Chelation-controlled addition of organozincs to α-chloro aldimines

Article abstract of DOI:10.1021/ja306781z

Nucleophilic additions to α-chiral α-halo carbonyl derivatives are well-known to generate Cornforth-Evans products via a nonchelation pathway. What was unprecedented before this report is C-X bonds reversing the diastereoselectivity through coordination t

Full text of DOI:10.1021/ja306781z

Article
pubs.acs.org/JACS
Chelation-Controlled Addition of Organozincs to α‑Chloro Aldimines
Gretchen R. Stanton,† Per-Ola Norrby,‡ Patrick J. Carroll,† and Patrick J. Walsh*,†
†Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,
Pennsylvania 19104-6323, United States
‡University of Gothenburg, Department of Chemistry and Molecular Biology, Kemigarden 4, #8076, SE-412 96 Goteborg, Sweden
̊
̈
S
* Supporting Information
ABSTRACT: Nucleophilic additions to α-chiral α-halo
carbonyl derivatives are well-known to generate Cornforth−
Evans products via a nonchelation pathway. What was
unprecedented before this report is C−X bonds reversing
the diastereoselectivity through coordination to metals during
C−C bond-forming reactions (chelation control). Herein we
describe chelation control involving C−X bonds in highly
diastereoselective additions of organozinc reagents to a variety
of α-chloro aldimines. The unique ability of alkylzinc halide
Lewis acids to coordinate to the Cl, N, and O of α-chloro sulfonyl imine substrates is supported by computational studies.
1. INTRODUCTION
The traditional approach to complex molecule synthesis is to
use existing substrate stereochemistry to guide the reaction of
achiral reagents and introduce new stereogenic centers.1 As a
result, substrate control continues to be a powerful tool for the
synthesis of small and complex molecules and new methods to
control diastereoselectivity remain in great demand.
Among substrate-controlled approaches to the construction
of carbon skeletons in organic synthesis, the addition of
nucleophiles to C−O and C−N double bonds containing
neighboring stereocenters is important both in the develop-
ment of a conceptual understanding of organic chemistry and in
its broad utility. From a practical standpoint, the introduction
of stereogenic centers on addition of organometallic reagents to
C−O and C−N double bonds is essential for the formation of
C−C bonds and assembly of oxygen- and nitrogen-containing
natural products.2 The seminal work of Cram and Elhafez
almost 60 years ago introduced concepts for predicting and
controlling diastereoselectivity in nucleophilic additions to
CO bonds adjacent to stereogenic centers.3 Since these
pioneering studies, key contributions from Cornforth,4 Felkin,5
Figure 1. Models for 1,2-asymmetric induction. (A) Polar Felkin−Anh
Anh and Eisenstein,6 and Evans7 among others8 have
and Cornforth−Evans models leading to 1,2-anti addition products.
collectively formed the foundation for the current stereo-
induction models. Within this conceptual framework, the
Cornforth−Evans model7,9 is used to rationalize stereochemical
outcomes in additions to α-halogenated carbonyl derivatives.10
This model is based on the premise that dipole (or
electrostatic) effects are responsible for the low energy anti-
parallel orientation of the CY (Y = O, N(PG)) and CX (X
= halogen) bonds leading to an acyclic transition state (Figure
1A). Although distinct from the Felkin−Anh model, the
stereochemical outcome is identical. The significance of these
principles has resulted in their coverage in advanced organic
chemistry textbooks.11
(B) Cram chelation model leading to 1,2-syn addition products.
Similarly, α- and β-silyloxy aldehydes and ketones undergo
nucleophilic additions following the Felkin−Anh model with
few exceptions (Figure 1A).8a,12 In our studies readdressing this
paradigm, we identified a remarkable class of Lewis acids, alkyl
zinc halides (RZnX) and fluorinated sulfonates (RZnO3SRF),
which chelate to α- and β-silyloxy aldehydes and ketones and
Received: July 12, 2012
Published: September 24, 2012
© 2012 American Chemical Society
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resulted in the formation of addition products with a 8:1
diastereomeric ratio (dr) favoring the syn diastereomer, albeit in
low yield (50%). Encouraged by the 8:1 dr, we set out to
minimize the formation of reduction product (4) and optimize
the diastereoselectivity of the reaction. Lowering the reaction
temperature to −15 °C resulted in a slightly improved yield of
60% but a diminished dr (entry 3). Increasing the EtZnBr to 3
equiv and reducing the amount of Et2Zn provided the
chelation-controlled product with a 11:1 dr and 6.8:1 ratio of
ethyl addition to reduction products (entries 4 and 5). Use of
EtZnBr without Et2Zn gave product with a 1.5:1 dr (entry 6).
Employing other zinc Lewis acids did not improve the
diastereoselectivity of the reaction (entries 7 and 8).
Using the optimized conditions in Table 1 (entry 5), various
α-chloro aldimine precursors afforded chelation-controlled
addition products with good to excellent diastereoselectivity
(Table 2). Similar results were obtained when the isolated
aldimine was used (Table 2, entries 1 and 3). Additionally,
commercially available dimethylzinc can be employed with
comparable diastereoselectivities and improved yields. The R
group on ZnR2 and RZnX should be identical due to rapid alkyl
exchange between zinc species.19
To determine the generality of chelation control with more
reactive organozinc nucleophiles, we investigated the addition
of vinylzinc reagents to α-chloro aldimines. It is noteworthy
that the addition products are valuable functionalized allylic
amines.20 We conceived a one-pot procedure in which both the
vinylzinc reagent and aldimine are formed in situ. Toward this
end, the Oppolzer−Srebnik procedure21 was utilized to
generate the (E)-vinylzinc intermediates. Thus, hydroboration
of a terminal or internal alkyne and subsequent B to Zn
transmetalation21c with ZnMe2 were followed by the addition
of EtZnBr and the aldimine precursor.
After extensive screening, we found that optimal yields and
diastereoselectivities were accomplished by initiating the
addition step at −78 °C and then warming the reaction
mixture to −45 °C. As illustrated in Table 3 (entries 1−7), a
variety of terminal and internal alkynes can be used to generate
allylic β-chloroamines with excellent dr values (≥20:1).
Moreover, substitution at the α-position can be varied while
maintaining high levels of diastereoselectivity (entries 8−11).
Notably, despite the structural variation of the vinylzinc
Figure 2. In situ generation of α-chloro aldimine.
enable the chelation-controlled addition of organozinc reagents
to these substrates.13
These surprising results led us to wonder if even less Lewis
basic groups might coordinate to alkyl zinc halide Lewis acids.
Far less Lewis basic than silyl ethers are alkyl halides.
Coordination of alkyl halides to transition metals has been
documented.14 However, we are aware of only three examples
of chelation-controlled addition of nucleophiles to α-halo
carbonyl or imino substrates, and all involve hydride addition to
α-fluoro carbonyl derivatives.15 Addition of carbon-based
nucleophiles presents a distinct set of challenges compared to
additions of the smaller hydride nucleophile. Herein we report
a highly diastereoselective approach for chelation-controlled
addition of a variety of alkyl and vinyl zinc reagents to α-chloro
aldimines to generate products arising from chelation of the
chlorine, nitrogen, and sulfonyl oxygen. Computational studies
to probe the reversal of selectivity predicted by the Cornforth−
Evans model support chelation of α-chloro aldimines to RZnBr.
These reactions represent the first examples of highly
diastereoselective halide directed chelation-controlled C−C
bond-forming reactions.
2. RESULTS AND DISCUSSION
To demonstrate the feasibility of developing an efficient
approach for chelation-controlled additions to α-chloro
aldimines, we examined the reaction of commercially available
diethylzinc with aldimine precursor 1.16 We envisioned a one-
pot procedure in which an excess of diethylzinc first acts as base
to generate the reactive α-chloro aldimine in situ, as outlined in
Figure 2.17 In the absence of a Lewis acid, the reaction of
diethylzinc with 1 provides reduction product 4 predominantly
and only trace amounts of addition product (Table 1, entry 1).
Reduction most likely occurred via a β-hydride transfer
mechanism.18 Employing 1.5 equiv of EtZnBr with ZnEt2
Table 1. Optimization of Addition Product Formation and syn-Diastereoselectivity in the Addition of Diethylzinc to α-Chloro
Aldimine 1
a
a
entry
Lewis acid (LA)
1:LA:Et2Zn
temp (°C)
addition:reduction
dr (2:3)
1
2
3
4
5
6
7
8
−
1.0:0:5.0
0
trace addition
1:1
−
EtZnBr
EtZnBr
EtZnBr
EtZnBr
EtZnBr
EtZnCl
EtZnONf
1.0:1.5:5.0
1.0:1.5:5.0
1.0:1.5:3.0
1.0:3.0:3.0
1.0:3.0:0
0
−15
0
8:1
2:1
8:1
11:1
1.5:1
7:1
3:1
1.5:1
3.5:1
0
6.8:1
1:0
0
1.0:3.0:3.0
1.0:3.0:3.0
0
6.3:1
0
1:1.5
a
1
Ratios determined by analysis of H NMR spectra of unpurified products.
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Table 2. Chelation-Controlled Addition of Diethyl- and
Dimethylzinc to in Situ Generated α-Chloro Aldimines
Table 3. One-Pot Chelation-Controlled Addition of
Vinylzinc Reagents to α-Chloro Aldimines
a
Aldimine generated in situ from sulfone precursor unless otherwise
b
stated. dr determined by analysis of 1H NMR spectra of the
unpurified reaction products and refers to the ratio of chelation:Corn-
c
forth/Felkin products. Isolated aldimine can be used, and comparable
diastereoselectivity and yield were observed. Relative product
stereochemistry was confirmed by X-ray analysis.
d
a
dr determined by 1H NMR of the crude reaction products and refers
b
to the ratio of chelation:Cornforth/Felkin products. Comparable
diastereoselectivity and yield obtained in the reaction using isolated
c
d
reagents and aldimine substrates, all reactions proceeded via
chelation control.
imine. Reaction on 5 mmol scale. Reaction carried out using
enantioenriched starting material with no erosion of ee (see
Supporting Information).
In addition to the fundamental significance of chelation-
controlled diastereoselectivity involving C−Cl bonds, these
addition reactions have practical utility. The reaction in entry 1
was performed on a 2 g scale to furnish the chelation-controlled
product in 89% yield with a >20:1 dr. Equally important for
practical application is the compatibility of the reaction
conditions with enantioenriched substrates. When the reaction
was conducted using an enantioenriched aldimine precursor, no
erosion of ee was observed in the addition product (entry 8; see
Supporting Information for details).
To gain insight into the generality of C−X bond
participation in chelation-controlled diastereoselective pro-
cesses, we investigated the reaction of diethylzinc with an α-
bromo aldimine (eq 1). Upon subjecting the α-bromo aldimine
precursor to diethylzinc and EtZnBr, the chelation controlled
addition product was isolated in 83% yield with 5:1 dr.
It is noteworthy that the products of the addition reactions
can be readily converted to the aziridines. Exposure of the β-
chloroamine products to K2CO3 in acetonitrile resulted in ring
closure to provide aziridines in high yield (eqs 2 and 3).
Computational Studies.22 Alkyl zinc additions to carbon-
yls have been extensively studied both experimentally23 and
theoretically.22,24 In the widely accepted mechanism, one Zn
moiety plays two roles: as a Lewis acid the Zn coordinates the
substrate while also binding a Lewis basic group to which the
dialkylzinc moiety bonds and reacts with the activated carbonyl.
In the current case, we hypothesize the alkyl zinc halide fills the
role of the activating moiety, with the halide available for
coordination to the second zinc. In most cases, it is believed
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Figure 5. Simplified transition states leading to the syn and anti
products. The four- and six-membered transition states are highlighted
in red. Note that for the purpose of clarity, enantiomeric aldimines are
used in drawings A,B vs C,D. In all cases, the dimethylzinc is attacking
the imine from the bottom face.
Figure 4. Transition states leading to syn and anti products based on
computational studies. (A) Six-membered ring TS leading to syn
product, 90% (best TS, M06/II, other levels >90%). (B) Four-
membered ring TS leading to syn product, 9% (ca. 6 kJ/mol higher
than best TS, M06/II). (C) Six-membered ring TS leading to anti
product, 0.9% (ca. 12 kJ/mol higher than best TS, M06/II). (D) Four-
membered ring TS leading to anti product, 0.1% (ca. 18 kJ/mol higher
than best TS, M06/II). Structures are drawn in Figure 5 and highlight
the four- and six-membered rings.
even if the energy difference decreases with the larger basis set
(Table 4). It is noteworthy that when two fairly different
methods of calculations (B3LYP and MO6 in this case) give the
same qualitative results, the conclusions can be considered
more reliable. Figure 5 highlights the key four- and six-
membered rings in the transition states in red. As shown in the
calculated structure, in the attack of dimethylzinc on the imine
carbonyl, the chelate structure with MeZnCl coordination to
the α-Cl is favored, restricting the bond rotation and enforcing
a specific orientation of the α-methyl group (Figure 4A). In the
TS leading to the syn-product, the α-methyl group points away
from the reaction center, giving a facile addition. For addition
leading to the anti-product (Figure 4C and 4D), the α-methyl
group is forced close to the reaction center, at a high steric cost,
irrespective of whether the four- or six-membered addition path
is followed. The relative barriers, at different levels of theory,
are shown in Table 4, with the highest accuracy expected from
the dispersion-corrected functional with the larger basis set,
MO6/BSIII.25 The high-energy difference between paths to
anti and syn products correspond well to the excellent
experimental selectivity.
Table 4. Relative Calculated Barriers for Different Additions
a
(kJ mol−1)
product
TS ring size
B3LYP/BSI
M06/BSII
M06/BSIII
anti
anti
syn
syn
4
6
4
6
36
15
22
0
27
14
10
0
17
12
6
0
a
Comparison of four- and six-membering ring transition states leading
to syn or anti addition products. See Figures 4 and 5 for transition state
structures.
that the dialkylzinc forms a four-membered ring transition state
(TS) with the carbonyl.22 However, it has been suggested that a
six-membered ring TS is also possible.24a,j In the current case,
we elected to investigate both possible addition types, with the
dialkylzinc moiety coordinated to either the N or O of the
sulfonyl imine in the TS. As a computational model system, we
selected the reaction of N-mesyl-protected α-chloro-propani-
mine, CH3CHClCHNSO2Me, with methyl zinc
chloride (MeZnCl) and dimethylzinc (Me2Zn). Upon geom-
etry optimization of the reactants, MeZnCl and Me2Zn form a
loose complex with the α μ-Cl bridge. Attempts to bring this
species into a chelate formed by the imine nitrogen and α-Cl
moiety instead result in a complex where the two sulfonyl
oxygens each coordinate one Zn atom. This complex has
virtually free rotation of the NCCCl bond and would
not be expected to lead to the high diastereoselectivities
observed. Interestingly, contrary to the expectation from earlier
studies of related systems, the six-membered ring TS is
preferred over the more commonly seen four-membered ring
TS (Figures 4A and 4B).24a,j,k This is true at all levels of theory,
3. CONCLUSION
Substrate control has become a cornerstone in asymmetric
synthesis. In particular, the models used to predict stereo-
chemical outcomes in nucleophilic additions to α-chiral
carbonyl and imine derivatives have been widely accepted for
quite some time. We disclosed a highly diastereoselective
addition reaction that proceeds through an unusual chelation-
controlled pathway involving binding of the α-chloro aldimine
N, O, and Cl to zinc, reversing the inherent selectivity predicted
by the Cornforth−Evans model (Figure 6).
The chelation-controlled pathway is strongly supported by
the experimentally observed stereochemical outcomes of the
addition reactions and by computational studies at several levels
of theory.
4. EXPERIMENTAL SECTION
General procedure for (E)-vinylzinc addition to α-chloro aldimine: A
dry 10 mL Schlenk flask, which was evacuated under vacuum and
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(2) (a) Bloch, R. Chem. Rev. 1998, 98, 1407. (b) Kobayashi, S.; Mori,
Y.; Fossey, J. S.; Salter, M. M. Chem. Rev. 2011, 111, 2626.
(3) (a) Cram, D. J.; Elhafez, F. A. A. J. Am. Chem. Soc. 1952, 74, 5828.
(b) Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81, 2748.
(4) Cornforth, J. W.; Cornforth, R. H.; Mathew, K. K. J. Chem. Soc.
1959, 112.
(5) Cher
2199.
́
est, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 18,
Figure 6.
(6) Anh, N.; Eisenstein, O. Nouv. J. Chim. 1977, 1, 61.
(7) Evans, D. A.; Siska, S. J.; Cee, V. J. Angew. Chem., Int. Ed. 2003,
42, 1761.
backfilled with N2 (g) three times, was charged with dicyclohexylbor-
ane (Cy2BH) (107 mg, 0.6 mmol) and dichloromethane (0.7 mL).
The solution was cooled to 0 °C followed by slow addition of alkyne
(0.6 mmol). After 5 min the reaction was warmed to room
temperature and stirred for an additional 15 min. The solution was
cooled to −78 °C, and dimethylzinc (Me2Zn) (0.75 mL, 2 M in
dichloromethane) was added. After stirring at −78 °C for 30 min,
EtZnBr (0.4 mmol) was added under a steady flow of N2 (g).
Immediately thereafter, the aldimine precursor (0.2 mmol, in 0.2 mL
of dichloromethane) was added. The reaction mixture was warmed to
−45 °C and monitored until completion as determined by TLC
(usually 4−6 h). The reaction mixture was quenched with 1 M HCl (2
mL) followed by addition of 5 mL of EtOAc. The organic layer was
separated, and the aqueous layer was extracted successively with
EtOAc (2 × 5 mL). The combined organic layers were successively
washed with aq. NaHCO3 and brine, dried over MgSO4, and filtered.
The filtrate was concentrated in vacuo and purified by column
chromatography on silica gel.
(8) (a) Chen, X.; Hortelano, E. R.; Eliel, E. L.; Frye, S. V. J. Am.
Chem. Soc. 1990, 112, 6130. (b) Karabatsos, G. J. J. Am. Chem. Soc.
1967, 89, 1367.
(9) Cee, V. J.; Cramer, C. J.; Evans, D. A. J. Am. Chem. Soc. 2006,
128, 2920.
(10) Mengel, A.; Reiser, O. Chem. Rev. 1999, 99, 1191.
(11) (a) Clayden, J.; Greeves, N. In Organic Chemistry; Oxford
University Press: New York, 2001; p 889. (b) Bruckner, R. In
Advanced Organic Chemistry: Reaction Mechanisms; Academic Press:
San Diego, 2002; p 315. (c) Carey, F. A.; Sundberg, R. J. In Advanced
Organic Chemistry: Part A: Structure and Mechanisms, 5th ed.; Springer:
New York, 2007; p 179.
(12) (a) Reetz, M. T.; Huellmann, M. J. Chem. Soc., Chem. Commun.
̈
1986, 1600. (b) Chen, X.; Hortelano, E. R.; Eliel, E. L.; Frye, S. V. J.
Am. Chem. Soc. 1992, 114, 1778. (c) Evans, D. A.; Allison, B. D.; Yang,
M. G. Tetrahedron Lett. 1999, 40, 4457. (d) Evans, D. A.; Allison, B.
D.; Yang, M. G.; Masse, C. E. J. Am. Chem. Soc. 2001, 123, 10840.
(e) Borg, T.; Danielsson, J.; Mohiti, M.; Restorp, P.; Somfai, P. Adv.
Synth. Catal. 2011, 353, 2022. (f) Dunning, T. H. J. Chem. Phys. 1989,
90, 1007.
Computational Details. Reported free energies (in kJ mol−1) are
calculated with Jaguar (version 7.7, Schrodinger, LLC, New York, NY,
2010) using the M06 level at B3LYP geometries,26 with corrections for
thermodynamic contributions and continuum benzene solvation,27 as
described in detail in the Supporting Information. For B3LYP
calculations, we use the LACVP*28 basis set (BSI). For single-point
M06 calculations, we use the cc-PVTZ*+ basis set29 for light elements,
with either the Hay−Wadt ECP(BSII) or an all-electron TZV* basis
set12f,30 (BSIII) for Zn.
(13) (a) Stanton, G. R.; Johnson, C. N.; Walsh, P. J. J. Am. Chem. Soc.
2010, 132, 4399. (b) Stanton, G. R.; Koz, G.; Walsh, P. J. J. Am. Chem.
Soc. 2011, 133, 7969. (c) Stanton, G. R.; Kauffman, M. C.; Walsh, P. J.
Org. Lett. 2012, 14, 3368.
(14) Kulawiec, R. J.; Crabtree, R. H. Coord. Chem. Rev. 1990, 99, 89.
(15) (a) Hanamoto, T.; Fuchikami, T. J. Org. Chem. 1990, 55, 4969.
(b) Mohanta, P. K.; Davis, T. A.; Gooch, J. R.; Flowers, R. A. I. J. Am.
Chem. Soc. 2005, 127, 11896. (c) Malamakal, R. M.; Hess, W. R.;
Davis, T. A. Org. Lett. 2010, 12, 2186.
(16) Chemla, F.; Hebbe, V.; Normant, J.-F. Synthesis 2000, 75.
̂ ́
(17) Cote, A.; Boezio, A. A.; Charette, A. B. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5405.
(18) DiMauro, E. F.; Kozlowski, M. C. J. Am. Chem. Soc. 2002, 124,
12668.
(19) Blake, A. J.; Shannon, J.; Stephens, J. C.; Woodward, S. Chem.
Eur. J. 2007, 13, 2462.
(20) Johannsen, M.; Jørgensen, K. A. Chem. Rev. 1998, 98, 1689.
(21) (a) Oppolzer, W.; Radinov, R. N. HeIv. Chim. Acta 1992, 75,
170. (b) Oppolzer, W.; Radinov, R. N.; Brabander, J. D. Tetrahedron
Lett. 1995, 36, 2607. (c) Srebnik, M. Tetrahedron Lett. 1991, 32, 2449.
(22) Yamakawa, M.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 6327.
(23) (a) Evans, D. Science 1988, 240, 420. (b) Noyori, R.; Kitamura,
M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49. (c) Soai, K.; Niwa, S.
Chem. Rev. 1992, 92, 833. (d) Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101,
757. (e) Buono, F.; Walsh, P. J.; Blackmond, D. G. J. Am. Chem. Soc.
2002, 124, 13652. (f) Chen, Y. K.; Costa, A. M.; Walsh, P. J. J. Am.
Chem. Soc. 2001, 123, 5378.
(24) (a) Rasmussen, T.; Norrby, P.-O. J. Am. Chem. Soc. 2001, 123,
2464. (b) Rasmussen, T.; Norrby, P.-O. J. Am. Chem. Soc. 2003, 125,
5130. (c) Panda, M.; Phuan, P.-W.; Kozlowski, M. C. J. Org. Chem.
2003, 68, 564. (d) Goldfuss, B.; Houk, K. N. J. Org. Chem. 1998, 63,
8998. (e) Goldfuss, B.; Steigelmann, M.; Khan, S. I.; Houk, K. N. J.
Org. Chem. 2000, 65, 77. (f) Goldfuss, B.; Steigelmann, M.; Rominger,
ASSOCIATED CONTENT
* Supporting Information
■
S
Procedures, full characterization of new compounds, calculated
structures and energies, and crystallographic data for 5c and 6b.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
pwalsh@sas.upenn.edu
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the NSF (CHE-0848467 and 1152488) for support
of this work. We are also grateful to Prof. Marisa Kozlowski
(University of Pennsylvania) for helpful discussions. G.R.S.
thanks UNCF−Merck and NOBCChE/GlaxoSmithKline pro-
grams, ACS Organic Division, and Amgen for graduate
scholarships.
REFERENCES
■
(1) (a) Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis;
Wiley: New York, 1989. (b) Hoveyda, A. H.; Evans, D. A.; Fu, G. C.
Chem. Rev. 1993, 93, 1307. (c) Carreira, E. M.; Kvaerno, L. Classics in
Stereoselective Synthesis; Wiley-VCH: Weinheim, Germany, 2009.
(d) Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis; VCH:
Weinheim, Germany, 1996.
F. Eur. J. Org. Chem. 2000, 2000, 1785. (g) Vaz
́ ̀
quez, J.; Pericas, M. A.;
Maseras, F.; Lledos, A. J. Org. Chem. 2000, 65, 7303. (h) Vidal-Ferran,
́
A.; Moyano, A.; Pericas, M. A.; Riera, A. Tetrahedron Lett. 1997, 38,
8773. (i) Yamakawa, M.; Noyori, R. Organometallics 1999, 18, 128.
(j) Brandt, P.; Hedberg, C.; Lawonn, K.; Pinho, P.; Andersson, P. G.
17603
dx.doi.org/10.1021/ja306781z | J. Am. Chem. Soc. 2012, 134, 17599−17604

Journal of the American Chemical Society
Article
Chem.Eur. J. 1999, 5, 1692. (k) Keinicke, L.; Fristrup, P.; Norrby, P.-
O.; Madsen, R. J. Am. Chem. Soc. 2005, 127, 15756.
(25) Averkiev, B. B.; Zhao, Y.; Truhlar, D. G. J. Mol. Catal. A: Chem.
2010, 324, 80.
(26) (a) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J.
J. Phys. Chem. 1994, 98, 11623. (b) Becke, A. D. J. Chem. Phys. 1993,
98, 5648. (c) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. Rev. B 1988, 37,
785.
(27) Marten, B.; Kim, K.; Cortis, C.; Friesner, R. A.; murphy, R. B.;
Ringnalda, M. N.; Sitkoff, D.; Honig, B. J. Phys. Chem. 1996, 100,
11775.
(28) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284.
(29) Woon, D. E.; Dunning, T. H. J. Chem. Phys. 1993, 98, 1358.
(30) Schafer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys. 1994, 100,
5829.
17604
dx.doi.org/10.1021/ja306781z | J. Am. Chem. Soc. 2012, 134, 17599−17604