mmol) and chloroiodomethane
(4.65 g, 26 mmol) in THF (50 mL) was stirred at -78 °C during
the dropwise addition of butyllithium (1.6 M in hexane, 16.5
mL, 26.4 mmol). At the end of the addition the mixture turned
into a slurry. Stirring was continued for 10-12 h at 20-25
°C. The mixture was diluted with hexane (100 mL) and
extracted with water (3 × 50 mL). The organic phase was
dried over magnesium sulfate, filtered, and concentrated under
vacuum. The 1H NMR spectrum of this crude product indi-
cated <5% remaining unchanged (S,S)-DIPED (1S,2R)-[1-
(benzyloxy)-2-methyl-3-(triphenylmethoxy)propyl]boronate (8b)
in the (S,S)-DIPED (2S,3R)-[2-(benzyloxy)-3-methyl-4-(tri-
phenylmethoxy)butyl]boronate (9b) (13.75 g, 97%): 300 MHz
1H NMR (CDCl3) δ 0.87-1.02 (m, 14), 1.02 (d, J ) 6.9 Hz, 3),
1.6 (m, 2), 2.18 (m, 1), 3.04 (dd, J ) 6.4 Hz, J ) 8.8 Hz, 1),
3.12 (dd, J ) 5.6 Hz, J ) 8.8 Hz, 1), 3.78 (m, 2), 3.83 (m, 1),
4.39 (AB, J ) 11.46 Hz, 1), 4.50 (AB, J ) 11.46 Hz, 1), 7.2-
7.5 (m, 20); 13C NMR (CDCl3) δ 12.98, 16.90, 18.00, 33.07,
38.34, 65.57, 70.85, 78.06, 84.16, 86.19, 126.77, 127.26, 127.53,
127.84, 128.76, 130.15, 139.17, 144.42.
1
(6b): 52.7 g (115.5 mmol, 75%); 300 MHz H NMR (CDCl3) δ
0.89 (d, J ) 6.8 Hz, 6), 0.91 (d, J ) 6.8 Hz, 6), 1.05 (d, J ) 7.4
Hz, 3), 1.50 (m, 1), 1.7 (m, 2), 3.11 (dd, J ) 6.7 Hz, J ) 8.2 Hz,
1), 3.19 (dd, J ) 6.9 Hz, J ) 8.2 Hz, 1), 3.85 (m, 2), 7.2-7.5
(m, 15). HRMS: Calcd for C30H37BO3 (M+) m/ e 456.2836,
found m/ e 456.2794.
(S,S)-DIP E D (1S,2R)-[(1-(Ben zyloxy)-2-m et h yl-3-(t r i-
p h en ylm eth oxy)p r op yl]bor on a te (8b). To a solution of
(S,S)-DIPED (1R)-[1-methyl-2-(triphenylmethoxy)ethyl]bor-
onate (6b) (41.33 g, 90 mmol) and methylene bromide (47.2 g,
271 mmol) in THF (300 mL) was added LDA (74 mL, 1.47 M,
108 mmol) dropwise at -78 °C. After the addition, anhydrous
(fused) zinc chloride (36.7 g, 270 mmol) was added. The
solution was allowed to warm to room temperature and kept
for 18 h. The solution was poured into saturated ammonium
chloride (300 mL, saturated) and ether/hexane (1:1, 400 mL).
The organic layer was dried over magnesium sulfate, and
filtered through a short pad of magnesium sulfate. Removal
of solvent gave a mixture of unchanged (S,S)-DIPED (1R)-[1-
methyl-2-(triphenylmethoxy)ethyl]boronate (6b) (5-10%) and
(S,S)-DIPED (1R,2R)-[1-bromo-2-methyl-3-(triphenylmethoxy)-
propyl]boronate (7b). The crude 7b was transferred to a
solution of sodium benzyl oxide in THF and DMSO at 0 °C.
The sodium benzyl oxide solution had been prepared by
addition of sodium hydride (4.32 g 108 mmol) (60% dispersion
in mineral oil) to benzyl alcohol (10.7 g, 99 mmol) in dimethyl
sulfoxide (200 mL) and THF (100 mL) at room temperature
overnight. The solution was allowed to warm to room tem-
perature and stirred for 18 h. The mixture was worked up by
addition of saturated aqueous ammonium chloride (300 mL)
and extraction with hexanes (2 × 300 mL). The organic
solution (hexanes layer) was washed with water (6 × 300 mL)
and brine (300 mL). Concentration in a rotary evaporator gave
crude (S,S)-DIPED (1S,2R)-[1-(benzyloxy)-2-methyl-3-(tri-
phenylmethoxy)propyl]boronate (8b) which contained 10%
unchanged 6b. The product was obtained by flash chroma-
tography on silica with 1:20 ether/hexane (44 g, 76.5 mmol,
85%): 200 MHz 1H NMR (CDCl3) δ 0.86 (d, J ) 6.8 Hz, 6),
0.87 (d, J ) 6.8 Hz, 6), 1.03 (d, J ) 6.96 Hz, 3), 1.7 (m, 2), 2.26
(m, 1), 3.06 (dd, J ) 6.3 Hz, J ) 8.7 Hz, 1), 3.19 (dd, J ) 5.2
Hz, J ) 8.7 Hz, 1), 3.39 (d, J ) 7.6 Hz), 3.81 (m, 2), 4.37 (AB,
J ) 11.85 Hz, 1), 4.52 (AB, J ) 11.85 Hz, 1), 7.2-7.5 (m, 20);
13C NMR (CDCl3) δ 14.70, 16.90, 17.95, 32.91, 36.29, 65.34,
72.52, 84.40, 86.09, 126.68, 127.14, 127.56, 127.65, 128.05,
128.82, 139.07, 144.42.
(2R,3R)-2-(Ben zyloxy)-3-m eth yl-4-(tr ip h en ylm eth oxy)-
1-bu ta n ol (10b). A solution of (S,S)-DIPED (2S,3R)-[2-
(benzyloxy)-3-methyl-4-(triphenylmethoxy)butyl]boronate (9b)
(11 g, 18.6 mmol) in THF (90 mL) was stirred in an ice bath.
Aqueous sodium hydroxide (3 M, 6.8 mL, 20.5 mmol) was
added. Hydrogen peroxide (30%, 2 mL, 25 mmol) was added
dropwise. The mixture was stirred for an additional 2 h at
20-25 °C. Water (100 mL) was added, and the mixture was
extracted with light petroleum ether (100 mL). The phases
were separated, the aqueous phase was extracted with light
petroleum ether (30 mL), and the combined organic phase was
washed with water (2 × 50 mL) and then dried over magne-
sium sulfate and concentrated under vacuum. The residue
was put into a sublimation apparatus and kept in an oil bath
at 65-75 °C under vacuum (0.1 Torr) for 2-3 days. The (S,S)-
DIPED sublimed, leaving an oily residue of (2R,3R)-2-(benzyl-
oxy)-3-methyl-4-(triphenylmethoxy)-1-butanol (10b): 8.2 g
1
(98%); 300 MHz H NMR (CDCl3) δ 1.03 (d, J ) 7 Hz, 3), 1.97
(1, br), 2.14 (m, 1), 3.18 (m, 2), 3.58 (m, 3), 4.43 (AB, J ) 11.3
Hz, 1), 4.47 (AB, J ) 11.3 Hz, 1), 7.2-7.5 (m, 20).
(2R ,3R )-2-(Be n zyloxy)-1-((p -m e t h oxyb e n zyl)oxy)-3-
m eth yl-4-(tr ip h en ylm eth oxy)bu ta n e (11b). A solution of
(2R,3R)-2-(benzyloxy)-3-methyl-4-(triphenylmethoxy)-1-bu-
tanol (10b) (8 mmol, 3.6 g), sodium hydride (0.32 g, 8 mmol)
(60% dispersion in mineral oil), dimethyl sulfoxide (20 mL),
and THF (40 mL) was stirred at room temperature for 5-8 h.
p-Methoxybenzyl chloride was added to the stirred mixture
at room temperature for 4 h and treated with water (40 mL)
and light petroleum ether (50 mL). The phases were sepa-
rated, the aqueous phase was extracted with light petroleum
ether (20 mL), and the combined organic phase was washed
with water (2 × 20 mL), dried over magnesium sulfate, and
concentrated under vacuum. The resulting viscous oil was
chromatographed on silica gel (230-400 mesh) with 1-4%
ethyl acetate in light petroleum ether. The yield of (2R,3R)-
(2-(benzyloxy)-1-((p-methoxybenzyl)oxy)-3-methyl-4-(triphenyl-
methoxy)butane (11b) was 4.35 g (95%): 300 MHz 1H NMR
(CDCl3) 0.98 (d, J ) 7 Hz, 3), 2.13 (m, 1), 3.10 (dd, J ) 5.9 Hz,
J ) 8.9 Hz, 1), 3.15 (dd, J ) 5.5 Hz, J ) 8.9 Hz, 1), 3.50-3.67
(m, 3), 3.79 (s, 3), 4.42 (s, 2), 4.43 + 4.64 (AB, J ) 11.6, 2),
(S,S)-DIP ED (1S,2R)-[1-Bu toxy-2-m eth yl-3-(tr ip h en yl-
m eth oxy)p r op yl]bor on a te a s a Byp r od u ct. Crude (S,S)-
DIPED (1R, 2R)-[1-bromo-2-methyl-3-(triphenylmethoxy)ethyl]-
boronate (7b) was treated with excess lithium benzyl oxide
under conditions similar to the reported procedure.3,4 In
addition to 8b (68%), (S,S)-DIPED (1S,2R)-[(1-butoxy-2-meth-
yl-3-(triphenylmethoxy)propyl]boronate (20%) was isolated by
7.15-7.5 (m, 24). HRMS: calcd for
572.2927, found m/ e 572.2874.
C
39H40O4 (M+) m/ e
1
chromatography: 500 MHz H NMR (CDCl3) δ 0.83-0.88 (m,
(2R ,3R )-2-(Be n zyloxy)-4-((p -m e t h oxyb e n zyl)oxy)-3-
m eth ylbu ta n ol (12b). A solution of (2R,3R)-2-(benzyloxy)-
1-((p-methoxybenzyl)oxy)-3-methyl-4-(triphenylmethoxy)bu-
tane (11b) (5.72 g, 10 mmol) was stirred in a mixture of formic
acid and diethyl ether (20 mL, 1:1) at room temperature for
1.5 h. After the end of the reaction the solution was diluted
with diethyl ether (20 mL), washed with brine and saturated
15), 1.01 (d, J ) 7 Hz, 3), 1.24 (m, 2), 1.41 (m, 2), 1.58 (m, 2),
2.18 (m, 1), 3.06 (dd, J ) 6.5 Hz, J ) 8.5 Hz, 1), 3.15 (dd, J )
4.5 Hz, J ) 8.5 Hz, 1), 3.20 (d, J ) 8.5 Hz), 3.25 (m, 1), 3.38
(m, 1), 3.80 (m, 2), 7.1-7.5 (m, 15); 13C NMR (CDCl3) δ 13.93,
14.57, 16.89, 17.95, 19.25, 32.09, 32.95, 36.15, 65.16, 70.80,
84.32, 86.01, 126.68, 127.56, 128.86, 144.50.

(Alkoxyalkyl)boronic Ester Intermediates
Organometallics, Vol. 15, No. 1, 1996 159
aqueous sodium hydrogen carbonate until neutral, dried, and
concentrated. The residue was chromatographed on silica gel
(230-400 mesh) with 10% ethyl acetate in hexane. The yield
of (2R,3R)-2-(benzyloxy)-4-((p-methoxybenzyl)oxy)-3-methylbu-
tanol (12b) was 2.97 g (90%): 300 MHz 1H NMR (CDCl3) 0.93
(d, J ) 7 Hz, 3), 2.0 (m, 1), 2.59 (br, 1, OH), 3.61 (m, 5), 3.80
(s, 3, OCH3), 4.49 (AB, 2), 4.53 + 4.74 (AB, J ) 11.6, 2), 6.8-
7.4 (m, 9); HRMS calcd for C20H26O4 (M+) m/ e 330.1831, found
m/ e 330.1772. The residue also contained 5% (2R,3R)-2-
g, 0.432 mol) and (S)-pinanediol in diethyl ether (200 mL)
stirred overnight at 20-25 °C, and then distilled, yielded (S)-
pinanediol (bromomethyl)boronate (113.8 g, 96.5%): bp 94 °C
(0.5 Torr); 200 MHz 1H NMR (CDCl3) δ 0.85 (s, 3), 1.20 (m, 1),
1.42 (s, 3), 1.70 (s, 3), 1.84-2.47 (m, 5), 2.64 (s, 2), 4.38 (dd, J
) 1.8, J ) 8.8 Hz, 1) (not characterized further). p-Methoxy-
benzyl alcohol (23.3 g, 0.169 mol) was added to a stirred
suspension of sodium hydride (6.74 g of 60% in mineral oil,
0.169 mol) in THF (300 mL) at 20-25 °C. Anhydrous dimethyl
sulfoxide (90 mL, 0.127 mol) was added, and the mixture was
stirred at 20-25 °C for 2-3 h. (S)-Pinanediol (bromomethyl)-
boronate (46.0 g, 169 mmol) was added, resulting in an
exothermic reaction and formation of a white precipitate. The
mixture was stirred at 20-25 °C overnight and then treated
with diethyl ether and saturated aqueous ammonium chloride.
The ether phase was washed with water followed by saturated
sodium chloride and then dried over sodium sulfate and
concentrated. The (S)-pinanediol [((p-methoxybenzyl)oxy)-
methyl]boronate was isolated by flash chromatography on
silica gel with petroleum ether/diethyl ether (12:1 to 5:1): 44.5
(benzyloxy)-4-((p-methoxybenzyl)oxy)-3-methylbutyl
for-
mate: HRMS calcd for C21H26O5 (M+) m/ e 358.1780, found
m/ e 358.1751.
(2S,3R)-2-(Ben zyloxy)-1-ch lor o-4-((p-m eth oxyben zyl)-
oxy)-3-m eth ylbu ta n e (13b). To a stirred solution of (0.72
mL, 8.25 mmol) of oxalyl chloride in 20 mL of dichloromethane
at 0 °C was added, dropwise over 3 min, N,N-dimethylform-
amide (0.65 mL, 8.25 mmol). The resulting white suspension
was allowed to warm to room temperature and after 10 min
was recooled to 0 °C, and (2R,3R)-2-(benzyloxy)-4-((p-meth-
oxybenzyl)oxy)-3-methylbutanol (12b) (2.5 g, 7.5 mmol) was
then added in one portion. The resulting solution was heated
at reflux for 4.5 h and then cooled to room temperature, poured
into 100 mL of saturated aqueous sodium chloride, and then
extracted with two 200 mL portions of ether. The organic
extracts were combined and dried over magnesium sulfate and
concentrated under vacuum. The resulting oil was chromato-
graphed on silica gel (230-400 mesh) with 4:6 ether/light
petroleum ether to yield 13b (2.35 g, 90%): 300 MHz 1H NMR
(CDCl3) 1.01 (d, J ) 6.8 Hz, 3), 2.22 (m, 1), 3.48-3.54 (m, 2),
3.59-3.67 (m, 2), 3.77 (m, 1), 3.80 (s, 3), 4.45 + 4.51 (AB, J )
11.7 Hz, 2), 4.51 + 4.70 (AB, J ) 11.7 Hz, 2), 6.86-7.34 (m,
9); 13C NMR (CDCl3) δ 14.42, 37.11, 48.79, 55.25, 69.33, 72.63,
73.02, 79.50, 113.75, 127.58, 127.91, 128.31, 129.28, 130.23,
138.40, 159.18. Anal. Calcd for C20H25O3Cl: C, 68.86; H, 7.22;
Cl, 10.16. Found: C, 69.02; H, 7.22; Cl, 10.17.
1
g (80%); 200 MHz H NMR (CDCl3) δ 0.83 (s, 3), 1.15 (m, 1),
1.28 (s, 3), 1.40 (s, 3), 1.83-2.43 (m, 5), 3.30 (s, 2), 3.80 (s, 3),
4.31 (dd, J ) 1.8, J ) 8.4 Hz, 1), 4.46 (s, 2), 6.87 (d, J ) 8.6
Hz, 2), 7.28 (d, J ) 8.6 Hz, 2). The 90 MHz 1H NMR spectrum
was reported previously.4
(R)-P in a n ed iol [((p -Met h oxyb en zyl)oxy)m et h yl]b or -
on a te (4c). (R)-Pinanediol (7.7 g, 45.3 mmol) and pinacol [((p-
methoxybenzyl)oxy)methyl]boronate (12.6 g,45.3 mmol) in 50
mL of diethyl ether were stirred overnight at 20-25 °C. Flash
chromatography on 220 g of silica gel with petroleum ether/
ethyl acetate (15:1) yielded (R)-pinanediol [((p-methoxy-
benzyl)oxy)methyl]boronate: 12.3 g (82%); 200 MHz 1H NMR
(CDCl3) same as (S)-isomer.
(R)-P in a n ed iol
(1R)-[2-((p -Met h oxyb en zyl)oxy)-1-
m eth yleth yl]bor on a te (6c). Lithium diisopropylamide (1.5
M as THF complex in cyclohexane, 12.2 mL, 18.2 mmol) was
added dropwise to a stirred solution of (R)-pinanediol [((p-
methoxybenzyl)oxy)methyl]boronate (5.00 g, 15.12 mmol) and
dibromomethane (7.65 g, 44 mmol) in THF (50 mL) at ∼78
°C. Anhydrous powdered zinc chloride (8.1 g, 59 mmol) was
added. After 30 min the cooling bath was removed, and the
mixture was stirred at 20-25 °C overnight. The mixture was
worked up with saturated aqueous ammonium chloride and
diethyl ether, and the ether phase was dried over magnesium
sulfate. The solution was concentrated under reduced pres-
sure, and the residue was found to be 95% (R)-pinanediol (1R)-
[1-bromo-2-((p-methoxybenzyl)oxy)ethyl]boronate8 (5c) and 5%
unchanged [((p-methoxybenzyl)oxy)methyl]boronate (4c) by
NMR analysis. This residue was dissolved in THF (35 mL)
and stirred at ∼78 °C during the dropwise addition of meth-
ylmagnesium bromide in ether (5.6 mL of 3 M, 16.8 mmol).
The mixture was stirred at 20-25 °C overnight and then
worked up with saturated aqueous ammonium chloride and
diethyl ether, and the ether phase was dried over magnesium
sulfate. Concentration followed by flash chromatography on
silica gel (60 g) with petroleum ether/ethyl acetate (15:1)
yielded 4.0 g (74%) of (R)-pinanediol (1R)-[2-((p-methoxyben-
(S,S)-DIP ED (2S,3R)-[2-(Ben zyloxy)-3-m eth yl-4-(for m yl-
oxy)bu tyl]bor on a te (9, R1 ) CHO) a n d (4R,5R)-2-Oxy-4-
(ben zyloxy)-5-m eth yl-1,2-oxabor in (14). A solution of (S,S)-
DIPED (2S,3R)-[2-(benzyloxy)-3-methyl-4-(triphenylmeth-
oxy)butyl]boronate (9b) (0.59 g, 1 mmol) in a mixture of formic
acid and diethyl ether (2 mL, 1:1) was stirred at room
temperature for 1.5 h. Brine (4 mL) was added, and the
mixture was extracted with ether (4 mL). The phases were
separated. The organic phase was washed with water (2 × 3
mL) and then dried over magnesium sulfate and concentrated
under vacuum. The residue was stirred in a mixture of
aqueous sodium hydroxide (1 M, 2 mL) and diethyl ether (2
mL) at room temperature for 3 h. The phases were separated.
The ether phase contained DIPED and a 5-10% yield of (S,S)-
DIPED (2S,3R)-[2-(benzyloxy)-3-methyl-4-(formyloxy)butyl]bo-
ronate (9, R1 ) CHO), which was separated by chromatogra-
1
phy: 300 MHz H NMR (CDCl3) δ 0.90-0.93 (m, 14), 0.99 (d,
J ) 6.9 Hz, 3), 1.65 (m, 2), 2.19 (m, 1), 3.68 (q, J ) 6.27 Hz, 1)
3.84 (m, 2), 4.14 (ddd, J ) 0.7, 6.5, 10.8 Hz, 1), 4.24 (ddd, J )
0.7, 5.1, 10.8 Hz, 1), 4.45 (AB, J ) 11.43 Hz, 1), 4.63 (AB, J )
11.43 Hz, 1), 7.3 (m, 5), 8.05 (s, 1); HRMS calcd for C21H33O5B
(M+) m/ e 376.2421, found m/ e 376.2434. The aqueous phase,
which contained most of the boron, was neutralized by HCl,
extracted with ether (10 mL), and dried over magnesium
sulfate. Concentration in a rotary evaporator gave (4R,5R)-
zyl)oxy)-1-methylethyl]boronate (6c): [R]21 ∼13.7° (c 0.99,
D
1
CHCl3); 300 MHz H NMR (CDCl3) δ 0.84 (s, 3), 1.05 (d, J )
7.0 Hz, 3), 1.15 (m, 1), 1.28 (s, 3), 1.37 (s, 3), 1.47 (m, 1), 1.78-
1.9 (m, 2), 2.0-2.06 (m, 1), 2.12-2.22 (m, 1), 2.26-2.38 (m,
1), 3.44 (m, 1), 3.54 (m, 1), 3.80 (s, 3), 4.26 (dd, J ) 2, J ) 9
Hz, 1), 4.44 (s, 2), 6.85 (d, J ) 8.5 Hz, 2), 7.26 (d, J ) 8.5 Hz,
2); 75.5 MHz 13C NMR (CDCl3) δ 12.7, 18.36 br, 23.95, 27.05,
28.64, 26.29, 35.48, 38.08, 39.47, 51.24, 55.21, 72.36, 73.28,
77.64, 85.46, 113.59, 129.03, 131.04, 158.93. Anal. Calcd for
1
2-oxy-4-(benzyloxy)-5-methyl-1,2-oxaborin (14): 500 MHz H
NMR (CDCl3) δ 0.96 (d, J ) 7 Hz, 3), 1.11 (dd, J ) 5.5, 17 Hz,
1), 1.24 (dd, J ) 6, 17 Hz, 1) 1.70 (1, br), 2.00 (m, 1), 3.71 (ddd,
J ) 5.5, 2.5, 6 Hz, 1), 3.87 (dd, J ) 4.5, 11 Hz, 1), 3.96 (dd, J
) 7.5, 11 Hz, 1), 4.44 (AB, J ) 12 Hz, 1), 4.47 (AB, J ) 12 Hz,
1), 7.2-7.4 (m, 5).
(S)-P in a n ed iol [((p -Met h oxyb en zyl)oxy)m et h yl]b or -
on a te (en t-4c). The procedure was similar to that described
previously,4 except that in place of (S)-pinanediol (chloro-
methyl)boronate and lithium p-methoxybenzyl oxide, (S)-
pinanediol (bromomethyl)boronate and sodium p-methoxyben-
zyl oxide were used. Diisopropyl (bromomethyl)boronate7 (96.4
C
21H31BO4: C, 70.40; H, 8.72; B, 3.02. Found: C, 70.27; H,
8.64; B, 3.02.
(R)-P in a n ed iol (1S,2R)-[1-(Ben zyloxy)-3-((p-m eth oxy-
ben zyl)oxy)-2-m eth ylp r op yl]bor on a te (8c). By the pro-
cedure described in the preceding paragraph for the prepara-
tion of 5c, (R)-pinanediol (1R)-[2-((p-methoxybenzyl)oxy)-1-

160 Organometallics, Vol. 15, No. 1, 1996
Matteson et al.
methylethyl]boronate (6c) (43.5 mmol) was converted to crude
(R)-pinanediol (1R,2R)-[1-bromo-3-((p-methoxybenzyl)oxy)-2-
methylpropyl]boronate (7c), which showed no evidence of
(2R,3R)-2-(Ben zyloxy)-1-{[(1,1-d im eth yleth yl)d im eth -
ylsilyl]oxy}-4-((p -m et h oxyb en zyl)oxy)-3-m et h ylb u t a n e
(11c). A solution of (2R,3R)-2-(benzyloxy)-4-((p-methoxyben-
zyl)oxy)-3-methylbutanol (2.57 g, 7.8 mmol), tert-butyldimeth-
ylsilyl chloride (1.52 g, 10.11 mmol), triethylamine (3.84 g, 38.9
mmol), and 4-(dimethylamino)pyridine (85 mg, 0.78 mmol) in
THF (16 mL) was stirred overnight at 42 °C. (Higher tem-
peratures resulted in less silylation.) The mixture was worked
up with diethyl ether and water. The ether phase was dried
over sodium sulfate and concentrated under vacuum. Flash
chromatography on silica gel (60 g) with petroleum ether/
diethyl ether (20:1) yielded (2R,3R)-2-(benzyloxy)-1-{[(1,1-
dimethylethyl)dimethylsilyl]oxy}-4-((p-methoxybenzyl)oxy)-3-
1
unchanged 6c in the H NMR spectrum. Dimethyl sulfoxide
(6.8 g, 87 mmol) followed by the crude (1R,2R)-[1-bromo-3-((p-
methoxybenzyl)oxy)-2-methylpropyl]boronate was added to a
solution of lithium benzyl oxide (87 mmol) at ∼78 °C, which
had been prepared by addition of butyllithium (54.4 mL of 1.6
M, 87 mmol) to benzyl alcohol (9.4 g, 87 mmol) in THF (100
mL) at ∼78 °C. The mixture was stirred at 20-25 °C
overnight and then worked up with saturated aqueous am-
monium chloride and diethyl ether, and the ether phase was
dried over magnesium sulfate. Concentration followed by flash
chromatography on silica gel (60 g) with petroleum ether/ethyl
acetate (15:1) yielded (R)-pinanediol (1S,2R)-[1-(benzyloxy)-
3-((p-methoxybenzyl)oxy)-2-methylpropyl]boronate (17.8 g,
85%): [R]21D ∼2.32° (c 0.9, CHCl3); 200 MHz 1H NMR (CDCl3)
δ 0.83 (s, 3), 1.00 (d, J ) 7.0 Hz, 3), 1.20 (m, 1), 1.28 (s, 3),
1.34 (s, 3), 1.77-2.43 (m, 5), 3.26-3.57 (m, 4), 3.80 (s, 3), 4.28
(dd, 1), 4.44 (s, 2), 4.46, 4.64 (AB, J ) 12.6 Hz, 2), 6.85 (d, 2),
7.29 (m, 7). Anal. Calcd for C29H39BO5: C, 72.80; H, 8.22; B,
2.26. Found: C, 71.90 (low); H, 8.37; B, 2.40.
methylbutane (11c) (2.85 g, 85%): [R]21 +18.86° (c 1.0,
D
CHCl3); 200 MHz 1H NMR (CDCl3) δ 0.04 (s, 6), 0.90 (s, 9),
0.99 (d, J ) 7 Hz, 3), 2.07 (m, 1), 3.39-3.55 + 3.65-3.82 (m,
5), 3.79 (s, 3), 4.40 (s, 2), 4.51, 4.72 (AB, J ) 11.5 Hz, 2), 6.87
(d, J ) 8.8 Hz, 2), 7.24 (d, J ) 8.8 Hz, 2), 7.3 (m, 5). Anal.
Calcd for C26H40O4Si: C, 70.23; H, 9.07. Found: C, 70.17; H,
9.19.
(2R,3R)-2-(Ben zyloxy)-1-{[d im eth yl(1,1-d im eth yleth yl-
)silyl]oxy}-4-((p-m eth oxyben zyl)oxy)-3-m eth ylbu tan e (11c)
fr om 10a . A solution of (2R,3R)-2-(benzyloxy)-4-((p-methoxy-
benzyl)oxy)-3-methyl-1-butanol (10a ) (50 mmol, 16.5 g), chloro-
(1,1-dimethylethyl)dimethylsilane (9.0 g, 60 mmol), triethyl-
amine (25.3 g, 250 mmol), and 4-(dimethylamino)pyridine (0.6
g, 5 mmol) in THF (50 mL) was stirred at 45-50 °C for 5-8
h. The mixture was cooled to room temperature and treated
with water (100 mL) and light petroleum ether (80 mL). The
phases were separated, the aqueous phase was extracted with
light petroleum ether (20 mL), and the combined organic phase
was washed with water (2 × 25 mL), dried over magnesium
sulfate, and concentrated under vacuum. The resulting
viscous oil was chromatographed on silica gel (230-400 mesh)
with 1-4% ethyl acetate in light petroleum ether. The yield
of (2R,3R)-2-(benzyloxy)-1-{[dimethyl(1,1-dimethylethyl)silyl]-
oxy}-4-((p-methoxybenzyl)oxy)-3-methylbutane (11c) was 20.2
g (91%): 200 MHz 1H NMR same as above; HRMS (C26H40O4-
Si) calcd m/ e 444.2696, found m/ e 444.2726.
(R)-P in a n ed iol (2S,3R)-[2-(Ben zyloxy)-4-((p-m eth oxy-
ben zyl)oxy)-3-m eth ylbu tyl]bor on a te (9c). n-Butyllithium
in hexane (1.6 M, 15.7 mL, 25.1 mmol) was added dropwise to
a stirred solution of (R)-pinanediol (1S,2R)-[1-(benzyloxy)-3-
((p-methoxybenzyl)oxy)-2-methylpropyl]boronate (8c) (10 g,
20.9 mmol) and chloroiodomethane (4.43 g, 25.1 mmol) in THF
(160 mL) at ∼78 °C. The mixture was stirred at 20-25 °C
overnight and then worked up with saturated aqueous am-
monium chloride and diethyl ether, and the ether phase was
dried over magnesium sulfate. Concentration followed by flash
chromatography on silica gel (500 g) with petroleum ether/
ethyl acetate (20:1) yielded (R)-pinanediol (2S,3R)-[2-(benzyl-
oxy)-4-((p-methoxybenzyl)oxy)-3-methylbutyl]boronate (9c) (8.0
g, 78%): [R]21D ∼4.2° (c 0.4, CHCl3); 500 MHz 1H NMR (CDCl3)
δ 0.81 (s, 3), 0.95 (d, J ) 7.0 Hz, 3), 1.0-1.08 (m, 1), 1.14 (m,
1), 1.16-1.23 (m, 1), 1.26 (s, 3), 1.33 (s, 3), 1.76-1.88 (m, 2),
1.98-2.04 (m, 1), 2.06-2.22 (m, 2), 2.24-2.35 (m, 1), 3.33 (m,
1), 3.47 (m, 1), 3.75 (m, 1), 3.79 (s, 3), 4.23 (dd, J ) 2, J ) 8.8
Hz, 1), 4.40 (s, 2), 4.46, 4.55 (AB, J ) 11.4 Hz, 2), 6.86 (d, 2),
7.28 (m, 7); 75.5 MHz 13C NMR (CDCl3) δ 12.93, 23.99, 27.06,
28.61, 26.38, 35.42, 37.88, 38.07, 39.44, 51.19, 55.21, 71.11,
72.47, 72.63, 77.63, 78.27, 85.51, 113.66, 127.17, 127.65,
128.11, 129.16, 130.85, 139.17, 158.99 (BC not observed).
Anal. Calcd for C30H41BO5: C, 73.17; H, 8.39; B 2.20.
Found: 73.07; H, 8.49; B, 2.20.
(2R,3R)-3-(Ben zyloxy)-4-{[(1,1-d im eth yleth yl)d im eth -
ylsilyl]oxy}-2-m eth yl-1-bu ta n ol (12c). (2R,3R)-2-(Benzyl-
oxy)-1-{[(1,1-dimethylethyl)dimethylsilyl]oxy}-4-((p-methoxy-
benzyl)oxy)-3-methylbutane (2.47 g, 5.76 mmol) and 2,3-
dichloro-5,6-dicyano-1,4-quinone (1.57 g, 6.91 mmol) in water
(30 mL) and dichloromethane (30 mL) were stirred for 1 h at
20-25 °C. The dichloromethane phase was filtered through
Celite, dried over sodium sulfate, and concentrated. Flash
chromatography on silica gel (60 g) with petroleum ether/
diethyl ether (5:1) yielded (2R,3R)-3-(benzyloxy)-4-{[(1,1-di-
methylethyl)dimethylsilyl]oxy}-2-methylbutanol (1.60 g,
85%): [R]21D +27.6° (c 0.95, CHCl3); 300 MHz 1H NMR (CDCl3)
δ 0.08 (s, 6), 0.91 (s, 9), 0.97 (d, J ) 7.0 Hz, 3), 1.97 (m, 1),
3.44 (m, 1), 3.60 (m, 2), 3.71, 3.81 (d of AB, J ) 4.5, J ) 10.9
Hz), 4.54, 4.75 (AB, J ) 11.5 Hz), 7.33 (m, 5). Anal. Calcd
for C18H32O3Si: C, 66.62; H, 9.94. Found: C, 66.83; H, 10.10.
(2S ,3R )-3-(B e n zy lo x y )-4-{[d im e t h y l(1,1-d im e t h y l-
eth yl)silyl]oxy}-2-m eth yl-1-iod obu ta n e (13c). This com-
pound was prepared from 12c in the same manner as 13a was
prepared from 12a . The crude yield was 95%, but 13c was
(2R ,3R )-2-(Be n zyloxy)-4-((p -m e t h oxyb e n zyl)oxy)-3-
m eth ylbu ta n ol (10c). (R)-Pinanediol (1S,2R)-[1-(benzyloxy)-
3-((p-methoxybenzyl)oxy)-2-methylpropyl]boronate (9.6 g, 20
mmol) was converted to (R)-pinanediol (2S,3R)-[2-(benzyloxy)-
4-((p-methoxybenzyl)oxy)-3-methylbutyl]boronate (9c), which
was not purified but dissolved in THF (270 mL) and treated
with hydrogen peroxide (30%, 2.5 mL) and 3 M aqueous
sodium hydroxide (6.6 mL). The mixture was allowed to warm
to 20-25 °C and stirred for 2 h. The mixture was worked up
with water and diethyl ether. The ether phase was dried over
sodium sulfate and concentrated. Flash chromatography on
silica gel (400 g) with petroleum ether/ethyl acetate (4:1)
1
not very stable: 200 MHz H NMR (CDCl3) δ 0.06 (s, 6), 0.91
yielded
(2R,3R)-2-(benzyloxy)-4-((p-methoxybenzyl)oxy)-3-
(s, 9), 1.01 (d, J ) 6.6 Hz, 3), 1.72 (m, 1), 3.25-3.87 (m, 5),
4.62 (AB, 2), 7.23-7.38 (m, 5).
methylbutanol (10c) (4.22 g, 64%): [R]21D +7.73° (c 0.9, CHCl3);
1
200 MHz H NMR (CDCl3) δ 0.99 (d, J ) 7.1 Hz, 3), 2.15 (m,
(S)-P in a n ed iol (1S,2R)-[2-(Ben zyloxy)-3-((p-m eth oxy-
ben zyl)oxy)-1-m eth ylp r op yl]bor on a te (17). Crude (S)-
pinanediol (1S,2S)-[2-(benzyloxy)-1-bromo-3-((p-methoxybenzyl)-
oxy)propyl]boronate (16) was prepared from (S)-pinanediol
(1R)-[1-(benzyloxy)-2-((p-methoxybenzyl)oxy)ethyl]boronate (15)
(1.11 mmol) by the procedure previously described.4 This
crude material was dissolved in THF (3 mL) and stirred at
-78 °C during the addition of methylmagnesium bromide in
diethyl ether (0.41 mL of 3 M, 1.22 mmol). The mixture was
stirred at 20-25 °C overnight and then at 45 °C for 3-4 h.
1), 3.38-3.66 (m, 5), 3.80 (s, 3), 4.43 (s, 2), 4.54, 4.57 (AB, J )
6.0 Hz, 2), 6.87 (d, 2), 7.26 (M, 7). Anal. Calcd for C20H26O4:
C, 72.70; H, 7.93. Found: C, 72.01 (low); H, 8.09. A major
byproduct was (2R)-3-((p-methoxybenzyl)oxy)-2-methylpropa-
nal (0.80 g, 19%): 200 MHz 1H NMR (CDCl3) δ 1.12 (d, J )
7.1 Hz, 3), 2.65 (m, 1), 3.62 (d, 1), 3.64 (d, 1), 3.80 (s, 3), 4.46
(s, 2), 6.88 (d, J ) 8.4 Hz, 2), 7.24 (d, J ) 8.6 Hz, 2), 9.71 (s,
1). Anal. Calcd for C12H16O3: C, 69.21; H, 7.74. Found: C,
67.94 (low); H, 7.94.

(Alkoxyalkyl)boronic Ester Intermediates
Organometallics, Vol. 15, No. 1, 1996 161
The mixture was worked up with diethyl ether and saturated
aqueous ammonium chloride. The ether phase was dried over
magnesium sulfate and concentrated under vacuum. Flash
chromatography on silica gel (30 g) with petroleum ether/ethyl
acetate (12:1) yielded (S)-pinanediol (1S,2R)-[2-(benzyloxy)-3-
((p-methoxybenzyl)oxy)-1-methylpropyl]boronate (17) (364 mg,
69%): [R]21D +15.5° (c 0.99, CHCl3); 200 MHz 1H NMR (CDCl3)
δ 0.81 (s, 3), 0.99 (d, J ) 7.3 Hz, 3), 1.14 (m, 1), 1.26 (s, 3),
1.29 (s, 3), 1.50 (m, 1), 1.70-2.39 (m, 5), 3.55 (d, 2), 3.77 (m,
1), 3.80 (s, 3), 4.22 (dd, 1), 4.43 + 4.50 (AB, J ) 12 Hz, 2), 4.59
+ 4.67 (AB, J ) 12 Hz, 2), 6.85 (d, 2), 7.26 (m, 7); 125.7 MHz
13C NMR (CDCl3) δ 10.69, 19.8 br (BC), 23.96, 27.01, 28.52,
26.15, 35.42, 38.05, 39.37, 51.15, 55.20, 70.86, 71.67, 72.79,
77.53, 80.83, 85.36, 113.62, 127.11, 127.47, 128.09, 129.32,
130.52, 139.22, 159.0. Anal. Calcd for C29H39BO5: C, 72.80;
H, 8.22; B, 2.26. Found: C, 72.52; H, 8.28; B, 2.32%.
(S)-P in a n ed iol (2R,3R)-[3-(Ben zyloxy)-4-((p-m eth oxy-
ben zyl)oxy)-2-m eth ylbu tyl]bor on a te (19). Following the
previously described procedure for generation of (bromometh-
yl)lithium,7 n-butyllithium in hexane (0.625 mL of 1.6 M, 1
mmol) was added dropwise to a stirred solution of (S)-
pinanediol (1S,2R)-[2-(benzyloxy)-3-((p-methoxybenzyl)oxy)-1-
methylpropyl]boronate (400 mg, 0.836 mmol) and dibro-
momethane (174 mg, 1 mmol) in THF (5 mL) cooled with a
-78 °C bath. The mixture was allowed to warm to 20-25 °C
and stirred overnight. The mixture was treated with petro-
leum ether and saturated aqueous ammonium chloride, and
the organic phase was dried over magnesium sulfate. Con-
centration under reduced pressure and flash chromatography
on silica gel (60 g) with petroleum ether/ethyl acetate yielded
(S)-pinanediol (2R,3R)-[3-(benzyloxy)-4-((p-methoxybenzyl)-
described.24 After 5 min, a solution of (R,R)-DICHED [(tri-
phenylmethoxy)methyl]boronate (22) (50.49 g, 99 mmol) in
THF (150 mL) was added via cannula. After 10 min, anhy-
drous zinc chloride (24.23 g, 178 mmol), which had been dried
by fusion and ground in a mortar, was added to the solution.
The solution was allowed to warm to room temperature and
kept for 18 h to form (R,R)-DICHED (1S)-[1-chloro-2-(tri-
phenylmethoxy)ethyl]boronate. [A sample of chloro compound
obtained by concentration of the crude solution showed the
following: 300 MHz 1H NMR (CDCl3) δ 0.9-1.4 and 1.55-1.8
(m, 22), 3.40 (dd J ) 5.5 and 9.0 Hz, 1), 3.53 (m, 2) 3.92-3.97
(m, 2) 7.19-7.50 (m, 15); 75 MHz 13C NMR (CDCl3) δ 25.82,
25.97, 26.39, 27.33, 28.21, 42.8, 65.92, 84.38, 86.68, 127.01,
127.75, 128.80, 143.87. HRMS: calcd for C35H42O3BCl (M+)
m/ e 556.2916, found m/ e 556.2946.] The solvent and the
excess dichloromethane were removed under vacuum before
the crude chloro compound was transferred to a solution of
sodium benzyl oxide in THF and DMSO at 0 °C, which had
been prepared by addition of sodium hydride (4.36 g 110 mmol)
(60% dispersion in mineral oil) to benzyl alcohol (13.9 g.130
mmol) in dimethyl sulfoxide (200 mL) and THF (100 mL) at
room temperature overnight. The mixture was allowed to
warm to room temperature and stirred for 18 h and then
worked up by addition of saturated aqueous ammonium
chloride (300 mL) followed by extraction with hexanes (2 ×
300 mL). The organic solution (hexanes layer) was washed
with water (6 × 300 mL) and brine (300 mL). Concentration
in a rotary evaporator gave crude (R,R)-DICHED (1R)-[(1-
(benzyloxy)-2-(triphenylmethoxy)ethyl]boronate (23) which con-
tain 10% unchanged starting material. The product was
purified by flash chromatography on silica with 1:20 ether/
hexane (85% yield): 300 MHz 1H NMR (CDCl3) δ 0.80-1.42
and 1.58-1.84 (m, 22), 3.33 (dd, J ) 5.5, and 9.9 Hz, 1), 3.39
(dd, J ) 3.7, and 9.9 Hz, 1) 3.54 (dd, J ) 3.7, and 5.5 Hz, 1)
3.89-3.93 (m, 2), 4.56 (AB, J ) 12 3 Hz, 1), 4.66 (AB, J ) 12.3
Hz, 1), 7.19-7.51 (m, 20); 75 MHz 13C NMR (CDCl3) δ 25.87,
25.97, 26.38, 27.38, 28.21, 42.79, 64.48, 72.24, 83.89, 86.44,
126.75, 127.64, 127.98, 128.07, 128.16, 128.92, 139.07, 144.20.
(R,R)-DICHED (1S,2R)-(2-(Ben zyloxy)-1-m eth yl-3-(tr i-
p h en ylm eth oxy)p r op yl)bor on a te (25). (Dichloromethyl)-
lithium was prepared by addition of 1-butyllithium (68.5 mL,
1.5 M, 103 mmol) to dichloromethane (20.12 g, 237 mmol) in
THF (150 mL) at -100 °C (as described for 23 above). After
5 min, a solution of crude (R,R)-DICHED (1R)-[(1-(benzyloxy)-
2-(triphenylmethoxy)ethyl]boronate (23) (50 g, 79 mmol) was
added to the solution via cannula. After 10 min, anhydrous
zinc chloride (30.1 g, 221 mmol) was added. The mixture was
allowed to warm to room temperature and kept for 18 h to
form a solution of (R,R)-DICHED (1S,2R)-[(2-(benzyloxy)-1-
chloro-3-triphenylmethoxy)propyl]boronate (24). The solution
was cooled to 0 °C, and methylmagnesium chloride (52.6 mL,
3 M, 158 mmol) was added dropwise. The solution was allowed
to warm to room temperature and kept for 36 h. Aqueous
ammonium chloride (10 mL) was added to the mixture. Some
gas (methane) was liberated. The solvent was removed by
rotary evaporator. To the mixture was added hexane (500 mL)
and aqueous ammonium chloride (100 mL). The organic
solution was washed with ammonium chloride (200 mL)
followed by water (3 × 200 mL) and dried over magnesium
sulfate. Removal of the solvent by rotary evaporator yielded
oxy)-2-methylbutyl]boronate (19) (290 mg, 70.6%) as a colorless
1
oil: [R]21 +11.4° (c 0.67, CHCl3); 200 MHz H NMR (CDCl3)
D
δ 0.82 (s, 3), 0.97 (d, J ) 6.8 Hz, 3), 1.0-1.23 (m, 2), 1.13 (m,
1), 1.27 (s, 3), 1.32 (s, 3), 1.6-2.4 (m, 6), 3.3-3.67 (m, 3), 3.80
(s, 3), 4.22 (dd, 1), 4.45 (s, 2), 4.59 + 4.71 (AB, J ) 12 Hz, 2),
6.86 (d, 2), 7.30 (m, 7); 125.7 MHz 13C NMR (CDCl3) δ 14.8 br
(BC), 18.52, 23.96, 27.02, 28.58, 26.46, 31.55, 35.46, 38.03,
39.43, 51.17, 55.21, 71.09, 72.29, 72.88, 77.41, 83.48, 85.28,
113.65, 127.19, 127.69, 128.14, 129.18, 130.60, 139.26, 159.02.
Anal. Calcd for
C30H41BO5: C, 73.17; H, 8.39; B, 2.20.
Found: C, 73.33; H, 8.45; B, 2.20%.
(E)-1-(2-Bu ten yl) p-Meth oxyben zyl eth er (20). This
compound was isolated as a byproduct from the preparation
of (S)-pinanediol (2R,3R)-[3-(benzyloxy)-4-((p-methoxybenzyl)-
oxy)-2-methylbutyl]boronate: 200 MHz 1H NMR (CDCl3) δ
1.72 (d, J ) 6 Hz, 3), 3.80 (s, 3), 3.93 (d, J ) 6 Hz, 2), 4.43 (s,
2), 5.78 (m, 2, CHdCH), 6.88 (d, 2), 7.27 (d, 2). A 500 MHz
spectrum with decoupling of the CH3 indicated that the
CHdCH J ) 15.6 Hz. Anal. Calcd for C12H16O2: C, 74.97; H,
8.39. Found: C, 74.56; H, 8.53.
(S)-P in an ediol [(Ben zyloxy)m eth yl]bor on ate (21). This
known compound3,23 was also isolated as a byproduct from the
preparation of (S)-pinanediol (2R,3R)-[3-(benzyloxy)-4-((p-
methoxybenzyl)oxy)-2-methylbutyl]boronate: 200 MHz 1H
NMR (CDCl3) δ 0.84 (s, 3), 1.16 (m, 1), 1.28 (s, 3), 1.41 (s, 3),
1.65-2.4 (m, 5), 3.34 (s, 2), 4.23 (dd, 1), 4.53 (s, 2), 7.33 (m, 5),
in accord with that previously reported.3 When the reaction
was run with dibromomethane, the apparent molar ratio of
this elimination product to chain extension product by NMR
analysis was 37:63, though the isolated yield of chain extension
product was 70%, and when chloroiodomethane was used
under the same conditions, the NMR analysis indicated 57%
elimination.
a
mixture containing a small amount of (R,R)-DICHED
methylboronate (∼10%) with the major product (R,R)-DICHED
(1S,2R)-(2-(benzyloxy)-1-methyl-3-(triphenylmethoxy)propyl)-
boronate (25) (46.65 g). Chromatography of 25 resulted in
partial decomposition. Therefore, the crude material was used
in the next step without further purification. A partially
purified analytical sample was obtained by flash chromatog-
raphy on silica with 1:30 ether/hexane: 300 MHz 1H NMR
(CDCl3) δ 0.92-1.38 and 1.48-1.8 (m, 23), 0.86 (d, J ) 7.5
Hz, 3), 3.20 (dd, J ) 5.7, 10 Hz, 1), 3.27 (dd, J ) 3.45, 10 Hz,
(R,R)-DICHED (1R)-[(1-(Ben zyloxy)-2-(tr ip h en ylm eth -
oxy)eth yl]bor on a te (23). (Dichloromethyl)lithium was pre-
pared by addition of 1-butyllithium (85.8 mL, 1.5 M, 129 mmol)
slowly down the side of chilled flask to stirred dichloromethane
(25.3 g, 298 mmol) in THF (150 mL) at -100 °C as previously
(23) Matteson, D. S.; Beedle, E. C. Tetrahedron Lett. 1987, 28, 4499-
4502.
(24) Matteson, D. S.; Majumdar, D. Organometallics 1983, 2, 230-
236.

162 Organometallics, Vol. 15, No. 1, 1996
Matteson et al.
1), 3.68-3.76 (m, 3), 4.58 (AB, J ) 11.9 Hz, 1), 4.75 (AB, J )
11.9 Hz, 1), 7.19-7.48 (m, 20); 75 MHz 13C NMR (CDCl3) δ
11.70, 25.79, 25.92, 26.39, 27.47, 28.28, 42.86, 64.93, 71.76,
81.74, 83.28, 86.50, 126.76, 126.91, 127.11, 128.03, 128.80,
139.42, 144.27; HRMS calcd for C44H53O4B (M+) m/ e 656.4036,
found m/ e 656.4068. Anal. Calcd for C44H53O4B: C, 80.44;
H, 8.14; B, 1.68. Found: C, 79.89 (low); H, 8.42; B, 1.54.
(R,R)-DICH E D (2R,3R)-[(3-(Ben zyloxy)-2-m et h yl-4-
(tr ip h en ylm eth oxy)bu tyl]bor on a te (27). (Dichlorometh-
yl)lithium was prepared by addition of 1-butyllithium (65 mL,
1.5 M, 97.5 mmol) to dichloromethane (19.1 g, 225 mmol) in
THF (200 mL) at -100 °C (as described for 23 above). After
5 min, a solution of crude (R,R)-DICHED (2S,3R)-(2-(benzyl-
oxy)-1-methyl-4-(triphenylmethoxy)butyl]boronate (25) (49.2 g,
75 mmol) was added to the solution via cannula. After 10 min,
anhydrous zinc chloride (25.8 g, 189 mmol) was added to the
mixture. The mixture was allowed to warm to room temper-
ature, kept for 18 h, and concentrated in a rotary evaporator
to yield crude (R,R)-DICHED (1S,2S,3R)-[3-(benzyloxy)-1-
chloro-2-methyl-4-(triphenylmethoxy)butyl]boronate (26):
HRMS calcd for C45H54O4BCl (M+) m/ e 704.3804, found m/ e
704.3826. The crude 26 was treated with DMSO (100 mL)
and sodium hydride (4.5 g 112.5 mmol) (60% dispersion in
mineral oil) at room temperature and stirred for 18 h. The
mixture was treated with hexanes (300 mL) and was washed
with ammonium chloride (300 mL) followed by water (3 × 200
mL) and dried over magnesium sulfate. Removal of the
solvent by rotary evaporator yielded a mixture containing a
small amount of (2?,3R)-3-(benzyloxy)-4-(triphenylmethoxy)-
2-butanol25 (∼10%), presumably from accidental oxidation of
25, with the major product (R,R)-DICHED (2R,3R)-[3-(benzy-
loxy)-2-methyl-4-(triphenylmethoxy)butyl]boronate (27) (45.23
g). The product 27 was purified by flash chromatography on
silica with 1:30 ether/hexane: 300 MHz 1H NMR (CDCl3) δ
0.66-0.71 (dd, J ) 9.3 Hz, 1), 0.8-1.8 (m, 23), 0.83 (d, J ) 6.8
Hz, 3), 2.1 (m, 1), 3.17 (dd, J ) 5.9, 10.05 Hz, 1), 3.26 (dd, J )
3, 10.05 Hz, 1), 3.38 (m, 1), 3.73-3.79 (m, 2)), 4.57 (AB, J )
11.7 Hz, 1), 4.74 (AB, J ) 11.7 Hz, 1), 7.20-7.49 (m, 20); 75
MHz 13C NMR (CDCl3) δ 18.35, 25.86, 26.00, 26.44, 27.48,
28.49, 31.65, 42.99, 64.35, 72.35, 83.28, 83.93, 86.55, 126.82,
127.2, 127.69, 128.17, 128.78, 139.29, 144.26; HRMS calcd for
containing the major product (R,R)-DICHED (1R,3R,4R)-[1-
allyl-4-(benzyloxy)-3-methyl-5-(triphenylmethoxy)pentyl]bor-
onate (2) together with 20-30 mol % benzyl chloride, identified
by GC-MS (EI) (in CHEM SYSTEM CHEM/database.
WILEY.1). A purified sample of 2 was obtained by flash
chromatography on silica with 1:20 ether/hexane: 3.26 g (60%);
300 MHz 1H NMR (CDCl3) δ 0.92-1.36 and 1.5-1.8 (m, 25)
0.76 (d, J ) 6.8 Hz, 3), 1.92 (m, 1), 2.06 (m, 1), 2.17 (m, 1) 3.16
(dd, J ) 6.03, 10.2 Hz, 1), 3.25 (dd, J ) 2.46, 10.2 Hz, 1), 3.37
(m, 1), 3.77-3.81 (m, 2), 4.55 (AB, J ) 11.7 Hz, 1), 4.70 (AB,
J ) 11.7 Hz, 1), 4.90 (dd, J ) 2.13, 10.11 Hz, 1), 4.96 (dd, J )
2.13, 17.07 Hz, 1), 5.76 (ddd, J ) 6.9, 10.11, 17.07 Hz, 1), 7.18-
7.49 (m, 20); 75 MHz 13C NMR (CDCl3) δ 14.92, 25.82, 25.92,
26.41, 27.58, 28.43, 34.34, 34.52, 36.51, 43.03, 64.22, 72.16,
83.33, 83.47, 86.54, 114.79, 126.77, 127.13, 127.56, 127.64,
128.11, 128.74, 138.61, 139.30, 144.27; HRMS calcd for
C
49H61O4B (M - 1)+ m/ e 723.4585, found m/ e 723.4565.
(4S,5S)-4,5-Dicycloh exyl-2-m et h oxy-1,3,2-d ioxa b or o-
la n e [(S,S)-DICHED Meth oxybor on a te] (28). (1S,2S)-1,2-
Dicyclohexylethane-1,2-diol [(S,S)-DICHED] (45.2 g, 0.2 mol)
was stirred with freshly distilled trimethyl borate (20.8 g, 0.2
mol) under argon, and the methanol produced was distilled
at atmospheric pressure. The product was distilled, bp 142
1
°C (1 Torr), 50.5 g (95%): 300 MHz H NMR (CDCl3) δ 0.89-
1.80 (m, 22), 3.59 (s, 3), 3.79 (m, 2); 75 MHz 13C NMR (CDCl3)
δ 25.8, 25.9, 26.4, 27.2, 28.2, 52.66, 82.55; HRMS C15H27BO3
calcd m/ e 266.2053, found m/ e 266.2058.
(4S,5S)-4,5-Dicycloh exyl-2-(3-pr open yl)-1,3,2-dioxabor o-
la n e [(S,S)-DICHED Allylbor on a te] (29). Allylmagnesium
chloride (50 mL of 2 M in THF, 0.1 mol) was added dropwise
to a stirred solution of (S,S)-DICHED methoxyboronate (28)
(26.6 g, 0.1 mol) in THF (100 mL) at 0 °C. The mixture was
stirred for 1 h at room temperature and treated with saturated
aqueous ammonium chloride (100 mL). The mixture was
extracted with petroleum ether (bp 35-60 °C) (200 mL), and
the organic phase was dried over anhydrous magnesium
sulfate. The solution was filtered and concentrated on a rotary
evaporator. The oily product 29 was distilled, bp 145-147 °C
1
(0.7 Torr), 26.2-27.0 g (95-98%): 300 MHz H NMR (CDCl3)
δ 0.92-1.76 (m, 24), 3.84 (m, 2), 4.89-5.03 (m, 2), 5.80-5.94
(m, 1); 75 MHz 13C NMR (CDCl3) δ 25.8, 25.9, 26.4, 27.3, 28.2,
42.9, 83.4, 114.7, 134.2; HRMS C17H29BO2 calcd m/ e 276.2260,
found m/ e 276.2255.
C
45H55O4B (M+) m/ e 670.4193, found m/ e 670.4162. Anal.
Calcd for C45H55O4B: C, 80.55; H, 8.27; B, 1.64. Found: C,
80.43; H, 8.31; B, 1.63.
(2′S,4S,5S)-4,5-Dicycloh exyl-2-(allyl(ben zyloxy)m eth yl)-
1,3,2-dioxabor olan e {(S,S)-DICHED (S)-[Allyl(ben zyloxy)-
m eth yl]bor on a te} (32). [(S,S)-DICHED (R)-[allylbromo-
methyl]boronate] (30) was prepared by the procedure described
for preparation of 5a (intermediate for 6a ), with (S,S)-DICHED
allylboronate (29) (24.1 g, 0.087 mol) in place of 4a , with
appropriate amounts of dibromomethane (45.6 g, 0.26 mol),
THF (125 mL), LDA (0.105 mol), and zinc chloride (22.6 g,
0.166 mol). After the mixture had warmed to room temper-
ature overnight, it was treated with petroleum ether and
saturated ammonium chloride, the organic phase was filtered
through a short column of magnesium sulfate, and the solution
was concentrated to yield a crude mixture of 30, DICHED
[diallylmethyl]boronate (31), and DICHED or its boric acid
(R,R)-DICH E D (1R,3R,4R)-[(1-Allyl-4-(b en zyloxy)-3-
m eth yl-5-(tr iph en ylm eth oxy)pen tyl]bor on ate (2). (Dichlo-
romethyl)lithium was prepared by addition of 1-butyllithium
(6.5 mL, 1.5 M, 9.75 mmol) to dichloromethane (1.9 g, 22.5
mmol) in THF (20 mL) at -100 °C (as described for 23 above).
After 5 min, a solution of (R,R)-DICHED (2R,3R)-[3-(benzyl-
oxy)-2-methyl-4-(triphenylmethoxy)butyl]boronate (27) (5 g,
7.5 mmol) was added to the solution via cannula. After 10
min, anhydrous zinc chloride (2.84 g, 20.8 mmol) was added
to the solution. The resulting solution of (R,R)-DICHED
(1S,3R,4R)-[4-(benzyloxy)-1-chloro-3-methyl-5-(triphenylmeth-
oxy)pentyl]boronate was allowed to warm to room temperature
and kept for 18 h. The solution was cooled to 0 °C, and
allylmagnesium chloride (7.5 mL, 2 M, 15 mmol) was added
dropwise. The solution was allowed to warm to room temper-
ature and kept for 36 h. Aqueous ammonium chloride (2 mL)
was added to the mixture. The solvent was removed by rotary
evaporator. To the mixture was added hexane (50 mL) and
aqueous ammonium chloride (10 mL). The organic solution
was washed with ammonium chloride (20 mL) followed by
water (3 × 20 mL) and dried over magnesium sulfate.
Removal of the solvent by rotary evaporator yielded a mixture
1
ester: 300 MHz H NMR (CDCl3) δ 0.85-1.4 and 1.6-1.8 (m,
theory 22, found 34) [31: 2.19 (m, 15% of 4); lit.19 butanediol
[diallylmethyl]boronate, 2.18], 2.66 (m, 2), 3.37 (t, 1) [impuri-
ties: 3.83, 3.85 (m’s, 0.6)], 3.95 (m, 2) [31: 4.93, 4.97, 5.03 (m’s,
∼15% of 4); lit.19 analogue 4.9-5.1], 5.08-5.12 and 5.15 (m’s,
2), 5.82 (m, 1) [31: 5.81 (m, mostly obscured by 30); lit.19
analogue 5.82]; HRMS (30) C18H30BBrO2 calcd, m/ e 368.1522;
found, m/ e 368.1541; HRMS (31) calcd for C21H35BO2, m/ e
330.2730, found, m/ e 330.2728. The crude 30 was dissolved
in THF (45 mL) and added dropwise to a stirred solution of
lithium benzyl oxide (0.13 mol) in an 0 °C bath, which had
been prepared by titrating benzyl alcohol (14.1 g) with butyl-
lithium to the 1,10-phenanthroline endpoint in THF (90 mL)
at 0 °C. Dimethyl sulfoxide (10 g, 0.13 mol was added, and
the solution was kept at room temperature overnight. The
(25) 300 MHz 1H NMR (CDCl3): δ 1.07 (d, J ) 6.4 Hz, 3), 2.6 (b),
3.19 (dd, J ) 4.6, 10.17 Hz, 1), 3.31 (m, 1), 3.40 (dd, J ) 3.75, 10.17
Hz, 1), 3.93 (m, 1), 4.47 (AB, J ) 11.4 Hz, 1), 4.76 (AB, J ) 11.4 Hz,
1) 7.20-7.49 (m, 20). 13C NMR (CDCl3): δ 18.77, 62.99, 67.75, 72.81,
82.96, 86.88, 127.06, 127.86, 127.94, 128.46, 128.64, 138.12, 143.82.
HRMS: calcd for C30H30O3 (M+) m/ e 438.2195, found m/ e 438.2203.

(Alkoxyalkyl)boronic Ester Intermediates
Organometallics, Vol. 15, No. 1, 1996 163
mixture was worked up with water and petroleum ether, the
petroleum ether phase was concentrated, and the residue of
32 was purified by chromatography on silica with 2% ethyl
acetate in petroleum ether (bp 35-60 °C): 15 g (43%); 300
MHz 1H NMR (CDCl3) δ 0.85-1.40 and 1.57-1.79 (m, 22), 2.47
(m, 2, CdCHCH2CH(OBn)B) [assignments based on decou-
pling, this frequency irradiated], 3.42 (t, 1, CH2CH(OBn)B),
3.91 (m, 2), 4.56 (AB, 2), 5.03 (m, 1), 5.11 (m, 1), 5.89 (m, 1,
CdCHCH2), 7.25-7.38 (m, 5); 75 MHz 13C NMR δ 25.86, 25.98,
26.41, 27.41, 28.27, 35.92, 42.88, 72.08, 83.76, 116.37, 127.32,
127.82, 128.18, 135.89, 139.00; HRMS C25H37BO3 calcd, m/ e
396.2836; found, m/ e 396.2849.
Ack n ow led gm en t. We thank the National Insti-
tutes of Health for Grant No. GM39063 and the Na-
tional Science Foundation for Grant No. CHE-9303074.
The Washington State University NMR Center was
supported by NIH Grant No. RR 0631401, NSF Grant
No. CHE-9115282, and Battelle Pacific Northwest Labo-
ratories Contract No. 12-097718-A-L2, and the depart-
mental Nicolet NT-200 NMR instrument by Boeing
Corp.
OM950574Q