New enantiomerically pure allylboronic esters in allyl additions: Synthesis and NMR investigation of intermediates

Article abstract of DOI:10.1055/s-2005-921756

Enantiomerically pure allylboronic esters 1 + 2 with a stereogenic center α to the boron moiety can be obtained by a sigmatropic rearrangement of boron containing allyl alcohols. Allyl additions with the new reagents are highly selective, which was shown

Full text of DOI:10.1055/s-2005-921756

24
PAPER
New Enantiomerically Pure Allylboronic Esters in Allyl Additions: Synthesis
and NMR Investigation of Intermediates
Allyl
Add
ö
itionof Enan
r
tiomeric
g
allyPure
A
llylbor
o
P
nic Esters ietruszka,* Niklas Schöne
Institut für Bioorganische Chemie der Heinrich-Heine-Universität Düsseldorf im Forschungszentrum Jülich, Stetternicher Forst,
Geb. 15.8, 52426 Jülich, Germany
Fax +49(2461)616196; E-mail: j.pietruszka@fz-juelich.de
Received 31 October 2005
Dedicated to Professor Dr. Steven V. Ley on the occasion of his 60th birthday
B*
O
B*
O
Abstract: Enantiomerically pure allylboronic esters 1 + 2 with a
stereogenic center a to the boron moiety can be obtained by a sig-
matropic rearrangement of boron containing allyl alcohols. Allyl
additions with the new reagents are highly selective, which was
shown via the direct measurement of the diastereoisomeric ratio of
the intermediates 5 + 6 by characteristic NMR chemical shifts. The
observations are not limited to ester containing reagents, but holds
also true for hydrocarbon side-chains (e.g. in 11 + 12) that were
readily obtained by reducing the ester.
R1
OEt
R1
OEt
1
2
allyl addition to R2CHO
*B
*B
O
O
O
O
R2
OEt
R2
OEt
OEt
R1
R1
6
5
1. NMR analysis of dr
2. workup:
Key words: spectroscopy, allylations, boron, stereoselectivity
column chromatography
OH
O
OH
O
One of the key reactions in organic synthesis is the allyl
addition, especially using allylboronic esters; regularly
homoallylic alcohols are conveniently formed in high
yield and enantiomeric excess.1–6 Reagents having a ste-
reogenic center in the position a to the boronic ester are
less often used since they are more difficult to prepare in
enantiomerically pure form.7–14 We have recently demon-
strated that highly stable reagents of the general type 1 or
2 are readily available via a Johnson rearrangement of the
corresponding boron-substituted allyl alcohols.15–17 The
derivatives are easy to handle and store, and add highly
selectively to a number of aldehydes giving either ho-
moallylic alcohol 3 or 4 with the enantiomeric excess
ranging from 92 to >99% (Scheme 1). The formation of
the Z-double bond and the configuration of the newly
formed stereogenic centers were unambiguously proven
by means of chemical correlation. The results could also
be rationalized by a transition state as shown in Scheme 1
– the substituent in position a to boron is preferentially ax-
ial – which is in full agreement with a previous report by
Hofmann and Weidmann.7
R2
OEt
ee determination,
R2
R1
R1
4
3
e.g. via Mosher´s ester
R1
H
H
Ph
Me
R2
Ph
yields:
(3a: 91%, 96% ee)
(3b: 93%, 98% ee)
(3c: 65%, 99% ee)
(4a: 89%, > 99% ee)
(4b: 97%, 92% ee)
(4c: 78%, > 99% ee)
PhCH2CH2
Ph
Ph
(3d: 95%, 97% ee) (4d: 90%, > 99% ee)
transition state of the allyl addition:
H
Ph
Ph
H
B*
R2
O
O
B
O
OMe
OMe
R1
H
B* =
R1 = H, Me, Ph
H
R3
R
2 = Ph, PhCH2CH2
Ph
Ph
R3 = CO2Et, CH3
Scheme 1 Allyl additions of 1 or 2.
diate boric esters (in our case 5 and 6) must occur with
similar rates. In many cases this might not be a problem;
however, occasionally we observed a rate difference that
would lead to incorrect results, even when direct methods
to determine the enantiomeric excess were used. An obvi-
ous solution to the problem would be the utilization of the
formed diastereoisomeric intermediates 5 and 6 that
should show distinct differences in their NMR spectra.
Hence we decided to start a NMR investigation of the re-
action before work-up and especially chromatographic
separation.
A drawback of the procedure was the fact that the enanti-
omeric excess of homoallylic alcohols was regularly de-
termined – as it is common practice – by forming
diastereoisomeric Mosher ester18,19 (when direct methods
fail) and thus only indirectly establishing the stereochem-
ical outcome of the transformation. Obviously, there are
two problems associated with the approach: A diastereo-
meric discrimination of the ester formation must be ruled
out and, more importantly, the hydrolysis of the interme-
First, we investigated the most simple derivatives 5a and
6a (Figure 1) and found that almost all signals in the pro-
ton NMR (500 MHz) show distinct differences in the
SYNTHESIS 2006, No. 1, pp 0024–0030
Advanced online publication: 16.12.2005
DOI: 10.1055/s-2005-921756; Art ID: C09405SS
© Georg Thieme Verlag Stuttgart · New York
0
6
.
0
1
.2
0
0
6

PAPER
Allyl Addition of Enantiomerically Pure Allylboronic Esters
25
chemical shift. Generally, the most telling signals corre- nience in all cases the arithmetic means of diastereotopic
spond to the proton of the newly formed stereogenic cen- protons were used in the tables in Figures 1 and 2 since
ter (6-H) and also the adjacent protons (5-H). However, the configuration of the individual protons could not be
the 5-H protons can usually not be used to determine the established.
diastereomeric ratio since the multiplicity of the signals
It was mentioned above that the ester group might influ-
make the integration imprecise. It is interesting to note
ence the conformation of the intermediates. Furthermore,
that also signals of relatively remote groups show an im-
one could speculate whether the group is actually essential
pressive difference in chemical shifts for the two diaste-
for the high selectivity of the allyl addition. To prove the
reoisomers. At this point it can be speculated whether the
generality of the concept, it would be essential to remove
carbonyl group of the ester moiety is coordinated to the
any group that would be able to coordinate to the boron
electrophilic boron. Nevertheless, the most important re-
moiety. Consequently, the esters 1a and 2a were used as
starting materials for the realization of the task
sult can be observed when comparing the spectra in the re-
gion around 6-H: within the accuracy of the NMR
(Scheme 2). Reduction with diisobutylaluminum hydride
method, neither of the diastereoisomers 5a or 6a is con-
(DIBAL-H) gave the corresponding alcohols 7 and 8 in
high yield (92 and 94%, respectively), without touching
taminated with the other!
We were pleased to find that the observation was not sin- the boron moiety. Activation of the alcohols as methylsul-
gular. As a matter of fact it was rather general, indepen- fonates 9 and 10 (95 and 93%, respectively) allowed the
dent of the aldehyde (Figure 2; diastereoisomers 5b and consecutive reduction with super hydride furnishing the
6b) or the kind of reagent (diastereoisomers 5c + d and 6c allylboronic esters 11 and 12 (68% and 74%, respectively)
+ d) used. It is interesting to note that the D ppm value is with an ethyl side-chain. All boron derivatives were sta-
diagnostic and the relative shifts are generally showing
the same trend. The only exceptions are the 5-H protons
of compounds 5c and 6c with the phenyl group obviously
inducing a different conformation and thus influencing
the magnetic environment. Both 5,6-disubstituted deriva-
tives 5c + d and 6c + d are most conveniently interpreted,
because of the reduced multiplicity: The 6-H protons (e.g.
in 5c and 6c) or even the 5-Me group in 5d and 6d give
simple doublets that allow a reliable determination of the
diastereoisomeric ratio. It should be noted that for conve-
Figure 1 Characteristic NMR data of diastereoisomeric boric esters
5a and 6a.
Figure 2 Characteristic NMR data of diastereoisomeric boric esters
5b–d and 6b–d; explanations for symbols used, see Figure 1.
Synthesis 2006, No. 1, 24–30 © Thieme Stuttgart · New York

26
J. Pietruszka, N. Schöne
PAPER
ble, could easily be purified and were hence isolated in NMR traces are a valuable general tool to follow this type
microanalytically pure form. Again, the configuration of of diastereoselective allylation and b) that there is no lim-
the two diastereoisomeric series could be confirmed by itation to reagents bearing a carboxylic ester side-chain:
the NMR data that show the same characteristic chemical Both the analytical tool remains and the selectivity is high
shift differences as previously observed, e.g. for 1a and for the addition step. We are currently trying to further ex-
2a. Furthermore, the stereochemical integrity was unam- tend the scope of the method, seeking for other alternative
biguously verified by an X-ray crystallographic analysis reagents. It should be noted that in all cases we can obtain
of boronic ester 11.20
either enantiomer from one given auxiliary.
The new reagents 11 and 12 were tested by using benzal- Finally, it was shown that the approach can potentially be
dehyde, thus leading to the known homoallylic alcohols extended to generally determine the enantiomeric excess
13 (83%) and 14 (69%) (Scheme 3).21,22 The NMR analy- of secondary alcohols. In a preliminary experiment, the
sis of the intermediate boric esters 15 and 16 was in full commercially available enantiomers of substituted prop-
agreement with the previous observations: Various pro- argylic alcohols 17 and 18 were esterified to boric esters
tons proved to be diagnostic and showed a distinct differ- 19 and 20, respectively, by stirring the alcohols in CDCl3
ence in both diastereoisomers. Especially useful were at room temperature with an excess of boric acid 2117
protons 1-H (D ppm: +0.13) and 6-H (D ppm: –0.09); (Figure 3). Again, the diastereoisomeric derivatives show
again the respective other diastereoisomer could not be different NMR chemical shifts, especially for the protons
detected (ee >95%). The results were independently vali- attached to the stereogenic center (D ppm: –0.10 for 19a/
dated by an HPLC and GC investigation of the alcohols 13 20a and +0.04 for 19b/20b), but also – and this will some-
and 14 on chiral stationary phases and the more precise times prove more practical for analytical purposes – for
values could be determined (>99% and >99% ee, respec- more remote groups (e.g. the CH3 group – 1-H – in 19b/
tively). The observation underlines a) that characteristic 20b; D ppm: +0.11). Obviously, direct methods will al-
Scheme 2 Transformation of esters 1 and 2; X-ray crystallographic
analysis of 11.20
Scheme 3 Allyl addition of 11 and 12 to benzaldehyde and repre-
sentative NMR data of the intermediates 15 and 16.
Synthesis 2006, No. 1, 24–30 © Thieme Stuttgart · New York

PAPER
Allyl Addition of Enantiomerically Pure Allylboronic Esters
27
with a CHIRALCEL OD column. 1H and 13C NMR spectra were re-
corded at 20 °C in CDCl3 on a Bruker ARX 300/500 spectrometer.
Chemical shifts are given in ppm relative to TMS as internal stan-
dard (1H) or relative to the resonance of the solvent (13C:
CDCl3 = 77.0 ppm); coupling constants J are given in Hz. Higher
order d and J values are not corrected. 13C signals were assigned by
means of H–H and C–H COSY spectroscopy. Microanalyses and
gas chromatographic determinations were performed at the Institut
für Organische Chemie, Stuttgart. Melting points or softening rang-
es (Büchi 510) are not corrected. Specific rotations were measured
at 20 °C. IR spectra were obtained on a Perkin-Elmer 283 spectrom-
eter. MS were recorded on a Finnigan MAT 95 (FAB, EI) or a Vari-
an MAT 711 (EI) spectrometer.
X-ray Crystallographic Analysis20
The crystal data for compound 11 were determined with a Siemens
P4 diffractometer with graphite monochromator in the w-scan mode
with Cu-Ka (l = 1.54178 Å) radiation. C35H37BO4, Mr = 532.48,
colorless, T = 293 K, crystal size 0.50 × 0.25 × 0.02 mm, monoclin-
ic, P2(1), a = 10.3707(6), b = 16.2076(19), c = 18.5250(14) Å,
V = 3105.2(5) Å3, Z = 4, Dcalcd = 1.139 g·cm–3, m = 0.570 mm–1,
F(000) = 1136, q range = 3.63–59.99°, 4963 measured/independent
reflections, 1691 reflections with [I > 2s(I)]. The structure was
solved by direct methods and refined by full-matrix least squares on
F2 for all data weights to R = 0.1718, wR = 0.2130, S = 0.981, H at-
oms were treated as riding atoms, max. shift/error <0.002, residual
max. = 0.186 Å–3.
Figure 3 Synthesis and NMR data of boric esters 19 and 20.
r
(i-Bu)2AlH-Reduction of 1a and 2a; General Procedure A
A solution of ester 1a or 2a (1.00 equiv) in THF (10 mL/mmol 1a/
2a) was cooled to –78 °C and DIBAL-H (1 M solution in heptane,
3.00 equiv) was added. The reaction mixture was warmed to 4 °C
over 2 h. Dilution with Et2O (10 mL/mmol 1a/2a) and careful addi-
tion of H2O [70 mL/mmol DIBAL-H], 2 M aq NaOH solution
[1.40 mL/mmol DIBAL-H] and H2O [70µL/mmol DIBAL-H] led to
a precipitate after 20 min. The mixture was filtered, the solvent of
ways be superior to the approach presented; however,
should these fail, diastereoisomeric boric esters might be
a valuable alternative.
In summary, we did describe the synthesis of a new pair
of allylation reagents 11 and 12 by a convenient sequence
starting from the known, diastereoisomerically pure boron
derivatives 1 and 2. The high yields and selectivities ob- the filtrate was evaporated and the crude product was purified by
flash column chromatography.
served for the consecutive allylation were thus not limited
to reagents bearing a carboxylic ester group. Furthermore,
(3S,4¢R,5¢R)-3-[4¢,5¢-Bis(methoxydiphenylmethyl)-1¢,3¢,2¢-
in view of potential problems occurring during the inves-
dioxaborolan-2¢-yl]pent-4-en-1-ol (7)
Prepared according to the general procedure A. Ester 1a (3.00 g,
tigation of the stereochemical course of the addition using
indirect methods, a reliable direct NMR approach was
presented. By analyzing the intermediate boric esters, er-
roneous data for a transformation can be omitted. While it
is especially practical for allyl additions, it might also be
extended for indirectly measuring the enantiomeric ex-
cess of secondary alcohols in general.
5.08 mmol) and DIBAL-H (1 M solution in heptane, 15.2 mL,
15.2 mmol) in THF (51 mL) were used. Purification by flash col-
umn chromatography on silica gel (51 g, PE–EtOAc, 85:15) yielded
2.57 g (92%) of 7 as spectroscopically pure colorless solid foam.
MPLC of a small sample (PE–EtOAc, 80:20) gave the analytically
pure colorless solid foam; recrystallization from pentane–CH2Cl2
yielded colorless crystals; mp 130 °C; Rf 0.10 (PE–EtOAc, 85:15);
[a]D20 –129 (c = 0.08, CHCl3).
The reactions were carried out by using standard Schlenk tech-
niques under dry N2 with magnetic stirring. Glassware was oven-
dried at 120 °C overnight. Solvents were dried and purified by con-
ventional methods prior to use; THF was freshly distilled from so-
dium/benzophenone. Common solvents for chromatography (PE,
EtOAc) were distilled prior to use; PE refers to a fraction with a
boiling point between 40–60 °C. Flash column chromatography
was performed on silica gel 60, 0.040–0.063 mm (230–400 mesh).
TLC (monitoring the course of the reactions) was performed on pre-
coated plastic sheets (Polygram® SIL G/UV254, Macherey–Nagel)
with detection by UV (254 nm) or by coloration with cerium molyb-
denum solution [phosphomolybdic acid (25 g), Ce(SO4)2·H2O
(10 g), conc. H2SO4 (60 mL), H2O (940 mL)]. Preparative medium
pressure liquid chromatography (MPLC) was performed with a La-
bomatic pump (MD80/100), a packed column (39 × 400 mm or
23 × 250 mm), LiChroprep, Si60 (15–25 mm) and UV-detector
(254 nm). HPLC was performed on a Pharmacia device equipped
IR (KBr): 3570, 3070, 3040, 3010, 2950, 2925, 2915, 2890, 2810,
1625, 1590, 1570, 1480, 1435, 1060, 740, 680 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.30–1.41 (m, 3 H, OH, 2-H),
1.43–1.50 (m, 1 H, 3-H), 3.01 (s, 6 H, OCH3), 3.35 (m, 2 H, 1-H),
3
2
4
4.73 (ddd, J = 17.2 Hz, J = 1.7 Hz, J = 1.3 Hz, 1 H, 5-HZ), 4.77
3
2
4
(ddd, J = 10.3 Hz, J = 1.7 Hz, J = 1.0 Hz, 1 H, 5-HE), 5.32 (s,
2 H, 4¢-H, 5¢-H), 5.50 (ddd, 3J = 17.2 Hz, 3J = 10.3 Hz, 3J = 8.3 Hz,
1 H, 4-H), 7.25–7.35 (m, 20 Harom).
13C NMR (126 MHz, CDCl3): d = 26.1 (br, C-3), 31.5 (C-2), 51.7
(OCH3), 62.1 (C-1), 77.6 (C-4¢, C-5¢), 83.3 (CPh2OMe), 113.3 (C-
5), 127.3, 127.3, 127.6, 127.8, 128.4, 129.7 (CHarom), 138.7 (C-4),
141.1, 141.1 (Carom).
MS (FAB, matrix: NBA + NaI): m/z (%) = 571 (43, [M+ + Na]), 197
(100, [CPh2OMe+]), 167 (10, [Ph2CH+]), 105 (11, [PhCO+]), 77 (6,
[Ph+]).
Synthesis 2006, No. 1, 24–30 © Thieme Stuttgart · New York

28
J. Pietruszka, N. Schöne
PAPER
Anal. Calcd for C35H37BO5 (548.48): C, 76.64; H, 6.80. Found: C,
76.41; H, 6.77.
13C NMR (126 MHz, CDCl3): d = 24.9 (br, C-3), 27.9 (C-2), 36.9
(SO2CH3), 51.7 (OCH3), 69.2 (C-1), 77.9 (C-4¢, C-5¢), 83.3
(CPh2OMe), 114.2 (C-5), 127.3, 127.4, 127.6, 127.8, 128.5, 129.7
(CHarom), 137.1 (C-4), 141.0 (Carom).
MS (EI, 70 eV): m/z (%) = 626 (0.2, [M+]), 594 (9, [M+ – MeOH]),
429 (2, [M+ – MeOPh2C]), 197 (100, [MeOPh2C+]), 167 (4,
[Ph2HC+]), 105 (11, [PhCO+]).
(3R,4¢R,5¢R)-3-[4¢,5¢-Bis(methoxydiphenylmethyl)-1¢,3¢,2¢-
dioxaborolan-2¢-yl]pent-4-en-1-ol (8)
Prepared according to the general procedure A. Ester 2a (3.00 g,
5.08 mmol) and DIBAL-H (1 M solution in heptane, 15.2 mL,
15.2 mmol) in THF (51 mL) were used. Purification by flash col-
umn chromatography on silica gel (49 g, PE–EtOAc, 85:15) yielded
2.62 g (94%) of 8 as spectroscopically pure colorless solid foam.
MPLC of a small sample (PE–EtOAc, 80:20) gave the analytically
pure alcohol 8. Softening range: 62–78 °C; Rf 0.10 (PE–EtOAc,
85:15); [a]D20 –140 (c = 0.92, CHCl3).
Anal. Calcd for C36H39BO7S (626.25): C, 69.01; H, 6.27. Found: C,
68.72; H, 6.28.
(3R,4¢R,5¢R)-3-[4¢,5¢-Bis(methoxydiphenylmethyl)-1¢,3¢,2¢-
dioxaborolan-2¢-yl]pent-4-en-1-yl Methanesulfonate (10)
Prepared according to the general procedure B. Alcohol 7 (2.61 g,
4.75 mmol), Et3N (988 mL, 721 mg, 7.13 mmol) and MeSO2Cl
(554 mL, 817 mg, 7.13 mmol) in CH2Cl2 (9.51 mL) were used. Pu-
rification by flash chromatography on silica gel (100 g, PE–EtOAc,
86:14) yielded 2.77 g (93%) of 10 as analytically pure colorless sol-
id foam. Softening range: 53–66 °C; Rf 0.25 (PE–EtOAc, 85:15);
[a]D20 –114 (c = 1.05, CHCl3).
IR (KBr): 3540, 3070, 3040, 3000, 2950, 2920, 2880, 2850, 2810,
1625, 1590, 1575, 1480, 1435, 1060, 740, 680 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.32–1.40 (m, 2 H, OH, 2-Ha),
1.41–1.48 (m, 2 H, 2-Hb, 3-H), 3.00 (s, 6 H, OCH3), 3.29–3.34 (m,
1 H, 1-Ha), 3.37–3.42 (m, 1 H, 1-Hb), 4.73 (ddd, 3J = 17.0 Hz,
2J = 1.8 Hz, 4J = 1.2 Hz, 1 H, 5-HZ), 4.75 (dd, 3J = 10.3 Hz,
2J = 1.8 Hz, 1 H, 5-HE), 5.33 (s, 2 H, 4¢-H, 5¢-H), 5.39 (ddd,
IR (KBr): 3070, 3040, 3010, 2940, 2920, 2890, 2810, 1620, 1590,
1570, 1480, 1435, 1345, 1165, 1060, 740, 680 cm–1.
3
3J = 17.0 Hz, 3J = 10.3 Hz, J = 8.4 Hz, 1 H, 4-H), 7.24–7.35 (m,
20 Harom).
1H NMR (500 MHz, CDCl3): d = 1.41–1.51 (m, 2 H, 2-Ha, 3-H),
1.58–1.65 (m, 1 H, 2-Hb), 2.85 (s, 3 H, SO2CH3), 3.00 (s, 6 H,
OCH3), 3.89 (ddd, 2J = 9.6 Hz, 3J = 7.3 Hz, 3J = 7.2 Hz, 1 H, 1-Ha),
13C NMR (126 MHz, CDCl3): d = 26.5 (br, C-3), 32.4 (C-2), 51.8
(OCH3), 62.7 (C-1), 77.8 (C-4¢, C-5¢), 83.4 (CPh2OMe), 113.6 (C-
5), 127.3, 127.4, 127.6, 127.8, 128.5, 129.7 (CHarom), 138.5 (C-4),
141.2, 141.2 (Carom).
MS (EI, 70 eV): m/z (%) = 548 (0.1, [M+]), 516 (2, [M+ – MeOH]),
197 (100, [CPh2OMe+]), 167 (3, [Ph2CH+]), 105 (13, [PhCO+]), 77
(5, [Ph+]).
2
3
3
3.94 (ddd, J = 9.6 Hz, J = 7.8 Hz, J = 5.0 Hz, 1 H, 1-Hb), 4.73
(ddd, 3J = 17.1 Hz, 2J = 1.6 Hz, 4J = 1.2 Hz, 1 H, 5-HZ), 4.81 (ddd,
3J = 10.3 Hz, 2J = 1.6 Hz, 4J = 0.9 Hz, 1 H, 5-HE), 5.31 (ddd,
3J = 17.1 Hz, 3J = 10.3 Hz, 3J = 8.3 Hz, 1 H, 4-H), 5.33 (s, 2 H, 4¢-
H, 5¢-H), 7.25–7.33 (m, 20 Harom).
Anal. Calcd for C35H37BO5 (548.48): C, 76.64; H, 6.80. Found: C,
76.47; H, 6.84.
13C NMR (126 MHz, CDCl3): d = 25.3 (br, C-3), 28.3 (C-2), 37.1
(SO2CH3), 51.8 (OCH3), 69.2 (C-1), 77.9 (C-4¢, C-5¢), 83.4
(CPh2OMe), 114.6 (C-5), 127.4, 127.4, 127.6, 127.8, 128.5, 129.7
(CHarom), 136.8 (C-4), 141.1, 141.1 (Carom).
Methanesulfonic Esters 9 and 10; General Procedure B
To a solution of the alcohol 7 or 8 (1.00 equiv) in CH2Cl2 (2 mL/
mmol 7/8) was added Et3N (1.50 equiv) and MeSO2Cl (1.50 equiv)
at 4 °C. The reaction mixture was allowed to warm to r.t. within
0.5 h and diluted with Et2O (5 mL/mmol 7/8). A half sat. aq solution
of NaHCO3 (5 mL/mmol 7/8) was added and the mixture stirred
vigorously for 0.5 h. The aqueous phase was extracted with Et2O
(3 × 5 mL/mmol 7/8). The combined organic layers were washed
with sat. aq solution of NH4Cl (5 mL/mmol 7/8) and brine (5 mL/
mmol 7/8), and dried (MgSO4). After filtration and evaporation of
the solvent, the crude product was purified by flash column chroma-
tography.
MS (FAB, matrix: NBA + NaI): m/z (%) = 652 (84, [M+ + Na]), 197
(100, [MeOPh2C+]), 167 (9, [Ph2HC+]), 105 (12, [PhCO+]).
Anal. Calcd for C36H39BO7S (626.25): C, 69.01; H, 6.27. Found: C,
68.67; H, 6.30.
Reduction of Methanesulfonic Esters 9 and 10 with LiEt3BH;
General Procedure C
To a vigorously stirred solution of the methanesulfonic ester 9 or 10
(1.00 equiv) in THF (1.00 mL/mmol 9/10) at r.t. was added
LiEt3BH (1 M solution in THF, 2.00 equiv) in one batch. A color-
less solid precipitated from the solution. After 1 h, a 3 M aq solution
of NaOH (0.80 mL/mmol 9/10) and a 30% aq solution of H2O2
(0.8 mL/mmol 10) was added to the mixture. Stirring was continued
for 1 h and then the mixture was diluted with Et2O (5 mL/mmol 9/
10) and H2O (5 mL/mmol 9/10). The aqueous phase was extracted
with Et2O (3 × 5 mL/mmol 9/10) and the combined organic layers
were dried (MgSO4). After filtration and evaporation of the sol-
vents, the crude product was purified by flash column chromatogra-
phy.
(3S,4¢R,5¢R)-3-[4¢,5¢-Bis(methoxydiphenylmethyl)-1¢,3¢,2¢-
dioxaborolan-2¢-yl]pent-4-en-1-yl Methanesulfonate (9)
Prepared according to the general procedure B. Alcohol 7 (2.51 g,
4.58 mmol), Et3N (952 mL, 695 mg, 6.87 mmol) and MeSO2Cl
(534 mL, 787 mg, 6.87 mmol) in CH2Cl2 (9.16 mL) were used. Pu-
rification by flash column chromatography on silica gel (100 g, PE–
EtOAc, 86:14) yielded 2.72 g (95%) of 9 as analytically pure color-
less solid foam. Softening range: 54–65 °C; Rf 0.25 (PE–EtOAc,
85:15); [a]D20 –100 (c = 1.65, CHCl3).
(3S,4¢R,5¢R)-3-[4¢,5¢-Bis(methoxydiphenylmethyl)-1¢,3¢,2¢-
dioxaborolan-2¢-yl]pent-1-ene (11)
IR (KBr): 3070, 3040, 3010, 2950, 2940, 2920, 2880, 2810, 1620,
1590, 1570, 1480, 1435, 1345, 1165, 1060, 740, 680 cm–1.
Prepared according to the general procedure C. Methanesulfonic es-
ter 9 (2.73 g, 4.36 mmol) and LiEt3BH (1 M solution in THF,
8.71 mL, 8.71 mmol) in THF (4.36 mL) were used. Purification by
flash column chromatography on silica gel (85 g, PE–EtOAc, 95:5
to 85:15) yielded 1.57 g (68%) of 11 as colorless solid foam. Soft-
ening range: 50–62 °C; Rf 0.38 (PE–EtOAc, 95:5); [a]D20 –140
(c = 1.30, CHCl3). Recrystallization from pentane–EtOH yielded
crystals suitable for X-ray crystallographic analysis; mp 116–
119 °C.
1H NMR (500 MHz, CDCl3): d = 1.42–1.51 (m, 2 H, 2-Ha, 3-H),
1.53–1.60 (m, 1 H, 2-Hb), 2.78 (s, 3 H, SO2CH3), 3.01 (s, 6 H,
3
2
OCH3), 3.86 (m, 2 H, 1-H), 4.73 (ddd, J = 17.2 Hz, J = 1.6 Hz,
4J = 1.2 Hz, 1 H, 5-HZ), 4.83 (ddd, 3J = 10.3 Hz, 2J = 1.6 Hz,
4J = 0.8 Hz, 1 H, 5-HE), 5.33 (s, 2 H, 4¢-H, 5¢-H), 5.42 (ddd,
3
3
3J = 17.2 Hz, J = 10.3 Hz, J = 7.8 Hz, 1 H, 4-H), 7.26–7.32 (m,
20 Harom).
Synthesis 2006, No. 1, 24–30 © Thieme Stuttgart · New York

PAPER
Allyl Addition of Enantiomerically Pure Allylboronic Esters
29
IR (KBr): 3070, 3040, 3015, 3005, 2940, 2920, 2890, 2850, 2810,
1620, 1590, 1570, 1480, 1435, 1060, 740, 680 cm–1.
Rf 0.10 (PE–EtOAc, 95:5); [a]D20 –58 (c = 1.80, CHCl3); ee >99%
[HPLC (CHIRACEL OD, hexane–i-PrOH, 99.4:0.6): tR = 12.5
min, and GC (Bondex-un-a, 40 °C, 1¢ iso, then 1.5 °C·min–1):
tR = 63.9 min].
3
1H NMR (500 MHz, CDCl3): d = 0.64 (t, J = 7.2 Hz, 3 H, 5-H),
1.06 (dqd, 2J = 14.7 Hz, 3J = 7.2 Hz, 3J = 3.1 Hz, 1 H, 4-Ha), 1.17–
1.25 (m, 2 H, 3-H, 4-Hb), 3.00 (s, 6 H, OCH3), 4.68 (ddd,
3J = 17.1 Hz, 2J = 2.2 Hz, 4J = 1.1 Hz, 1 H, 1-HZ), 4.75 (dd,
3J = 10.3 Hz, 2J = 2.2 Hz, 1 H, 1-HE), 5.29 (s, 2 H, 4-H¢, 5¢-H), 5.43
(ddd, 3J = 17.1 Hz, 3J = 10.3 Hz, 3J = 8.3 Hz, 1 H, 2-H), 7.22–7.35
(m, 20 Harom).
IR (film): 3530, 3070, 3040, 3010, 2990, 2940, 2910, 2850, 1645,
1590, 1480, 1440, 1030, 735, 680 cm–1.
3
1H NMR (500 MHz, CDCl3): d = 0.91 (t, J = 7.5 Hz, 3 H, 6-H),
2.01 (dqdd, 2J = 14.6 Hz, 2J = 7.5 Hz, 3J = 7.3 Hz, 4J = 1.6 Hz, 1 H,
5-Ha), 2.03 (dqdd, 2J = 14.6 Hz, 2J = 7.5 Hz, 3J = 7.3 Hz,
4J = 1.6 Hz, 1 H, 5-Hb), 2.12 (d, 3J = 2.6 Hz, 1 H, OH), 2.45 (dddd,
2J = 14.3 Hz, 3J = 6.9 Hz, 3J = 5.4 Hz, 4J = 1.6 Hz, 1 H, 2-Ha), 2.55
13C NMR (126 MHz, CDCl3): d = 13.2 (C-5), 21.8 (C-4), 31.4 (C-
3), 51.7 (OCH3), 77.7 (C-4¢, C-5¢), 83.4 (CPh2OMe), 113.0 (C-1),
127.2, 127.3, 127.4, 127.7, 128.5, 129.7 (CHarom), 139.1 (C-2),
141.3, 141.5 (Carom).
2
3
3
4
(dddd, J = 14.3 Hz, J = 6.9 Hz, J = 7.8 Hz, J = 1.6 Hz, 1 H, 2-
Hb), 4.67 (ddd, 3J = 7.8 Hz, 3J = 5.4 Hz, J = 2.6 Hz, 1 H, 1-H),
5.34 (dtt, J = 10.8 Hz, J = 6.9 Hz, J = 1.6 Hz, 1 H, 3-H), 5.54
(dtt, J = 10.8 Hz, J = 7.3 Hz, J = 1.6 Hz, 1 H, 4-H), 7.23–7.27,
3
3
3
4
MS [DCI (CH4)]: m/z (%) = 532 (0.14, [M+]), 500 (8, [M+
–
3
3
4
MeOH]), 197 (100, [MeOPh2C+]), 167 (5, [Ph2HC+]), 105 (5, [Ph-
CO+]).
7.31–7.36 (m, 5 Harom).
13C NMR (126 MHz, CDCl3): d = 14.1 (C-6), 20.6 (C-5), 37.1 (C-
2), 73.9 (C-1), 124.0 (C-3), 125.8, 127.4, 128.3 (CHarom), 135.2 (C-
4), 144.1 (Carom).
Anal. Calcd for C35H37BO4 (532.48): C, 78.95; H, 7.00. Found: C,
78.78; H, 7.03.
(3R,4¢R,5¢R)-3-[4¢,5¢-Bis(methoxydiphenylmethyl)-1¢,3¢,2¢-
dioxaborolan-2¢-yl]pent-1-ene (12)
MS [CI (NH3)]: m/z (%) = 370.3 (2, [(2M + NH4)+]), 352 (27,
[(2M)+]), 317 (9), 194 (26, [(M + NH4)+]), 176 (100, [M+]), 159 (45,
[(M + H – H2O)+]).
Prepared according to the general procedure C. Methanesulfonic es-
ter 10 (1.58 g, 2.52 mmol) and LiEt3BH (1 M solution in THF,
5.04 mL, 5.04 mmol) in THF (2.52 mL) were used. Purification by
flash column chromatography on silica gel (83 g, PE–EtOAc, 95:5
to 85:15) yielded 1.00 g (74%) of 12 as colorless solid foam. Soft-
ening range: 47–62 °C; Rf 0.38 (PE–EtOAc, 95:5); [a]D20 –146
(c = 1.14, CHCl3).
HRMS (EI, 70 eV): m/z calcd for C12H16O: 176.1201; found:
176.1202.
(1R,3Z)-1-Phenylhex-3-en-1-ol (14)
Prepared according to the general procedure D. Allylboronic ester
12 (193 mg, 0.36 mmol) and benzaldehyde (44 mL, 46 mg,
0.44 mmol) in CH2Cl2 (181 mL) were used. Purification by column
chromatography on silica gel (31 g, PE–EtOAc, 95:5 to 85:15) and
MPLC (PE–EtOAc, 95:5) yielded 44 mg (69%) of 14 as spectro-
scopically pure colorless oil; [a]D20 +65 (c = 0.76, CHCl3);
ee = >99% [HPLC (CHIRACEL OD, hexane–i-PrOH, 99.4:0.6):
tR = 9.4 min; and GC (Bondex-un-a, 40 °C, 1¢ iso, then
1.5 °C·min–1): tR = 64.4].
IR (KBr): 3070, 3040, 3010, 2940, 2920, 2890, 2850, 2810, 1620,
1590, 1570, 1480, 1435, 1060, 740, 680 cm–1.
3
1H NMR (500 MHz, CDCl3): d = 0.63 (t, J = 7.3 Hz, 3 H, 5-H),
1.06 (ddq, 2J = 13.1 Hz, 3J = 9.1 Hz, 3J = 7.3 Hz, 1 H, 4-Ha), 1.17–
1.22 (m, 1 H, 3-H), 1.26 (dqd, 2J = 13.1 Hz, 3J = 7.3 Hz,
3J = 5.1 Hz, 1 H, 4-Hb), 2.99 (s, 6 H, OCH3), 4.69 (dm,
3
2
3J = 17.1 Hz, 1 H, 1-HZ), 4.74 (dd, J = 10.3 Hz, J = 2.1 Hz, 1 H,
1-HE), 5.29 (s, 2 H, 4¢-H, 5¢-H), 5.35 (ddd, 3J = 17.1 Hz,
3J = 10.3 Hz, 3J = 8.6 Hz, 1 H, 2-H), 7.23–7.35 (m, 20 Harom).
For the remaining data, see those of the enantiomeric compound
(1S,3Z)-1-phenylhex-3-en-1-ol (13).
13C NMR (126 MHz, CDCl3): d = 13.3 (C-5), 22.2 (C-4), 31.8 (C-
3), 51.8 (OCH3), 77.7 (C-4¢, C-5¢), 83.4 (CPh2OMe), 113.3 (C-1),
127.2, 127.3, 127.4, 127.7, 128.5, 129.7 (CHarom), 139.0 (C-2),
141.4, 141.5 (Carom).
MS (FAB, matrix: NBA + NaI): m/z (%) = 555 (0.21, [M+ + Na]),
501 (2, [M+ – MeO]), 469(1, [M+ – MeO – MeOH]), 423 (1, [M+ –
MeOH – Ph]), 197 (100, [MeOPh2C+]), 167 (8, [Ph2HC+]), 105 (7,
[PhCO+]).
Acknowledgment
We gratefully acknowledge the Deutsche Forschungsgemeinschaft,
the Fonds der Chemischen Industrie, the Otto-Röhm-Gedächtnis-
stiftung and the Landesgraduiertenförderung Baden Württemberg
(‘Graduiertenstipendium’ for N.S.) for the generous support of our
projects. Donations from the Boehringer Ingelheim KG, the Degus-
sa AG, the Bayer AG, the BASF AG, the Wacker AG, and the No-
vartis AG were greatly appreciated. We thank Dr. Wolfgang Frey
for performing the X-ray structure analysis.
Anal. Calcd for C35H37BO4 (532.48): C, 78.95; H, 7.00. Found: C,
78.89; H, 7.02.
Allyl Addition of 11 and 12 to Aldehydes; General Procedure D
To a stirred solution of the allylboronic ester 11 or 12 (1.00 equiv)
in CH2Cl2 (0.50 mL/mmol 11/12) at 4 °C was added the aldehyde
(1.20 equiv). The solution was stirred at 4 °C overnight and 2 d at
r.t. The solvents were evaporated; the crude product was investigat-
ed by NMR and purified by column chromatography.
References
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Synthesis 2006, No. 1, 24–30 © Thieme Stuttgart · New York

30
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Synthesis 2006, No. 1, 24–30 © Thieme Stuttgart · New York