Molybdenum-catalyzed asymmetric allylic alkylation of 3-alkyloxindoles: Reaction development and applications

Article abstract of DOI:10.1002/chem.201002569

We report a full account of our work towards the development of Mo-catalyzed asymmetric allylic alkylation reactions with 3-alkyloxindoles as nucleophiles. The reaction is complementary to the Pd-catalyzed reaction with regard to the scope of oxindole nucleophiles. A number of 3-alkyloxindoles were alkylated successfully under mild conditions to give products with excellent yields and good-to-excellent enantioselectivities. Applications of this method to the preparation of indoline alkaloids such as (-)-physostigmine, ent-(-)-debromoflustramine B, and the indolinoquinoline rings of communesin B are reported.

Full text of DOI:10.1002/chem.201002569

DOI: 10.1002/chem.201002569
Molybdenum-Catalyzed Asymmetric Allylic Alkylation of 3-Alkyloxindoles:
Reaction Development and Applications
Barry M. Trost and Yong Zhang*[a]
Abstract: We report a full account of
our work towards the development of
Mo-catalyzed asymmetric allylic alkyla-
tion reactions with 3-alkyloxindoles as
nucleophiles. The reaction is comple-
mentary to the Pd-catalyzed reaction
with regard to the scope of oxindole
nucleophiles. A number of 3-alkyloxin-
doles were alkylated successfully under
mild conditions to give products with
excellent yields and good-to-excellent
enantioselectivities. Applications of
this method to the preparation of indo-
line alkaloids such as (À)-physostig-
mine, ent-(À)-debromoflustramine B,
and the indolinoquinoline rings of com-
munesin B are reported.
Keywords: alkylation · asymmetric
catalysis
·
molybdenum
·
natural products · total synthesis
Introduction
The 3,3’-disubstituted oxindoles are important synthetic tar-
gets because they are found widely in alkaloid natural prod-
ucts and pharmaceutical candidates.[1–2] Furthermore, the ox-
indole moiety can be easily elaborated to an indoline struc-
ture and, hence, they serve as valuable precursors to indo-
line compounds that bear a quaternary carbon stereocenter
at the C-3 position.[3] Development of a general and efficient
method for the asymmetric preparation of this structural
motif, however, has proven challenging due to the difficult
installation of a quaternary carbon.[4] While significant ad-
vances have been achieved involving resolution or diastereo-
selective method by the use of stoichiometric chiral auxilia-
ries or existing chirality, catalytic asymmetric synthesis of
this class of molecules has not been reported until recently.
In 1993, Wong first demonstrated that alkylation of a pro-
chiral oxindole via phase-transfer catalysis provided the
chiral oxindoles with high yield and modest selectivity.[5]
Since then, a number of enantioselective approaches to 3,3’-
disubstituted oxindoles have appeared.[6–12]
Transition-metal-catalyzed asymmetric allylic alkylation
reactions (AAA reactions) of prochiral nucleophiles have
been shown to be an effective method for the construction
of quaternary carbon centers.[13] The catalytic cycles is as fol-
lows (Scheme 1): complexation of the alkene to the metal,
ionization of the leaving group to generate the p-allyl com-
plex, alkylation by the nucleophile, and finally decomplexa-
tion to regenerate the catalyst. The selectivity at the nucleo-
Scheme 1. Transition-metal-catalyzed AAA reactions (M=Pd, Mo, Ir,
Rh, Ru, etc., LG=leaving group).
phile is determined at the step where the nucleophile at-
tacks the p-allyl metal complex. Two types of mechanisms
for this step are possible: an outer sphere mechanism involv-
ing direct attack of the nucleophile on the allyl moiety from
the face opposite the metal and chiral ligand, or an inner
sphere mechanism where the nucleophile pre-coordinates to
the metal followed by reductive elimination. The inner-
sphere process positions the nucleophile and the chiral
ligand in close proximity, and hence, should provide more
opportunity for asymmetric induction. Pd-catalyzed allylic
alkylation reactions generally follow the outer-sphere mech-
anism and because the alkylation step occurs outside the co-
ordination sphere of the metal, achieving high enantioselec-
tivity has proven difficult under standard reaction condi-
tions. Recently, both our group[14] and the Stoltz group[15]
have reported Pd-catalyzed decarboxylative asymmetric al-
lylic alkylation reactions, where a switch to inner-sphere
mechanism was proposed to explain the excellent level of
selectivity at the nucleophile.
[a] Prof. B. M. Trost, Dr. Y. Zhang
Department of Chemistry, Stanford University
Stanford University, CA 94305-5080 (USA)
Fax : (+1) 650-725-0002
In 2004, our group reported that 3-aryloxindoles were ef-
ficiently allylated to form the quaternary stereocenters at
the 3-position with Pd catalyst.[11a] The same reaction with 3-
alkyloxindoles as nucleophiles, however, generally proceed-
E-mail: bmtrost@stanford.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002569.
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FULL PAPER
Table 2. Screening of additive for Equation (1).[a]
ed with low selectivities, even under the decarboxylative
conditions. Therefore, we turned our attention to the Mo-
catalyzed AAA reaction,[16–18] which had been shown to pro-
ceed via an inner sphere mechanism of coordination of nu-
cleophile and reductive elimination. We conjectured that the
Mo reaction would be more effective with 3-alkyloxindoles
as nucleophiles in forming the desired quaternary centers
with high selectivities. Herein, we describe in detail its suc-
cessful implementation and application. A preliminary com-
munication of a portion of this work was recently disclo-
sed.[11b]
Entry Base (1.2 equiv) Additive (1.0 equiv)
ee [%] Yield [%][b]
1
2
3
4
5
6
7
8
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
ZnCl2
MgBr2
HoCl3
YbCl3
Bu3B
n-hexyl4NCl
BSA
HMDS (2 equiv)
HMDS (4 equiv)
TMDEA
–
–
–
–
75
75
72
73
70
69
n.r.
n.r.
n.r.
n.r.
n.d.
n.d.
20
80
80
80
9
10
[a] The reaction was performed with 0.1 mmol of oxindole 1a, 0.12 mmol
of allyl tert-butyl carbonate, 10% [Mo(C7H8)(CO)3], 15% L1, 0.12 mmol
of LiHMDS in THF(1 mL). [b] Isolated yield.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Results and Discussion
Reaction optimization: Initial studies were focused on the
optimization of the base and solvent for the allylation of ox-
indole 1 (Table 1). The countercation of the base has the
largest effects on the selectivity of the reaction. The reaction
zane, a by-product from deprotonation of oxindole with
LiHMDS, affects the selectivity of the reaction. Although
the effect was small, addition of excess amount of hexame-
thyldisilazane decreased the enantioselectivity of the reac-
tion (entry 8–9). Addition of tetramethylenediamine
(TMEDA) also lowered the selectivity of the reaction
(entry 10).
Table 1. Screening of base and solvent according to Equation (1).[a]
These results prompted us to investigate the use of
lithium bases that would not generate amine byprod-
uct (Table 3). Except for lithium methoxide, which
gave no product (entry 2), reactions with lithium alk-
oxide bases all gave slightly better enantioselectivity
than the reaction with LiHMDS (entry 3–6). Lithium
tert-butoxide was selected as the optimal base as it is
the most readily available. Finally, the best yield and
enantioselectivity was achieved when the reaction was
conducted with two equivalents of lithium tert-butox-
ide in THF at room temperature (entry 7).
Entry
Base
Solvent
T [8C]
ee [%]
Yield [%][b]
1
2
3
4
5
6
7
8
9
Cs2CO3
THF
THF
THF
THF
toluene
Et2O
DME
dioxane
CH2Cl2
67
67
67
67
67
40
67
67
40
–
n.r.
n.d.
n.d.
75–92
60
n.r.
80
80
KHMDS
NaHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
38
60
75
20
–
63
55
–
The Merck group has reported an X-ray structure
of a p-allyl molybdenum ligand complex and showed
that the complex is not symmetrical: the ligand is co-
ordinated to the metal via a three-point binding, and
it was postulated that the labile oxygen ligand dissoci-
ates to make room for the incoming nucleophile
during the nucleophilic substitution step.[18a] Several
symmetrical and unsymmetrical ligands with different heter-
ocyclic substitutions and amine linkages were examined to
0
[a] The reaction was performed with 0.1 mmol of oxindole 1a, 0.12 mmol
of allyl tert-butyl carbonate, 10% [Mo(C7H8)(CO)3], 15% L1, 0.12 mmol
(1 mL). [b] Isolated yield, n.r.=no reaction, n.d.=not de-
AHCTUNGTRENNUNG
of base in THF
termined.
ACHTUNGTRENNUNG
performed with cesium carbonate as the base gave no prod-
uct (entry 1). The reactions with KHMDS and NaHMDS
gave good reactivity but low selectivity (entry 2–3). The
highest enantioselectivity was obtained when a silylazide
base with lithium as the countercation was used (entry 4).
The reaction performed in THF afforded the best selectivity.
Other organic solvent such as toluene, diethyl ether, DME,
dioxane and dichloromethane were less effective compared
to THF (entry 5–9).
Further screening of a more extensive list of counterac-
tions was carried out by using LiHMDS as the base in con-
junction with one equivalence of Lewis acid additive
(Table 2). Disappointingly, addition of Zn, Mg, Yb or Ho
salts shut down the reaction (entry 1–4). Addition of tetra-
n-hexylammonium salt, tri-n-butylborane, and O,N-bis(tri-
methylsilyl)acetamide (BSA) did not improve the reaction
(entry 5–7). We also investigated whether hexamethyldisila-
Table 3. Screening of base and temperature for Equation (1).[a]
Entry
Base (1 equiv)
T [8C]
ee [%]
Yield [%][b]
1
2
3
4
5
6
7
8
9
sBuLi
LiOMe
LiOtBu
LiOtBu
LiOtAmyl
LiOtHept
LiOtBu (2 equiv)
LiOtBu (2 equiv)
LiOtBu (2 equiv)
678C
678C
678C
RT
RT
RT
RT
4
À10
71
–
n.d.
n.r.
80
70–90
70
70
95–98
95
79
82
81
81
82
83
73
90
[a] The reaction was performed with 0.1 mmol of oxindole 1a, 0.12 mmol
of allyl tert-butyl carbonate, 10% [Mo(C7H8)(CO)3], 15% L1, 0.12 mmol
of base in THF(1 mL). [b] Isolated yield.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
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B. M. Trost and Y. Zhang
Table 4. Screening of chiral ligands for Equation (1).[a]
selectivity (entry 7–8). These results indicate the coordina-
tion of the pyridine ring and amide groups is important for
the selectivity of the reaction.
To summarize, the optimized conditions for the synthesis
of allylated 3-alkyloxindoles consisted of performing the re-
Entry
Ligand
ee [%]
Conversion [%]
1
2
3
4
5
6
7
8
L2
L3
L4
L5
L6
L7
L8
L9
72
75
72
75
61
64
24
10
>95
>95
>95
>95
>95
>95
>95
>95
action with ligand L1 (15% mol), [MoACHTNURGTNEUNG(C7H8)(CO)3] (10%
mol), and LiOtBu (2 equiv) in THF at room temperature.
Reaction scope synthesis of substrates: A variety of 3-mono-
substituted oxindole substrates were prepared by three dif-
ferent synthetic sequences (Scheme 2). 1,3-Dimethyloxin-
dole was synthesized by oxidation of 1,3-dimethylindole
with DMSO in the presence of concentrated hydrochloric
acid [Eq. (2)].[20] This method, while straightforward, is lim-
ited by the availability of 3-substituted indoles. The use of
concentrated HCl also limits certain functional groups that
can be tolerated. The majority of the substrates were pre-
pared by mono-alkylation of unsubstituted oxindoles, many
of which are commercially available or readily prepared by
reduction of the corresponding isatins [Eq. (3)]. Nakazawa
et al. reported that mono-alkylation of the unsubstituted ox-
indole in the presence of HMPA minimizes the formation of
bis-alkylation by-product and provides the desired 3-mono-
substutited oxindoles in reasonable yield.[21] Since the use of
HMPA is undesirable, we also adopted a method reported
by Overman for the mono-alkylation of oxindoles, which in-
volves a Knoevenagel condensation between an oxindole
and a non-enolizable aldehyde, followed by N-alkylation
and lastly hydrogenation to reduce the double bond
[Eq. (4)].[28] We found that the condensation step was most
conveniently performed in a microwave reactor with a small
amount of ethanol as solvent. The product is crystalline and
was isolated by filtration. The subsequent N-alkylation and
hydrogenation steps were both straightforward.
[a] The reaction was performed with 0.1 mmol of oxindole 1a, 0.12 mmol
of allyl tert-butyl carbonate, 10% [Mo(C7H8)(CO)3], 15% ligand
0.2 mmol of LiOtBu in THF(1 mL) at 678C.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
The optimized condition was then applied to examine the
scope and limitations of the reaction (Scheme 3). Gratifying-
ly, in nearly all cases, excellent yields and good-to-excellent
enantioselectivities were obtained and a variety of function-
al groups at the 3-position of the oxindoles were tolerated.
The enantioselectivity of the reaction correlates with the
study whether variation of the electronic and steric proper-
ties of the chelating groups would provide enhanced selec-
tivity. As shown in Table 4, all
the ligands tested gave full con-
version but with very different
selectivities. Reactions per-
formed with ligands that con-
tain amide linkages and at least
one pyridine ring afforded com-
parable enantioselectivities as
the reaction with L1 (entry 1–
4). However, when both pyri-
dine rings were substituted with
other chelating heterocycles,
the enantioselectivities dropped
significantly (entry 5–6). Fur-
thermore, reaction with ligand
containing carbamate or sulfa-
mide linkage gave much worse Scheme 2. Representative synthesis of oxindole substrates.
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Molybdenum-Catalyzed Asymmetric Allylic Alkylation
FULL PAPER
Formal synthesis of (À)-physostigmine and (À)-phenserine:
Physostigmine, originally isolated from the seeds of the Af-
rican Calabar bean, is a potent reversible inhibitor for choli-
nesterase and has been used clinically to treat a myriad of
conditions including glaucoma and g-hydroxybutyric acid
overdose.[22–24] Phenserine is a synthetic analogue of physos-
tigmine with more favorable pharmacological properties.
Phenserine had also been examined for the treament of Alz-
hermerꢁs disease.[25–26]
Physostigmine and phenserine share the same pyrrolidi-
noindoline ring system and differ only by carbamate substi-
tutions. It has been shown that phenserine can be prepared
from physostigmine via a two-step sequence of hydrolysis
and re-protection.[27] Due to their biological importance, a
number of asymmetric syntheses of these molecules have
been reported.[6a,9b,12c,28] Our synthesis commenced from pro-
chiral oxindole 1a readily prepared from 4-methoxy-N-
methylaniline and chloroacetone in two steps.[29] Allylation
of 1a under the optimized conditions proceeded with 95%
yield and 82% ee. Oxidation of the allylated product 2a
(OsO4, NMO, and then NaIO4) provided the aldehyde 3 in
92% yield. Two recrystallizations from isopropyl alcohol
and cyclohexane upgraded the enantiopurity of 3 to 99%.
Reductive cyclization of 3 using conditions optimized by
Overman and co-workers afforded (À)-esermethole,[6a]
which had been transformed to (À)-physostigmine and (À)-
phenserine in two steps. Thus, our work constitutes a formal
synthesis of (À)-physostigmine (Scheme 4) and (À)-phenser-
ine, in seven steps from commercially available starting ma-
terials.
Scheme 3. Scope of the reaction. The reaction was performed with
0.1 mmol of oxindole 1, 0.12 mmol of allyl tert-butyl carbonate, 10%
[MoACHTUNGTRENNUNG(C7H8)(CO)3], 15% L1, 0.2 mmol of LiOtBu in THF (1 mL) at room
temperature.
size of the substituents on the oxindole. Increasing the size
of the 3-alkyl group increased the enantioselectivity. Howev-
er, increasing the size of the N-alkyl group was detrimental
to the enantioselectivity. This is not unexpected as the oxin-
dole enolate is likely coordinated to the bulky molybdenum
catalyst during the reaction and would try to minimize the
steric interaction by steering the large substituents away
from the catalyst. We have pre-
Synthesis of ent-(À)-debromoflustramine B: The flustra-
mines are a family of prenylated or “reverse” prenylated
pyrrolidinoindoline marine alkaloids isolated from the
viously reported that 3-aryl-sub-
stituted oxindoles are good sub-
strates for Pd-catalyzed AAA
reactions.[11a] When we tested 3-
phenyloxinole in the Mo-cata-
lyzed AAA reaction under the
optimized conditions, however,
only moderate enantioselectivi-
ty was observed (2p). Thus, the
Mo reaction complements the
Pd reaction with regard to the
scope of the nucleophile in this
case.
Scheme 4. Formal synthesis of (À)-physostigmine.
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B. M. Trost and Y. Zhang
marine bryozoan Flustra foliacea.[30–31] Flustramine B was
shown to be effective blockers for voltage-activated potassi-
um channels and exhibit both skeletal and smooth muscle
relaxant activities.[31] Synthetic interests in this family of nat-
ural products were stimulated primarily by their deceptively
simple yet unique structures. A number of racemic syntheses
of various members of this family have been developed
since their isolations.[32] The only asymmetric synthesis of
flustramines using catalytic enantioselective methods was re-
ported in 2004 by MacMillan and co-workers.[33]
We envisioned that the C-3 stereocenter of debromoflustr-
amine B can be constructed using the Mo-AAA reaction
and we chose a cyano group as a methylamine surrogate.
Disappointingly, oxindole 5b bearing a prenyl group on the
nitrogen gave only 74% ee for the allylation reaction. This
is in line with our observations from the earlier studies that
a large N-substituent is detrimental to the enantioselectivity
of the reaction. Switching to a smaller N-allyl group im-
proved the enantioselectivity of the reaction to 93%. A
double cross-metathesis reaction with 2-methylbutene and
the Grubbsꢁ second-generation catalyst then yielded the re-
quired bis-prenyl functionality.[34] Reductive cyclization and
N-methylation under previous reported conditions afforded
debromoflustramine B in 55% yield.[32a] Comparison of opti-
cal rotation with literature reports revealed that the enantio-
mer of the natural product was synthesized (Scheme 5).[31b]
and insecticidal activity against silk worms (LD50
5 mgmLÀ1).[39] Perophoramidine is cytotoxic against the
HCT-116 colon carcinoma cell line (IC50 60 mm) and induces
apoptosis via PARP cleavage.[36]
Given our success with the Mo reactions at forming C-3
quartenary centers of oxindoles, we anticipated that the
quartenary centers in communesin B can be formed by alky-
lation of oxindole 8 (Scheme 6). Reductive cyclization of the
aniline nitrogen with the oxindole amide in 9 should provide
the indolinoquinoline ring system of communesin B. The
second quaternary center would be then constructed via a
diastereoselctive nitrile alkylation.
Scheme 6. Retrosynthetic analysis of communesin B.
Synthesis of a model substrate, oxindole 14, was initiated
with condensation of oxindole 11 with aldehyde 12 under
microwave heating to give 13 as a mixture of alkene iso-
mers. N-Methylation and hydrogenation of 13 then provided
14 in 95% yield. The Mo-catalyzed AAA reaction proceed-
ed well and the allylated product 15 was isolated in 96%
yield and 95% ee. Deprotection of the Boc group with TFA
and dehydrative cyclization with titanium tetraisopropoxide
then provided the dihydro-indolinoquinoline 16 (Scheme 7).
With the establishment of the core ring system asymmetri-
cally, we turned our attention to installing a substituent to in
the benzylic position of the six-membered ring to facilitate
formation of the spiro-fused ring. Thus, a separate model
Scheme 5. Synthesis of debromoflustramine.
Synthesis of the dihydro-indolinoquinoline core of commu-
nesin B and perophoramidine: Closely related polycyclic in-
doline compounds communesin B and perophoramidine
were isolated from marine alga Entermoropha intestinalis[35]
and the Philippine ascidian Perophora namei, respectively.[36]
Synthetic interests in these two and other related structures
have been fueled by a desire to understand their structure–
activity relationships as both compounds contain unusual
structural features and exhibit significant biological activi-
ties.[37–38] Communesin B, in particular, shows both potent
cytotoxicity against P-388 leukemia (ED50 =0.45 mgmLÀ1)
Scheme 7. Preparation of indolinoquinoline 14.
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Molybdenum-Catalyzed Asymmetric Allylic Alkylation
FULL PAPER
system, it was demonstrated that a benzylic cyano group in
17a was tolerated and gave the desired allylated product in
high ee. The stereochemistry of the cyano group was irrele-
vant since we would be subsequently deprotonating it to
effect a diastereoselective alkylation (Scheme 8). However,
in the presence of the ortho-NHBoc group that is required
for the formation of the dihydroquinoline ring, oxindole 17b
underwent an unexpected fragmentation reaction to gener-
ate the allylated product 19.[40]
Conclusion
Transition-metal-catalyzed AAA reactions are powerful
methods for the generation of quaternary carbon centers.
Exploration of metals other than palladium has led to dis-
covery of many new selective transformations. In this in-
stance, we have developed the first enantioselective Mo-cat-
alyzed AAA reaction for the generation of quaternary ste-
reocenters at a prochiral nucleophile, in this case the 3-posi-
tion of 3-alkyl oxindoles. The reaction is successful with a
variety of alkyl substitutions, and its utility is demonstrated
in the synthesis of (À)-physostigmine, ent-(À)-debromo-
flustramine, and the indolinoquinoline core of communesin
B and perophoramidine.
Experimental Section
Representative procedure for Mo-catalyzed AAA reactions: In a sealed
pyrex test tube, a solution of (R,R)-ligand L1 (2.4 mg, 0.015 mmol) and
[(h3-C7H8)Mo(CO)3] (1.4 mg, 0.01 mmol) in THF (freshly distilled and
degassed, 0.3 mL) was stirred at 608C for 5 min under Ar atmosphere. A
second pyrex test tube containing 0.1 mmol of oxindole 1a was trans-
ferred to the dry box and to it LiOtBu (0.2 mmol) was added. The test
tube was sealed, taken out of the dry box, and to it was added THF
(0.7 mL). The resulting solution was stirred for 5 min at room tempera-
ture before the solution of the active catalyst solution was added via can-
nula, followed by the addition of allyl tert-butyl carbonate (0.12 mmol)
via syringe. The reaction was stirred at room temperature for 3–6 h until
TLC indicates complete consumption of 1a. The reaction mixture was
then concentrated and purified through silica gel to give the desired
product 2a (22 mg, 95%, 82% ee). Chiral HPLC, OJ-column, flow rate
1.0 mLminÀ1, heptane/iPrOH 90:10, tA (major)=9.70 min, tB (minor)=
10.90 min; 1H NMR (400 MHz, CDCl3): d=6.92–6.72 (m, 3H), 5.50–5.40
(m, 1H), 5.02–4.91 (m, 2H), 3.80 (s, 3H), 3.17 (s, 3H), 2.54–2.44 (m, 1H),
1.36 ppm (s, 3H); 13C NMR (125 MHz, CDCl3) d=180.1, 156.2, 136.9,
135.2, 132.8, 118.9, 111.8, 110.9, 108.3, 56.0, 48.9, 42.6, 26.4, 23.0 ppm; IR
(film): n˜ = 3077, 2929, 2835, 1715, 1643, 1600, 1504, 1470, 1373, 1291,
Scheme 8. Mo-AAA reaction with oxindole 17a and 17b.
Determination of the absolute chemistry of the product and
proposed mechanism of the reaction: The formal synthesis
of (À)-physostigmine and synthesis of ent-(À)-debromo-
flustramine allowed us to establish the absolute stereochem-
istry of the products of the Mo reactions. The selectivity is
in agreement with the transition state depicted in Scheme 9.
The facial approach in A is favored because it lessens the
steric congestion between the ligand and the enolate of the
oxindole as the C-terminus of the enolate moves towards
the p-allyl. In the alternative approach in B, the steric inter-
action becomes more severe as the bulk of the oxindole is
pushed towards the ligand during the bond formation.
1235, 1204, 1177, 1122, 1037, 920, 741 cmÀ1
.
Acknowledgements
We thank the National Institutes of Health (NIH) (GM33049) and the
National Science Foundation (CHE0846427) for their generous support
of our programs. Mass spectra were provided by the Mass spectrometry
Regional Center of the University of California, San Francisco, supported
by the NIH Division of Research Resources.
[1] For recent reviews of oxindole alkaloids, see: a) C. Marti, E. M. Car-
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Angew. Chem. 2007, 119, 8902; Angew. Chem. Int. Ed. 2007, 46,
8748; c) B. M. Trost, M. K. Brennan, Synthesis 2009, 3003.
[2] For recent synthesis of oxindole alkaloids, see: a) P. S. Baran, J. M.
Richter, J. Am. Chem. Soc. 2005, 127, 15394; b) B. M. Trost, N.
Cramer, H. Bernsmann, J. Am. Chem. Soc. 2007, 129, 3086; c) G. D.
Artman, A. W. Grubbs, R. M. Williams, J. Am. Chem. Soc. 2007,
129, 6336.
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Scheme 9. Model for enantiodiscrimination.
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B. M. Trost and Y. Zhang
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Received: September 4, 2010
Published online: February 2, 2011
2922
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Chem. Eur. J. 2011, 17, 2916 – 2922