Brucine-derived amino alcohol catalyzed asymmetric Henry reaction: An orthogonal enantioselectivity approach

Article abstract of DOI:10.1021/ol902380z

[Chemical Equation Presented] A new approach to both enantioenriched Henry products Is developed by use of different molecularities of metal-ligand complexes generated i from Cu(I) and Zn(II) metals with readily available chiral amino alcohol 1.

Full text of DOI:10.1021/ol902380z

ORGANIC
LETTERS
2
009
Vol. 11, No. 24
682-5685
Brucine-Derived Amino Alcohol
Catalyzed Asymmetric Henry Reaction:
An Orthogonal Enantioselectivity
Approach
5
Hun Young Kim and Kyungsoo Oh*
Department of Chemistry and Chemical Biology, Indiana UniVersity Purdue UniVersity
Indianapolis (IUPUI), Indianapolis, Indiana 46202
ohk@iupui.edu
Received October 15, 2009
ABSTRACT
A new approach to both enantioenriched Henry products is developed by use of different molecularities of metal-ligand complexes generated
from Cu(I) and Zn(II) metals with readily available chiral amino alcohol 1.
II
III
5
II
6
The control of absolute configuration of molecules is of
paramount importance in modern asymmetric catalysis.
While this is typically achieved by employment of chiral
ligands in metal-catalyzed reactions, the syntheses of cor-
responding antipode ligands are sometimes not trivial since
optical resolution and chiral pool synthesis are exclusively
magnesium (Mg ) and yttrium (Y ), or copper (Cu ) in
the presence of same chiral ligands. One particular drawback
of this asymmetric approach is the lack of rational catalyst
2
design methods because most of the C -symmetric chiral
ligands employed in the past were not designed to generate
the number of possible isomeric metal complexes. In the
1
7
used to prepare “man-made” chiral ligands. An alternative
pioneering work of Shibasaki and co-workers in 2001, it
approach to the control of absolute configuration in asym-
metric catalysis is the use of an enantiopure ligand in
conjunction with different metals, where two distinctive
was found that different molecularities of the M-L* catalyst
IV
III
species between titanium (Ti ) and gadolinium (Gd ) or
2
III
samarium (Sm ) were responsible for a highly orthogonal
metal (M)-ligand (L*) catalyst species could be generated.
In fact, this orthogonal enantioselectivity has been occasion-
ally observed in the asymmetric catalysis between rhodium
enantioselectivity in the silacyanation reaction of unsym-
metric ketones. The formation of a 2:3 complex between a
lanthanoid and a carbohydate-derived phosphine oxide ligand
was postulated as the active catalyst species, in contrast to
I
I
3
III
III
4
(
Rh ) and iridium (Ir ), scandium (Sc ) and yttrium (Y ),
IV
a 1:1 complex formation in the Ti -catalyzed reaction.
(
1) Acid Catalysis in Modern Organic Synthesis; Yamamoto, H.,
Ishihara, K., Eds.; Wiley-VCH: Weinheim, 2008.
2) For recent reviews, see: (a) Sibi, M. P.; Liu, M. Curr. Org. Chem.
001, 5, 719. (b) Zanoni, G.; Castronovo, F.; Franzini, M.; Vidari, G.;
(4) Desimoni, G.; Faita, G.; Guala, M.; Laurenti, A.; Mella, M.
Chem.sEur. J. 2005, 11, 3816.
(
2
(5) Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron Lett. 1996,
37, 3815.
Giannini, E. Chem. Soc. ReV. 2003, 32, 115. (c) Tanaka, T.; Hayashi, M.
Synthesis 2008, 3361.
(6) Sibi, M. P.; Chen, J. J. Am. Chem. Soc. 2001, 123, 9472.
(7) Yabu, K.; Masumoto, S.; Yamasaki, S.; Hamashima, Y.; Kanai, M.;
Du, W.; Curran, D. P.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 9908.
(
3) Nishibayashi, Y.; Segawa, K.; Ohe, K.; Uemura, S. Organometallics
1
995, 14, 5486.
10.1021/ol902380z  2009 American Chemical Society
Published on Web 11/18/2009

Previously, we exploited this concept of different catalyst
molecularity in the asymmetric 1,3-dipolar cycloaddition
reaction of azomethine ylides, where two distinctive cata-
reactions, we examined the role of copper and zinc metals
in the presence of amino alcohol ligand 1.
1
8
8
lytically active species were postulated in the presence of
brucine-derived amino alcohol 1 (Figure 1) and metals with
different ionic radii: Cu(I)-L* and Ag(I)-(L*)2+n com-
plexes. Herein, we present a further extension of this
orthogonal enantioselectivity approach in the context of
catalytic asymmetric nitroaldol (Henry) reaction. Our strategy
in the asymmetric Henry reaction was based on the possible
orthogonal enantioselection of Cu(I)-L* and (Zn(II))2+n-L*
complexes.
a
Table 1. Selected Optimization Conditions
b
c
yield
(%)
ee (%)/
entry
metal
additive
solvent
CH Cl
config
1
2
3
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
CuOAc
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Zn(OTf)
Et
Et
3
N
N
2
2
50
50
65
75
60
72
95
95
95
45
60
80
96
95
85
59/S
76/S
83/S
87/S
83/S
95/S
3/R
46/R
48/R
19/R
2/R
3
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
t-BuOH
t-BuOH
t-BuOH
t-BuOH
DBU
d
4
e
5
e
6
2 2
CH Cl
d
7
2
2
2
2
2
2
2
2
2
PhCH
PhCH
PhCH
3
d
8
i-Pr
2
EtN
3
3
d
9
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
Et
3
N
N
N
N
N
N
N
d
1
1
1
1
1
1
0
1
2
3
4
5
CHCl
Et
3
d
2
O
Figure 1. Brucine-derived amino alcohol 1.
d
2-MeTHF
THF
40/R
73/R
75/R
80/R
d
d, f
e, f
THF
THF
9
Since the seminal contribution of Shibasaki in 1992, the
catalytic asymmetric Henry reactions have received much
attention from the synthetic community due to the versatile
a
Reaction with metal (10 mol %) and ligand 1 (10 mol %) in 0.16 M
solvent. Isolated yield of 4a after column chromatography. Determined
by HPLC. Reaction at 0 °C. Reaction at -15 °C. H O (30 mol %) was
b
c
d
e
f
1
0
2
nature of the nitro group. Although there was a decade
long dormant period in its history, the subsequent develop-
ment of catalytic asymmetric Henry reactions using metal
used.
1
1
12
13
14
15
catalysis (Zn, Co, Cu, Mg, and Cr ) and organoca-
We first examined the Cu(I)-catalyzed asymmetric Henry
reaction of benzaldehyde 2a in the presence of 10 mol % of
amino alcohol ligand 1 at room temperature. Our brief test
reactions swiftly led to the identification of optimal Cu(I)
source; therefore, we further optimized the reaction condi-
tions using additives and temperature (Table 1). Initially, we
employed 20 mol % base to improve the sluggish reaction
16
talysis has greatly expanded our understanding of the basis
of reactivity and selectivity. One particular noteworthy aspect
of the asymmetric Henry reaction is the possible involvement
of M-L* complexes with a different molecularity; for
example, the Cu-catalyzed reactions are known to proceed
19
1
3
by a monometallic form of active species, whereas there
is strong evidence of multimetallic complexes as active
11a
species in the Zn-catalyzed reactions as proposed by Trost
(13) For Cu(II) catalysis, see: (a) Christensen, C.; Juhl, K.; Jørgensen,
K. A. Chem. Commun. 2001, 2222. (b) Evans, D. A.; Seidel, D.; Rueping,
M.; Lam, H. W.; Shaw, J. T.; Downey, C. W. J. Am. Chem. Soc. 2003,
1
1b
and Palomo. The recent mechanistic studies by Shibasaki
indeed confirm that the preferential nucleation of ligands in
his heterobimetallic catalyst systems were responsible for
the prominent enantioamplification in the asymmetric Henry
1
25, 12692. (c) Gan, C.; Lai, G.; Zhang, Z.; Wang, Z.; Zhou, M.-M.
Tetrahedron: Asymmetry 2006, 17, 725. (d) Maheswaran, H.; Prasanth,
K. L.; Krishna, G. G.; Ravikumar, K.; Sridhar, B.; Kantam, M. L. Chem.
Commun. 2006, 4066. (e) Ma, K.; You, J. Chem.sEur. J. 2007, 13, 1863.
(f) Bandini, M.; Piccinelli, F.; Tommasi, S.; Umani-Ronchi, A.; Ventrici,
C. Chem. Commun. 2007, 616. (g) Colak, M.; Aral, T.; Hosg o¨ ren, H.;
Demirel, N. Tetrahedron: Asymmetry 2007, 18, 1129. (h) Blay, G.; Climent,
E.; Fernandez, I.; Hernandez-Olmos, V.; Pedro, J. R. Tetrahedron:
Asymmetry 2007, 18, 1603. (i) Arai, T.; Watanabe, M.; Yanagisawa, A.
Org. Lett. 2007, 9, 3595. (j) Arai, T.; Yokoyama, N.; Yanagisawa, A.
Chem.sEur. J. 2008, 14, 2052. (k) Blay, G.; Domingo, L. R.; Hernandez-
Olmos, V.; Pedro, J. R. Chem.sEur. J. 2008, 14, 4725. For Cu(I) catalysis,
see: (l) Arai, T.; Watanabe, M.; Fujiwara, A.; Yokoyama, N.; Yanagisawa,
A. Angew. Chem., Int. Ed. 2006, 45, 5978. (m) Jiang, J.-J.; Shi, M.
Tetrahedron: Asymmetry 2007, 18, 1376. (n) Xiang, Y.; Wang, F.; Huang,
X.; Wen, Y.; Feng, X. Chem.sEur. J. 2007, 13, 829. (o) Qin, B.; Xiao, X.;
Liu, X.; Huang, J.; Wen, Y.; Feng, X. J. Org. Chem. 2007, 72, 9323. (p)
Arai, T.; Takashita, R.; Endo, Y.; Watanabe, M.; Yanagisawa, A. J. Org.
Chem. 2008, 73, 4903.
1
7
reaction. In order to investigate the orthogonal enantiose-
lectivity of M-L* complexes in catalytic asymmetric Henry
(
8) Kim, H, Y.; Shih, H. -J.; Knabe, W. E.; Oh, K. Angew. Chem., Int.
Ed. 2009, 48, 7420.
9) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem.
Soc. 1992, 114, 4418.
10) For recent reviews, see: (a) Shibasaki, M.; Gr o¨ ger, H. In Compre-
(
(
hensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H.,
Eds.; Springer: Berlin, Germany, 1999; Vol. III, pp 1075-1090. (b) Palomo,
C.; Oiarbide, M.; Mielgo, A. Angew. Chem., Int. Ed. 2004, 43, 5442. (c)
Boruwa, J.; Gogoi, N.; Saikia, P.; Barua, N. C. Tetrahedron: Asymmetry
2
006, 17, 3315. (d) Palomo, C.; Oiarbide, M.; Laso, A. Eur. J. Org. Chem.
007, 2561.
2
(
11) (a) Trost, B. M.; Yeh, V. S. C. Angew. Chem., Int. Ed. 2002, 41,
(14) Choudary, B. M.; Ranganath, K. V. S.; Pal, U.; Kantam, M. L.;
Sreedhar, B. J. Am. Chem. Soc. 2007, 127, 13167.
8
4
61. (b) Palomo, C.; Oiarbide, M.; Laso, A. Angew. Chem., Int. Ed. 2005,
4, 3881. (c) Liu, S.; Wolf, C. Org. Lett. 2008, 10, 1831.
(15) (a) Kowalczyk, R.; Sidorowicz, L.; Skarzewski, J. Tetrahedron:
Asymmetry 2007, 18, 2581. (b) Kowalczyk, R.; Kwiatkowski, P.; Skarze-
wski, J.; Jurczak, J. J. Org. Chem. 2009, 74, 753.
(
12) Kogami, Y.; Nakajima, T.; Ashizawa, T.; Kezuka, S.; Ikeno, T.;
Yamada, T. Chem. Lett. 2004, 33, 614.
Org. Lett., Vol. 11, No. 24, 2009
5683

rate (Table 1, entries 1 and 2); however, we soon realized
that acetate effectively plays the role of base in the presence
of 30 mol % of t-BuOH. This experimental modification
resulted in the improvement of both reaction rate and
enantioselectivity (Table 1, entry 3). Next, we investigated
the effect of reaction temperature. Although the observed
reactivity and the enantioselectivity were further improved
by conducting the reactions at lower temperature (Table 1,
catalytic system for aromatic aldehydes with different
electronics (Table 2, entries 1-4) and for sterically demand-
ing aromatic aldehydes (Table 2, entries 5-7). This trend
of enantioselectivity continued for heteroaromatic (Table 2,
entry 8) and aliphatic aldehydes (Table 2, entries 9 and 10).
The corresponding antipodes, (R)-4a-j, were also obtained
using the Zn(II)/1 catalytic system with good to excellent
enantioselectivities. Evidently, there exists some limitation
with our Zn(II)/1 catalytic system upon the use of sterically
hindered aromatic aldehydes (Table 2, entries 5 and 6), where
lower enantioselectivities were observed in the range of
entries 4 and 5), the use of CH
2 2
Cl as solvent was crucial in
the further optimization of CuOAc-catalyzed reaction to 72%
2
0
yield and 95% ee (Table 1, entry 6).
6
7-76% ee. Consequently, the further extension of our
To investigate the scope of orthogonal enantioselectivity
in the catalytic asymmetric Henry reaction, we next explored
Zn(II)/1 catalytic system was significantly impaired in the
cases of aliphatic aldehydes (Table 2, entries 9 and 10).
the Zn(II)/1 catalytic system. Zn(OTf)
2
quickly emerged as
the optimal source of Zn(II) source, outperforming ZnMe
2
2
1
and ZnEt
2
,
but the reaction required a base to render an
enhanced reactivity (Table 1, entries 7-9). In contrast to
the marked increase in reactivity using bases, the observed
enantioselectivity was highly sensitive to the nature of solvent
employed (Table 1, entries 10-13). For instance, utilizing
Table 2. Scope of Aldehydes
2
Et O as solvent resulted in the isolation of product (R)-4a
in 60% yield and 2% ee, but otherwise identical reaction
conditions in THF the Henry product was obtained in 95%
yield and 73% ee (Table 1, entries 11 and 13). Upon
observation of such a drastic solvent influence on the
a
b
CuOAc/1
2
Zn(OTf) /1
c
d
c
d
yield
(%)
ee (%)
yield
(%)
ee (%)
(R)-4
2
2
enantioselectivity, we next examined the effect of water.
To our delight, using 30 mol % of H O as additive at -15
C the reaction was further improved to give enantiomerically
enriched (R)-4a in 85% yield and 80% ee (Table 1, entry
5).
With our optimized conditions in hand, the reaction scope
entry
aldehydes R
(S)-4
2
1
2
3
4
5
6
7
8
9
Ph
72
69
89
67
62
71
82
80
70
63
95
95
90
95
94
94
90
97
96
97
85
79
80
70
70
72
75
88
30
<5
80
80
83
88
67
76
80
90
42
nd
°
p-toluyl
p-Cl-Ph
p-anisyl
o-toluyl
m-toluyl
2-naphthyl
2-furyl
i-Pr
1
of aldehydes was investigated (Table 2). Excellent enanti-
oselectivities (g90% ee) were obtained with our Cu(I)/1
(
16) (a) Ooi, T.; Doda, K.; Maruoka, K. J. Am. Chem. Soc. 2003, 125,
10
t-Bu
2
054. (b) Marcelli, T.; van der Hass, R. N. S.; van Maarseveen, J. H.;
a
Hiemstra, H. Angew. Chem., Int. Ed. 2006, 45, 929. (c) Sohtome, Y.;
Hashimoto, Y.; Nagasawa, K. Eur. J. Org. Chem. 2006, 2894. (d) Mandal,
T.; Samanta, S.; Zhao, C.-G. Org. Lett. 2007, 9, 943. (e) Uraguchi, D.;
Sakaki, S.; Ooi, T. J. Am. Chem. Soc. 2007, 129, 12392. (f) Sohtome, Y.;
Takemura, N.; Takada, K.; Takagi, R.; Iguchi, T.; Nagasawa, K. Chem.
Asian J. 2007, 2, 1150.
Reaction with CuOAc (10 mol %), 1 (10 mol %), and t-BuOH (30
mol %) in CH Cl (0.16 M). Reaction performed using Zn(OTf) (10 mol
b
2
2
2
%), 1 (10 mol %), Et N (20 mol %), and H O (30 mol %) in THF (0.16
3
2
c
d
M). Isolated yields. Determined by HPLC.
(
17) (a) Arai, T.; Yamada, Y. M. A.; Yamamoto, N.; Sasai, H.;
Shibasaki, M. Chem.sEur. J. 1996, 2, 1368. (b) Handa, S.; Nagawa, K.;
Sohtome, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2008,
The development of catalytic asymmetric Henry reactions
of nitroalkanes other than nitromethane has been a notori-
ously challenging task, presumably due to the presence of
two distinctive mechanistic models: a chelation model for
syn-selectivity and a nonchelation model for anti-selectiv-
ity. Although we were mindful of the necessity of further
reaction optimizations with our Cu(I)- and Zn(II)-catalyzed
Henry reactions in this direction, we briefly examined the
feasibility of our orthogonal enantioselectivity approach in
the context of asymmetric Henry reactions using nitroethane
4
7, 3230. (c) Nitabaru, T.; Nojiro, A.; Kobayashi, M.; Kumagai, N.;
Shibasaki, M. J. Am. Chem. Soc. 2009, 131, 13860.
(
18) Using R-keto esters and nitromethane, Henry products with less
than 60% ee were obtained from Cu(II)/bis(thiazoline) catalysis; see: (a)
Lu, S.-F.; Du, D.-M.; Zhang, S.-W.; Xu, J. Tetrahedron: Asymmetry 2004,
2
15, 3433. Enantiomeric Henry products were observed in the Et Zn catalysis
2
3
in the range of 13-85% ee; see: (b) Du, D.-M.; Lu, S.-F.; Fang, T.; Xu, J.
J. Org. Chem. 2005, 70, 3712. Using aldehydes and nitromethane, Henry
2
products with 75-95% ee were obtained in the presence of 3 equiv of Et Zn
and 8 mol % of chiral bisoxazolidine; see: (c) ref 11c. Reversal of
enantioselectivity was observed in the Cu(I) catalysis in the range of
7
4-97% ee; see: (d) Spangler, K. Y.; Wolf, C. Org. Lett. 2009, 11, 4724.
19) Other copper salts were also screened in the presence of 20 mol %
of Et N in CH Cl /CuCl (53% ee), CuI (24% ee), CuCN (16% ee),
Cu(NCCH PF (40% ee), and CuCl (0% ee).
(
(Figure 2). Gratifyingly, an excellent orthogonal enantiose-
3
2
2
3
)
4
6
2
lectivity was observed with 2-furaldehyde, leading to Henry
products 5a with 94 and 96% ee’s using the Cu(I)/1 system,
while the corresponding antipodes 6a were obtained in 60
(
20) Use of 2-Me-THF at -15 °C resulted in the partial suspension of
CuOAc/1 catalyst. Use of 5 mol % of catalyst loading gave (S)-4a in 75%
yield and 83% ee.
(
21) Use of 10 mol % of Et
ee and 54% ee, respectively.
22) The potential role of H
H.; Suzuki, T.; Itoh, N.; Shibasaki, M. Tetrahedron Lett. 1993, 34, 851.
b) See also ref 17c.
2
Zn and Me
2
Zn in toluene at 0 °C gave 40%
(
2
O was previously discussed; see: (a) Sasai,
(23) For two mechanistic models, see: (a) Seebach, D.; Beck, A. K.;
Mukhopadhyay, T.; Thomas, E. HelV. Chim. Acta 1982, 65, 1101. For recent
contributions, see refs 16 and 17 and references cited therein.
(
5684
Org. Lett., Vol. 11, No. 24, 2009

and 92% ee’s with the Zn(II)/1 system. The high level of
reversal of enantioselectivity with syn-stereoisomers was also
observed with benzaldehyde (92% ee using Cu(I)/1 and 76%
ee using Zn(II)/1) and cyclohexanecarbaldehyde (98% ee
using Cu(I)/1 and 52% ee using Zn(II)/1). Interestingly, our
Cu(I)-catalyzed asymmetric Henry reaction also delivered
anti-Henry products with good to excellent enantioselectiv-
ites, whereas modest results were observed with our Zn(II)-
catalyzed system. Notably, an enhanced diastereoselectivity
was obtained with cyclohexanecarbaldehyde, preferring syn-
Henry products. In particular, the Zn(II)/1 system improved
its reactivity (69% yield) with cyclohexanecarbaldehyde, but
no reversal of enantioselectivity was realized with the minor
anti-Henry product.
Zn(II)-catalyzed reaction, we propose a dinuclear zinc species
(Figure 3b), where the neighboring C22-OH group now
participates in the creation of secondary Zn(II) metal site
for the Si-face attack, which is in turn coordinated to the
primary Zn(II) metal site. It is not possible to speculate on
the exact stereochemical environments of those two Zn(II)
metal sites, but our preliminary studies using a varied ratio
of Zn(II) and 1 or additives suggest that the ligand sites (L
2
6
and L* in Figure 3b) might not be saturated by 1.
Nevertheless, further mechanistic investigation is required
to understand the origin of enantioselectivity in the Zn(II)-
catalyzed reaction.
Figure 3. Working models for catalytic systems.
In summary, we have presented a new rational design
method for orthogonal enantioselectivity approach in the
catalytic asymmetric Henry reactions. Our two catalyst
systems are highly stereoselective with a wide range of
2
7
Figure 2
.
Asymmetric Henry reactions using nitroethane.
aldehydes and nitroalkanes, providing a novel way of
absolute stereochemical control in the catalytic asymmetric
C-C bond formation. Further investigations into the full
reaction scope and the asymmetric origin of our catalysts
are currently ongoing.
Although the lack of structural information on the catalyti-
cally active species enforces further studies, the key to our
success in the Zn(II)-catalyzed Henry reactions could be
attributed to the generation of multimetallic complexes as
shown in Figure 3. Whereas the Cu(I)-catalyzed asymmetric
Henry reactions are known to generate monometallic cata-
lysts from a 1:1 metal and chiral ligand mixture, a high order
molecularity of catalytically active species has been sug-
gested using the Zn(II) species with chiral ligands due to
the oxophilic nature of zinc metals.
moiety (N19) and the C21-OH group are expected to partici-
pate in the formation of monometallic complex (Figure 3a),
where a Re-face attack of the nitronate anion to the aldehyde
occurs through a chairlike transition state. We believe that
the C22-OH group does not act as a H-bond donor in our
Cu(I)-catalyzed Henry reaction since a varied amount of
Acknowledgment. This research was supported by IUPUI.
The Bruker 500 MHz NMR was purchased via a NSF-MRI
award (CHE-0619254).
Supporting Information Available: Experimental pro-
cedures and spectral data for all compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
1
1a,b
The tertiary amine
OL902380Z
24
(
25) No significant change in ee was observed with varying amounts of
t-BuOH, 15 mol % (74% ee), 30 mol % (79% ee), 50 mol % (76% ee), and
with different alcohols, 30 mol % of i-PrOH (73% ee), CF CH OH (72%
3 2
ee), PhOH (70% ee).
(
26) The reaction is extremely sensitive to the ratio of Zn(OTf)
for instance, use of 20 mol % of Zn(OTf)
mol % of 1, ethylene glycol, or ethanolamine gave products with 40-50%
2
and 1;
2
resulted in 11% ee while 20
2
5
t-BuOH did not affect either yield or ee value. As for the
ee.
(
27) Employment of 1-nitropropane gave results similar to those of
(
24) Upon using the modified ligands (having either the nitrogen atom
nitroethane, but the chiral HPLC separations for these products are not fully
resolved using AS-H, AD-H, and OD-H columns. Our full account for these
cases will be reported elsewhere.
or the C21-OH group protected), significantly lower ee’s were observed (0%
ee and 23% ee).
Org. Lett., Vol. 11, No. 24, 2009
5685