Enantioselective synthesis of cyclic allylboronates by Mo-catalyzed asymmetric ring-closing metathesis (ARCM). A one-pot protocol for net catalytic enantioselective cross metathesis

Article abstract of DOI:10.1016/j.tet.2004.06.017

Mo-catalyzed asymmetric ring-closing metathesis (ARCM) reactions are used to synthesize cyclic allylboronates of high optical purity (89% ee to >98% ee). A one-pot procedure involving formation of allylboronates, Mo-catalyzed ARCM and functionalization of

Full text of DOI:10.1016/j.tet.2004.06.017

Tetrahedron 60 (2004) 7345–7351
Enantioselective synthesis of cyclic allylboronates by
Mo-catalyzed asymmetric ring-closing metathesis (ARCM).
A one-pot protocol for net catalytic enantioselective
cross metathesis
Jesper A. Jernelius,a Richard R. Schrockb and Amir H. Hoveydaa
,
*
aDepartment of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA
bDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02138, USA
Received 19 April 2004; revised 28 May 2004; accepted 4 June 2004
Available online 25 June 2004
This work is dedicated to our colleague and friend, Professor Robert H. Grubbs, for his groundbreaking contributions to organometallic chemistry and
catalytic metathesis
Abstract—Mo-catalyzed asymmetric ring-closing metathesis (ARCM) reactions are used to synthesize cyclic allylboronates of high optical
purity (89% ee to .98% ee). A one-pot procedure involving formation of allylboronates, Mo-catalyzed ARCM and functionalization of the
optically enriched cyclic allylboronates constitutes net asymmetric cross metathesis (ACM). Structural modification of ARCM products
include reactions with aldehydes to afford optically enriched compounds that bear quaternary carbon centers with excellent
diastereoselectivity. These studies emphasize the significance of the availability of chiral Mo-based complex as a class of chiral metathesis
catalysts that frequently complement one another in terms of reactivity and selectivity.
q 2004 Published by Elsevier Ltd.
1. Introduction
(i!ii, Scheme 1) is yet to be realized. However, an
alternative approach, one that involves a one-pot operation
and the intermediacy of cyclic allylboronates,8 is illustrated
in Scheme 1. Thus, formation of allylboronate iii, followed
by catalytic ARCM may afford cyclic iv which can then be
functionalized to afford net ACM products (e.g., ii after
oxidation). Such a strategy provides opportunities for
stereoselective formation of additional C–C bonds through
reaction of iv with different electrophiles (e.g., carbonyl-
containing compounds).
Catalytic enantioselective olefin metathesis allows efficient
access to a range of optically enriched organic molecules
that cannot be readily synthesized by alternative methods.1
Accordingly, research in these laboratories has focused on
the design and development of effective chiral complexes
for asymmetric olefin metathesis.1 We have disclosed the
synthesis, characterization and activity of a number of chiral
Mo-based alkylidenes (see Chart 1) that readily promote
asymmetric ring-closing (ARCM)2 and ring-opening
metathesis (AROM)3 reactions. We recently outlined the
synthesis of supported chiral catalysts4 (e.g., 5 in Chart 1) as
well as practical procedures involving in situ preparation
and use of related Mo complexes.5 Applications to
enantioselective synthesis of biologically active compounds
are beginning to emerge.6
Herein we report an approach to net ACM which involves
the intermediacy of optically enriched cyclic allylboronates
formed through Mo-catalyzed ARCM. The present protocol
offers an efficient route for the preparation of synthetically
versatile organic molecules of high optical purity (up to
.98% ee). Research outlined further underlines the
significance of the modular character of high oxidation
state Mo-based complexes that has led to the availability of
a class of chiral catalysts for enantioselective olefin
metathesis.1a,b,9
One area of research that poses a challenging task, but is of
high potential in enantioselective organic synthesis, relates
to the development of catalytic asymmetric cross metathesis
(ACM) reactions.7 Discovery of a direct catalytic ACM
2. Optically pure cyclic allylboronates by Mo-catalyzed
kinetic resolution
Keywords: Allylboronates; Asymmetric cross metathesis; Asymmetric
ring-closing metathesis.
*
Corresponding author. Tel.: þ1-617-552-3618; fax: þ1-617-552-1442;
e-mail address: amir.hoveyda@bc.edu
We began our investigation by examining the possibility of
0040–4020/$ - see front matter q 2004 Published by Elsevier Ltd.
doi:10.1016/j.tet.2004.06.017

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J. A. Jernelius et al. / Tetrahedron 60 (2004) 7345–7351
Chart 1. Representative chiral Mo catalysts for olefin metathesis.
the one-pot Mo-catalyzed strategy shown in Scheme 1 to
effect kinetic resolution of dienes 6 and 11 (Scheme 2). As
illustrated in Scheme 2, treatment of rac-diene 6 with one
equivalent of allyl boronate 7 in benzene at 22 8C results in
the smooth formation of a solution of triene 8 (400 MHz 1H
NMR analysis). Since high oxidation state Mo complexes
are sensitive to unprotected alcohols, i-PrOH generated in
the course of the formation of 8 must be removed in vacuo
before the addition of chiral metathesis catalysts. Screening
studies indicated that in the presence of 5 mol% 2a (see
Chart 1), ARCM proceeds smoothly to afford 9 (,50%
conv. after 80 min). The resulting cyclic allylboronate can
be directly (not isolated) subjected to oxidation conditions
(H2O2, NaOH) to afford optically pure 10 in 37% overall
isolated yield (.30:1 Z/E; maximum theoretical
yield¼50%). In a similar fashion rac-11 is converted, by
the one-pot protocol, to stereosiomerically pure 12 in 35%
yield. It should be noted that catalytic ARCM of the
allylboronate derived from rac-11 proceeds most selectively
in the presence of chiral complex 1b (vs. 2a for rac-6; see
below for additional discussion).
3. Enantioselective synthesis of cyclic allylboronates by
Mo-catalyzed ARCM
With the feasibility of the general approach described in
Scheme 1 substantiated through our investigation of the Mo-
catalyzed kinetic resolutions shown in Scheme 2, we turned
our attention to the possibility of achieving net ACM
through one-pot desymmetrizations of achiral substrates.
Scheme 1. Catalytic asymmetric CM and a one-pot multistep alternative.

J. A. Jernelius et al. / Tetrahedron 60 (2004) 7345–7351
7347
(Chart 1) leads to formation of the desired cyclic
allylboronate (cf. 9, Scheme 2) which is directly oxidized
to afford 14 in .98% ee and 57% overall isolated yield.10
Catalytic enantioselective desymmetrization of allylic
alcohol 15 is promoted by dichloroimido complex 1c to
deliver 16 in optically pure form and 58% yield after silica
gel chromatography. As the data in entry 3 of Table 1
indicate, one-pot desymmetrization of homoallylic alcohol
17 in the presence of 5 mol% o-(trifluoromethyl)phenyl-
imido complex 19 leads to the formation of 18 in 89% ee
and 64% isolated yield. Net Mo-catalyzed ACM with
tertiary homoallylic alcohol 20 is less efficient and
proceeds to ,80% conv. in the presence of 5 mol% of a
variety of Mo catalysts; the highest enantioselectivity is
obtained with adamantylimido complex 4 (Chart 1) to
generate 21 in .98% ee and 38% isolated yield (from
20).
Several issues regarding the experiments summarized in
Table 1 are worthy of note:
(1) An underlining feature of the present catalytic method
is that in each of the cases described above a different
chiral Mo complex is used to obtain optimal levels of
reactivity and selectivity. This should not be viewed as
a drawback of the protocol. As we have described in
detail elsewhere,1a,b the identity of the optimal chiral
metathesis catalyst should not be generalized; the
availability of a class of catalysts increases the
possibility of obtaining the most desirable conversion
and enantioselectivities. If 1a were the only available
chiral complex, high selectivities would be feasible in
Scheme 2. Catalytic kinetic resolution through ARCM/oxidation (net
asymmetric CM)a.
The results of these investigations are summarized in
Table 1. Treatment of diene 13 with 1 equiv. of allyl-
boronate 7 (Scheme 2), removal of i-PrOH in vacuo and
treatment with chiral binaphtholate-based Mo complex 2a
Table 1. Mo-catalyzed one-pot net ACM reactionsa
Entry
Substrate
Product
Catalyst Time (h) Conv. (%);b yield (%)c ee (%)d
1
2a
12
78; 57
.98
2
3
1c
19
4
1
90; 58
80; 64
80; 38e
.98
.89
.98
14
24
4
a
Conditions: 5 mol% chiral catalyst, C6H6, 22 8C.
Conversions determined through 400 MHz 1H NMR analysis.
Isolated yields of purified products (overall from starting diene).
Determined by GLC (entries 1–3, a-dex column) and HPLC (entry 4, chiral OJ column).
40% of tetrasubstituted olefin 22 also formed.
b
c
d
e

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J. A. Jernelius et al. / Tetrahedron 60 (2004) 7345–7351
Scheme 3. Mo-catalyzed conversiton of diene 17 to optically pure b-hydroxyketone 24.
net ACM with rac-11 (Scheme 2); other transform-
ations shown here would proceed with similar levels of
efficiency but with significantly lower selectivities.
(2) The lower efficiency of the catalytic ARCM involving
tertiary alcohol 20 is likely due to inefficient formation
of the acyclic allylboronate intermediate (cf. iii in
Scheme 1). As a result, cyclic tertiary alcohol 22,
bearing a tetrasubstituted olefin, is formed as a
significant byproduct (40% yield). This observation
indicates that not only is chiral alkylimido complex 4
capable of promoting the formation of tetrasubstituted
olefins by RCM but also that sterically congested
alcohols may be viewed as viable substrates for this
class of chiral metathesis catalysts. Studies to investi-
gate and exploit such attributes of chiral Mo complex 4
are underway.
aldol adduct 24. Conversion of 25 to the same compound
based on previously reported protocols,12 as illustrated in
Scheme 3, secures the stereochemical identity of the major
enantiomer in the catalytic ARCM.13
Optically enriched allylboronates are attractive because
they can serve as effective nucleophiles. The example
shown in Scheme 4 is illustrative. Treatment of optically
pure 26, obtained from catalytic ARCM of the allyboronate
derived from 13, with trioxane in toluene at 80 8C leads to
the formation of diol 27 as a single enantiomer and
diastereomer (68% overall yield from 13). The facile
synthesis and stereoselective formation of the quaternary
carbon center14 in 27 augurs well for the utility of cyclic
allylboronates generated by catalytic ARCM reactions.15,16
Such C–C bond forming reactions are less feasible with the
corresponding cyclic siloxanes that can also be obtained
through Mo-catalyzed ARCM reactions.17 Although Mo-
catalyzed ARCM of allylsiloxanes allows access to products
shown in Scheme 2 and Table 1 through oxidations of the
C–Si bonds, the present method offers a more attractive
option. This preference is for two reasons: (i) C–Si
oxidation is generally less efficient than those of C–B
bonds and with allylsilane compounds such processes can
occur with low regioselectivity. (ii) In contrast to the one pot
procedure described herein, installation of the silyl ether and
its subsequent oxidation must be carried out in separate
vessels, thus reducing the efficiency of the overall protocol.
4. Functionalization and synthetic utility of optically
enriched allylboronates
The allylboronates obtained in the Mo-catalyzed ARCM
reactions discussed above can be functionalized in a variety
of manners (in addition to oxidations). One example is
shown in Scheme 3. Regioselective Rh-catalyzed hydro-
genation11 of cyclic boronate 23 (89% ee; see entry 3 in
Table 1), followed by ozonolytic cleavage of the tri-
substituted cyclic olefin leads to the formation of the acetate
5. Conclusions
In summary, we disclose an efficient catalytic enantio-
selective method for the preparation of synthetically
Scheme 4. Diastereo- and enantioselective synthesis of quarternary carbons.

J. A. Jernelius et al. / Tetrahedron 60 (2004) 7345–7351
7349
versatile cyclic allylboronates through ring-closing meta-
thesis. The products obtained after functionalization of the
optically enriched allylboronates can be considered as
products of catalytic ACM reactions. Design and develop-
ment of additional effective catalysts that promote a wide
variety of metathesis reactions and applications to the
synthesis of biologically active molecules continue in these
laboratories.
1H NMR spectrum showed complete removal of isopro-
panol by absence of 1H resonance at 4.04 ppm. A portion of
the resulting oil (11.8 mg, 0.050 mmol) was dissolved in
0.50 mL of benzene and chiral complex (R)-2a (2.9 mg,
0.03 mmol, 0.05 equiv.) was added. The mixture was
allowed to stir at 22 8C for 80 minutes. At this time, the
reaction vessel was removed from the glovebox, and the
reaction was quenched by exposure of the solution to air.18
The unpurified mixture was dissolved in THF (500 mL) and
ethanol (500 mL). To this stirring solution was added
aqueous NaOH (500 mL of a 3.8 M solution) and H2O2
(500 mL of a 30% aqueous solution). The mixture was
allowed to stir at 22 8C for 2 h during which the solution
changed in color from dark brown to light yellow. After 2 h,
the solution was washed with 5.0 mL of Et2O. The organic
layer was dried over anhydrous Na2SO4, filtered, and
concentrated in vacuo. The resulting light yellow oil was
dissolved in 2 mL of hexanes and purified by silica gel
chromatography (1:1 hexanes/Et2O) to afford diol 10 as a
colorless oil (3.7 mg, 0.023 mmol, 46%). Rf¼0.1 (1:1
hexanes/Et2O). IR (neat): 3377 (s), 2974 (m), 2930 (m),
1652 (w), 1445 (m), 1381 (m), 1060 (s), 1023 (s), 872
6. Experimental
6.1. General
Infrared (IR) spectra were recorded on a Nicolet 210
spectrophotometer, nmax is in cm21. Bands are character-
ized as broad (br), strong (s), medium (m), and weak (w). 1H
NMR spectra were recorded on Varian GN-400 (400 MHz),
and Varian Gemini 2000 (400 MHz) spectrometers. Chemi-
cal shifts are reported in ppm from tetramethylsilane with
the solvent resonance as the internal standard (CDCl3: d
7.26, C6D6: d 7.15). Data are reported as follows: chemical
shift, multiplicity (s¼singlet, d¼doublet, t¼triplet, q¼
quartet, br¼broad, m¼multiplet), coupling constants (Hz),
integration, and assignment. 13C NMR spectra were
recorded on Varian GN-400 (100 MHz), and Varian Gemini
2000 (100 MHz) spectrometers with complete proton
decoupling. Chemical shifts are reported in ppm from
tetramethylsilane with the solvent as the internal reference
(CDCl3: d 77.2 ppm, C6D6: d 128.1 ppm). Enantiomer ratios
were determined by chiral GLC (Supelco alphadex 120
column (30 m£0.25 mm)) or chiral HPLC analysis (Chiral
Technologies chiracel OJ (0.46 cm£25 cm)) in comparison
with authentic racemic materials.
(m) cm21
;
1H NMR (CDCl3, 400 MHz): d 5.55 (t,
J¼8.2 Hz, 1H, CvCHCH2OH), 4.89 (m, 1H, CHAHBvC),
4.81 (m, 1H, CHAHBvC), 4.66 (dd, J¼9.2, 5.1 Hz, 1H,
CHOH), 4.26 (dd, J¼12.7, 8.5 Hz, 1H, CHAHBOH), 4.08
(dd, J¼12.5, 6.0 Hz, 1H, CHAHBOH), 2.36 (dd, J¼13.6,
8.7 Hz, 1H, CHAHBCHOH), 2.19 (dd, J¼13.6, 4.9 Hz, 1H,
CHAHBCHOH), 1.78 (s, 6H, –CH3). 13C NMR (CDCl3,
100 MHz): d 142.2, 141.0, 126.2, 113.9, 67.7, 58.0, 43.8,
22.5, 18.4; HRMS calcd for C9H16O2Na: 179.1048. Found:
179.1046.
6.1.2. (4R)-Diol 12. Rf¼0.1 (1:1 hexanes/Et2O). IR (neat):
3327 (s), 3068 (w), 2943 (s), 1652 (m), 1628 (m), 1451 (s),
1
1376 (m), 1067 (m), 1004 (s), 891 (m) cm21; H NMR
All reactions were conducted in oven- (135 8C) and flame-
dried glassware under an inert atmosphere of dry nitrogen.
Solvents were purified under a positive pressure of dry
argon by a modified Innovative Technologies purification
system. Benzene and toluene were purged with argon before
being passed through activated copper and alumina
columns. Tetrahydrofuran, and diethyl ether are purged
with Ar before being passed through activated alumina
columns. Olefin-free pentane was generated by allowing
(commercial grade) pentane to stir in the presence of
concentrated sulfuric acid (20 mL per L of pentane) for
24 h. The pentane was poured over fresh concentrated
sulfuric acid. The process was repeated until the acid layer
remained colorless for 48 h. The pentane was separated,
washed with water, dried over Na2SO4, filtered, purged with
Ar and then passed through activated copper and alumina
columns. All handling of the molybdenum catalysts was
performed in a glove box under nitrogen atmosphere. All
substrates were rigorously dried by repeated azeotropic
distillation using anhydrous benzene (3 times) prior to use.
(CDCl3, 400 MHz): d 5.54 (dd, J¼6.8, 6.8 Hz, 1H,
CvCHCH2OH), 4.74 (m, 1H, CHAHBvC), 4.71 (m, 1H,
CHAHBvC), 4.52 (t, J¼6.8 Hz, 1H, CHOH), 4.25 (dd,
J¼12.8, 8.4 Hz, 1H, CHAHBOH), 4.06 (ddd, J¼12.8, 6.4,
1.2 Hz, 1H, CHAHBOH), 3.70 (br s, 2H, –OH), 2.03 (m, 2H,
CH2CvCH2), 1.81 (m, 1H, CHAHBCHOH), 1.76 (s, 3H,
–CH3), 1.74 (s, 3H, –CH3), 1.62 (m, 1H, CHAHBCHOH);
13C NMR (CDCl3, 100 MHz): d 145.3, 141.4, 126.2, 110.3,
69.7, 58.1, 34.1, 32.9, 22.7, 18.3; HRMS calcd for
C10H18O2Na: 193.1204. Found: 193.1208.
6.1.3. (4R)-Diol 14. Rf¼0.1 (1:1 hexanes/Et2O). IR (neat):
3376 (br s), 2971 (m), 2921 (s), 2853 (m), 1721 (m), 1658
(m), 1449 (m), 1381 (m), 1256 (w), 1230 (w), 1060 (s), 1017
(s), 994 (s), 903 (m) cm21; 1H NMR (CDCl3, 400 MHz): d
5.64 (dd, J¼6.6, 6.6 Hz, 1H, CvCHCH2OH), 5.10 (s, 1H,
CvCHAHB), 4.95 (s, 1H, CvCHAHB), 4.91 (s, 1H,
CHOH), 4.32 (dd, J¼12.4, 8.2 Hz, 1H, CHAHBOH), 4.14
(dd, J¼12.4, 6.0 Hz, 1H, CHAHBOH), 2.06 (br s, 2H, –OH),
1.66 (s, 3H, –CH3) 1.64 (s, 3H, –CH3); 13C NMR (CDCl3,
100 MHz): d 145.0, 139.4, 127.5, 110.8, 73.4, 58.5, 19.4,
18.4; HRMS calcd for C8H14O2Na: 165.0891. Found:
165.0891.
6.1.1. (4R)-Diol 10. To a round bottom flask was added rac-
dieneol 6 (150 mg, 1.19 mmol, 1.0 equiv.), diisopropoxy-
allylboronate 7 (202 mg, 1.19 mmol, 1.0 equiv.) and
benzene (12.0 mL) (in a glovebox). The resulting mixture
was allowed to stir for 16 h at 22 8C. At this time, benzene
was removed in vacuo to afford the desired mixed boronate
as a colorless oil (222.0 mg, 0.940 mmol). Analysis of the
6.1.4. (4R)-Diol 16. Rf¼0.1 (1:1 hexanes/Et2O). IR (neat):
3394 (s), 2953 (s), 2924 (s), 2853 (m), 1729 (m), 1474 (m),
1367 (m), 1099 (s), 1022 (s), 802 (m) cm21 1H NMR
;

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J. A. Jernelius et al. / Tetrahedron 60 (2004) 7345–7351
(CDCl3, MeOD 400 MHz):
d
5.73–5.68 (m, 2H,
CHOH), 3.66 (m, 2H, CH2OH), 1.79 (s, 3H, CH3) 1.06 (s,
CvCHCHOH), 5.64–5.53 (m, 2H, CHvCHCHOH), 4.93
(t, J¼7.6 Hz, 1H, CHOH), 4.35–4.30 (dd, J¼12.8, 7.2 Hz,
1H, CHAHBOH), 4.23–4.18 (dd, J¼12.8, 6.4 Hz, 1H,
CHAHBOH), 1.71 (dd, J¼6.8 Hz, 3H, –CH3); 13C NMR
(CDCl3, MeOD 100 MHz): d 133.5, 132.4, 130.0, 127.1,
68.7, 58.2, 18.2; HRMS calcd for C7H13O2: 129.0916.
Found: 129.0918.
3H, CH3); 13C NMR (CDCl3, 100 MHz): d 146.0, 141.8,
114.9, 113.9, 81.2, 70.4, 46.0, 21.3, 16.3; HRMS calcd for
C9H16O2Na: 179.1048. Found: 179.1043.
6.1.8. Benzylidene acetal derived from diol 27 (for proof
of relative stereochemistry). To a solution of diol 27
(5.0 mg, 0.032 mmol) in benzene (300 mL) was added
benzaldehyde (16 mL, 0.16 mmol, 5.0 equiv.) and 100 mL
of a solution consisting of 1.0 mL CH2Cl2, 3.0 mg
pTsOH·H2O, 0.10 mL MeOH (to dissolve p-TsOH). The
resulting mixture was placed under N2 atmosphere and
heated to 100 8C (temperature controlled oil bath) for 10 h.
The solution was allowed to cool to ambient temperature
and was loaded directly onto a silica gel column (eluted with
100:1 hexanes/Et2O) to give 28 as a colorless oil (6.8 mg,
0.28 mmol, 87%). Rf¼0.9 (10:1 hexanes/Et2O). IR (neat):
3081 (m), 3062 (m), 3024 (m), 2967 (s), 2917 (s), 2848 (s),
1734 (w), 1646 (m), 1457 (s), 1407 (s), 1394 (s), 1350 (s),
1300 (m), 1224 (m), 1174 (m), 1099 (s), 1029 (s), 979 (m),
916 (m), 752 (m), 696 (s), 658 (m) cm21; 1H NMR (CDCl3,
400 MHz): d 7.53 (dd, J¼8.1, 1.8 Hz, 2H, Ar–H), 7.37 (m,
3H, Ar–H), 5.74 (dd, J¼17.0, 11.3 Hz, 1H, CHvCH2),
5.56 (s, 1H, Ar–CH(O)O), 5.18 (s, 1H, CHAHBvCH), 5.14
(dd, J¼7.1, 1.1 Hz, 1H, CHAHBvCH), 5.02 (m, 1H,
CHAHBvC), 4.96 (m, 1H, CHAHBvC), 4.21 (s, 1H,
CH–CvCH2), 3.85 (d, J¼11.4 Hz, 1H, CHAHBO), 3.69
(d, J¼11.2 Hz, 1H, CHAHB O), 1.76 (s, 3H, –CH3) 1.27 (s,
3H, –CH3); 13C NMR (CDCl3, 100 MHz): d 142.3, 140.9,
138.7, 129.0, 128.4, 126.4, 115.5, 113.5, 101.8, 86.1, 77.2,
40.6, 21.9, 15.6; HRMS calcd for C16H20O2Na: 267.1361.
Found: 267.1359.
6.1.5. (5R)-Diol 18. Rf¼0.1 (1:1 hexanes/Et2O). IR (neat):
3323 (s), 3075 (w), 2967 (s), 2934 (s), 2916 (m), 1658 (w),
1628 (m), 1445 (s), 1376 (m), 1068 (m), 1046 (w), 1024 (s),
;
997 (s), 890 (m), 669 (w) cm21 1H NMR (CDCl3,
400 MHz): d 5.76 (dd, J¼8.2, 7.1 Hz, 1H, CvCHCH2OH),
4.92 (m, 1H, CHAHBvC), 4.83 (m, 1H, CHAHBvC) 4.17
(dd, J¼11.8, 8.2 Hz, 1H, CHAHBOH), 3.92 (dd, J¼11.8,
7.0 Hz, 1H, CHAHBOH), 3.84 (ddt, J¼9.7, 6.4, 2.7 Hz, 1H,
CHOH), 2.51 (dd, J¼13.5, 9.7 Hz, 1H, CH2CvCCHAHM-
CHOH), 2.23 (d, J¼6.4 Hz, 2H, CH2CHOH), 2.02 (dd,
J¼13.5, 2.7 Hz, 1H, CH2CvCCHAHMCHOH), 1.81 (s, 3H,
–CH3), 1.79 (s, 3H, –CH3); 13C NMR (CDCl3, 100 MHz): d
142.5, 127.0, 114.1, 113.4, 65.8, 57.9, 46.7, 39.5, 24.0, 22.5;
HRMS calcd for C10H18O2Na: 193.1204. Found: 193.1205.
6.1.6. (5R)-Diol 21. Rf¼0.1 (1:1 hexanes/Et2O). IR (neat):
3384 (s), 3067 (w), 3027 (w), 2960 (s), 2921 (s), 2869 (m),
1709 (m), 1636 (m), 1446 (s), 1370 (s), 1070 (m), 996 (m),
889 (m) 701 (s) cm21; 1H NMR (CDCl3, 400 MHz): d 7.42
(d, J¼7.1 Hz, 2H, Ar–H), 7.31 (dd, J¼7.3, 7.1 Hz, 2H, Ar–
H), 7.22 (dd, J¼7.3, 7.2 Hz, 1H, Ar–H), 5.63 (dd, J¼6.6,
6.6 Hz, 1H, CvCHCH2OH), 4.89 (m, 1H, CHAHBvC),
4.77 (m, 1H, CHAHBvC), 4.06 (dd, J¼11.7, 8.1 Hz, 1H,
CHAHBOH), 3.86 (dd, J¼11.7, 7.3 Hz, 1H, CHAHBOH),
2.82 (dd, J¼13.6, 3.5 Hz, 2H, CH2COH), 2.60 (d,
J¼13.4 Hz, 1H, CHAHBCOH), 2.51 (d, J¼13.4 Hz, 1H,
CHAHBCOH), 1.30 (s, 3H, –CH3), 1.28 (s, 3H, –CH3); 13
C
NMR (CDCl3, 100 MHz): d 145.8, 142.4, 137.0, 128.5,
128.2, 126.9, 125.7, 116.6, 74.4, 58.5, 51.4, 46.0, 26.1, 24.4;
HRMS calcd for C16H22O2Na: 269.1517. Found: 269.1515.
6.1.7. Diol 27. Paraformaldehyde (42 mg, 1.0 mmol) was
added (while stirring) to a solution of boronate 26 (7.8 mg,
0.050 mmol) in toluene (200 mL). The resulting mixture
was placed under nitrogen and heated to 80 8C (temperature
controlled oil bath) for 12 h. At this time, the solution was
allowed to cool to 22 8C, and volatiles were removed in
vacuo to afford a viscous black oil. The resulting black oil
was dissolved in MeOH (1.0 mL of a solution of MeOH
(5.0 mL) at 0 8C (ice bath) and acetyl chloride (100 mL,
1.4 mmol)) was added slowly with vigorous stirring
(caution: highly exothermic) and then allowed to stand at
22 8C for 5 minutes. Evaporation of volatiles (3 times)
resulted in the removal of volatile boron-derived impurities.
The resulting black oil was dissolved in a 0.5 mL of 1:1
hexanes/Et2O and purified by silica gel chromatography
(1:1 hexanes /Et2O) to give 27 as a colorless oil (6.6 mg,
0.043 mmol, 85%). Rf¼0.1 (1:1 hexanes/Et2O). IR (neat):
3386 (s), 3075 (w), 2974 (s), 2924 (s), 2873 (m), 1728 (w),
1652 (m), 1457 (m), 1426 (m), 1375 (m), 1161 (w), 1037 (s),
Acknowledgements
This research was generously supported by the NIH (GM-
57212).
References and notes
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