Synthesis of axially chiral amino acid and amino alcohols via additive-ligand-free Pd-catalyzed domino coupling reaction and subsequent transformations of the product amidoaza[5]helicene

Article abstract of DOI:10.1021/jo101524t

Novel optically active axially chiral amino acid and amino alcohols have been synthesized efficiently via lactam ring-opening, with the aid of an optically active alcohol, amidoaza[5]helicene 5, which has been readily prepared by an additive-ligand-free P

Full text of DOI:10.1021/jo101524t

pubs.acs.org/joc
Unnatural amino acids are chiral molecules that have
Synthesis of Axially Chiral Amino Acid and Amino
Alcohols via Additive-Ligand-Free Pd-Catalyzed
Domino Coupling Reaction and Subsequent
attracted attention as promising organocatalysts2 and
ligands3 for asymmetric synthesis as well as chiral building
blocks for peptidomimetics.4 Although unnatural amino
acids possessing central chirality have been well developed,5
the synthesis and application of axially chiral amino acids
have not yet been fully exploited.6 C2-Symmetric 2,20-diamino
analogue 27 and 2,20-dicarboxylic acid analogue 38 have been
widely employed as chiral inducers in a variety of asymmetric
syntheses. However, the corresponding non-C2-symmetric
binaphthyl amino acid 1, one of the simplest axially chiral
amino acids possessing amino and carboxylic acid groups at
the C-2 and C-20 positions, has not been reported to date
(Figure 1).
Transformations of the Product Amidoaza[5]helicene
Takumi Furuta,*,† Junya Yamamoto,† Yuki Kitamura,‡
Ayano Hashimoto,‡ Hyuma Masu,§ Isao Azumaya,§
Toshiyuki Kan,‡ and Takeo Kawabata†
†Institute for Chemical Research, Kyoto University,
Uji 611-0011, Kyoto, Japan, ‡School of Pharmaceutical
Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku,
Shizuoka 422-8526, Japan, and §Faculty of Pharmaceutical
Sciences at Kagawa Campus, Tokushima Bunri University,
1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
furuta@fos.kuicr.kyoto-u.ac.jp
Received August 3, 2010
FIGURE 1. Axially chiral binaphthyls.
Non-C2-symmetric axially chiral biaryl compounds have
been most commonly prepared by using transition-metal
catalyzed cross-coupling reactions between aryl halides or
triflates and aryl metal species. Although cross-coupling
(4) For reviews on amino acids as building blocks for peptidomimetics,
see: (a) Seebach, D.; Gardiner, J. Acc. Chem. Res. 2008, 41, 1366–1375.
(b) Horne, W. S.; Gellman, S. H. Acc. Chem. Res. 2008, 41, 1399–1408.
(5) For reviews on central chiral unnatural amino acids, see: (a) Perdih,
A.; Dolenc, S. Curr. Org. Chem. 2007, 11, 801–832. (b) de Graaf, A. J.;
Kooijman, M.; Hennink, W. E.; Mastrobattista, E. Bioconjugate Chem.
2009, 20, 1281–1295.
(6) For examples of axially chiral amino acid, see: (a) Ridvan, L.;
Abdallah, N.; Holakovsky, R.; Tichy, M.; Zvada, J. Tetrahedron: Asymme-
try 1996, 7, 231–236. (b) Mazaleyrat, J.-P.; Gaucher, A.; Wakselman, M.;
Tchertanov, L.; Guilhem, J. Tetrahedron Lett. 1996, 37, 2971–2974.
Novel optically active axially chiral amino acid and
amino alcohols have been synthesized efficiently via
lactam ring-opening, with the aid of an optically active
alcohol, amidoaza[5]helicene 5, which has been readily
prepared by an additive-ligand-free Pd catalyzed domino
coupling reaction in a single step. The stereostructures of
these chiral molecules have also been clarified.
ꢀ
(c) Tichy, M.; Holanova, J.; Zavada, J. Tetrahedron: Asymmetry 1998, 9,
3497–3504. (d) Ridvan, L.; Budesinsky, M.; Tichy, M.; Malon, P.;
ꢀ
ꢀ
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Zavada, J.; Podlaha, J.; Cısarova, I. Tetrahedron 1999, 55, 12331–12348.
(e) Formaggio, F.; Crisma, M.; Toniolo, C.; Tchertanov, L.; Guilhem, J.;
Mazaleyrat, J.-P.; Gaucher, A.; Wakselman, M. Tetrahedron 2000, 56, 8721–
8734. (f) Formaggio, F.; Peggion, C.; Crisma, M.; Toniolo, C.; Tchertanov,
L.; Guilhem, J.; Mazaleyrat, J.-P.; Goubard, Y.; Gaucher, A.; Wakselman,
M. Helv. Chem. Acta 2001, 84, 481–501. (g) Kano, T.; Takai, J.; Tokuda, O.;
Maruoka, K. Angew. Chem., Int. Ed. 2005, 44, 3055–3057. (h) Kano, T.;
Tokuda, O.; Maruoka, K. Tetrahedron Lett. 2006, 47, 7423–7426. (i) Kano,
T.; Tokuda, O.; Takai, J.; Maruoka, K. Chem. Asian. J. 2006, 1-2, 210–215.
(j) Wright, K.; Lohier, J.-F.; Wakselman, M.; Mazaleyrat, J.-P.; Formaggio,
F.; Peggion, C.; Zotti, M. D.; Toniolo, C. Tetrahedron 2008, 64, 2307–2320.
(k) Dutot, L.; Wright, K.; Gaucher, A.; Wakselman, M.; Mazaleyrat, J.-P.;
Zotti, M. D.; Peggion, C.; Formaggio, F.; Toniolo, C. J. Am. Chem. Soc.
2008, 130, 5986–5992.
Axially chiral biaryls, such as BINOL and BINAP are
well-known as reliable chiral inducers in asymmetric synthe-
sis as well as key components of asymmetric molecular
recognition in host-guest chemistry. The discovery of novel
axially chiral biaryl groups and the development of efficient
synthetic methods to prepare them are increasing in impor-
tance with the increasing prevalence of chirality in pharma-
ceuticals and organic materials.1
(7) For examples, see: (a) Huang, H.; Okuno, T.; Tsuda, K.; Yoshimura,
M.; Kitamura, M. J. Am. Chem. Soc. 2006, 128, 8716–8717. (b) Kano, T.;
Tanaka, Y.; Maruoka, K. Org. Lett. 2006, 8, 2687–2689. (c) Sakakura, A.;
Suzuki, K.; Nakano, K.; Ishihara, K. Org. Lett. 2006, 8, 2229–2232.
(d) Sakakura, A.; Suzuki, K.; Ishihara, K. Adv. Synth. Catal. 2006, 348,
2457–2465. (e) Kano, T.; Tanaka, Y.; Maruoka, K. Tetrahedron 2007, 63,
8658–8664. (f) Kano, T.; Tanaka, Y.; Osawa, K.; Yurino, T.; Maruoka, K.
J. Org. Chem. 2008, 73, 7387–7389. (g) Rabalakos, C.; Wulff, W. D. J. Am.
Chem. Soc. 2008, 130, 13524–13525. (h) Alamsetti, S. K.; Mannam, S.;
(1) For reviews on axially chiral biaryls, see: (a) Bringmann, G.; Price
Mortimer, A. J.; Keller, P. A.; Gresser, M. J.; Garner, J.; Breuning, M.
Angew. Chem., Int. Ed. 2005, 44, 5384–5427. (b) Baudoin, O. Eur. J. Org.
Chem. 2005, 4223–4229.
(2) For reviews on amino acids as organocatalysts, see: (a) List, B. Acc.
Chem. Res. 2004, 37, 548–557. (b) Notz, W.; Tanaka, F.; Barbas, C. F., III.
Acc. Chem. Res. 2004, 37, 580–591. (c) List, B. Chem. Commun. 2006, 819–
824.
Mutupandi, P.; Sekar, G. Chem. Eur. J. 2009, 15, 1086–1090.
;
(8) For examples, see: (a) Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc.
2007, 129, 10054–10055. (b) Hashimoto, T.; Hirose, M.; Maruoka, K. J. Am.
Chem. Soc. 2008, 130, 7556–7557.
(3) For a review on amino acids as ligands, see: Ma, D.; Cai, Q. Acc. Chem.
Res. 2008, 41, 1450–1460.
7010 J. Org. Chem. 2010, 75, 7010–7013
Published on Web 09/14/2010
DOI: 10.1021/jo101524t
r
2010 American Chemical Society

Furuta et al.
JOCNote
SCHEME 1. Synthetic Plan
TABLE 1. Domino Coupling under Additive-Ligand-Free Conditions
entry
4
Rb
cat.c
base
solvent time (h)
5
yield (%)
1
2
3
4
5
6
4a PMB Pd(OAc)2 Cs2CO3 dioxane
4a PMB Pd(OAc)2 Cs2CO3 toluene
4a PMB Pd(OAc)2 Cs2CO3 DMF
4a PMB Pd2(dba)3 Cs2CO3 DMF
4a PMB Pd2(dba)3 Na2CO3 DMF
4a PMB Pd2(dba)3 K2CO3 DMF
32
24
18
12
12
12
30
16
10
48
12
12
5a
5a
5a
5a
5a
5a
5a
5b
5c
5d
5e
5f
78
46
60
78
74
100
96
98
91
51
38
reactions represent a promising strategy for the synthesis of
axially chiral compounds, they require the separate prepara-
tion of each coupling partner. This requirement sometimes
complicates the preparation of non-C2-symmetric biaryl
groups compared with the preparation of C2-symmetric com-
pounds because the latter can be prepared by using a homo-
coupling reaction from a single starting material.
One drawback to the use of transition-metal-catalyzed
coupling reactions is the requirement for expensive ligands
under many reaction conditions. Therefore, ligand-free cou-
pling reactions have recently been investigated for ecological
and economic benefits.9 Ligand-free conditions that facil-
itate the large scale synthesis of axially chiral biaryl com-
pounds, however, have scarcely been investigated.10
We have previously developed the Pd-catalyzed domino
homocoupling reaction of o-bromoarylamide derivatives to
yield phenanthridinone derivatives in the presence of phos-
phine ligands.11 During the course of our investigation of the
domino coupling reactions, we found that the coupling
reaction of o-bromonaphthamide derivative 4 proceeded
smoothly under an additive-ligand-free conditions to afford
coupling product 5 (Scheme 1). The homocoupling of a single
starting material 4 afforded a non-C2-symmetric binaphthyl
compound possessing amide nitrogen and carbonyl substitu-
ents on the distinct naphthyl moieties of 5. Because compound
5 contains an amide group within a fused pentacyclic-ring
system, it represents a novel variant of a azahelicene derivative
that could be named amidoaza[5]helicene.
7a 4a PMB Pd2(dba)3 K2CO3 DMF
8
9
4b Bn Pd2(dba)3 K2CO3 DMF
4c n-Bu Pd2(dba)3 K2CO3 DMF
10 4d PMP Pd2(dba)3 K2CO3 DMF
11 4e Pd2(dba)3 K2CO3 DMF
12 4f Boc Pd2(dba)3 K2CO3 DMF
H
aThe reaction was conducted with 0.5 mol % of Pd2(dba)3. bPMB =
p-methoxybenzyl, PMP = p-methoxyphenyl. cdba = dibenzylideneacetone.
ring-opening and optical resolution (Scheme 1). Herein, we
report the syntheses of optically active amino acid 1 and
amino alcohol 6, which were accessed from compound 5.
We initially investigated the additive-ligand-free domino
coupling conditions of o-bromonaphthamide derivatives 4 to
generate amidoaza[5]helicene 5 (Table 1). Upon treatment
of N-PMB (p-methoxybenzyl)bromonaphthamide 4a with
Pd(OAc)2 (6 mol %) in the presence of Cs2CO3, the domino
coupling reaction proceeded smoothly to afford 5a in good
yield (Table 1, entry 1). This reaction included successive
C-C (green colored) and C-N bond (red colored) forma-
tions concomitant with a deamidation event.12 Further
optimization of the reaction conditions, including changing
the Pd reagents, base, and solvent, was performed. Use of
toluene or DMF as the solvent was found to diminish the
yield of 5a (Table 1, entries 2 and 3). On the other hand, the
yield was improved in the presence of Pd2(dba)3 and K2CO3
in DMF to afford 5a in quantitative yield (Table 1, entry 6).
Furthermore, the coupling reaction proceeded in the pre-
sence of 0.5 mol % of Pd catalyst to afford 5a in high yield
(Table 1, entry 7). These conditions were readily applicable
to a scale-up synthesis that afforded 5a in gram quantities
(see the Experimental Section). The additive-ligand-free
domino coupling reaction was applicable not only to N-alkyl-
substituted derivatives (entries 8 and 9) but also to an N-aryl
(PMP: p-methoxyphenyl)-substituted substrate (entry 10).
Primary amide 4e13 was also applicable as a substrate for
the reaction (entry 11). However, the coupling reaction of
N-Boc-protected substrate 4f under the optimized conditions
did not occur (entry 12). To the best of our knowledge, this
reaction represents the first example of an additive-ligand-free
Pd-catalyzed domino coupling reaction to yield helicene-type
molecules in a single step.
We envisioned that the amidoaza[5]helicene 5 would be a
valuable intermediate to form novel axially chiral amino acid
1, amino alcohol 6, and related chiral molecules via lactam
(9) For examples, see: (a) Dyker, G. J. Org. Chem. 1993, 58, 6426–6428.
(b) Okano, K.; Tokuyama, H.; Fukuyama, T. Org. Lett. 2003, 5, 4987–4990.
(c) Dyker, G. Angew. Chem., Int. Ed. 2004, 33, 103–105. (d) Felpin, F.-X.
J. Org. Chem. 2005, 70, 8575–8578. (e) Liu, L.; Zhang, Y.; Xin, B. J. Org.
Chem. 2006, 71, 3994–3997. (f) Deng, C.-L.; Guo, S.-M.; Xie, Y.-X.; Li, J.-H.
Eur. J. Org. Chem. 2007, 1457–1462. (g) Maegawa, T.; Kitamura, Y.; Sako,
S.; Udzu, T.; Sakurai, A.; Tanaka, A.; Kobayashi, Y.; Endo, K.; Bora, U.;
Kurita, T.; Kozaki, A.; Monguchi, Y.; Sajiki, H. Chem. Eur. J. 2007, 13,
;
5937–5943. (h) Kitamura, Y.; Sako, S.; Udzu, T.; Tsutsui, A.; Maegawa, T.;
Monguchi, Y.; Sajiki, H. Chem. Commun. 2007, 5069–5071. (i) Felpin, F.-X.;
Lory, C.; Sow, H.; Acherar, S. Tetrahedron 2007, 63, 3010–3016. (j) Liu, C.;
Shen, D.-M.; Chen, Q.-Y. J. Org. Chem. 2007, 72, 2732–2736. (k) Gauthier,
D.; Beckendorf, S.; Gøgsig, T. M.; Lindhardt, A. T.; Skrydstrup, T. J. Org.
Chem. 2009, 74, 3536–3539. (l) Su, Y.; Jiao, N. Org. Lett. 2009, 11, 2980–
2983.
(10) Ullmann coupling reactions are a few examples of a ligand-free
method to afford axially chiral biaryls, although an equivalent amount of Cu
reagent was required. See: (a) Degnan, A. P.; Meyers, A. I. J. Am. Chem. Soc.
1999, 121, 2762–2769. (b) Kelly, T. R.; Xie, R. L. J. Org. Chem. 1998, 63,
8045–8048. (c) Seki, M.; Yamada, S.; Kuroda, T.; Imashiro, R.; Shimizu, T.
Synthesis 2000, 1677–1680.
X-ray crystallographic analysis of PMP-protected deriva-
tive 5d clearly showed the helically twisted structure of the
(12) For a possible reaction mechanism, see ref 11. Also see: Ferraccioli,
R.; Carenzi, D.; Motti, E.; Catellani, M. J. Am. Chem. Soc. 2006, 128,
722–723.
(11) Furuta, T.; Kitamura, Y.; Hashimoto, A.; Fujii, S.; Tanaka, K.;
Kan, T. Org. Lett. 2007, 9, 183–186.
€
ꢀ
(13) Muller, P.; Bolea, C. Helv. Chem. Acta 2001, 84, 1093–1111.
J. Org. Chem. Vol. 75, No. 20, 2010 7011

Furuta et al.
JOCNote
SCHEME 3. Transformation to Axially Chiral Amino Alcohols
and Secondary Aminea
FIGURE 2. Stereostructure of 5d: (a) side view; (b) top view.
(c) [5]Helicene-related compounds.
pentacyclic-ring sysem, in which the dihedral angle of a,b-c,
d was 31° (Figure 2a,b). HPLC analysis of 5a on a chiral
stationary phase exhibited two peaks corresponding to the
enantiomers. The racemization barrier of 5a was estimated
to be 24.6 kcal/mol by following the decrease of optical
purity of the isolated enantiomer of 5a by HPLC analysis.14
This racemization barrier was found to be higher than that of
carbo[5]helicene 7 (23.5 kcal/mol)15 and binaphthyl lactone 8
(21.8 kcal/mol) (Figure 2c).16
aReagent and conditions: (a) LiBH4, THF, 0 °C to rt, (54%); (b) 10%
TFA, CH2Cl2 (83%); (c) PhLi (3 equiv), THF, -78 °C to rt (82%);
(d) t-BuONa, THF, 60 °C (61%); (e) AcOH (10%), EtOAc, H2O (90%).
SCHEME 2. Transformation to Axially Chiral Amino Acida
The ester moiety was removed to generate N-Boc amino
acid (S)-10 in 99% ee. The Boc group of (S)-10 was readily
deprotected with TFA to give novel axially chiral amino acid
(S)-1. Compound 1 was found to be relatively unstable
and spontaneously cyclized to the lactam ring, generating
amidoaza[5]helicene 5e within a few days. The instability of
(S)-1 might explain why the synthesis of this amino acid has not
been reported to date, even though this compound possesses a
simple structure and a promising binaphthyl framework. Grat-
ifyingly, the sodium salt of (S)-1 was stable could be stored
under ambient temperature.
Amino alcohols 6 were also prepared from (S,S)-9
(Scheme 3). Upon treatment of (S,S)-9 with LiBH4, selective
reduction of the ester group proceeded to give N-Boc amino
alcohol (S)-11a. Subsequent deprotection of the Boc group
under acidic conditions afforded (S)-6a in good yield.
Furthermore, amino alcohol (S)-6b that included a diphenyl-
carbinol moiety was also readily synthesized.
Addition of 3 equiv of PhLi to (S,S)-9 yielded (S)-11b,
which was then transformed to amino alcohol (S)-6b by
removal of the Boc group under basic conditions. X-ray
analysis of the racemic form of 11b showed that both the
Boc-protected amine group and hydroxy group were located
around the chiral axis (Figure 3), suggesting that free amino
aReagent and conditions: (a) TFA (100%); (b) n-BuLi, THF, -78 to
0 °C; Boc2O, 0 °C (78%); (c) NaH, (S)-phenylethanol, THF, -78 °C to rt,
(100%); recrystallizaion from hexane-EtOH ((S,S)-9, 40%, 99% de);
(d) Pd(OH)2, MeOH, rt (95%); (e) 10% TFA, CH2Cl2 (76%); (f) NaOH.
Next, we focused on the conversion of 5a to axially chiral
amino acid 1 (Scheme 2). The PMB group of 5a was removed
under acidic conditions to yield 5e. Subsequent introduc-
tion of a Boc group was achieved by treatment of 5e with
n-BuLi and Boc2O to afford 5f. The imide moiety of 5f was
directly cleaved by the in situ generated sodium alkoxide of
(S)-phenylethanol to afford N-Boc ester 9. The diastereomers
of 9were easily separated by recrystallization to afford optically
active (S,S)-9, in which the absolute configuration of the axial
chirality was unambiguously determined by X-ray crystallo-
graphic analysis.17
(14) See the Supporting Information.
(15) For the racemization barrier of 7, see: Goedicke, C.; Stegemeyer, H.
Tetrahedron Lett. 1970, 937–940.
(16) For the racemization barrier of 8, see: Bringmann, G.; Haubes, M.;
€
€
Breuning, M.; Gobel, L.; Ochse, M.; Schoner, B.; Schupp, O. J. Org. Chem.
2000, 65, 722–728.
(17) See the Supporting Information.
FIGURE 3. Stereostructure of racemic 11b: (a) side view; (b) top
view.
7012 J. Org. Chem. Vol. 75, No. 20, 2010

Furuta et al.
JOCNote
FIGURE 4. Stereostructure of racemic 12: (a) side view; (b) top view.
FIGURE 5. Stereostructure of racemic 10: (a) side view; (b) top
view.
alcohols 6a and 6b may be useful as chiral ligands and
catalysts.
through an additive-ligand-free Pd catalyzed domino coupl-
ing to racemic amidoaza[5]helicenes 5, followed by lactam
ring-opening with an optically active alcohol and subsequent
separation of diastereomeric mixture of 9. These novel
binaphthyl molecules have unique structural features that have
the potential to be useful as chiral ligands and catalysts as well
as chiral building blocks. Applications of these molecules in
catalytic asymmetric reactions are currently under investigation
in our laboratory.
Interestingly, treatment of (S)-11b with acetic acid afforded
chiral secondary amine (S)-12 (Scheme 3). The stereostructure
and optical behavior of axially chiral 12 were investigated
(Figure 4). The side view of the X-ray structure of racemic 12
exhibited a twisted π-system having a wider dihedral angle
(a,b-c,d: 45°) than that of amidoaza[5]helicene 5d (Figure 4b
vs Figure 2b). The chirality of the binaphtyl moiety was trans-
ferred to the orientation of the gem-diphenyl moiety. The
stereostructure indicated that the two phenyl groups were
located in the pseudoaxial and equatorial positions. These
conformational properties might be responsible for the higher
racemization barrier of (S)-12 (26.2 kcal/mol)18 than that of 5a.
These results provide evidence that 12 has the potential to be
useful as a chiral amine catalyst.
Experimental Section
Typical Procedure for an Additive-Ligand-Free Domino Coupl-
ing (Table 1, Entry 7). The mixture of 4a (16 g, 43 mmol), Pd2(dba)3
(198 mg, 0.22 mmol, 0.5 mol %), and K2CO3 (6.6 g, 48 mmol) in
DMF (80 mL) was stirred for 30 h at 100 °C under Ar atmosphere.
After the reaction mixture was cooled to rt, H2O was added, and the
mixture was extracted with AcOEt. The organic layer was washed
with H2O and brine, dried over Na2SO4, and evaporated. The
residue was purified by column chromatography on silica gel
(hexane/AcOEt, 5:1) to afford 5a (8.6 g, 96%) as light yellow
needles.
SCHEME 4. Synthesis of Dipeptide
Light yellow needles (n-hexane-AcOEt): mp 229 °C;
1H NMR (400 MHz, CDCl3) δ 3.74 (s, 3H), 5.57 (br d, J = 13.8
Hz, 1H), 5.82 (br s, 1H), 6.82 (d, J = 8.7 Hz, 2H), 7.20-7.35 (m,
4H), 7.39-7.44 (m, 1H), 7.56-7.64 (m, 2H), 7.81-7.94 (m, 3H),
7.96-8.09 (m, 3H), 8.60 (d, J = 8.7 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 46.3, 55.2, 113.5, 114.2, 115.4, 123.7, 124.8, 124.9, 125.3,
125.7, 127.7, 127.8, 128.0, 128.1, 128.5, 128.7, 129.1, 129.2, 129.5,
130.4, 132.8, 135.4, 136.5, 158.7, 162.2; IR (KBr) 1690, 2956, 3057,
3446 cm-1; MS (FAB) m/z 416 (M þ H)þ, 438 (M þ Na)þ; HRMS
(FAB) m/z calcd for C29H22NO2 (M þ H)þ 416.1650, found
416.1649.
As a preliminary application of the utility of axially chiral
amino acids, N-Boc amino acid (S)-10 was tested as a chiral
building block. Condensation of (S)-10 with L-phenylalanine
benzyl ester afforded N-Boc dipeptide 13 in good yield (Scheme 4).
Taking the crystal structure of racemic 10 (dihedral angle
of a,b-c,d: 93°) into account (Figure 5), (S)-10 would be
useful as a chiral building block in peptidomimetic applica-
tions.4 The inclusion of (S)-10 in novel peptides could enforce
unique turn structures because the moieties at C2 and C20 are
located in a perpendicular geometry around the chiral axis.
In summary, we have developed a practical synthesis of
optically active binaphthyl amino acid and amino alcohols
Acknowledgment. This work was financially supported by
Takeda Science Foundation.
Supporting Information Available: Experimental methods,
characterization data for all new compounds, and copies of
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
(18) For the determination of the racemization barrier of 12, see the
Supporting Information.
J. Org. Chem. Vol. 75, No. 20, 2010 7013