Remote control of diastereoselectivity in intramolecular reactions of chiral allylsilanes

Article abstract of DOI:10.1021/ja063411+

During investigations of cyclization reactions between chiral allylsilanes and N-acyliminium ions, it was discovered that a suitably positioned benzyloxy group on the allylsilane component caused a reversal in the diastereoselectivity of these reactions r

Full text of DOI:10.1021/ja063411+

Published on Web 10/03/2006
Remote Control of Diastereoselectivity in Intramolecular
Reactions of Chiral Allylsilanes
Weston R. Judd, Sooho Ban, and Jeffrey Aube´*
Contribution from the Department of Medicinal Chemistry, UniVersity of Kansas, 1251 Wescoe
Hall DriVe, Malott Hall, Room 4070, Lawrence, Kansas 66045-7582
Received May 16, 2006; E-mail: jaube@ku.edu
Abstract: During investigations of cyclization reactions between chiral allylsilanes and N-acyliminium ions,
it was discovered that a suitably positioned benzyloxy group on the allylsilane component caused a reversal
in the diastereoselectivity of these reactions relative to that normally observed with alkyl-substituted
allylsilanes. This effect was subsequently observed in two other reaction types. Investigations into this
effect led to the proposal of product formation through thermodynamic control facilitated by neighboring
group interactions with a transient cationic species. This hypothesis was experimentally supported by the
isolation of an intermediate in the proposed mechanistic pathway.
The reactions of allylsilanes with electrophilic species, in
particular iminium ions, have become standard means for the
formation of carbon-carbon bonds.1-4 This strategy has been
enriched by the introduction of chiral allylsilane derivatives,
which can afford products with a high degree of stereochemical
control.5-18 Still this strategy has considerable untapped promise,
especially when combined with nonstandard methods of gen-
erating the electrophilic component.
placement of a benzyloxy group γ to the silicon moiety. We
have ascertained that this observation holds in at least two other
reactions of allylsilanes. These observations will be discussed
in the context of kinetic vs thermodynamic control of the
stereochemistry of a cationic intermediate in the reaction through
neighboring group interactions.
Results
Previous work in this laboratory has shown that reactive
iminium ions can be prepared through the intramolecular
reactions of an arylimine bearing an NHBoc substituent in the
ortho position and that this reaction affords a route to interesting
ring systems.19,20 As an extension of this methodology, we
wished to examine chiral silanes in this reaction, with the overall
goal being the synthesis of enantiomerically pure products. In
this work, a most unexpected outcome was observed: the
diastereoselectiVity of the reactions can be reversed by the
Preparation of Chiral Allylsilanes. Initially, chiral alkenyl-
silanes 1 and 2, each containing a terminal azido group, were
prepared in enantiomerically pure form. Thus, enantiomerically
pure (S)-1,2,4-butanetriol derived from malic acid was converted
into allylic alcohol 3 by a standard series of functional group
transformations and protecting group manipulation steps (Scheme
1; see the Supporting Information for details). Conversion of
this allylic alcohol to alkenylsilane 5a was accomplished by
the 1,3-transpositive bissilylation protocol developed by Ito.21-23
This process has been shown to proceed with syn relative
stereocontrol and with high retention of enantiomeric purity.
Conversion of the product 5a to azide 1 was accomplished
through straightforward transformations.
We synthesized chiral allylsilanes containing more highly
functionalized side chains as shown in Scheme 2. The oxygen-
ated allylsilane 2 was originally envisioned as an intermediate
en route to martinelline.20 Allylic alcohol 8 was furnished
through Wipf’s zirconium-mediated coupling24 between a suit-
ably substituted alkyne and aldehyde 7. A Sharpless asymmetric
kinetic resolution was used to prepare chiral allylic alcohol (R)-
8, which was then subjected to the Ito protocol.25 Although
(1) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004, 3173-3199.
(2) Langkopf, E.; Schinzer, D. Chem. ReV. 1995, 95, 1375-1408.
(3) Masse, C. E.; Panek, J. S. Chem. ReV. 1995, 95, 1293-1316.
(4) Fleming, I. Org. React. 1989, 37, 57-575.
(5) Fleming, I.; Barbero, A.; Walter, D. Chem. ReV. 1997, 97, 2063-2192.
(6) Hayashi, T.; Konishi, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 4962-
4963.
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5924.
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972.
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(10) Panek, J. S.; Yang, M.; Xu, F. J. Org. Chem. 1992, 57, 5790-5792.
(11) Dias, L. C.; Meira, P. R. R. Synlett 2000, 37-40.
(12) Yamaguchi, R.; Tanaka, M.; Matsuda, T.; Okano, T.; Nagura, T.; Fujita,
K. Tetrahedron Lett. 2002, 43, 8871-8874.
(13) Mikami, K.; Maeda, T.; Kishi, N.; Nakai, T. Tetrahedron Lett. 1984, 25,
5151-5154.
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11028-11029.
(21) Murakami, M.; Andersson, P.; Suginome, M.; Ito, Y. J. Am. Chem. Soc.
1991, 113, 3987-3988.
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(16) Masse, C. E.; Dakin, L. A.; Knight, B. S.; Panek, J. S. J. Org. Chem. 1997,
62, 9335-9338.
(22) Suginome, M.; Matsumoto, A.; Nagata, K.; Ito, Y. J. Organomet. Chem.
1995, 499, C1-C3.
(17) Suginome, M.; Iwanami, T.; Ito, Y. J. Org. Chem. 1998, 63, 6096-6097.
(18) Huang, H.; Spande, T. F.; Panek, J. S. J. Am. Chem. Soc. 2003, 125, 626-
627.
(23) Suginome, M.; Matsumoto, A.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3061-
3062.
(24) Wipf, P.; Xu, W. Org. Synth. 1997, 74, 205-211.
(25) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.;
Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765-5780.
(19) Frank, K. E.; Aube´, J. Tetrahedron Lett. 1998, 39, 7239-7242.
(20) Frank, K. E.; Aube´, J. J. Org. Chem. 2000, 65, 655-666.
9
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J. AM. CHEM. SOC. 2006, 128, 13736-13741
10.1021/ja063411+ CCC: $33.50 © 2006 American Chemical Society

Diastereoselectivity Control in Allylsilane Reactions
A R T I C L E S
Scheme 1
Scheme 3
Scheme 2
readily apparent in the NMR spectrum and could be assigned
by coupling constant analysis to isomers a, b, and c as shown
in Table 1. Details of all structural assignments are provided in
the Supporting Information. We cannot rule out the formation
of small amounts of the Z olefin analogue of isomer a, but it
was not detected spectroscopically. Absolute configurations were
determined for both cases by preparing derivatives of 12b and
13a, and subjecting the derivatives to anomalous dispersion
X-ray analysis (Scheme 4). Derivatization of 12b was effected
through an oxidative cleavage/reduction sequence of the product
mixture 12a-c followed by chromatographic separation of the
resulting diastereomeric mixture of alcohols. Subsequent es-
terification of the major diastereomer 19 (derived from 12b,c)
gave the corresponding p-bromobenzoyl ester. Preparation of
the p-bromobenzoyl derivative of 13a (isolated from the product
mixture containing 13a-c by crystallization) required only
esterification of the terminal alcohol (Scheme 4b). Chiral
chromatography of product 12 derivatives and of purified 13a
verified that the trans isomers were obtained in high enantio-
meric purity (12a in 97:3 er, 13a in g99:1 er). However, the
corresponding enantiomeric ratios for the cis isomers were not
determined due to incomplete resolution.
exemplified for the O-benzyl derivative 2, this route was also
adapted to the synthesis of several related allylsilanes chosen
in response to observations made on the alkylation chemistry
of 1 vs 2 (see below).
Once prepared, the azides 1 and 2 were separately ligated to
ethyl 4-(N-tert-butoxycarbonylamino)-3-formylbenzoate20 to af-
ford imines that were then treated with TiCl4 (Scheme 3). This
generated an iminium ion by attack of the imine nitrogen on
the o-Boc group (possibly via the isocyanate intermediate
shown). The electrophilic species thus generated smoothly
reacted with the appended allylsilane species to afford a mixture
of stereoisomeric products (Table 1). Interestingly, a benzylic
allylsilane (i.e., 1 in which the terminal ethyl group is replaced
by phenyl, not shown) did not undergo cyclization in several
attempts. When the chiral allylsilanes 1 and 2 were incorporated
into this scheme (through imines 10 and 11), the product ureas
were isolated in good yields and as a mixture of inseparable
stereoisomers. In the reaction of the terminal benzyloxy-
substituted example 11, the benzyl group was lost during the
course of cyclization, affording alcohols 13a-c. The removal
of benzyl groups under Lewis acid conditions has been
previously observed.26
The most striking observation in these experiments concerned
the diastereoselectivity of the reactions, specifically the cis:trans
ratio with respect to H1 and H10b. Thus, the ethyl-substituted
silane 1 reacted (via imine 10) to afford products 12, in which
the alkenyl side chain emerged cis to the bulky aryl substituent
in an overall ratio of 5.7:1 (counting both E and Z double bond
isomers together). This ratio is similar to that observed in the
unsubstituted case previously reported (shown in Table 1, entry
5, for comparison).20 In contrast, imine 11, containing a
benzyloxy group at the terminus, reacted to afford analogues
13 in which the trans isomer predominated (1:6.7 cis:trans).
This remarkable stereochemical dependence on a remote sub-
stituent merited additional attention.
The stereoselectivity of each reaction was determined by 1H
NMR spectroscopy of the crude reaction mixture. In each of
the reactions, three of the four possible diastereomers were
We hypothesized a change in mechanism involving the
interaction of the ether oxygen with an intermediate along the
(26) Hori, H.; Nishida, Y.; Ohrui, H.; Meguro, H. J. Org. Chem. 1989, 54, 1346-
1353.
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J. AM. CHEM. SOC. VOL. 128, NO. 42, 2006 13737

A R T I C L E S
Judd et al.
Table 1. TiCl4-Promoted Cyclizations of Allylsilane-Tethered Arylimines
isomer ratiob (%)
yielda
(%)
cis:trans
ratioc
overall
E:Z ratiod
entry
imine
product
a
b
c
1
2
3
4
5f
(S)-10, R ) CH2CH3
12, R ) CH2CH3
13, R ) CH2CH2OH
15, R ) CH2(CH2)3OH
13, R ) CH2CH2OH
18, R ) H
85
80
73
64
80g
15
87
20
53
15
66
10
68
42
85
19
3
12
5
5.7:1
1:6.7
4.0:1
1:1.1
5.7:1
81:19
97:3
88:12
95:5
(S)-11, R ) CH2CH2OBn
(()-14, R ) CH2(CH2)3OBne
(()-16,R ) CH2CH2OTBDPSe
17, R ) H
a Overall yield of isolated product from starting azide (two steps). b Determined by 1H NMR integration and normalized to 100%. c Refers to the relative
stereochemistry of H1 and H10b, ratio of b + c to a. d Double bond isomers, ratio of a + b to c. e Prepared in analogy to compound 2 (see the Supporting
Information). f Reference 20, included for comparison. g Yield based on purified imine.
Scheme 4
shows that the highest E olefin selectivity occurred with the
terminally benzyloxy-substituted allylsilane (entry 2), while the
lowest E selectivity occurred in the absence of a terminal ether
substituent (entry 1).
Extension to Other Cyclization Types. In an effort to
explore the generality of the influence of a terminal benzyloxy
substituent on the diastereoselectivity of intramolecular allyl-
silane reactions, we investigated two additional reaction types.
Thus, a series of Speckamp/Royer acyliminium cyclization
substrates were prepared from the corresponding alcohols by a
Mitsunobu/reduction sequence (Supporting Information).29-31
Reaction under protic acid promotion gave good yields of the
cyclization products, again isolated as isomeric mixtures (Table
2).
We again observed three of the four possible isomers in the
1H NMR of the product mixtures, which were assigned by 2D
NMR experiments and coupling constant analysis as isomers
a, b, and c (cis/trans descriptors refer to the relative stereo-
chemistry of H1 and H8a). The diastereomeric trends observed
in these reactions paralleled those of the o-NHBoc-arylimine
cyclizations (cf. Table 1). Most notably, reversal of diastereo-
selectivity was again observed with the benzyloxy-substituted
allylsilane, which afforded a 1:5 cis:trans diastereomeric ratio
(entry 2); all other examples provided cis products as major
isomers. The highest product E olefin selectivity was also
observed in the presence of a γ-benzyloxy substituent (entry
2). Absolute configurations of 22c and 24a were determined
by anomalous dispersion X-ray analysis of the corresponding
p-bromobenzoyl derivatives. In general, p-bromobenzoyl deriva-
tives were prepared through an oxidative cleavage/reduction
sequence, followed by esterification of the resulting alcohol
(Scheme 5 and Supporting Information). Single isomers for
X-ray analysis were obtained by crystallization of the alcohol
mixture (affording 32) or after esterification (affording 31c).
Alcohol 32 was converted to 32a to obtain heavy-atom-
containing crystals; oddly, the double addition product shown
was obtained in this step (probably during an acidic workup).
reaction pathway and synthesized additional examples to address
this point. Thus, compound 14, in which the ether was moved
two methylene units further from the allylsilane moiety, was
synthesized in racemic form and brought into the reaction
manifold (Table 1, entry 3). This compound gave results similar
to those obtained using the nonfunctionalized examples, giving
a 4:1 ratio favoring the cis isomer of products 15. To determine
whether the Lewis basicity of the oxygen in benzyloxy example
2 was a factor, the analogue (()-16 containing a bulky alkyl-
diphenylsilyl group, known to limit the coordinating ability of
the oxygen atom,27,28 was tested (entry 4). In this case, a nearly
1:1 mixture of isomers was obtained, strongly suggesting an
involvement of the oxygen atom lone pairs in this phenomenon.
Finally, a comparison of the overall product E:Z olefin ratios
(29) Hiemstra, H.; Sno, M. H. A. M.; Vijn, R. J.; Speckamp, W. N. J. Org.
Chem. 1985, 50, 4014-4020.
(30) Hubert, J. C.; Steege, W.; Speckamp, W. N. Synth. Commun. 1971, 1, 103-
(27) Frye, S. V.; Eliel, E. L. Tetrahedron Lett. 1986, 27, 3223-3226.
(28) Chen, X.; Hortelano, E. R.; Eliel, E. L.; Frye, S. V. J. Am. Chem. Soc.
1992, 114, 1778-1784.
109.
(31) Hubert, J. C.; Wijnberg, J. B. P. A.; Speckamp, W. N. Tetrahedron 1975,
31, 1437-1441.
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Diastereoselectivity Control in Allylsilane Reactions
A R T I C L E S
Table 2. TFA-Promoted Cyclizations of Hydroxy Lactams
isomer ratiob (%)
yielda
(%)
cis:trans
ratioc
overall
E:Z ratiod
entry
imide
product
a
b
c
1
2
3
4
5
(S)-21, R ) CH2CH3
22
24
26
28
30
92
85
98
74
71
8
28
5
25
19
90
64
12
56
48
12:1
1:5
4.2:1
2.0:1
9:1
36:64
88:12
44:56
52:48
(S)-23, R ) CH2CH2OBn
(()-25, R ) CH2(CH2)3OBn
(()-27, R ) CH2CH2OTBDPS
29, R ) H
83
19
33
10
1
a Overall isolated yield. b Determined by H NMR integration and normalized to 100%. c Refers to the relative stereochemistry of H1 and H8a, ratio of
b + c to a. d Double bond isomers, ratio of a + b to c.
Scheme 5
Scheme 6
(Scheme 6). As before, remarkably different diastereomeric
outcomes were realized, with compound 33 being obtained with
completely cis stereoselectivity at C-2/C-3 and 34 arising from
a strongly 2,3-trans-biased reaction. The stereochemical as-
signments for the cyclized products 33 and 34 were made on
the basis of NOE difference spectra.
Discussion
The reaction shown in Scheme 7 is for tricyclic urea formation
under TiCl4 promotion, but analogous analyses may be extended
to the other reaction types. If one assumes kinetic control, anti
addition relative to the C-Si bond, and coordinated C-C bond
formation with loss of SiMe3, product types a-c could be
rationalized as shown. The predominant isomers for unfunc-
tionalized side chains (i.e., where X ) alkyl or H) have cis
stereochemistry across the pyrrolidine or tetrahydrofuran ring
in all three series (major compounds 12b, 18b, 22c, 30b, and
33). These products are consistent with the chairlike transition
states shown. Differences in double bond geometry are known
to be coupled with the face selectivity of the allylsilane
component (cf. products b and c),5 which was confirmed in the
four cases where absolute stereochemistry was determined. The
E:Z isomer ratios in a given series (i.e., in the competition
between the two chairs leading to isomers b and c) also depend
on the minimization of nonbonded interactions in the specific
reaction being studied. Differences observed in the E:Z ratios
Chiral chromatography of derivatized purified product mixtures
22 and 24 again showed that the trans products were formed in
high enantiomeric purity (22b in 93:7 er, 24a in 97:3 er).
Allylsilanes also react with tethered oxenium ions (via initial
acetal formation between an alcohol moiety on the allylsilane
and an aldehyde) to afford substituted tetrahydrofurans.17,32
Accordingly, we reacted racemic versions of 1 and 2 with
benzaldehyde under TMSOTf promotion at low temperature
(32) Mohr, P. Tetrahedron Lett. 1993, 34, 6251-6254.
9
J. AM. CHEM. SOC. VOL. 128, NO. 42, 2006 13739

A R T I C L E S
Scheme 7
Judd et al.
Scheme 8
this case, we propose that the presence of a suitably positioned
basic ether oxygen either changes the mechanism of the reaction
or otherwise participates in the transition state to effect a change
in the diastereoselectivity. In considering these options, we noted
that the presence of the γ ether turned the reaction in favor of
the thermodynamically more favored isomer in all three reaction
types, i.e., the heterocycles containing an exo side chain in
compounds 13 and 24 and the trans isomer of tetrahydrofuran
34. One way that this could happen is suggested in Scheme 8.
In reactions with the γ-benzyloxy-substituted allylsilane, the
potential for interception of the emerging â-silyl cation by the
alkoxy group, forming a five-membered oxonium ion, arises.
The participation of ether groups with cations49 has been invoked
by Angle and co-workers in their annulation chemistry37,38 and
by Molander in explaining long-range stereoselectivity.50 In the
present case, such participation could lead to a kinetic distribu-
tion of products giving rise to the same major product as
observed in the nonfunctionalized allylsilane reactions. However,
the fact that trans-fused, rather than cis-fused, products pre-
dominate for reactions with a γ-benzyloxy-substituted allylsilane
suggests that an additional element may be operative in this
process. A likely explanation is that the oxonium species shown
in Scheme 8 (and the analogous intermediates that would be
for the examples shown in Table 1 vs Table 2 likely depend on
the interplay between the steric demands of the substrates and
the timing of the transition state (early or late). The only
observed trans isomer (relative to the five-membered ring being
formed) requires a boatlike transition state as shown for series
a.
The observation that a particularly situated basic oxygen could
reverse the stereoselectivity of these reactions was unexpected.
Other researchers have shown that â-silyl cation intermediates
in allylsilane reactions can be intercepted and lead to alternative
reaction product types, as occurs in formal [2 + 2] and [3 + 2]
cycloadditions with aldehydes, imines, or isocyanates.33-48 In
(33) Peng, Z.-H.; Woerpel, K. A. Org. Lett. 2000, 2, 1379-1381.
(34) Akiyama, T.; Yamanaka, M. Synlett 1996, 1095-1096.
(35) Schinzer, D.; Panke, G. J. Org. Chem. 1996, 61, 4496-4497.
(36) Angle, S. R.; El-Said, N. A. J. Am. Chem. Soc. 2002, 124, 3608-3613.
(37) Angle, S. R.; Belanger, N. A.; El-Said, N. A. J. Org. Chem. 2002, 67,
7699-7705.
(38) Osumi, H.; Sugimura, H. Tetrahedron Lett. 1995, 36, 5789-5792.
(39) Banuls, V.; Escudier, J.-M. Tetrahedron Lett. 1999, 55, 5831-5838.
(40) Micalizio, G. C.; Roush, W. R. Org. Lett. 2000, 2, 461-464.
(41) Nair, V.; Rajesh, C.; Dhanya, R.; Rath, N. P. Tetrahedron Lett. 2002, 43,
5349-5351.
(42) Panek, J. S.; Hu, T. J. Org. Chem. 1997, 62, 4914-4915.
(43) Peng, Z.-H.; Woerpel, K. A. Org. Lett. 2001, 3, 675-678.
(44) Sugita, Y.; Kumura, Y.; Yokoe, I. Tetrahedron Lett. 1999, 40, 5877-5880.
(45) Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113, 9868-9870.
(46) Panek, J. S.; Su, Q. J. Am. Chem. Soc. 2004, 126, 2425-2430.
(47) Isaka, M.; Willard, P. G.; Nakamura, E. Bull. Chem. Soc. Jpn. 1999, 72,
2115-2116.
(48) Roberson, C. W.; Woerpel, K. A. J. Am. Chem. Soc. 2002, 124, 11342-
11348.
(49) Winstein, S.; Allred, E.; Heck, R.; Glick, R. Tetrahedron 1958, 3, 1-13.
(50) Molander, G. A.; Haar, J. P., Jr. J. Am. Chem. Soc. 1993, 115, 40-9.
9
13740 J. AM. CHEM. SOC. VOL. 128, NO. 42, 2006

Diastereoselectivity Control in Allylsilane Reactions
A R T I C L E S
Scheme 9
formed in the other reaction types) are sufficiently stable to allow
equilibrium between the cis- and trans-fused oxonium ions and
probably the analogous carbocations and that the thermody-
namically favored trans products therefore result. This addition-
ally assumes that SiR3 elimination from the initial addition step
(as depicted in Scheme 7) or from the oxonium-containing
intermediates (in which the SiR3 group cannot readily achieve
overlap with the ether oxygen) is slow enough to allow for
equilibrium of the cation pool.51,52 Moreover, bond rotation
would more likely occur before elimination of the silyl group,
which would explain the higher amounts of E olefin isomers in
two of the three reaction types investigated.
On the basis of the proposed mechanistic rationale, the cis
products predominated, or reactions were poorly selective, in
cases in which the allylsilane contained structural elements
inconsistent with the formation of the cyclic oxonium intermedi-
ate. Thus, the presence of the bulky OTBDPS group attenuated
the ability of these substituents to engage in neighboring group
participation relative to that of the OBn substituent, resulting
in a nearly 1:1 mixture of cis and trans isomers in one case
(Table 1, entry 4) and the predominant formation of the cis
isomer in another (Table 2, entry 4). When the benzyloxy
substituent is moved two additional methylene units away from
the silyl group (ꢀ-OBn), the cis products predominate as a result
of the decreased ability of the more distal ether oxygen to engage
in the formation of the cyclic oxonium species through
interaction with the emerging â carbocation, as this would
require the formation of a less favorable seven-membered ring
(cf. entry 3 in Tables 1 and 2).
With the aim of providing experimental support for the
proposed mechanism of diastereoselection through ether oxygen
participation, we considered substrates that would allow for the
isolation of a silyl-substituted tetrahydrofuran-containing product
(formed via the oxonium intermediate proposed in Scheme 8).
We reasoned that this might be accomplished by using an acid-
labile p-methoxybenzyl (PMB) ether-substituted allylsilane in
the N-acyliminium cyclization. Thus, incorporation of a PMB
ether-substituted allylsilane into the cyclization substrate 35
followed by acid-promoted cyclization gave a product mixture
of the cyclic ether 37 and the lactam products 38, from which
cyclic ether-containing product 37 could be isolated in 20% yield
(along with a mixture of 37 contaminated with additional 38,
Scheme 9). Unfortunately, it was not possible to unambiguously
determine the relative stereochemistry of 37 by NMR. The
stereostructure shown is hypothesized on the basis of the
proposal shown in Scheme 8. The fact that compound 37 was
observed in this reaction lends support for the proposed
intermediacy of the cyclic oxonium species arising from
neighboring group participation.
Summary
These studies show that a reversal in the diastereoselectivity
in intramolecular reactions of chiral allylsilanes can be effected
by a γ-benzyloxy substituent. The postulated mechanism
involves interaction of the terminal ether oxygen with the
incipient â-silyl carbocation, ultimately forming the thermody-
namically favored trans products. Experiments to determine the
generality of this phenomenon are ongoing.
Acknowledgment. This research was supported by the
National Institute of General Medical Sciences of the National
Institutes of Health (Grant GM-49093). We thank the reviewers
for their careful review and useful suggestions.
Supporting Information Available: Details of starting mate-
rial preparations, experimental details, determination of isomer
ratios and enantiomeric purities, and 1H and 13C spectra for new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(51) Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.; Yamamoto, A.; Fujiwara,
K. J. Am. Chem. Soc. 1999, 121, 9546-9549.
(52) Yoshida, J.; Suga, S. Chem.sEur. J. 2002, 8, 2650-2658.
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